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Item 1. Business

2023-03-13 compared with 2022-03-14 · 2842 added, 2486 removed, 339 unchanged (94% of the section changed)

Annual Report on Form 10-K (including the section regarding Management’s Discussion and Analysis of Financial Condition

and Results of Operations) contains forward-looking statements regarding our business, financial condition, results of operations

and prospects.

Words such as “expects,” “anticipates,” “intends,” “plans,” “believes,”

“seeks,” “estimates” and similar expressions or variations of such words are intended to identify forward-looking

statements, but are not deemed to represent an all-inclusive means of identifying forward-looking statements as denoted in this

Annual Report on Form 10-K.

Additionally, statements concerning future matters are forward-looking statements.

forward-looking statements in this Annual Report on Form 10-K reflect the good faith judgment of our Management, such statements

can only be based on facts and factors currently known by us.

Consequently, forward-looking statements are inherently subject

to risks and uncertainties and actual results and outcomes may differ materially from the results and outcomes discussed in or

anticipated by the forward-looking statements.

Factors that could cause or contribute to such differences in results and outcomes

include, without limitation, those specifically addressed under the heading “Risks Factors” below, as well as those

discussed elsewhere in this Annual Report on Form 10-K.

Readers are urged not to place undue reliance on these forward-looking

statements, which speak only as of the date of this Annual Report on Form 10-K.

We file reports with the Securities and Exchange

Commission (“SEC”).

You can read and copy any materials we file or will file with the SEC, which, among other places,

can be found on the SEC's website at http://www.sec.gov, as well as on our corporate website at www.tonixpharma.com).

undertake no obligation to revise or update any forward-looking statements in order to reflect any event or circumstance that

may arise after the date of this Annual Report on Form 10-K.

Readers are urged to carefully review and consider the various disclosures

made throughout the entirety of this Annual Report, which attempt to advise interested parties of the risks and factors that may

affect our business, financial condition, results of operations and prospects.

Pharmaceuticals ® , Tonmya ® , Protectic™, Angstro-Technology™ and other trademarks and

intellectual property of ours appearing in this report are our property.

This report contains additional trade names and trademarks

of other companies.

We do not intend our use or display of other companies’ trade names or trademarks to imply an endorsement

or sponsorship of us by such companies, or any relationship with any of these companies.

Annual Report on Form 10-K (including the section regarding Management’s Discussion and Analysis of Financial Condition and Results

of Operations) contains forward-looking statements regarding our business, financial condition, results of operations and prospects.

such as “expects,” “anticipates,” “intends,” “plans,” “believes,” “seeks,”

“estimates” and similar expressions or variations of such words are intended to identify forward-looking statements, but are

not deemed to represent an all-inclusive means of identifying forward-looking statements as denoted in this Annual Report on Form 10-K.

Additionally,

statements concerning future matters are forward-looking statements.

forward-looking statements in this Annual Report on Form 10-K reflect the good faith judgment of our Management, such statements can only

be based on facts and factors currently known by us.

Consequently, forward-looking statements are inherently subject to risks and uncertainties

and actual results and outcomes may differ materially from the results and outcomes discussed in or anticipated by the forward-looking

Factors that could cause or contribute to such differences in results and outcomes include, without limitation, those specifically

addressed under the heading “Risks Factors” below, as well as those discussed elsewhere in this Annual Report on Form 10-K.

Readers are urged not to place undue reliance on these forward-looking statements, which speak only as of the date of this Annual Report

on Form 10-K.

We file reports with the Securities and Exchange Commission (“SEC”).

You can read and copy any materials we

file or will file with the SEC, which, among other places, can be found on the SEC’s website at http://www.sec.gov, as well as on

our corporate website at www.tonixpharma.com).

undertake no obligation to revise or update any forward-looking statements in order to reflect any event or circumstance that may arise

after the date of this Annual Report on Form 10-K.

Readers are urged to carefully review and consider the various disclosures made throughout

the entirety of this Annual Report, which attempt to advise interested parties of the risks and factors that may affect our business,

financial condition, results of operations and prospects.

Pharmaceuticals ® , Tonmya ® , Protectic™, Angstro-Technology™ and other trademarks and intellectual

property of ours appearing in this report are our property.

This report contains additional trade names and trademarks of other companies.

We do not intend our use or display of other companies’ trade names or trademarks to imply an endorsement or sponsorship of

us by such companies, or any relationship with any of these companies.

We are a clinical-stage biopharmaceutical

company focused on discovering, licensing, acquiring and developing therapeutics and diagnostics to treat and prevent human disease and

alleviate suffering.

We are building capabilities in synthetic biology, precision medicine, protein engineering and vaccine manufacturing

through internal efforts as well as through collaborations with academic institutions and contract research organizations.

Our therapeutics

under development include both small molecules and biologics.

All of our drug, biologic and diagnostic candidates are still in development.

Tonix’s portfolio is primarily

composed of immunology, central nervous system, or CNS, and infectious disease product candidates.

Tonix’s immunology portfolio

includes biologics to address organ transplant rejection, autoimmune diseases and cancer.

The CNS portfolio includes small molecules and

biologics to treat pain, neurologic, psychiatric and addiction conditions.

Tonix’s infectious disease portfolio of product candidates

includes next-generation vaccines to prevent COVID-19, an antiviral to treat COVID-19, and a potential treatment for Long COVID.

The infectious

disease portfolio also includes a vaccine in development to prevent smallpox and monkeypox.

Tonix’s lead candidate within

its immunology pipeline is TNX-1500*, a humanized monoclonal antibody, or mAb, directed against CD40-ligand,

or CD40L, engineered to modulate binding to Fc receptors, that is being developed as a prophylaxis against organ transplant rejection

as well as to treat autoimmune conditions.

In experiments at the Massachusetts General Hospital, a teaching hospital of Harvard Medical

School, TNX-1500 is being studied as monotherapy or in combination with other immunosuppressive agents in heart and kidney organ transplants

in non-human primates.

Preliminary results from an ongoing experiment in heart transplants indicate that TNX-1500 appears to have comparable

efficacy to historical experiments using the chimeric mouse/human IgG1 version (5c8H1) of the anti-CD40L mAb 5c8.

First generation anti-CD40L

mAb were associated with an increased risk of blood clots or thrombosis.

In the non-human primate studies with TNX-1500, no evidence of

thrombosis has been observed so far.

We expect to start a Phase 1 study of TNX-1500 in the second half of 2022.

Among the CNS candidates

in development is TNX-1300* (double-mutant cocaine esterase) which is in Phase 2 for the treatment of life-threatening cocaine intoxication.

TNX-1300 has been granted Breakthrough Therapy designation, or BTD, by the U.S.

Food and Drug Administration, or FDA.

TNX-1300 was licensed

from Columbia University in 2019 after a Phase 2 study showed that it rapidly and efficiently disintegrates cocaine in the blood of volunteers

who received intravenous, or i.v., cocaine.

We expect to initiate a Phase 2 open-label safety study of TNX-1300 in an emergency room setting

in the first half of 2022.

Our latest stage CNS product candidate is TNX-102 SL*, a proprietary sublingual

tablet formulation of CBP, designed for bedtime administration.

TNX-102 SL has active INDs for fibromyalgia, or FM, posttraumatic

stress disorder, or PTSD, agitation in Alzheimer’s disease, or AAD, and alcohol use disorder, or AUD.

We also intend to develop

TNX-102 SL as a treatment for Long COVID, which is also known as post-acute sequelae of COVID-19, or PASC.

TNX-102 SL is in mid-Phase

3 development for the management of FM, a pain disorder characterized by chronic widespread pain, non-restorative sleep, fatigue and impaired

In December 2020, we reported positive results from the Phase 3 RELIEF study of TNX-102 SL 5.6 mg for the management of FM.

company focused on developing therapeutics and vaccines to treat and prevent human disease and alleviate suffering.

We have a rich pipeline

of products in development that has been curated from internal discovery, as well as licenses, acquisitions and collaborations with academic

institutions and contract research organizations.

We continue to build capabilities in synthetic biology, precision medicine, protein

engineering, medicinal chemistry, molecular biology, pharmacogenomics and clinical-scale manufacturing.

Our therapeutics under development

include both small molecules and biologics.

Our portfolio consists of central nervous system, or CNS, rare disease,

immunology, and infectious disease product candidates.

The CNS portfolio includes small molecules and biologics to treat pain, neurologic,

psychiatric and addiction conditions.

Our rare disease portfolio focuses on developing novel therapies for patients with rare diseases,

including those caused by genetic disorders which are characterized by complex symptoms and for which no drug is approved.

Our immunology

portfolio includes biologics to address organ transplant rejection, autoimmune diseases and cancer.

Our infectious disease portfolio includes

a vaccine in development to prevent smallpox and mpox (formerly known as monkeypox), next-generation vaccines to prevent COVID-19, a platform

to make fully human monoclonal antibodies, or mAbs, to treat COVID-19 and humanized anti-SARS-CoV-2 mAbs.

Our vaccine in development to

prevent smallpox and mpox also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious

latest stage CNS product candidate is TNX-102 SL*, a proprietary sublingual tablet formulation of cyclobenzaprine (CBP) designed for

bedtime administration.

TNX-102 SL has active INDs for fibromyalgia, or FM, FM-type Long COVID or PASC (post-acute sequelae of

SARS-CoV-2 infection), posttraumatic stress disorder, or PTSD, agitation in Alzheimer’s disease, or AAD, and alcohol use

disorder, or AUD.

SL is in mid-Phase 3 development for the management of FM, a pain disorder characterized by chronic widespread pain, non-restorative

sleep, fatigue and impaired cognition.

In December 2020, we reported positive results from the Phase 3 RELIEF study of TNX-102 SL

5.6 mg for the management of FM.

In July 2021, we reported pre-planned interim analysis results from a second Phase 3 study, RALLY.

Based on the recommendation from the

independent data monitoring committee that the RALLY trial was unlikely to demonstrate a statistically significant improvement in the

primary endpoint, we stopped enrollment of new participants but allowed those participants who were already enrolled to complete the study.

We expect to report topline data from the completed study in the first quarter of 2022.

We expect to analyze the RALLY results to improve

the design of subsequent Phase 3 studies.

In addition, we plan to employ pharmacogenomic techniques to compare the RALLY and RELIEF study

populations, which may provide a path to precision medicine-based companion diagnostics for TNX-102 SL in FM.

We intend to start a new

Phase 3 study of TNX-102 SL in FM in the first half of 2022.

TNX-102 SL is also being developed as a potential treatment for Long COVID.

We met with the FDA in the third quarter of 2021 to seek agreement on the design of a Phase 2 potential pivotal study and the overall

clinical development plan to qualify TNX-102 SL as an indicated treatment for Long COVID.

We intend to focus our clinical development

on the subgroup of Long COVID patients whose symptoms overlap with FM, particularly with respect to widespread pain.

We received the official

minutes from this meeting in the third quarter of 2021 and intend to initiate a Phase 2 study in the first half of 2022.

TNX-102 SL in PTSD, we completed the Phase 3 RECOVERY trial and reported topline results in the fourth quarter of 2020 in which

TNX-102 SL did not meet the primary efficacy endpoint.

PTSD is a serious psychiatric condition that develops in response to experiencing

a traumatic event.

We subsequently completed a meeting with the FDA to discuss potential new endpoints for the indication of treatment

of PTSD, and we expect to begin enrolling a Phase 2 study of TNX-102 SL in police in Kenya in the first half of 2022.

program is Phase 2 ready with an active IND and FDA Fast Track designation.

Based on the recommendation from the independent data monitoring committee (IDMC) that the RALLY trial was unlikely to demonstrate a

statistically significant improvement in the primary endpoint, we stopped enrollment of new participants but allowed those

participants who were already enrolled to complete the study.

We reported topline data from the completed study in March of 2022.

expected, based on interim analysis results, TNX-102 SL did not achieve statistical significance over placebo on the primary endpoint

of reduction in daily pain, and relative to the previous positive Phase 3 Study (RELIEF), RALLY had an unexpected increase in study

participant adverse event-related discontinuations in both drug and placebo groups.

In April 2022, we started a new potentially

confirmatory Phase 3 study of TNX-102 SL in FM, RESILIENT.

Interim analysis results are expected in the second quarter of 2023 and

topline results are expected in the fourth quarter of 2023.

Following a positive outcome of the RESILIENT study, Tonix believes we

would be positioned to file a New Drug Application (NDA) for TNX-102 SL for the management of FM.

TNX-102 SL is also

being developed as a potential treatment for a type of Long COVID, the symptoms of which overlap with FM, that we term FM-type

We initiated enrollment in the Phase 2 study PREVAIL, in August 2022.

The primary endpoint is a change in daily pain

scores from baseline.

For TNX-102 SL in PTSD,

we completed the Phase 3 RECOVERY trial and reported topline results in the fourth quarter of 2020 in which TNX-102 SL did not

meet the primary efficacy endpoint.

PTSD is a serious psychiatric condition that develops in response to experiencing a traumatic

We subsequently completed a meeting with the FDA to discuss potential new endpoints going forward for the indication of

treatment of PTSD.

Future studies will employ the one month look-back CAPS-5 as the primary endpoint rather than the one week look-back

as used in prior studies.

AAD program is Phase 2 ready with an active IND and FDA Fast Track designation.

AAD, which includes emotional lability, restlessness,

irritability, and aggression, is one of the most distressing and debilitating of the behavioral complications of Alzheimer’s

irritability, and aggression, is one of the most distressing and debilitating of the behavioral complications of Alzheimer’s disease.

Tonix does not have any near-term plans to start a Phase 2 study in AAD.

The AUD program is also Phase 2 ready with an

AUD is a chronic relapsing brain disease characterized by compulsive alcohol use, loss of control over alcohol intake,

and a negative emotional state when not using alcohol.

Tonix does not have any near-term plans to start a Phase 2 study in AUD.

TNX-1900* (intranasal potentiated oxytocin) is in development for prophylaxis

of chronic migraine and for the treatment of craniofacial pain, insulin resistance and related conditions as well binge eating disorder,

AUD program is also Phase 2 ready with an active IND.

AUD is a chronic relapsing brain disease characterized by compulsive alcohol use,

loss of control over alcohol intake, and a negative emotional state when not using alcohol.

Tonix does not have any near-term plans to

start a Phase 2 study in AUD.

TNX-1900* (intranasal

potentiated oxytocin) is in development for the treatment of chronic migraine and obesity-associated binge eating disorder, or BED.

TNX-1900 was acquired from Trigemina, Inc.

1 unchanged sentence

The potentiated formulation includes

magnesium, which has been shown in animals to potentiate binding of oxytocin to the oxytocin receptor in the trigeminal ganglion.

IND clearance from the FDA in the fourth quarter of 2021 and intend to initiate a Phase 2 study in migraine in the second half of 2022.

Tonix also licensed technology to use TNX-1900 for the treatment of insulin resistance from the University of Geneva.

TNX-1900 will be

studied as a potential treatment for BED in an investigator-initiated Phase 2 clinical trial.

The Phase 2 clinical trial is expected to

start in the second half of 2022.

In March 2022, we announced an agreement with Massachusetts General Hospital, a teaching hospital of

Harvard Medical School, to conduct this study.

Tonix does not own an IND for BED.

TNX-2900* is another intranasal oxytocin-based therapeutic in development

for the treatment of Prader-Willi syndrome, or PWS.

The technology for TNX-2900 was licensed from Inserm, the French National Institute

of Health and Medical Research.

PWS, an orphan condition, is a rare genetic disorder of failure to thrive in infancy, associated with

uncontrolled appetite beginning in childhood with complications of obesity and diabetes.

We have sponsored a research program at the Inserm

to study oxytocin on suckling behavior in mice that have been engineered to express one of the Prader-Willi genes.

TNX-2900 has been granted

Orphan-Drug Designation for the treatment of PWS.

TNX-601 CR* (tianeptine oxalate and naloxone controlled-release tablets)

is a CNS product candidate in development as a treatment for major depressive disorder, or depression, for PTSD, and for neurocognitive

dysfunction associated with corticosteroid use.

We completed a Phase 1 trial for formulation development outside of the U.S.

official minutes from a pre-IND meeting with the FDA, we expect to initiate a pharmacokinetic study in the third quarter of 2022, and

a Phase 2 study in the first quarter of 2023.

infectious disease portfolio includes vaccines based on Tonix’s recombinant pox vaccine, or “RPV” technology platform.

RPV vaccines are believed to protect against negative outcomes of infectious diseases by eliciting T cell responses in addition to antibody

TNX-801* is an RPV live horsepox virus vaccine for percutaneous administration in the pre-IND stage of development to protect

against smallpox and monkeypox.

TNX-801 vaccinated non-human primates were protected from monkeypox in studies reported in the first

quarter of 2020.

is a live virus vaccine that expresses the SARS-CoV-2 spike protein from the ancestral Wuhan strain, which has shown encouraging results

in non-human primates.

Because the subsequent omicron variant has out-competed the ancestral Wuhan strain, we are now planning new vaccine

versions, TNX-1840* and TNX-1850*, that are designed to express spike protein from the omicron variant and from the BA.2 variant, respectively.

The COVID-19 vaccines that are approved for use, or have emergency use authorization, or EUA, in the U.S.

have provided significant health

benefits to the vaccinated population;

however, they are showing limitations in the durability of protection conferred and, in their ability,

magnesium, which has been shown in animal studies to potentiate binding of oxytocin to the oxytocin receptor.

We received IND

clearance from the FDA in the fourth quarter of 2021 to study TNX-1900 in chronic migraine and we initiated a Phase 2 study in

migraine in the first quarter of 2023.

We expect interim analysis results from the first 50 percent of patients enrolled in the

fourth quarter of 2023.

In March 2022, we announced an agreement with Massachusetts General Hospital, a teaching hospital of Harvard

Medical School, to conduct an investigator-initiated Phase 2 clinical trial to study TNX-1900 in BED.

The Phase 2 clinical trial is

expected to start in the second quarter of 2023.

We do not own an IND for BED.

We also licensed technology to use TNX-1900 for the

treatment of insulin resistance from the University of Geneva and also have rights to develop it as a treatment for craniofacial

pain, but we are not imminently pursuing clinical trials in either of these indications at this time.

TNX-601 ER* (tianeptine hemioxalate extended-release tablets) is a CNS

product candidate in development as a treatment for major depressive disorder, or depression, and with possible additional indications

of PTSD, and neurocognitive dysfunction associated with corticosteroid use.

TNX-601 ER represents a novel approach to treating depression

in the U.S., since the active ingredient tianeptine induces a neuroprotective and resilient phenotype in both neurons and microglia under

conditions of stress in animals.

The dramatic and unique effects of tianeptine are illustrated in animal models by the restoration of

dendritic arborization of pyramidal neurons of CA3 region of hippocampus and the dentate gyrus region new neuron formation and integration

into hippocampal networks.

In contrast, antidepressants that are marketed in the U.S.

act by modulating the levels or receptor binding

of neurotransmitters in the synapse.

We have completed a Phase 1 trial for formulation development outside of the U.S.

We expect to initiate

a potentially pivotal Phase 2 study in the first quarter of 2023 for the treatment of major depressive disorder and we expect interim

analysis results from the first 50 percent of patients enrolled in the fourth quarter of 2023.

Another CNS candidate in development

is TNX-1300* (double-mutant cocaine esterase) which is in Phase 2 for the treatment of life-threatening cocaine intoxication.

has been granted Breakthrough Therapy designation, or BTD, by the U.S.

Food and Drug Administration, or FDA.

TNX-1300 was licensed from

Columbia University in 2019 after a Phase 2 study showed that it rapidly and efficiently disintegrates cocaine in the blood of volunteers

who received intravenous, or i.v., cocaine.

In August of 2022, we received a Federal Grant from the National Institute on Drug Abuse (NIDA)

to advance the development of TNX-1300 as a treatment for cocaine intoxication.

We expect to initiate a potentially pivotal Phase 2 study

of TNX-1300 in emergency rooms in the second quarter of 2023.

our CNS pipeline includes TNX-1600*, an inhibitor of the reuptake of neurotransmitters serotonin, norepinephrine and dopamine, or a triple

reuptake inhibitor.

TNX-1600 was licensed from Wayne State University in 2019 and is expected to be developed as a treatment for PTSD,

depression and attention-deficit/hyperactivity disorder, or ADHD.

TNX-1600 is in the preclinical stage of development.

Our rare disease portfolio

consists of TNX-2900*, another magnesium-potentiated intranasal oxytocin-based therapeutic in development for the treatment of Prader-Willi

syndrome, or PWS.

The technology for TNX-2900 was licensed from Inserm, the French National Institute of Health and Medical Research.

PWS, an orphan condition, is a rare genetic disorder of failure to thrive in infancy, associated with uncontrolled appetite beginning

in childhood with complications of obesity and diabetes.

We have sponsored a research program at Inserm to study oxytocin on suckling

behavior in mice that have been engineered to express one of the Prader-Willi genes.

TNX-2900 has been granted Orphan-Drug Designation

for the treatment of PWS and is in the pre-IND stage of development.

Our lead candidate

in the immunology pipeline is TNX-1500*, a humanized mAb, directed against CD40-ligand, or CD40L (also

known as CD154), engineered to modulate binding to Fc receptors, that is being developed as a prophylaxis against organ transplant

rejection as well as to treat autoimmune conditions.

In experiments at the Massachusetts General Hospital or MGH, a teaching hospital

of Harvard Medical School, TNX-1500 is being studied as monotherapy or in combination with other immunosuppressive agents in heart

and kidney allogeneic organ transplants in non-human primates.

Preliminary results from ongoing experiments in kidney and heart

transplants indicate that TNX-1500 appears to have comparable efficacy to historical experiments using the chimeric mouse/human

IgG1 version (5c8H1) of the anti-CD40L mAb 5c8.

First generation anti-CD40L mAb therapies were associated with an increased risk

of blood clots or thrombosis.

In the non-human primate studies with TNX-1500 for the prevention of rejection in allogeneic organ

transplants, no evidence of thrombosis has been observed so far.

We expect to start a Phase 1 study of TNX-1500 in the second quarter

TNX-1500 also is being studied in combination with other immunosuppressive agents in xenogeneic organ transplants in non-human

primates at MGH and at the University of Maryland at Baltimore or UMB.

In experiments at UMB, TNX-1500 is being studied to prevent

rejection of xenogeneic hearts from genetically engineered pigs developed by the Revivicor division of United Therapeutics Corporation.

Our immunology pipeline

also includes TNX-1700*, a recombinant Trefoil Factor Family 2, or rTFF2, fusion protein that was licensed from Columbia University

TNX-1700 consists of TFF2 fused to human serum albumin or HSA and is a biologic being developed to treat gastric and colorectal

cancers by an immune-oncology mechanism, in combination with PD1 blockers, and is in the preclinical stage of development.

presented data that show a murine version of TNX-1700 consisting of a fusion protein with murine serum albumin or MSA was able

to evoke anti-tumor immunity in the MC38 mouse model of colorectal cancer as monotherapy and that TNX-1700 augmented the efficacy

of anti-PD1 therapy in both the MC38 model and the CT26.wt mouse models of colorectal cancer.

Our infectious disease

portfolio includes vaccines based on our live virus vaccine or recombinant pox vaccine, “RPV” platform.

vaccines are believed to protect against poor clinical outcomes of infectious diseases by eliciting T cell responses in addition

to antibody responses.

TNX-801*, a live attenuated vaccine based on synthesized horsepox, is in the pre-IND stage of development

to protect against smallpox and mpox.

Non-human primates vaccinated with TNX-801 were protected from mpox in studies reported in

the first quarter of 2020.

A Phase 1 study of TNX-801 in humans is expected to start in the second half of 2023.

serves as the live virus vaccine platform for other infectious diseases for which subsequent products will be designed by expressing

other viral antigens in the horsepox vector.

TNX-1850* is a live

virus vaccine that expresses the SARS-CoV-2 spike protein from the BA.2 strain that has not yet been tested in animals.

is a live virus vaccine that expresses the SARS-CoV-2 spike protein from the ancestral Wuhan strain, which has shown encouraging

results in non-human primates.

Because the subsequent omicron variant out-competed the ancestral Wuhan strain, we began work on

new vaccine versions, TNX-1840* and TNX-1850*, that are designed to express spike protein from the omicron variant and from the

BA.2 variant, respectively.

Of those, based on the trajectory of COVID-19, the focus is now on TNX-1850.

The COVID-19 vaccines

that are approved for use, or have emergency use authorization, or EUA, in the U.S.

have provided significant health benefits to

the vaccinated population;

however, they have shown limitations in the durability of protection conferred and in their ability

to block forward transmission.

Live virus vaccines that protect against other viral diseases by eliciting T cell responses have shown

durability of protection that lasts years to decades and some live virus vaccines have significantly inhibited forward transmission.

respect to TNX-1800 vaccination, we reported positive efficacy data from animal challenge studies using live SARS-CoV-2 in the first quarter

In this study, TNX-1800 vaccinated, SARS-CoV-2 challenged animals had undetectable SARS-CoV-2 in the upper airways, which we

believe relates to potential inhibition of forward transmission of this respiratory pathogen.

(sangivamycin) is an antiviral inhibitor of SARS-CoV-2 which has demonstrated broad-spectrum activity in laboratory-based assays against

the coronaviruses SARS-CoV-2 and MERS-CoV.

Tonix licensed this technology from OyaGen, Inc.

and intends to develop it as a treatment for

COVID-19 and potentially other viral diseases.

The active ingredient of TNX-3500 has been studied for safety in humans in prior studies

with cancer patients at the U.S.

National Cancer Institute but has not been approved for marketing in any jurisdiction.

Tonix intends

to conduct further animal studies in preparation for filing an IND.

TNX-3600* refers to a series of

fully human mAbs generated by a human-human hybridomas from COVID-19 convalescent volunteers.

Tonix is collaborating with Columbia University

to produce these fully human mAbs to SARS-CoV-2 spike proteins from variants such as delta and omicron and to other viral targets.

initial focus is to develop COVID-19 therapeutic mAbs.

Tonix plans to seek indications similar to current EUA therapeutic mAbs for treating

individuals with mild-to-moderate COVID-19 who are at high risk for progression to severe disease.

TNX-3600 mAbs may also be used in combination

therapy with other COVID-19 therapeutic mAbs.

Combination therapies with other anti-SARS-CoV-2 mAbs may reduce the emergence of resistant

viral strains.

Given the unpredictable trajectory of the SARS-CoV-2 virus and new variants, we seek to contribute to a broad set of mAbs

from a variety of patients, that can be scaled up quickly and potentially combined with other mAbs.

We envision the future of mAb therapy

for COVID-19 to be cocktails of mAbs with specificity to variants of concern.

Live virus vaccines that protect against other viral diseases by eliciting T cell responses have

shown durability of protection that lasts years to decades and some live virus vaccines have significantly inhibited forward transmission.

With respect to TNX-1800 vaccination, we reported positive efficacy data from animal challenge studies using live SARS-CoV-2 in

the first quarter of 2021.

In this study, TNX-1800 vaccinated, SARS-CoV-2 challenged animals had undetectable SARS-CoV-2 in the

upper airways, which we believe relates to potential inhibition of forward transmission of this respiratory pathogen.

TNX-2300* is a live

virus vaccine based on bovine parainfluenza virus in development to protect against COVID-19.

In April 2022, Tonix extended a sponsored

research agreement with Kansas State University to develop a vaccine candidate, TNX-2300, for the prevention of COVID-19 that utilizes

a novel live virus vaccine vector platform based on bovine parainfluenza virus.

The efficacy of co-expression of the CD40-ligand,

also known as CD154, to stimulate T cell immunity will also be tested.

Attenuated bovine parainfluenza virus has previously been

shown to be an effective antigen delivery vector in humans.

Previous work by others has shown that attenuated BPI3V is well tolerated

and immunogenic in non-human primates and human infants and children.

We believe the vector is well suited for mucosal immunization

using a nasal atomizer, and can also be delivered parenterally.

TNX-2300 is in the preclinical stage of development.

Tonix intends to study inhibition of SARS-CoV-2 variants in tissue culture and initiate animal studies in the first half of 2022.

is collaborating with Columbia University to better understand immune responses to SARS-CoV-2 in healthy individuals who have recovered

from COVID-19, which is expected to provide a foundation for tailoring therapeutics to appropriate individuals using precision medicine.

is a COVID-19 mRNA vaccine candidate employing a zinc nanoparticle (ZNP) formulation.

In collaboration with Kansas State University, Tonix

is developing this ZNP technology as a potential replacement for the lipid nanoparticle (LNP) technology used in current mRNA vaccines.

ZNP technology potentially allows for improved stability which facilitates shipping and storage and addresses the limitations in current

mRNA vaccines which require ultra-cold storage and shipping.

TNX-3600* and TNX-3800*

are mAbs directed against SARS-CoV-2 which are in development as potential therapeutic or preventative agents for COVID-19.

the unpredictable trajectory of the SARS-CoV-2 virus and new variants, we seek to contribute a broad set of anti-SARS-CoV-2 mAbs,

that can be scaled up quickly and potentially combined with other mAbs.

We envision the future of mAb therapy for COVID-19 to be

cocktails of mAbs with specificity to variants of concern.

TNX-3600 refers to a series of fully human mAbs generated by

human-human hybridomas from COVID-19 convalescent volunteers.

We are collaborating with Columbia University to produce these fully

human mAbs to SARS-CoV-2 spike proteins from variants such as delta, omicron and XBB1.5 and to other viral targets.

TNX-3800 refers

to three humanized murine mAbs which we licensed exclusively in December 2022 from Curia Global, Inc.

for the treatment or prophylaxis

of SARS-CoV-2 infection.

The initial focus is to develop COVID-19 therapeutic mAbs.

We plan to seek indications similar to previously

EUA-approved therapeutic mAbs for treating individuals with mild-to-moderate COVID-19 who are at high risk for progression to severe

disease or for prophylaxis in individuals with compromised immune systems who are at high risk for severe COVID-19 disease.

None of the previously EUA-approved therapeutic or preventative mAbs are still available, because each has become obsolete since

the SARS-CoV-2 virus has mutated to evade their binding.

TNX-3600 and TNX-3800 mAbs may also be used in combination therapy with

other COVID-19 therapeutic mAbs.

Combination therapies with other anti-SARS-CoV-2 mAbs may reduce the emergence of resistant viral

TNX-3600 and TNX-3800 are in the preclinical stage of development.

TNX-3700* is a COVID-19

mRNA vaccine candidate employing a zinc nanoparticle (ZNP) formulation.

In collaboration with Kansas State University, we are developing

this ZNP technology as a potential replacement for the lipid nanoparticle (LNP) technology used in current mRNA vaccines.

ZNP technology

potentially allows for improved stability which facilitates shipping and storage and addresses the limitations in current mRNA

vaccines which require ultra-cold storage and shipping.

This current requirement limits the use of mRNA vaccines in less developed

We plan to seek initial indications as a booster, similar to the current FDA approved mRNA vaccines.

Tonix intends to conduct

research with Kansas State University on ZNP SARS-CoV-2 spike based vaccines in tissue culture and animals in the first half of 2022.

is an in vivo diagnostic skin test we are developing to measure SARS-CoV-2 exposure and T cell immunity.

T cell immunity is more

durable than antibody immunity since serum antibodies wane between six months and one year after vaccination.

TNX-2100 is a potential

test to measure delayed-type hypersensitivity (DTH) response to SARS-CoV-2.

The DTH response for other pathogens, notably tuberculosis,

can serve as an in vivo measure of functional T cell immunity.

TNX-2100 is comprised of GMP peptides designed to mimic SARS-CoV-2

proteins and stimulate SARS-CoV-2 specific T cells.

We initiated a first-in-human, dose-finding clinical study in the first quarter of

2022 and expect study results in the first half of 2022.

Our immunology pipeline also includes TNX-1700*.

is a recombinant modified form of Trefoil Family Factor 2, or rTFF2, that was licensed from Columbia University in 2019.

TNX-1700 is a

biologic being developed to treat gastric and colorectal cancers by an immune-oncology mechanism and is in the preclinical stage of development.

Our biodefense

pipeline includes TNX-701*, an undisclosed small molecule technology being developed to prevent deleterious effects of radiation exposure

which has the potential to be used as a medical countermeasure to improve biodefense.

TNX-701 is in the preclinical stage of development.

our CNS pipeline includes TNX-1600*, an inhibitor of the reuptake of neurotransmitters serotonin, norepinephrine and dopamine, or a triple

reuptake inhibitor.

TNX-1600 was licensed from Wayne State University in 2019 and is being developed as a treatment for PTSD, depression

and attention-deficit/hyperactivity disorder, or ADHD.

We plan to seek initial indications as a booster, similar to the current FDA approved mRNA vaccines for COVID-19.

intend to conduct research with Kansas State University on ZNP SARS-CoV-2 spike based vaccines in tissue culture and animals in

the first half of 2023.

TNX-3700 is in the preclinical stage of development.

to our COVID-19 and other infectious disease development programs, we are developing the resources necessary to enable internal research,

development and manufacturing capabilities necessary to meet the goal of producing new vaccine candidates within 100 days of recognition

and new diagnostics within weeks of obtaining sequence information.

As articulated in the American Pandemic Preparedness Plan, or AP3,

released by the U.S.

Office of Science and Technology Policy, this 100-day goal for vaccines is a key component of preparedness for future

We intend to establish the infrastructure necessary to support the pandemic preparedness goals established in the AP3, specifically

with respect to our RPV vaccine and skin test platforms and potentially to other vaccine, diagnostic and therapeutic platforms.

This infrastructure

consists of (i) our infectious disease R&D Center, or “RDC”, (ii) our Advanced Development Center, or ADC, and (iii) our

Commercial Manufacturing Center, or CMC.

We acquired the infectious disease RDC in Frederick, Maryland consisting of two buildings totaling

approximately 48,000 square feet.

The acquisition closed in October 2021 and was operational at closing, but as of December 31, 2021,

the facility was not ready for its intended use.

It is our intention to have the facility ready for use in the first half of 2022.

RDC facility will focus on our development of vaccines and antiviral drugs against SARS-CoV-2, its variants, and other infectious diseases.

The RDC facility is currently biosafety level 2 (BSL-2), but we intend to upgrade components to BSL-3.

We are in the process of a substantial

renovation of the ADC located in the New Bedford business park in Dartmouth, Massachusetts.

This facility is intended to accelerate development

and clinical scale manufacturing of live-virus vaccines to support Phase 1 and Phase 2 clinical trials.

It is currently under construction

and will be an approximately 45,000 square foot BSL-2 facility once completed.

It is expected to be partially operational in the first

half of 2022.

We also plan to build the CMC in Hamilton, Montana, where we purchased approximately 44 acres of land.

The CMC will focus

on developing and manufacturing commercial scale live-virus vaccines and is also intended to be BSL-2.

Site enabling work is expected

to be initiated for the CMC in 2022.

Together, we expect these facilities may qualify the RPV vaccine and skin test platforms for

programs that are designed to carry out the goals of AP3.

of Tonix’s product candidates are investigational new drugs or biologics and have not been approved for any indication.

We are led by a management team with significant industry experience in

drug development.

We complement our management team with a network of scientific, clinical, and regulatory advisors that includes recognized

experts in their respective fields.

Corporate Information

We were incorporated on November

16, 2007 under the laws of the State of Nevada as Tamandare Explorations Inc.

On October 11, 2011, we changed our name to Tonix Pharmaceuticals

Holding Corp.

Our common stock is listed on The NASDAQ Capital Market under the symbol “TNXP”.

Our principal executive offices

are located at 26 Main Street, Suite 101, Chatham, New Jersey 07928, and our telephone number is (862) 799-8599.

Our website addresses

are www.tonixpharma.com, www.tonix.com, and www.krele.com .

Our objective is to develop and commercialize our

product candidates.

The principal components of our strategy are to:

Pursue CNS, infectious disease and immunology

indications with high unmet medical need and significant commercial potential.

Within the therapeutic areas that Tonix is focusing,

we are pursuing multiple indications that are underserved with limited, effective treatment options.

One of our latest stage product candidates,

TNX-102 SL for the management of FM, affects between 6-12 million adults in the U.S.

and fewer than half of those treated for FM receive

relief from the three FDA-approved drugs.

We are also pursuing a treatment for Long COVID using TNX-102 SL, a condition for which there

is no currently approved therapy.

Our broader development strategy is to leverage the patented formulation to explore the clinical potential

of TNX-102 SL in multiple other pain, psychiatric, and addiction conditions, including PTSD, Agitation in Alzheimer’s and Alcohol

Use Disorder (AUD), all of which are underserved by currently approved medications or have no approved treatment thus representing large

unmet medical needs.

Within CNS, Tonix is also developing TNX-1300, a treatment for cocaine intoxication, one of the leading causes of

overdose deaths and for which there is no currently approved drug.

Within infectious diseases, we are currently focusing on the development

of TNX-1840 and TNX-1850 for protection against COVID-19.

While there are FDA-approved COVID-19 vaccines which use mRNA technology, we

believe that there are limitations to these vaccines relating to durability of protection and their relative inability to block forward

transmission.

We believe that the live virus technology intended to be employed in TNX-1840 and TNX-1850 has the potential to solve these

problems and serve as a booster or initial vaccine to the U.S.

Finally, with TNX-1500, we are pursuing a treatment to prevent

organ transplant rejection as well as autoimmune conditions.

TNX-1500 is a third generation humanized mAb targeting the CD40L that has

the potential to deliver efficacy without compromising safety, based on modulated binding to Fc receptors.

At this time, no mAb against

CD40L has been licensed anywhere in the world.

the commercial potential of our lead product candidates .

We plan to commercialize

each of our lead product candidates, including our latest stage candidate, TNX-102 SL,

either on our own or through collaboration with partners.

We believe our lead candidates

can be marketed to U.S.

physicians either by an internal sales force that we would build

or by a contract sales organization, which we would engage.

An alternative strategy would

be to enter into partnership agreements with drug companies that already have significant

marketing capabilities in the same, or similar, therapeutic areas.

If we determine that

such a strategy would be more favorable than developing our own sales capabilities, we

would seek to enter into collaborations with pharmaceutical or biotechnology companies

for commercialization.

a broad intellectual property strategy to protect our product candidates .

are pursuing a broad patent strategy for our product candidates, and we endeavor to generate

new patent applications as supported by our innovations and conceptions as well as to

advance their prosecution.

In the case of TNX-102 SL, we own patents and patent applications

protecting its composition-of-matter, certain methods of its use, its formulation, and

its pharmacokinetic properties.

In the case of TNX-801, TNX-1800, TNX-1840 and TNX-1850, we own

patent applications protecting their composition-of-matter and certain methods of use.

We also own patents through in-licensing transactions for TNX-1900, TNX-1700, TNX-2900

and TNX-1300.

We own patents outright for TNX-601 CR and have filed patent applications

for TNX-2100, TNX-3500, TNX-3700 and TNX-1500.

We plan to opportunistically apply for

new patents to protect our product candidates.

Relating to our COVID-19 and other infectious disease development programs,

we are developing the resources necessary to enable internal research, development and manufacturing capabilities necessary to meet the

goal of producing new vaccine candidates within 100 days of recognition within weeks of obtaining sequence information from a novel pathogen.

We seek to be a leader in the movement to re-build domestic U.S.

research, development and manufacturing capabilities.

Because this movement

follows a protracted period when domestic research, development and manufacturing were moved out of the U.S., or “off-shore”

by other companies to save on labor and other costs, the movement to reverse that trend has been described as “on-shoring”

or “re-domestication”.

The COVID-19 pandemic taught that national borders may close during a health emergency.

domestic capabilities are essential for the health security of the U.S., which has also been described as pandemic preparedness and biodefense.

As articulated in the American Pandemic Preparedness Plan, or AP3, released by the U.S.

Office of Science and Technology Policy, this

100-day goal for vaccines is a key component of preparedness for future pandemics.

We believe we have established the infrastructure necessary

to support the pandemic preparedness goals established in the AP3, specifically with respect to our RPV vaccine and potentially to other

vaccine and therapeutic platforms.

This infrastructure consists of (i) our R&D Center, or “RDC”, (ii) our Advanced Development

Center, or “ADC”, and (iii) our Commercial Manufacturing Center, or “CMC”.

We acquired the RDC in Frederick, Maryland

consisting of one building totaling approximately 48,000 square feet.

The acquisition closed in October 2021 and the facility is operational.

The RDC facility focuses on our development of vaccines and antiviral drugs against SARS-CoV-2, its variants, and other infectious diseases.

The RDC also conducts research on central nervous systema and immunology drugs.

The RDC facility is mostly biosafety level 2 (BSL-2),

with some components designated BSL-3.

We completed the substantial renovation of the ADC located in the New Bedford business park in

Dartmouth, Massachusetts, which became operational as of the fourth quarter 2022.

This approximately 45,000 square foot BSL-2 facility

is intended to accelerate development and clinical scale manufacturing of live-virus vaccines and biologics to support clinical trials.

We also plan to build the CMC in Hamilton, Montana, where we purchased approximately 44 acres of land and have built a field office to

manage construction of the facility.

The CMC will focus on developing and manufacturing commercial scale live-virus vaccines and biologics

and is also intended to be BSL-2.

Site enabling work is expected to be initiated for the CMC in 2023.

Together, we expect these facilities

may qualify the RPV vaccine platform for programs that are designed to carry out the goals of AP3.

of our product candidates are investigational new drugs or biologics and have not been approved for any indication.

are led by a management team with significant industry experience in drug development.

We complement our management team with a network

of scientific, clinical, and regulatory advisors that includes recognized experts in their respective fields.

We were incorporated on November 16, 2007 under the laws of the State of

Nevada as Tamandare Explorations Inc.

On October 11, 2011, we changed our name to Tonix Pharmaceuticals Holding Corp.

Our common stock

is listed on The NASDAQ Capital Market under the symbol “TNXP”.

Our principal executive offices are located at 26 Main Street,

Suite 101, Chatham, New Jersey 07928, and our telephone number is (862) 799-8599.

Our website address is www.tonixpharma.com.

strategy is to use our integrated development engine to advance innovative programs across multiple therapeutic areas into the clinic

while maximizing asset potential, with the objective of developing and commercializing our product candidates.

The principal components

of our strategy are to:

CNS, rare disease, immunology, and infectious disease indications with high unmet medical need and significant commercial potential.

the therapeutic areas that Tonix is focusing on, we are pursuing multiple indications that are underserved with limited, effective

treatment options.

One of our latest stage product candidates, TNX-102 SL for the management of FM, a condition which affects

between 6-12 million adults in the U.S.

and fewer than half of those treated for FM receive relief from the three FDA-approved

We are also pursuing a treatment using TNX-102 SL for FM-type Long COVID,

a condition for which there is no currently approved therapy.

Our broader development strategy is to leverage the patented formulation

and proven mechanism of action to explore the clinical potential of TNX-102 SL in multiple other, psychiatric, and addiction conditions,

including PTSD, Agitation in Alzheimer’s disease and Alcohol Use Disorder (AUD), all of which are underserved by currently approved

medications or have no approved treatment thus representing large unmet medical needs.

Within CNS, Tonix is also developing TNX-1900 to

treat chronic migraine, TNX-601 ER to treat major depressive disorder and TNX-1300 to treat cocaine intoxication.

Although a number of

drugs are approved for chronic migraine and major depressive disorder, there remains dissatisfaction with available options.

Cocaine intoxication

is one of the leading causes of overdose deaths and for which there is no currently approved drug.

With TNX-1500, we are pursuing a treatment

to prevent organ transplant rejection as well as autoimmune conditions.

TNX-1500 is a third generation humanized mAb targeting the CD40L

that has the potential to deliver efficacy without compromising safety, based on modulated binding to Fc receptors.

At this time, no mAb

against CD40L has been licensed anywhere in the world.

Within infectious diseases, we are currently focusing on the development of TNX-801

to prevent smallpox and mpox, and TNX-1850 to protect against COVID-19.

While there are FDA-approved vaccines to prevent smallpox and

mpox, we believe TNX-801 has potential to provide durable protection.

While there are FDA-approved COVID-19 vaccines which use mRNA technology,

or other technologies, we believe that there are limitations to these vaccines relating to durability of protection and their relative

inability to block forward transmission.

Maximize the commercial potential

of our lead product candidates .

We plan to commercialize each of our lead product candidates, including our latest stage candidate,

TNX-102 SL, either on our own or through collaboration with partners.

We believe our lead candidates can be marketed to U.S.

either by an internal sales force that we would build or by a contract sales organization, which we would engage.

An alternative strategy

would be to enter into partnership agreements with drug companies that already have significant marketing capabilities in the same, or

similar, therapeutic areas.

If we determine that such a strategy would be more favorable than developing our own sales capabilities, we

would seek to enter into collaborations with pharmaceutical or biotechnology companies for commercialization.

Pursue a broad intellectual

property strategy to protect our product candidates .

We are pursuing a broad patent strategy for our product candidates, and we

endeavor to generate new patent applications as supported by our innovations and conceptions as well as to advance their prosecution.

In the case of TNX-102 SL, we own patents and patent applications protecting its composition-of-matter, certain methods of its use, its

formulation, and its pharmacokinetic properties.

In the case of TNX-801 and TNX-1850, we own patent applications protecting their composition-of-matter

and certain methods of use.

We also own patents through in-licensing transactions for TNX-1300, TNX-1900, TNX-2900, and TNX-1700.

patents outright for TNX-601 ER and have filed patent applications for TNX-1500 and TNX-3700.

We plan to opportunistically apply for new

patents to protect our product candidates.

additional indications and commercial opportunities for our product candidates.

We will seek to maximize the value of our

other product candidates by pursuing other indications and commercial opportunities for such candidates.

For example, we own rights

related to the development and commercialization of TNX-102 SL for generalized anxiety disorder, depression, and fatigue related to

disordered sleep.

For TNX-1900, we own the rights to develop this for craniofacial pain, episodic migraine, acute migraine and

insulin resistance, in addition to chronic migraine.

For TNX-601 CR, we own the rights to develop this for PTSD and neurocognitive

disorder from corticosteroid use, in addition to major depressive disorder.

Finally, our live virus platform using our RPV

technology may be developed for future pandemics, infectious diseases generally and oncology, in addition to COVID-19.

We will seek to maximize the value of our other

product candidates by pursuing other indications and commercial opportunities for such candidates.

For example, we own rights related

to the development and commercialization of TNX-102 SL for generalized anxiety disorder, depression, and fatigue related to disordered

For TNX-1900, we own the rights to develop this for craniofacial pain, episodic migraine, acute migraine and insulin resistance,

in addition to chronic migraine.

For TNX-601 ER, we own the rights to develop this for PTSD and neurocognitive disorder from corticosteroid

use, in addition to major depressive disorder.

Finally, our live virus platform using our RPV technology may be developed as vaccines

for future pandemics, infectious diseases generally and oncology, in addition to smallpox and mpox.

and Market Overview

product candidates address disorders that are not well served by currently available therapies or have no approved treatment which

represent large potential commercial market opportunities.

Background information on the disorders and related commercial markets

that may be addressed by our product candidates in or nearing the clinical-stage is set forth below.

Organ Transplant Rejection

Organ transplant

rejection occurs when the immune system of the organ recipient attacks the new organ as if it was an infection or tumor.

Often transplantation

is the last resort for most end-stage organ failure patients, affecting either kidneys, liver, heart, lungs, and/or pancreas.

disparity between organ donor and recipient is often at the root of the rejection.

Mismatched or not closely matched organs triggers

an immune reaction that leads to rejection.

Overcoming this difficulty is paramount to a patient’s survival as organ donations

are in limited supply.

and Colorectal cancers

or stomach cancer is a disease in which malignant cancer cells line the inner lumen of the stomach.

Development of this form of cancer

is often influenced by age, diet and other stomach disease.

This type of cancer begins to form in the mucosa, the surface of the lumen

that is in direct contact with the contents of the stomach, and spreads through the outer layers of the stomach as the tumor grows.

per the National Cancer Institute, the 5-year relative survival for stomach cancer is 32.4%.

The lifetime risk of developing stomach

cancer is higher in men (about 1 in 96) than in women (about 1 in 152).

2 In 2018, there were an estimated 120,301 people living

with stomach cancer in the United States.

cancer includes cancers in the colon and the rectum, organs that are crucial to absorption of water by the body and the elimination of

Most colorectal cancers start as a growth or polyp on the inner lining of the colon or rectum.

Some types of polyps can change

into cancer over time (usually many years), but not all polyps become cancer.

Adenomatous polyps are the ones that turn malignant with

Similar to gastric cancer, the malignancy begins in the mucosal layer and spreads outwards.

5-year relative survival rate is 64.7%.

Overall, the lifetime risk of developing colorectal cancer is about 1 in 23 (4.3%) for men and

1 in 25 (4.0%) for women.

In 2018, there were an estimated 1,365,135 people living with colorectal cancer in the United States.

product candidates address disorders that are not well served by currently available therapies or have no approved treatment which represent

large potential commercial market opportunities.

Background information on the disorders and related commercial markets that may be addressed

by our product candidates in or nearing the clinical-stage is set forth below.

Nervous System

is an illegal recreational drug taken for its pleasurable effects and associated euphoria.

Pharmacologically, cocaine blocks the

reuptake of the neurotransmitter dopamine from central nervous system synapses, resulting in the accumulation of dopamine within

the synapse and an amplification of dopamine signaling that is related to its role in creating positive feeling.

With the continued

use of cocaine, however, intense cocaine cravings occur resulting in a high potential for abuse and addiction, or dependence,

as well as the risk of cocaine intoxication.

Cocaine intoxication refers to the deleterious effects on other parts of the body,

especially those involving the cardiovascular system.

Common symptoms of cocaine intoxication include tachyarrhythmias and

elevated blood pressure, either of which can be life-threatening.

As a result, individuals with known or suspected cocaine

intoxication are sent immediately to the emergency department, preferably by ambulance in case cardiac arrest occurs during transit.

There are approximately 505,000 emergency room visits for cocaine abuse each year in the U.S., of which 61,000 require detoxification

According to the National Institute on Drug Abuse, over 15,883 individuals died of cocaine overdose in 2019.

is a chronic syndrome characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory and mood issues.

The peak incidence of FM occurs between 20-50 years of age, and 80-90% of diagnosed patients are female.

FM may have a substantial

negative impact on social and occupational function, including disrupted relationships with family and friends, social isolation,

reduced activities of daily living and leisure activities, avoidance of physical activity, and loss of career or inability to

advance in career or education.

According to the American Chronic Pain Association, an estimated six to twelve million adults

to a report by Frost and Sullivan that we commissioned, despite the availability of approved medications, the majority of patients

fail therapy due to either insufficient efficacy, poor tolerability, or both.

Prescription pain and sleep medications are frequently

prescribed off-label for symptomatic relief, despite the lack of evidence that such medications provide a meaningful or durable

therapeutic benefit, and many of these medications carry significant safety risks and risk of dependence.

For example, approximately

30% of patients diagnosed with FM take chronic opioids, despite the lack of evidence for their effectiveness and the risk of addiction

and toxicity, including overdose.

COVID, or PASC, is a condition that some survivors of COVID-19 infection experience in varying degrees

It is a chronic disabling condition that is expected to result in a significant global health and economic burden.

include intense fatigue, fevers, sleep problems, pain, and cognitive issues (“brain fog”).

Post infection, many patients

experience one or many of the symptoms of Long COVID:

incidence of FM occurs between 20-50 years of age, and 80-90% of diagnosed patients are female.

FM may have a substantial negative impact

on social and occupational function, including disrupted relationships with family and friends, social isolation, reduced activities of

daily living and leisure activities, avoidance of physical activity, and loss of career or inability to advance in career or education.

According to the American Chronic Pain Association, an estimated six to twelve million adults in the U.S.

to a report by Frost and Sullivan that we commissioned, despite the availability of approved medications, the majority of patients fail

therapy due to either insufficient efficacy, poor tolerability, or both.

Prescription pain and sleep medications are frequently prescribed

off-label for symptomatic relief, despite the lack of evidence that such medications provide a meaningful or durable therapeutic benefit,

and many of these medications carry significant safety risks and risk of dependence.

For example, approximately 30% of patients diagnosed

with FM take chronic opioids, despite the lack of evidence for their effectiveness and the risk of addiction and toxicity, including overdose.

Long COVID, or PASC, is a condition that some survivors of COVID-19 infection

experience in varying degrees of severity.

It is a chronic disabling condition that is expected to result in a significant global health

and economic burden.

We are focusing development of TNX-102 SL on FM-type Long COVID.

The symptoms include intense fatigue, sleep

problems, multi-site pain, and cognitive issues (“brain fog”).

The proposed indication is for the management of multi-site

pain associated with PASC.

infection, many patients experience one or many of the symptoms of Long COVID:

some patients have initial symptoms that become prolonged;

others manifest entirely

new syndromes that impact more than one system or organ.

According to a recent publication in the Journal of American Medical Association

(JAMA), over 1 in 10 healthcare workers who had recovered from COVID-19 were still coping with at least one moderate to severe symptom

eight months later.

Several cohort studies have reported that persistence of symptoms following SARS-CoV-2 infection occurs in more than

30% of patients.

There is currently no approved drug for the treatment of Long COVID.

Posttraumatic

Stress Disorder, or PTSD

is a chronic condition that may develop after a person is exposed to one or more traumatic events, such as warfare, sexual assault,

serious injury, or threat of imminent death.

The core symptom clusters of PTSD are avoidance, emotional numbing, hyperarousal,

and intrusion, where the triggering traumatic event is commonly re-experienced by the individual through intrusive, recurrent

recollections, flashbacks, and nightmares.

People with PTSD suffer significant impairment in their daily functioning, including

occupational activities and social relations, and are at elevated risk for impulsive violent behaviors toward others and themselves,

including suicide.

Of those who experience a significant trauma, approximately 20% of women and 8% of men develop PTSD.

12 million adults annually in the U.S.

suffer from PTSD.

According to the U.S.

Department of Veterans Affairs, the prevalence

rate of PTSD in the military population is higher than that among civilians.

As of 2012, there were approximately 638,000 veterans

receiving treatment for PTSD in the Veterans Health Administration, or VHA.

Based on March 2015 VHA data, more than 19% of military

veterans involved in recent conflicts in Iraq and Afghanistan were seen at VHA facilities for potential or provisional PTSD.

patients fail to adequately respond to the medications approved for PTSD and approved medications show little evidence of a treatment

effect in men, lack evidence of efficacy in those for whom the traumatic event was combat-related, and carry suicidality warnings.

Sleep disturbances are central features of PTSD and are predictive of disease severity, depression, substance abuse, and suicidal

ideation, yet are resistant to the approved medications and present a difficult therapeutic challenge.

Current PTSD treatments

include off-label use of anxiolytics, sedative-hypnotics, and antipsychotics, many of which lack reliable evidence of efficacy,

and several have significant safety liabilities and dependence risk.

others manifest entirely new syndromes that impact more than one system or organ.

According to a 2021 publication in the Journal of American

Medical Association (JAMA), over 1 in 10 healthcare workers who had recovered from COVID-19 were still coping with at least one moderate

to severe symptom eight months later.

Research shows that Long COVID occurs in approximately 13% of recovered COVID-19 patients.

is currently no approved drug for the treatment of Long COVID.

is a primary headache disorder characterized by recurrent headaches that are moderate to severe.

Typically, episodes affect one

side of the head, are pulsating in nature, and last from a few hours to three days.

Associated symptoms may include nausea, vomiting,

and sensitivity to light, sound, or smell.

The pain is generally made worse by physical activity, although regular exercise may

have prophylactic effects.

Up to one-third of people affected have aura, typically a short period of visual disturbance that signals

that the headache will soon occur.

Typically, episodes affect one side of

the head, are pulsating in nature, and last from a few hours to three days.

Associated symptoms may include nausea, vomiting, and sensitivity

to light, sound, or smell.

The pain is generally made worse by physical activity, although regular exercise may have prophylactic effects.

Up to one-third of people affected have aura, typically a short period of visual disturbance that signals that the headache will soon

Occasionally, aura can occur with little or no headache following it.

Approximately one billion

individuals worldwide suffer from migraine (~14% of the population).

Migraine is the second leading cause of years lived with

Chronic migraine (≥ 15 headache/migraine days per month) affects about 1-2% of individuals (~75-150 million individuals

Approximately one billion individuals worldwide suffer from

migraine (~14% of the population).

Migraine is the second leading cause of years lived with disability.

Chronic migraine (≥ 15 headache/migraine

days per month) affects about 1-2% of individuals (~75-150 million individuals worldwide;

3-7 million in the U.S.).

CGRP antibodies are the only migraine specific prophylaxis drugs approved in decades, but

they require parenteral administration and there are long term safety concerns with prolonged systemic blockade of CGRP receptor.

Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is

recognized as the most common genetic cause of life-threatening childhood obesity and affects males and females with equal frequency and

all races and ethnicities.

The hallmarks of PWS are lack of suckling in infants and, in children and adults, severe hyperphagia, an overriding

physiological drive to eat, leading to severe obesity and other complications associated with significant mortality.

PWS is an orphan

disease that occurs in approximately one in 15,000 births.

There is currently no approved treatment for the obesity and hyperphagia in

adults and older children associated with PWS.

Major Depressive Disorder

According to the National Institute

of Mental Health, depression affects approximately 17 million adults in the U.S., with approximately 2.5 million adults treated with adjunctive

Depression is a condition characterized by symptoms such as a depressed mood or loss of interest or pleasure in daily activities

most of the time for two weeks or more, accompanied by appetite changes, sleep disturbances, motor restlessness or retardation, loss of

energy, feelings of worthlessness or excessive guilt, poor concentration, and suicidal thoughts and behaviors.

These symptoms cause clinically

significant distress or impairment in social, occupational, or other important areas of functioning.

The majority of people who suffer

from depression do not respond adequately to initial antidepressant therapy.

Infectious Diseases

SARS-CoV-2 is a contagious virus

causing the disease COVID-19 that became a global pandemic in 2019 and has resulted in more than three million deaths.

While the infection

and mortality rates have slowed in regions of the world with high vaccination rates, the struggle with the pathogen is ongoing and evolving

since SARS-CoV-2 is mutating into new variants.

COVID-19 is characterized by fever, sore throat, acute shortness of breath, cough, and

oxygen desaturation in the blood.

At least three major variants have swept across the world in successive waves and overwhelmed healthcare

systems during these waves.

With new variants of the virus emerging, therapeutic research is addressing the challenge of keeping up with

this rapidly mutating virus.

The early vaccines have been effective in limiting the severity of disease in vaccinated individuals.

that elicit strong T cell responses are believed to have the potential to provide long-term or durable protection.

Smallpox and Monkeypox

Smallpox is an acute contagious

disease caused by the variola virus, or VARV, which is a member of the orthopoxvirus family.

Smallpox was declared eradicated in 1980

following a global immunization campaign.

Smallpox is transmitted from person to person by infective droplets during close contact with

infected symptomatic people.

Monkeypox is an acute contagious disease caused by the monkeypox virus or MPXV, which is also a member of

the orthopoxvirus family.

Monkeypox symptoms are similar to those of smallpox, although less severe.

Monkeypox is emerging as an important

zoonotic infection in humans in Central and West Africa.

Some cases of monkeypox have been reported outside of Africa in patients who

had been infected while in Africa.

CGRP antibodies are

the only migraine specific prophylaxis drugs approved in decades, but they require parenteral administration and there are long term safety

concerns with prolonged systemic blockade of CGRP or its receptor.

Depressive Disorder

According to the Substance Abuse and Mental Health Services Administration,

an estimated 21.0 million adults in the U.S.

in 2020 experienced at least one major depressive episode, representing 8.4% of all U.S.

to the National Institute of Mental Health, depression affects approximately 17 million adults in the U.S., with approximately 2.5 million

adults treated with adjunctive therapy.

Depression is a condition characterized by symptoms such as a depressed mood or loss of interest

or pleasure in daily activities most of the time for two weeks or more, accompanied by appetite changes, sleep disturbances, motor restlessness

or retardation, loss of energy, feelings of worthlessness or excessive guilt, poor concentration, and suicidal thoughts and behaviors.

These symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

majority of people who suffer from depression do not respond adequately to initial antidepressant therapy.

Cocaine is an illegal

recreational drug taken for its pleasurable effects and associated euphoria.

Pharmacologically, cocaine blocks the reuptake of the

neurotransmitter dopamine from central nervous system synapses, resulting in the accumulation of dopamine within the synapse and an

amplification of dopamine signaling that is related to its role in creating positive feeling.

With the continued use of cocaine,

however, intense cocaine cravings occur resulting in a high potential for abuse and addiction, or dependence, as well as the risk of

cocaine intoxication.

Cocaine intoxication refers to the deleterious effects on other parts of the body, especially those involving

the cardiovascular system.

Common symptoms of cocaine intoxication include tachyarrhythmias and elevated blood pressure,

either of which can be life-threatening.

As a result, individuals with known or suspected cocaine intoxication are sent

immediately to the emergency department, preferably by ambulance in case cardiac arrest occurs during transit.

approximately 505,000 emergency room visits for cocaine abuse each year in the U.S., of which 61,000 require detoxification

According to the National Institute on Drug Abuse, cocaine-involved deaths rose nearly 54% from 2019 to 2021,

resulting in over 24,486 deaths total.

Posttraumatic Stress Disorder, or PTSD

PTSD is a chronic condition that

may develop after a person is exposed to one or more traumatic events, such as warfare, sexual assault, serious injury, or threat of imminent

The core symptom clusters of PTSD are avoidance, emotional numbing, hyperarousal, and intrusion, where the triggering traumatic

event is commonly re-experienced by the individual through intrusive, recurrent recollections, flashbacks, and nightmares.

PTSD suffer significant impairment in their daily functioning, including occupational activities and social relations, and are at elevated

risk for impulsive violent behaviors toward others and themselves, including suicide.

Of those who experience a significant trauma, approximately

20% of women and 8% of men develop PTSD.

An estimated 12 million adults annually in the U.S.

suffer from PTSD.

According to the U.S.

of Veterans Affairs, the prevalence rate of PTSD in the military population is higher than that among civilians.

Many patients fail to adequately

respond to the medications approved for PTSD and approved medications show little evidence of a treatment effect in men, lack evidence

of efficacy in those for whom the traumatic event was combat-related, and carry suicidality warnings.

Sleep disturbances are central features

of PTSD and are predictive of disease severity, depression, substance abuse, and suicidal ideation, yet are resistant to the approved

medications and present a difficult therapeutic challenge.

Current PTSD treatments include off-label use of anxiolytics, sedative-hypnotics,

and antipsychotics, many of which lack reliable evidence of efficacy, and several have significant safety liabilities and dependence risk.

syndrome (PWS) is recognized as the most common genetic cause of life-threatening childhood obesity and affects males and females

with equal frequency and all races and ethnicities.

The hallmarks of PWS are lack of suckling in infants and, in children and

adults, severe hyperphagia, an overriding physiological drive to eat, leading to severe obesity and other complications associated

with significant morbidity and mortality.

PWS is an orphan disease that occurs in approximately one in 15,000 births.

currently no approved treatment for obesity and hyperphagia in adults and older children associated with PWS.

Transplant Rejection

transplant rejection occurs when the immune system of the organ recipient attacks the new organ as if it was an infection or tumor.

transplantation is the last resort for most end-stage organ failure patients, affecting either kidneys, liver, heart, lungs, and/or pancreas.

Genetic disparity between organ donor and recipient is often at the root of the rejection.

Mismatched or not closely matched organs triggers

an immune reaction that leads to rejection.

Overcoming this difficulty is paramount to a patient’s survival as organ donations are

in limited supply.

and Colorectal cancers

Gastric or stomach cancer is a

disease in which malignant cancer cells line the inner lumen of the stomach.

Development of this form of cancer is often influenced by

age, diet and other stomach diseases.

This type of cancer begins to form in the mucosa, the surface of the lumen that is in direct contact

with the contents of the stomach, and spreads through the outer layers of the stomach as the tumor grows.

Currently, per the National Cancer

Institute, the 5-year relative survival for stomach cancer is 33.3%.

According to 2017-2019 data, approximately 0.8 percent of men and

women will be diagnosed with stomach cancer during their lifetime.

In 2019, there were an estimated 123,920 people living with stomach

cancer in the U.S.

Colorectal cancer includes cancers

in the colon and the rectum, organs that are crucial to absorption of water by the body and the elimination of food-waste.

Most colorectal

cancers start as a growth or polyp on the inner lining of the colon or rectum.

Some types of polyps can change into cancer over time (usually

many years), but not all polyps become cancer.

Adenomatous polyps are the ones that turn malignant with time.

Similar to gastric cancer,

the malignancy begins in the mucosal layer and spreads outwards.

The 5-year relative survival rate

is 65.1%, per the National Cancer Institute.

According to 2017-2019 data, approximately 4.1 percent of men and women will be diagnosed

with colorectal cancer during their lifetime.

In 2019, there were an estimated 1,369,005 people living with colorectal cancer in the United

Smallpox is an acute contagious disease caused by the variola virus, or

VARV, which is a member of the orthopoxvirus family.

Smallpox was declared eradicated in 1980 following a global immunization campaign.

Smallpox is transmitted from person to person by infective droplets during close contact with infected symptomatic people.

acute contagious disease caused by the monkeypox virus or MPXV, which is also a member of the orthopoxvirus family.

Mpox symptoms are

similar to those of smallpox, although less severe.

Mpox is emerging as an important zoonotic infection in humans in Central and West

Until 2022, only a few cases of mpox had been reported outside of Africa in patients who had been infected while in Africa.

in May of 2022, mpox cases spread rapidly in the U.S.

and other countries.

More than 30,000 cases in the U.S.

have been reported according

Centers for Disease Control and Prevention.

Smallpox was eradicated by a World

4 unchanged sentences

security and a proportion of military personnel, including members of the Global Response Force continue to be vaccinated.

We are developing

TNX-801 as a potential smallpox-preventing vaccine for the U.S.

strategic national stockpile and for potential widespread immunization

smallpox and mpox are stockpiled by the U.S.

government in the strategic national stockpile and for potential widespread immunization

in the event of malicious reintroduction of VARV.

Lead Product Candidates

We believe that our product candidates

offer innovative therapeutic approaches and may provide significant advantages relative to available therapies.

We have worldwide commercialization

rights to all of our product candidates listed below.

The following table summarizes our product candidates:

Product Candidate

Stage of Development

Organ transplant rejection

Phase 1 Start Expected 2H22

is a contagious virus causing the disease COVID-19 that became a global pandemic in 2019 and has resulted in more than three million deaths.

While the infection and mortality rates have slowed in regions of the world with high vaccination rates, the struggle with the pathogen

is ongoing and evolving since SARS-CoV-2 is mutating into new variants.

COVID-19 is characterized by fever, sore throat, acute shortness

of breath, cough, and oxygen desaturation in the blood.

At least three major variants have swept across the world in successive waves

and overwhelmed healthcare systems during these waves.

With new variants of the virus emerging, therapeutic research is addressing the

challenge of keeping up with this rapidly mutating virus.

The early vaccines have been effective in limiting the severity of disease in

vaccinated individuals.

Vaccines that elicit strong T cell responses are believed to have the potential to provide long-term or durable

Product Candidates

believe that our product candidates offer innovative therapeutic approaches and may provide significant advantages relative to available

We have worldwide commercialization rights to all of our product candidates listed below.

The following table summarizes our

later stage product candidates that are in or nearing the clinic:

of Development

Mid-Phase 3, >50% enrolled

FM-type Long COVID

Phase 2 enrolling

Chronic migraine

Phase 2, enrolling

Phase 2, targeted 1Q 2023 start

Cocaine Intoxication

Phase 2 Ready

Posttraumatic stress disorder

Phase 2 ready

Phase 2 Start Expected 1H22

Binge eating disorder

Phase 2 Start Expected 2H22

Phase 2 Start Expected 1Q23

Smallpox and monkeypox vaccine

TNX-1800/1840/1850

COVID-19 vaccine

COVID-19 Skin test

Phase 1 ongoing

TNX-1500 is a humanized mAb directed

against CD40-ligand, or CD40L, engineered to modulate binding to Fc receptors, that is being developed to prevent and treat organ transplant

rejection as well as to treat autoimmune conditions.

TNX-1500 incorporates the antigen binding fragment (Fab) region of hu5c8, which has

been extensively characterized including at the atomic level in complex with CD40-ligand.

In experiments at the Massachusetts

General Hospital, a teaching hospital of Harvard Medical School, TNX-1500 is being studied as monotherapy or in combination with immunosuppressive

drugs in heart and kidney organ transplants in non-human primates.

Preliminary results from an ongoing experiment in heart transplants

indicates that TNX-1500 appears to have comparable efficacy to historical experiments using the chimeric mouse/primate version of the

anti-CD40L mAb 5c8.

In the non-human primate studies with TNX-1500 no evidence of thrombosis has been observed so far.

is a protein expressed on the surface of activated T lymphocytes that mediates T cell helper function.

CD40-ligand is also known as CD154,

the T cell-B cell activating molecule (T-BAM), TRAP and gp39.

CD154 is a member of the Tumor Necrosis Factor (TNF) Super Family.

against CD154 has been approved for commercial use anywhere in the world.

Other TNF Super Family members have been successfully targeted

by antagonist mAbs.

Approved mAbs against TNFα include:

infliximab (Remicade®), adalimumab (Humira®), certolizumab pegol

(Cimzia®), and golimumab (Simponi®) for the treatment of certain autoimmune conditions.

Also, etanercept (Enbrel®) is a TNFα

antagonist receptor fusion protein.

An approved mAb against RANKL (CD254) is denosumab (Prolia® or Xgeva®) for the treatment of

osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.

In January 2021, the World Intellectual

Property Organization has published a patent application filed under the Patent Cooperation Treaty covering TNX-1500, a humanized mAb

directed against CD40-ligand, which is also known as CD154, T-BAM, 5c8 antigen, TRAP and gp39.

The patent application is titled “Anti-CD154

Antibodies and Uses Thereof” and published under International Publication No.

WO 2021/001458 A1.

The application entered national phase in December 2021.

The patent applications

include claims related to proprietary anti-human CD40-ligand mAbs that were engineered to have modified effector function, including TNX-1500,

which have reduced potential for Fc binding to FcγRII.

The patent applications also claim uses of TNX-1500 for preventing and treating

conditions, such as organ transplant rejection and autoimmune disorders.

If claims are granted, a patent

issuing from a national stage of this application could potentially provide U.S.

patent coverage for the TNX-1500 composition of matter

through 2040 excluding possible patent term extensions or patent term adjustments.

We also have filed a PCT patent application, PCT/US2022/011404, in January

2022, entitled “Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies.” It claims methods of inducing immune

tolerance in transplant recipients using anti-CD154 antibodies having modified effector functions.

We expect to start a Phase 1 study of TNX-1500 in the second

half of 2022.

Remicade® and Simponi® are trademarks of Janssen;

Humira® is a trademark of AbbVie Inc.;

Cimzia® is a trademark of UCB S.

Enbrel®, Prolia® and Xgeva® are trademarks

of Amgen Inc.

TNX-1300 (T172R/G173Q double-mutant

cocaine esterase 200 mg, i.v.

solution) is being developed for the treatment of cocaine intoxication.

TNX-1300 is a recombinant protein

enzyme produced through rDNA technology in a non-disease-producing strain of E.

coli bacteria.

Cocaine Esterase (CocE) was identified

in bacteria (Rhodococcus) that use cocaine as the sole source of carbon and nitrogen and that grow in soil surrounding coca plants.

The gene encoding CocE was identified and the protein was extensively characterized.

1-4 CocE catalyzes the breakdown of cocaine

into metabolite ecgonine methyl ester and benzoic acid.

Wild-type CocE is unstable at body temperature, so targeted mutations were introduced

in the CocE gene and resulted in the T172R/G173Q double-mutant CocE, which is active for approximately 6 hours at body temperature 5 .

Currently there is no specific

pharmacotherapy indicated for cocaine intoxication, a state characterized by acute agitation, hyperthermia, tachycardia, arrhythmias,

and hypertension, with the potential life-threatening sequalae of myocardial infarction, cerebrovascular accident, rhabdomyolysis, respiratory

failure, and seizures.

Patients are currently managed only by supportive care for the adverse effects of cocaine overdose on the cardiovascular

and central nervous systems.

By targeting the cause of cocaine intoxication, rather than the symptoms like other medicines in emergency

usage, we believe TNX-1300 may offer significant advantages to the current standard of care for cocaine overdose.

TNX-1300 was developed

by Columbia University, University of Kentucky and University of Michigan, and in-licensed by Tonix from Columbia University in 2019.

TNX-1300 is designated as a breakthrough therapy by the FDA.

In a Phase 2 randomized, double-blind,

placebo-controlled clinical study, TNX-1300 at 100 mg or 200 mg i.v.

doses was well tolerated and interrupted cocaine effects after cocaine

6 Tonix expects to initiate a Phase 2 open-label, safety study of TNX-1300 to take place in emergency

departments in the U.S.

in the first half of 2022.

a biologic and new molecular entity, TNX-1300 is eligible for 12 years of U.S.

market exclusivity upon approval by the FDA, in addition

to expected patent protection through 2029.

Since in-licensing, Tonix has requalified existing inventory, developed a lyophilized drug

product to facilitate enhanced stability and handling conditions applicable for an ER treatment, updated the process and analytical methods

to current standards and are in the process of manufacturing Phase 2/3 drug product clinical supply.

1 Bresler MM, Rosser SJ, Basran A, Bruce

Gene cloning and nucleotide sequencing and properties of a cocaine esterase from Rhodococcus sp.

Appl Environ Microbiol.

2 Larsen NA, Turner JM, Stevens J, Rosser

SJ, Basran A, Lerner RA, Bruce NC, Wilson IA.

Crystal structure of a bacterial cocaine esterase.

Nat Struct Biol.

3 Turner JM, Larsen NA, Basran A, Barbas

CF 3rd, Bruce NC, Wilson IA, Lerner RA.

Biochemical characterization and structural analysis of a highly proficient cocaine esterase.

Biochemistry.

41(41):12297-307.

4 Gao D, Narasimhan DL, Macdonald J, Brim

R, Ko MC, Landry DW, Woods JH, Sunahara RK, Zhan CG.

Thermostable variants of cocaine esterase for long-time protection against cocaine

Mol Pharmacol.

75(2):318-23 .

5 Overdose Death Rates - National Institute

on Drug Abuse - https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates;

accessed May 11, 2019

6 Nasser AF, Fudala PJ, Zheng B, Liu Y,

Heidbreder C.

A randomized, double-blind, placebo-controlled trial of RBP-8000 in cocaine abusers:

pharmacokinetic profile of rbp-8000

and cocaine and effects of RBP-8000 on cocaine-induced physiological effects.

J Addict Dis.

2014;33(4):289-302.

Mid-Phase 2, targeted 2Q 2023 start

Kidney Transplant Rejection

Phase 1, targeted 2Q 2023 start

Smallpox and Mpox vaccine

Phase 1, targeted 2H 2023 start

Prader-Willi Syndrome

SL, in clinical development for registration in five indications.

TNX-102 SL is a proprietary sublingual tablet formulation of

CBP that efficiently delivers CBP across the oral mucosal membrane into the systemic circulation.

We are developing TNX-102 SL

as a bedtime treatment for FM, PTSD, PASC or Long Covid and AAD and AUD.

We own all rights to TNX-102 SL in all geographies, and

we bear no obligations to third-parties for any future development or commercialization.

Excipients used in TNX-102 SL are approved

for pharmaceutical use.

Some of the excipients were specially selected to promote a local oral environment that facilitates mucosal

absorption of cyclobenzaprine or CBP.

TNX-102 SL is a proprietary sublingual tablet formulation of CBP that

efficiently delivers CBP across the oral mucosal membrane into the systemic circulation.

We are developing TNX-102 SL as a bedtime treatment

for FM, PTSD, PASC or Long Covid, AAD and AUD.

We own all rights to TNX-102 SL in all geographies, and we bear no obligations to third-parties

for any future development or commercialization.

Excipients used in TNX-102 SL are approved for pharmaceutical use.

Some of the excipients

were specially selected to promote a local oral environment that facilitates mucosal absorption of cyclobenzaprine or CBP.

current TNX-102 SL sublingual tablets contain 2.8 mg of CBP.

For the treatment of FM, TNX-102 SL 5.6 mg (two 2.8 mg tablets) at

bedtime is in Phase 3 development.

We selected this dose with the goal of providing a balance of efficacy, safety, and tolerability

that would be acceptable as a first-line therapy and for long-term use, and in-patient populations characterized by burdensome

symptoms and sensitivity to medications.

active ingredient in TNX-102 SL, is CBP, a serotonin-2A and alpha-1 adrenergic receptor antagonist as well as an inhibitor of

serotonin and norepinephrine reuptake.

In addition, TNX-102 SL acts upon other receptors in the central nervous system including

muscarinic M 1 and histaminergic H 1 receptors.

For the treatment of FM, TNX-102 SL 5.6 mg (two 2.8 mg tablets) at bedtime

is in Phase 3 development.

We selected this dose with the goal of providing a balance of efficacy, safety, and tolerability that would

be acceptable as a first-line therapy and for long-term use, and in-patient populations characterized by burdensome symptoms and sensitivity

to medications.

active ingredient in TNX-102 SL, is CBP, a serotonin-2A and alpha-1 adrenergic receptor antagonist as well as an inhibitor of serotonin

and norepinephrine reuptake.

In addition, TNX-102 SL acts upon other receptors in the central nervous system including muscarinic M1 and

histaminergic H1 receptors.

is the active ingredient of two products that are approved in the U.S.

for the treatment of muscle spasm:

Flexeril ® (5

mg and 10 mg oral immediate-release, or IR, tablet) and Amrix ® (15 mg and 30 mg oral extended-release capsule).

The Flexeril brand of CBP IR tablet has been discontinued since May 2013.

There are numerous generic versions of CBP IR tablets

on the market.

CBP-containing products are approved for short term use (two to three weeks) only as an adjunct to rest and physical

therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions.

CBP IR tablets are recommended for

three times per day dosing, which results in relatively stable blood levels of CBP after several days of treatment.

Extended-release

CBP capsules taken once a day mimic, and flatten, the pharmacokinetic profile of three times per day CBP IR tablets.

Flexeril® (5 mg and

10 mg oral immediate-release, or IR, tablet) and Amrix ® (15 mg and 30 mg oral extended-release capsule).

brand of CBP IR tablet has been discontinued since May 2013.

There are numerous generic versions of CBP IR tablets on the market.

CBP-containing

products are approved for short term use (two to three weeks) only as an adjunct to rest and physical therapy for relief of muscle spasm

associated with acute, painful musculoskeletal conditions.

CBP IR tablets are recommended for three times per day dosing, which results

in relatively stable blood levels of CBP after several days of treatment.

Extended-release CBP capsules taken once a day mimic, and flatten,

the pharmacokinetic profile of three times per day CBP IR tablets.

designed TNX-102 SL to be administered once-daily at bedtime and with the intention for long-term use.

We believe the selected

dose of TNX-102 SL and its unique pharmacokinetic profile will enable it to achieve a desirable balance of efficacy, safety, and

tolerability.

Our Phase 1 comparative trials showed that, on a dose-adjusted basis, TNX-102 SL results in faster systemic absorption

and significantly higher plasma levels of CBP in the first hour following sublingual administration relative to oral IR CBP tablets.

It also showed that the sublingual route of administration, which largely bypasses the “first pass” hepatic metabolism

that swallowed medications undergo, results in a higher plasma ratio of CBP to its main active metabolite, norcyclobenzaprine.

In clinical studies, TNX-102 SL 2.8 mg and TNX-102 SL 5.6 mg were generally well-tolerated, with no drug-related serious and unexpected

adverse reactions reported in these studies.

We believe the selected dose of

TNX-102 SL and its unique pharmacokinetic profile will enable it to achieve a desirable balance of efficacy, safety, and tolerability.

Our Phase 1 comparative trials showed that, on a dose-adjusted basis, TNX-102 SL results in faster systemic absorption and significantly

higher plasma levels of CBP in the first hour following sublingual administration relative to oral IR CBP tablets.

It also showed that

the sublingual route of administration, which largely bypasses the “first pass” hepatic metabolism that swallowed medications

undergo, results in a higher plasma ratio of CBP to its main active metabolite, norcyclobenzaprine.

In clinical studies, TNX-102 SL 2.8

mg and TNX-102 SL 5.6 mg were generally well-tolerated, with no drug-related serious and unexpected adverse reactions reported in these

Some subjects experienced transient numbness of the tongue after TNX-102 SL administration.

have successfully completed the pivotal exposure bridging study with TNX-102 SL compared to Amrix.

Results from this study

support the approval of TNX-102 SL under Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act, or FDCA, with Amrix as

the reference listed drug, or RLD.

In general, the development timeline for a 505(b)(2) NDA is shorter and less expensive than

an NDA developed under Section 505(b)(1), which is for new chemical entities, or NCEs, that have never been approved in the U.S.

We believe that TNX-102 SL has the potential to provide clinical benefit to FM, PTSD and Long COVID patients and possibly other

CNS (central nervous system) indications that are underserved by currently marketed products or have no approved treatment.

We have successfully completed

the pivotal exposure bridging study with TNX-102 SL compared to Amrix.

Results from this study support the approval of TNX-102 SL

under Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act, or FDCA, with Amrix as the reference listed drug, or RLD.

the development timeline for a 505(b)(2) NDA is shorter and less expensive than an NDA developed under Section 505(b)(1), which is for

new chemical entities, or NCEs, that have never been approved in the U.S.

We believe that TNX-102 SL has the potential to provide clinical

benefit to FM, Long COVID, and PTSD patients and possibly other CNS (central nervous system) indications that are underserved by currently

marketed products or have no approved treatment.

SL – FM program

are developing TNX-102 SL as a bedtime treatment for FM under an active IND application.

The potential approval of TNX-102 SL

for FM is expected to be under Section 505(b)(2) of the FDCA.

The potential approval of TNX-102 SL for FM is

expected to be under Section 505(b)(2) of the FDCA.

Development Plan

3 RALLY Study (F306)

Phase 3 RALLY study is clinically complete.

We enrolled the first patient in September 2020.

The RALLY study is a double-blind,

randomized, placebo-controlled adaptive design trial designed to evaluate the efficacy and safety of TNX-102 SL in FM.

was expected to enroll approximately 670 patients across approximately 40 U.S.

For the first two weeks of treatment, there

was a run-in period in which patients started on TNX-102 SL 2.8 mg (1 tablet) or placebo.

After the first two weeks, all patients

had the dose increased to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for 12 weeks.

The primary endpoint was

daily diary pain severity score change from baseline to Week 14 (using the weekly averages of the daily numerical rating scale

scores), analyzed by mixed model repeated measures with multiple imputation.

RALLY study had one pre-specified unblinded interim analysis by an Independent Data Monitoring Committee, or IDMC, to be conducted

when the study has results from approximately the first 50% of efficacy-evaluable patients.

In July 2021, we reported interim

analysis and, based on the recommendation from the IDMC that the RALLY trial was unlikely to demonstrate a statistically significant

improvement in the primary endpoint, we stopped enrollment of new participants but allowed those participants who were already

enrolled to complete the study.

We expect to report topline data from the completed study in the first quarter of 2022.

to analyze the RALLY results to improve the design of subsequent Phase 3 studies.

In addition, we plan to employ pharmacogenomic

techniques to compare the RALLY and RELIEF study populations, which may provide a path to precision medicine-based companion diagnostics

for TNX-102 SL in FM.

intends to initiate a new Phase 3 study in FM, F307, in the first half of 2022.

Following analysis of F306 results, including

pharmacogenomic comparison of RELIEF and RALLY, Tonix may modify the protocol for this next Phase 3 study.

3 RESILIENT (F307)

The first patient was enrolled in the potentially pivotal Phase 3 RESILIENT

study in April 2022.

The RESILIENT study is a double-blind, randomized, placebo-controlled adaptive design trial designed to evaluate

the efficacy and safety of TNX-102 SL in FM.

The two-arm trial is expected to enroll approximately 470 participants in the U.S.

50% enrolled as of December 2022.

The first two weeks of treatment consist of a run-in period in which participants start on TNX-102 SL

2.8 mg (1 tablet) or placebo.

Thereafter, all participants increase their dose to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo

tablets for the remaining 12 weeks.

The primary endpoint is the daily diary pain severity score change (TNX-102 SL 5.6 mg vs.

from baseline to Week 14 (using the weekly averages of the daily numerical rating scale scores), analyzed by mixed model repeated measures

with multiple imputation.

An interim analysis by an IDMC will be conducted on the primary endpoint based on the first 50% of enrolled

participants for a potential sample size adjustment or early stop for futility.

Interim data is expected in the second quarter of 2023.

Topline data is expected in the fourth quarter of 2023.

Phase 3 RALLY Study (F306)

We reported pre-planned interim analysis results from a Phase 3 study,

RALLY (F306), in July 2021.

Based on the recommendation from the independent data monitoring committee that the RALLY trial was unlikely

to demonstrate a statistically significant improvement in the primary endpoint, we stopped enrollment of new participants but allowed

those participants who were already enrolled to complete the study.

We reported topline data from the completed study in March of 2022.

As expected based on interim analysis results, TNX-102 SL did not achieve statistical significance over placebo on the primary endpoint

of reduction in daily pain, and relative to the previous positive Phase 3 Study (RELIEF), RALLY had an unexpected increase in study participant

adverse event-related discontinuations in both drug and placebo groups.

The RALLY study was a double-blind, randomized, placebo-controlled

adaptive design trial intended to evaluate the efficacy and safety of TNX-102 SL in FM.

The trial was expected to enroll approximately

670 patients across approximately 40 U.S.

For the first two weeks of treatment, there was a run-in period in which patients started

on TNX-102 SL 2.8 mg (1 tablet) or placebo.

After the first two weeks, all patients had the dose increased to TNX-102 SL 5.6 mg (2 x 2.8

mg tablets) or two placebo tablets for 12 weeks.

The primary endpoint was daily diary pain severity score change from baseline to Week

14 (using the weekly averages of the daily numerical rating scale scores), analyzed by mixed model repeated measures with multiple imputation.

Phase 3 RELIEF Study (F304)

the fourth quarter of 2020, we announced the results of a randomized, double-blind, placebo-controlled, 12-week Phase 3 study

of TNX-102 SL in 503 participants with FM, which we refer to as the RELIEF study.

The primary objective of this study was to evaluate

the potential clinical benefit of using TNX-102 SL to treat FM at a dose of 5.6 mg, administered sublingually once daily at bedtime

for 12 weeks.

The primary endpoint of the RELIEF trial was the daily diary pain severity score change from baseline to Week 14

(using the weekly averages of the daily numerical rating scale scores), analyzed by mixed model repeated measures with multiple

The RELIEF study achieved statistical significance on the primary efficacy endpoint:

change from baseline in the weekly

average of daily diary pain severity numerical rating scale (NRS) scores for TNX-102 SL 5.6 mg (LS mean [SE]:

-1.9 [0.12] units)

versus placebo (-1.5 [0.12] units), analyzed by mixed model repeated measures with multiple imputation (LS mean [SE] difference:

the fourth quarter of 2020, we announced the results of a randomized, double-blind, placebo-controlled, 12-week Phase 3 study of TNX-102

SL in 503 participants with FM, which we refer to as the RELIEF study.

The primary objective of this study was to evaluate the potential

clinical benefit of using TNX-102 SL to treat FM at a dose of 5.6 mg, administered sublingually once daily at bedtime for 12 weeks.

primary endpoint of the RELIEF trial was the daily diary pain severity score change from baseline to Week 14 (using the weekly averages

of the daily numerical rating scale scores), analyzed by mixed model repeated measures with multiple imputation.

The RELIEF study achieved

statistical significance on the primary efficacy endpoint:

change from baseline in the weekly average of daily diary pain severity numerical

rating scale (NRS) scores for TNX-102 SL 5.6 mg (LS mean [SE]:

-1.9 [0.12] units) versus placebo (-1.5 [0.12] units), analyzed by mixed

model repeated measures with multiple imputation (LS mean [SE] difference:

-0.4 [0.16] units, p=0.010).

The statistically significant improvement in pain is further substantiated when diary pain was analyzed

by another standard statistical approach, a 30 percent responder analysis, with 46.8% on active and 34.9% on placebo having a

30 percent or greater reduction in pain (logistic regression;

statistically significant improvement in pain is further substantiated when diary pain was analyzed by another standard statistical approach,

a 30 percent responder analysis, with 46.8% on active and 34.9% on placebo having a 30 percent or greater reduction in pain (logistic

odds ratio [95% CI]:

1.67 [1.16, 2.40];

Consistent with

the proposed mechanism that TNX-102 SL acts in fibromyalgia through improving sleep quality, TNX-102 SL showed nominal improvement

of sleep by several measures.

For daily diary sleep quality ratings, TNX-102 SL (-2.0 [0.12] units) compared to placebo (-1.5

[0.12] units) was nominally significant (LS mean difference:

Consistent with the proposed mechanism that TNX-102 SL acts in fibromyalgia

through improving sleep quality, TNX-102 SL showed nominal improvement of sleep by several measures.

For daily diary sleep quality ratings,

TNX-102 SL (-2.0 [0.12] units) compared to placebo (-1.5 [0.12] units) was nominally significant (LS mean difference:

-0.6 [0.17] units;

For the PROMIS Sleep Disturbance

instrument, TNX-102 SL was also nominally significant over placebo on T-scores (LS mean difference:

For the PROMIS Sleep Disturbance instrument, TNX-102 SL was also nominally significant over placebo on T-scores (LS mean

-2.9 [0.82] units;

The effect sizes on the diary sleep ratings and PROMIS Sleep Disturbance instrument were 0.31 and 0.32, respectively.

the RELIEF study, TNX-102 SL was similarly well tolerated as in the Phase 2 BESTFIT and Phase 3 AFFIRM studies, which both studied

TNX-102 SL at a lower dose of 2.8 mg daily.

There were no new safety signals observed in the RELIEF study at the 5.6 mg daily

Among participants randomized to the TNX-102 SL and placebo arms, 82.3% and 83.5%, respectively, completed the 14-week dosing

As expected based on prior TNX-102 SL studies, administration site reactions are the most commonly reported adverse events

and were higher in the TNX-102 SL treatment group, including rates of oral numbness (17.3% vs.

0.8%), oral pain/discomfort (11.7%

The effect sizes on the diary sleep ratings and PROMIS Sleep Disturbance instrument were 0.31

and 0.32, respectively.

In the RELIEF study, TNX-102 SL was similarly well tolerated as in the

Phase 2 BESTFIT and Phase 3 AFFIRM studies, which both studied TNX-102 SL at a lower dose of 2.8 mg daily.

There were no new safety signals

observed in the RELIEF study at the 5.6 mg daily dose.

Among participants randomized to the TNX-102 SL and placebo arms, 82.3% and 83.5%,

respectively, completed the 14-week dosing period.

As expected, based on prior TNX-102 SL studies, administration site reactions are the

most commonly reported adverse events and were higher in the TNX-102 SL treatment group, including rates of oral numbness (17.3% vs.

oral pain/discomfort (11.7% v.

2.0%), taste impairment (6.5% vs.

0.4%), and oral tingling (5.6% v.

Oral numbness or tingling and taste impairment were

local administration site effects nearly always temporally related to dose administration and transiently expressed (<60 minutes)

in almost all occurrences.

The only systemic treatment-emergent adverse events that occurred at a rate of 5.0% or greater in either

arm was somnolence/sedation at 5.6 percent in the TNX-102 SL arm vs.

Oral numbness or tingling and

taste impairment were local administration site effects nearly always temporally related to dose administration and transiently expressed

(<60 minutes) in almost all occurrences.

The only systemic treatment-emergent adverse events that occurred at a rate of 5.0% or greater

in either arm was somnolence/sedation at 5.6% in the TNX-102 SL arm vs.

1.2% in placebo, which was consistent with known side effects

of marketed oral cyclobenzaprine.

Adverse events resulted in premature study discontinuation in 8.9% of those who received TNX-102

SL compared with 3.9% of placebo recipients.

There were a total of seven serious adverse events reported during the study, none

of which were deemed related to investigational product;

Adverse events resulted in premature study discontinuation in 8.9% of those who received TNX-102 SL

compared with 3.9% of placebo recipients.

There was a total of seven serious adverse events reported during the study, none of which were

deemed related to investigational product;

five in placebo arm, and two in TNX-102 SL arm.

Of the two in the TNX-102

SL arm, one was a motor vehicle accident with multiple bone fractures, and the other was a pneumonia secondary to an infection.

Of the two in the TNX-102 SL arm, one was a

motor vehicle accident with multiple bone fractures, and the other was a pneumonia secondary to an infection.

Phase 3 AFFIRM Study (F301)

the third quarter of 2016, we announced the results of a randomized, double-blind, placebo-controlled, 12-week Phase 3 study of

TNX-102 SL in 519 participants with FM, which we refer to as the AFFIRM study.

The primary objective of this study was to evaluate

the potential clinical benefit of using TNX-102 SL to treat FM at a dose of 2.8 mg, administered sublingually once daily at bedtime

for 12 weeks.

The primary endpoint of the AFFIRM trial was the 30% pain responder analysis in which a responder is defined as

a subject for whom pain intensity was reduced by at least 30% at Week 12 as compared to baseline.

AFFIRM did not achieve statistical

significance at the primary endpoint (p=0.095).

Yet, statistical significance was achieved when pain was analyzed instead

as a continuous variable, either by MMRM (p<0.001) or by MMRM with multiple imputation for missing data (p=0.005), a generally

accepted approach to pain data.

TNX-102 SL also showed statistically significant improvements in the declared secondary analyses

of the Patient Global Impression of Change, or PGIC (p=0.038) and the Fibromyalgia Impact Questionnaire-Revised, or FIQ-R (p<0.001).

The study also showed statistically significant improvement with TNX-102 SL on measures of sleep quality, including the Patient-Reported

Outcomes Measurement Information System, or PROMIS, Sleep Disturbance instrument (p<0.001).

the third quarter of 2016, we announced the results of a randomized, double-blind, placebo-controlled, 12-week Phase 3 study of TNX-102

SL in 519 participants with FM, which we refer to as the AFFIRM study.

The primary objective of this study was to evaluate the potential

clinical benefit of using TNX-102 SL to treat FM at a dose of 2.8 mg, administered sublingually once daily at bedtime for 12 weeks.

primary endpoint of the AFFIRM trial was the 30% pain responder analysis in which a responder is defined as a subject for whom pain intensity

was reduced by at least 30% at Week 12 as compared to baseline.

AFFIRM did not achieve statistical significance at the primary endpoint

Yet, statistical significance was achieved when pain was analyzed instead as a continuous variable, either by MMRM (p<0.001)

or by MMRM with multiple imputation for missing data (p=0.005), a generally accepted approach to pain data.

TNX-102 SL also showed

statistically significant improvements in the declared secondary analyses of the Patient Global Impression of Change, or PGIC (p=0.038)

and the Fibromyalgia Impact Questionnaire-Revised, or FIQ-R (p<0.001).

The study also showed statistically significant improvement

with TNX-102 SL on measures of sleep quality, including the Patient-Reported Outcomes Measurement Information System, or PROMIS, Sleep

Disturbance instrument (p<0.001).

SL was well tolerated in the AFFIRM trial.

Among patients randomized to the active and control arms, 78% and 86%, respectively,

completed the 12-week dosing period.

The most common adverse events were local in nature, with transient tongue or mouth numbness

occurring in 40% of participants on TNX-102 SL vs.

Among patients randomized to the active and control arms, 78% and 86%, respectively, completed

the 12-week dosing period.

The most common adverse events were local in nature, with transient tongue or mouth numbness occurring in 40%

of participants on TNX-102 SL vs.

1% on placebo.

These local adverse events did not appear to affect either rates

of retention of study participants or their compliance with taking TNX-102 SL.

Systemic adverse events were similar between TNX-102

SL and placebo.

No serious adverse events were reported.

These local adverse events did not appear to affect either rates of retention of study

participants or their compliance with taking TNX-102 SL.

Systemic adverse events were similar between TNX-102 SL and placebo.

adverse events were reported.

NDA Requirements

Agreed Initial Pediatric Study Plan, or Agreed iPSP, was accepted by the FDA in September 2015.

An amendment to the Agreed iPSP

will be submitted for FDA agreement prior to marketing application.

on our discussions with the FDA and the FDA official meeting minutes, we will not have to conduct special populations, such as

geriatric and renal/hepatic impaired patients, drug-drug interaction or cardiovascular safety studies to support the TNX-102 SL

NDA filing since the pivotal systemic exposure bridging study using Amrix as the reference listed drug, or RLD, has been successfully

Due to the well-established safety profile of CBP at much higher doses than we proposed for FM and the long-term safety

data in PTSD, up to 15 months, on TNX-102 SL 5.6 mg, the FDA has not requested a risk management plan or medication guide for

this product.

An amendment to the Agreed iPSP will be

submitted for FDA agreement prior to marketing application.

on our discussions with the FDA and the FDA official meeting minutes, we will not have to conduct special populations, such as geriatric

and renal/hepatic impaired patients, drug-drug interaction or cardiovascular safety studies to support the TNX-102 SL NDA filing since

the pivotal systemic exposure bridging study using Amrix as the reference listed drug, or RLD, has been successfully completed.

the well-established safety profile of CBP at much higher doses than we proposed for FM and the long-term safety data in PTSD, up to 15

months, on TNX-102 SL 5.6 mg, the FDA has not requested a risk management plan or medication guide for this product.

1 Bioequivalence, Bridging PK, Food-Effect and Dose-Proportionality Studies

have completed the required Phase 1 bioequivalence, multi-dose bridging pharmacokinetic, and food effect and dose-proportionality

have completed the required Phase 1 bioequivalence, multi-dose bridging pharmacokinetic, and food effect and dose-proportionality studies.

Cyclobenzaprine

Hydrochloride Nonclinical Development

October 2016, we completed the six-month repeated-dose toxicology study of the active ingredient, CBP, in rats and a nine-month

repeated-dose toxicology study in dogs required for the NDA filing.

These chronic toxicity studies were requested by the FDA to

augment the nonclinical information in the AMRIX prescribing information, or labeling, which is necessary to support the TNX-102

SL labeling for long-term use.

Due to the lack of evidence of potential abuse in clinical studies of TNX-102 SL, the FDA agreed

that nonclinical study to assess CBP abuse and dependency potential is not required to support the TNX-102 SL NDA filing.

is planning to develop TNX-102 SL for the treatment of FM in Japan.

Cyclobenzaprine, the active ingredient of TNX-102 SL, has

not been approved in Japan, and is considered a NCE (new chemical entity).

In February 2022, Tonix held an End of Phase 2 Consultation

with the Pharmaceuticals and Medical Devices Agency, or PMDA, an independent administrative institution responsible for ensuring

the safety, efficacy and quality of pharmaceuticals and medical devices in Japan, to discuss the Japan development plan.

was reached on the design of a Phase 1 bridging study (TNX-CY-F108/F108) in ethnic Japanese healthy volunteers to enable clinical

studies of TNX-102 SL in Japan.

PMDA also provided guidance on the overall nonclinical package to support a Japan NDA filing for

TNX-102 SL for the treatment of FM.

F108 Phase 1 study will be initiated in March 2022.

has initiated nonclinical safety, pharmacology and embryo-fetal development toxicology studies as part of the agreed IND-enabling nonclinical

data package to support clinical studies of TNX-102 SL in Japan.

102 SL – Long COVID Program

We are developing TNX-102 SL as

a bedtime treatment for Long COVID.

The potential approval of TNX-102 SL for Long COVID is expected to be under Section 505(b)(2) of the

Tonix completed a pre-IND meeting

with the FDA in August 2021 to develop TNX-102 as a potential treatment for Long COVID.

Tonix expects to initiate a Phase 2 study of TNX-102

SL as an indicated treatment for a subset of patients affected by Long COVID whose symptoms overlap with fibromyalgia.

Long COVID is a

protracted syndrome experienced by many people following SARS-CoV-2 infection that can include a number of persistent disabling symptoms,

including fatigue, widespread pain, sleep disturbance, brain fog or difficulty concentrating, arthralgias, diffuse myalgia, olfactory

dysfunction, and headache.

The Phase 2 study will focus on Long COVID patients whose primary symptoms overlap with fibromyalgia, and,

therefore, the Long COVID program leverages learnings about the pharmacodynamic activity of TNX-102 SL from more than 1,000 participants

who have been or are enrolled in Tonix’s fibromyalgia trials to date.

Long COVID has been compared to fibromyalgia because of the

common symptoms of sleep disturbance, persistent widespread pain, fatigue, and brain fog.

Additionally, Long COVID, like fibromyalgia,

is experienced by women at a rate approximately four times that of men.

In October 2016, we completed

the six-month repeated-dose toxicology study of the active ingredient, CBP, in rats and a nine-month repeated-dose toxicology study in

dogs required for the NDA filing.

These chronic toxicity studies were requested by the FDA to augment the nonclinical information in the

AMRIX prescribing information, or labeling, which is necessary to support the TNX-102 SL labeling for long-term use.

Due to the lack of

evidence of potential abuse in clinical studies of TNX-102 SL, the FDA agreed that nonclinical study to assess CBP abuse potential is

not required to support the TNX-102 SL NDA filing.

We are planning to develop TNX-102 SL for the treatment of FM in Japan.

Cyclobenzaprine, the active ingredient of TNX-102 SL, has not been approved in Japan, and is considered a NCE (new chemical entity).

February 2022, we held an End of Phase 2 Consultation with the Pharmaceuticals and Medical Devices Agency, or PMDA, an independent administrative

institution responsible for ensuring the safety, efficacy and quality of pharmaceuticals and medical devices in Japan, to discuss the

Japan development plan.

Agreement was reached on the design of a Phase 1 bridging study (TNX-CY-F108/F108) in ethnic Japanese healthy

volunteers to enable clinical studies of TNX-102 SL in Japan.

PMDA also provided guidance on the overall nonclinical package to support

a Japan NDA filing for TNX-102 SL for the treatment of FM.

The F108 Phase 1 study was initiated

in March 2022 and the clinical phase was completed in May 2022 and we are awaiting the final study report at the time of this filing.

We are completing nonclinical safety, pharmacology and embryo-fetal development

toxicology studies as part of the agreed IND-enabling nonclinical data package to support clinical studies of TNX-102 SL in Japan.

102 SL – FM-type Long COVID Program

are developing TNX-102 SL as a bedtime treatment for FM-type Long COVID.

The potential approval of TNX-102 SL for Long COVID is expected

to be under Section 505(b)(2) of the FDCA.

2 PREVAIL Study (PA201)

initiated a Phase 2 study of TNX-102 SL as a treatment for FM-type Long COVID, which is a subset of patients affected by Long COVID whose

symptoms overlap with fibromyalgia.

The trial initiated in August 2022.

The study is a randomized, double-blind, placebo-controlled study

designed to evaluate the efficacy and safety of TNX-102 SL for FM-type Long COVID.

completed a pre-IND meeting with the FDA in August 2021 to develop TNX-102 SL as a potential treatment for Long COVID.

Long COVID is

a protracted syndrome experienced by many people following SARS-CoV-2 infection that can include a number of persistent disabling

symptoms, including fatigue, widespread pain, sleep disturbance, brain fog or difficulty concentrating, arthralgias, diffuse

myalgia, olfactory dysfunction, and headache.

The currently enrolling Phase 2 study focuses on Long COVID patients whose primary

symptoms overlap with fibromyalgia, and, therefore, the Long COVID program leverages learnings about the pharmacodynamic activity of

TNX-102 SL from more than 1,000 participants who have been or are enrolled in our fibromyalgia trials to date.

Long COVID has been

compared to fibromyalgia because of the common symptoms of sleep disturbance, persistent widespread pain, fatigue, and brain fog.

Additionally, Long COVID, like fibromyalgia, is experienced by women at a rate approximately four times that of men.

SL – Posttraumatic Stress Disorder Program

are developing TNX-102 SL as a bedtime treatment of PTSD under an active IND application.

The potential approval of TNX-102 SL

for PTSD is expected to be under Section 505(b)(2) of the FDCA.

The potential approval of TNX-102 SL for PTSD

is expected to be under Section 505(b)(2) of the FDCA.

3 RECOVERY Study (P302)

initiated the RECOVERY study (P302) in March 2019.

The RECOVERY Phase 3 study was a double-blind, randomized, placebo-controlled

study of TNX-102 SL 5.6 mg (2 x 2.8 mg sublingual tablets) over 12 weeks of treatment.

The RECOVERY study was conducted at approximately

The study planned to enroll 250 participants with civilian and military-related PTSD.

restricts enrollment of study participants to individuals with PTSD who experienced an index trauma within nine years of screening.

The two previous PTSD studies of TNX-102 SL (P201 and P301) restricted enrollment to participants who experienced traumas during

military service since 2001.

The primary efficacy endpoint in P302 was the Week 12 mean change from baseline in the severity

of PTSD symptoms as measured by CAPS-5 between those treated with TNX-102 SL and those receiving placebo.

Based on interim

analysis results of the first 50% of enrolled participants, an Independent Data Monitoring Committee recommended stopping the

Phase 3 RECOVERY trial (P302) in PTSD for futility as TNX-102 SL was unlikely to demonstrate a statistically significant improvement

in the primary endpoint of overall change from baseline in the severity of PTSD symptoms between those treated with TNX-102 SL

and those receiving placebo.

New enrollment for the RECOVERY study was stopped in February 2020, but we continued studying those

participants currently enrolled until completion and proceeded with a full analysis of the unblinded data to determine the next

steps in this program.

Topline data was reported during the fourth quarter of 2020, which revealed that the RECOVERY study did

not achieve statistical significance in the prespecified primary efficacy endpoint of change from baseline to Week 12 in the CAPS-5

between TNX-102 SL and placebo (p=0.343).

We initiated the RECOVERY study (P302) in March 2019.

The RECOVERY Phase

3 study was a double-blind, randomized, placebo-controlled study of TNX-102 SL 5.6 mg (2 x 2.8 mg sublingual tablets) over 12 weeks of

The RECOVERY study was conducted at approximately 30 U.S.

The study planned to enroll 250 participants with

civilian and military-related PTSD.

RECOVERY restricts enrollment of study participants to individuals with PTSD who experienced

an index trauma within nine years of screening.

The two previous PTSD studies of TNX-102 SL (P201 and P301) restricted enrollment to participants

who experienced traumas during military service since 2001.

The primary efficacy endpoint in P302 was the Week 12 mean change from

baseline in the severity of PTSD symptoms as measured by CAPS-5 between those treated with TNX-102 SL and those receiving placebo.

Based on interim analysis (IA) results of the first 50% of enrolled participants, an IDMC recommended stopping the Phase 3 RECOVERY trial

(P302) in PTSD for futility as TNX-102 SL was unlikely to demonstrate a statistically significant improvement in the primary endpoint

of overall change from baseline in the severity of PTSD symptoms between those treated with TNX-102 SL and those receiving placebo.

enrollment for the RECOVERY study was stopped in February 2020, but we continued studying those participants currently enrolled until

completion and proceeded with a full analysis of the unblinded data to determine the next steps in this program.

Topline data was reported

during the fourth quarter of 2020, which revealed that the RECOVERY study did not achieve statistical significance in the prespecified

primary efficacy endpoint of change from baseline to Week 12 in the CAPS-5 between TNX-102 SL and placebo (p=0.343;

effect size (ES)=0.15).

TNX-102 SL separated from placebo in the first key secondary endpoint, CGI-S scale (p=0.024;

and in the PGIC, (p=0.007).

TNX-102 SL also trended for improvement on the PROMIS Sleep Disturbance scale (p=0.055), consistent

with the proposed mechanism of targeting the PTSD sleep disturbance.

TNX-102 SL is generally well tolerated and no new safety

signals were observed.

Tonix met with the FDA to discuss potential new endpoints for the indication of treatment of PTSD.

new PTSD study can use 1 month look-back CAPS-5 as endpoint v.

ES=0.36) and in the PGIC, (p=0.007;

TNX-102 SL also trended for improvement on the PROMIS Sleep Disturbance scale (p=0.055;

ES=0.30), consistent with the proposed mechanism

of targeting the PTSD sleep disturbance.

TNX-102 SL is generally well tolerated and no new safety signals were observed.

Tonix met with

the FDA to discuss potential new endpoints for the indication of treatment of PTSD.

The next PTSD study can use 1 month look-back CAPS-5

as endpoint v.

1 week look-back.

intends to initiate a new Phase 2 study of TNX-102 SL in police in Kenya in the first half of 2022.

Phase 3 HONOR Study (P301)

the third quarter of 2018, we announced the results of a randomized, double-blind, placebo-controlled Phase 3 study of TNX-102

SL, planned for enrollment of approximately 550 participants with military-related PTSD conducted at approximately 40 U.S.

which we refer to as the HONOR study.

the third quarter of 2018, we announced the results of a randomized, double-blind, placebo-controlled Phase 3 study of TNX-102 SL, planned

for enrollment of approximately 550 participants with military-related PTSD conducted at approximately 40 U.S.

sites, which we refer to

as the HONOR study.

This study was an adaptive design study based on the results of the Phase 2 AtEase study.

The study design was very similar to the Phase 2 AtEase study, except there was one planned IA and the involvement of an

IDMC, which reviewed the unblinded IA results.

In addition, only one active dose (5.6 mg administered as 2 x 2.8 mg tablets) was

investigated and the baseline severity entrance criterion was a CAPS-5 total score ≥ 33 in this Phase 3 study.

efficacy endpoint of the HONOR study was the 12-week mean change from baseline in the severity of PTSD symptoms as measured by

the Clinician-Administered PTSD Scale for DSM-5, or CAPS-5, between those treated with TNX-102 SL and those receiving placebo.

The CAPS-5 is a standardized structured clinical interview and serves as the standard in research for measuring the symptom severity

The IA was conducted when approximately 50% of the initially planned participant enrollment was evaluable for efficacy.

HONOR was discontinued after the results of the IA indicated a pre-defined threshold p-value for continuing enrollment was not

achieved, i.e.

The study design was very

similar to the Phase 2 AtEase study, except there was one planned IA and the involvement of an IDMC, which reviewed the unblinded

In addition, only one active dose (5.6 mg administered as 2 x 2.8 mg tablets) was investigated, and the baseline severity entrance

criterion was a CAPS-5 total score ≥ 33 in this Phase 3 study.

The primary efficacy endpoint of the HONOR study was the 12-week

mean change from baseline in the severity of PTSD symptoms as measured by the Clinician-Administered PTSD Scale for DSM-5, or CAPS-5,

between those treated with TNX-102 SL and those receiving placebo.

The CAPS-5 is a standardized structured clinical interview and serves

as the standard in research for measuring the symptom severity of PTSD.

The IA was conducted when approximately 50% of the initially

planned participant enrollment was evaluable for efficacy.

HONOR was discontinued after the results of the IA indicated a pre-defined

threshold p-value for continuing enrollment was not achieved, i.e.

IDMC recommended stopping for futility.

The modified Intent-to-Treat (mITT) population analyzed at the time

of the IA included 252 participants.

most common adverse events were mostly related to local administration site reactions, such as oral hypoaesthesia (37.3%), abnormal

product taste (11.9%), and oral paraesthesia (9.7%).

The modified Intent-to-Treat

(mITT) population analyzed at the time of the IA included 252 participants.

most common adverse events were mostly related to local administration site reactions, such as oral hypoaesthesia (37.3%), abnormal product

taste (11.9%), and oral paraesthesia (9.7%).

The most common systemic adverse event was somnolence (15.7%).

Retrospective

analysis of the HONOR study revealed a treatment effect in participants who experienced trauma less than or equal to nine years

prior to screening.

In the participants who experienced trauma within nine years, the p-value of the CAPS-5 primary endpoint at

Week 12, using mixed model repeated measures with multiple imputation (MMRM with MI), was 0.039, with a least-squares mean difference

from placebo of -5.9 units.

In contrast, there was no difference in CAPS-5 in the participants who experienced trauma more than

nine years prior to screening compared to placebo.

This analysis defined an optimal treatment window for treatment with TNX-102

SL for PTSD of the first nine years after the index trauma that resulted in PTSD and guided the design of the next Phase 3 study

in PTSD, RECOVERY.

Retrospective analysis of

the HONOR study revealed a treatment effect in participants who experienced trauma less than or equal to nine years prior to screening.

the participants who experienced trauma within nine years, the p-value of the CAPS-5 primary endpoint at Week 12, using mixed model repeated

measures with multiple imputation (MMRM with MI), was 0.039, with a least-squares mean difference from placebo of -5.9 units.

there was no difference in CAPS-5 in the participants who experienced trauma more than nine years prior to screening compared to placebo.

This analysis defined an optimal treatment window for treatment with TNX-102 SL for PTSD of the first nine years after the index trauma

that resulted in PTSD and guided the design of the next Phase 3 study in PTSD, RECOVERY.

Safety Exposure Study for TNX-102 SL

October 2019, we completed long-term safety exposure studies in participants with PTSD to evaluate the tolerability of TNX-102

SL 5.6 mg to support an NDA for the treatment of PTSD.

The data provide us with exposure data of daily dosing of TNX-102

SL 5.6 mg for at least 12 months in more than 50 individuals, and daily dosing of TNX-102 SL 5.6 mg for at least 6 months in more

than 100 individuals.

October 2019, we completed long-term safety exposure studies in participants with PTSD to evaluate the tolerability of TNX-102 SL 5.6

mg to support an NDA for the treatment of PTSD.

The data provide us with exposure data of daily dosing of TNX-102 SL 5.6 mg for

at least 12 months in more than 50 individuals, and daily dosing of TNX-102 SL 5.6 mg for at least 6 months in more than 100 individuals.

The data was collected in OLE studies of the PTSD program.

Based on the FDA’s guidance, the

long-term safety exposure studies in PTSD are also expected to support an NDA for the management of FM.

Based on the FDA’s guidance, the long-term safety exposure studies

in PTSD are also expected to support an NDA for the management of FM.

NDA Requirements

Agreed Initial Pediatric Study Plan, or Agreed iPSP, is required for the initial NDA submission.

We submitted a revised iPSP in

the first quarter of 2017, which incorporated the FDA comments received on our iPSP submitted in the third quarter of 2016.

comments from the FDA were received in second quarter of 2017 on our revised iPSP.

We plan to submit an Agreed PSP once a therapeutic

dose in adults is established.

We submitted a revised iPSP in the first

quarter of 2017, which incorporated the FDA comments received on our iPSP submitted in the third quarter of 2016.

Additional comments

from the FDA were received in second quarter of 2017 on our revised iPSP.

We plan to submit an Agreed PSP once a therapeutic dose in adults

is established.

An acceptable Pediatric Study Plan will be determined at the time of the NDA approval.

on our discussions with the FDA and the FDA official meeting minutes, we will not have to conduct special populations (geriatric

and renal/hepatic impaired), drug-drug interaction or cardiovascular safety studies to support the TNX-102 SL NDA filing since

the pivotal systemic exposure bridging study using AMRIX as the reference listed drug, or RLD, has been successfully completed.

Due to the well-established safety profile of CBP at much higher doses than we proposed for PTSD and the long-term safety data

(up to 15 months) on TNX-102 SL 2.8 mg in a prior FM program, the FDA has not requested a risk management plan or medication guide

for this product.

on our discussions with the FDA and the FDA official meeting minutes, we will not have to conduct special populations (geriatric and renal/hepatic

impaired), drug-drug interaction or cardiovascular safety studies to support the TNX-102 SL NDA filing since the pivotal systemic exposure

bridging study using AMRIX as the reference listed drug, or RLD, has been successfully completed.

Due to the well-established safety profile

of CBP at much higher doses than we proposed for PTSD and the long-term safety data (up to 15 months) on TNX-102 SL 2.8 mg in a prior

FM program, the FDA has not requested a risk management plan or medication guide for this product.

Manufacturing

SL drug product for Phase 3 and the associated registration batches for the NDA were manufactured at commercial cGMP facilities.

We currently have in excess of 24 months stability data in the proposed packaging configurations ready for commercialization.

The FDA has reviewed the proposed CMC data package to support TNX-102 SL’s NDA approval and commercial manufacturing plans

as part of the IND process.

TNX-102 SL drug product for Phase 3 and the associated registration batches

for the NDA were manufactured at commercial cGMP facilities.

We currently have 36-month stability data in the proposed packaging configurations

ready for commercialization.

The FDA has reviewed the proposed CMC data package to support TNX-102 SL’s NDA approval and commercial

manufacturing plans as part of the IND process.

Tonix is ready to manufacture TNX-102 SL commercial product for the forecasted FM market.

(intranasal potentiated oxytocin) is a proprietary formulation of oxytocin in development for BED, prophylaxis of chronic migraine

and for the treatment of craniofacial pain, insulin resistance and related conditions.

In 2020, TNX-1900 was acquired from Trigemina,

TNX-1900 – Migraine, Craniofacial Pain and Obesity-Associated Binge

Eating Disorder

(intranasal potentiated oxytocin) is a proprietary formulation of oxytocin in development for BED, prophylaxis of chronic migraine and

for the treatment of craniofacial pain, insulin resistance and related conditions.

In 2020, TNX-1900 was acquired from Trigemina, Inc.

and licensed from Stanford University.

TNX-1900 is a drug-device combination product, based on an intranasal actuator device

that delivers oxytocin into the nose.

TNX-1900 is a drug-device combination product, based on an intranasal actuator device that delivers

oxytocin into the nose.

is a naturally occurring human hormone that acts as a neurotransmitter in the brain.

Oxytocin has no recognized addiction potential.

It has been observed that low oxytocin levels in the body can lead to increase in migraine headache frequency, and that increased

oxytocin levels can relieve migraine headaches.

Certain other chronic pain conditions are also associated with decreased oxytocin

Migraine attacks are caused, in part, by the activity of pain-sensing trigeminal nerve cells which, when activated, release

of CGRP which binds to receptors on other nerve cells and starts a cascade of events that is believed to result in headache.

when delivered via the nasal route, concentrates in the trigeminal system 1 resulting in binding of oxytocin to receptors

on neurons in the trigeminal system, inhibiting the release of CGRP and transmission of pain signals.

2 Blocking CGRP

release is a distinct mechanism compared with CGRP antagonist and anti-CGRP antibody drugs, which block the binding of CGRP to

its receptor.

TNX-1900, the addition of magnesium to the oxytocin formula enhances oxytocin receptor binding 3 as well as its effects

on trigeminal neurons and craniofacial analgesic effects in animal models 5 .

Intranasal oxytocin has been well tolerated

in several clinical trials in both adults and children 4 .

Targeted nasal delivery results in low systemic exposure and

lower risk of non-nervous system, off-target effects which could potentially occur with systemic CGRP antagonists such as anti-CGRP

antibodies 6 .

For example, CGRP has roles in dilating blood vessels in response to ischemia, including in the heart.

We believe nasally targeted delivery of oxytocin could translate into selective blockade of CGRP release in the trigeminal ganglion

and not throughout the body, which could be a potential safety advantage over systemic CGRP inhibition.

In addition, daily dosing

is more quickly reversible, in contrast to monthly or quarterly dosing, as is the case with anti-CGRP antibodies, giving physicians

and their patients greater control.

intend to initiate a Phase 2 study in chronic migraine in the second half of 2022.

We also plan to develop TNX-1900 for treatment

of episodic migraine, craniofacial pain and insulin resistance.

Tonix has a license with the University of Geneva to use TNX-1900

for the treatment of insulin resistance and related conditions.

TNX-1900 is also being studied as a potential treatment for binge

eating disorder in an investigator-initiated Phase 2 clinical trial.

The Phase 2 clinical trial is expected to start in the second

half of 2022.

In March 2022, we announced an agreement with Massachusetts General Hospital, a teaching hospital of Harvard Medical

School, to conduct this study.

has been observed that low oxytocin levels in the body can lead to an increase in migraine headache frequency, and that increased oxytocin

levels can relieve migraine headaches.

Certain other chronic pain conditions are also associated with decreased oxytocin levels.

attacks are caused, in part, by the activity of pain-sensing trigeminal nerve cells which, when activated, release CGRP which binds to

receptors on other nerve cells and starts a cascade of events that is believed to result in headache.

Oxytocin when delivered via the

nasal route, concentrates in the trigeminal system resulting in binding of oxytocin to receptors on neurons in the trigeminal system,

inhibiting the release of CGRP and transmission of pain signals.

Blocking CGRP release is a distinct mechanism compared with CGRP antagonist

and anti-CGRP antibody drugs, which block the binding of CGRP to its receptor.

TNX-1900, the addition of magnesium to the oxytocin formula enhances oxytocin receptor binding as well as its effects on trigeminal neurons

and craniofacial analgesic effects in animal models.

Intranasal oxytocin has been well tolerated in several clinical trials in both adults

and children.

Targeted nasal delivery results in low systemic exposure and lower risk of non-nervous system, off-target effects which

could potentially occur with systemic CGRP antagonists such as anti-CGRP antibodies.

For example, CGRP has roles in dilating blood vessels

in response to ischemia, including in the heart.

We believe nasally targeted delivery of oxytocin could translate into selective blockade

of CGRP release in the trigeminal ganglion and not throughout the body, which could be a potential safety advantage over systemic CGRP

In addition, daily dosing is more quickly reversible, in contrast to monthly or quarterly dosing, as is the case with anti-CGRP

antibodies, giving physicians and their patients greater control.

We initiated a Phase 2 study in chronic migraine in the first quarter of

We also plan to develop TNX-1900 for treatment of episodic migraine, craniofacial pain and insulin resistance.

Tonix has a license

with the University of Geneva to use TNX-1900 for the treatment of insulin resistance and related conditions.

TNX-1900 is also being studied

as a potential treatment for BED in an investigator-initiated Phase 2 clinical trial.

The Phase 2 clinical trial is expected to start

in the second quarter of 2023.

In March 2022, we announced an agreement with Massachusetts General Hospital, a teaching hospital of Harvard

Medical School, to conduct this study.

Tonix does not own this IND.

Yeomans DC, et al.

Transl Psychiatry.

Tzabazis A, et al.

36(10):943-50.

Antoni FA and Chadio SE.

257(2):611-4.

Yeomans, DC et al.

US patent US2017368095.

Cai Q, et al., Psychiatry Clin Neurosci.

Mar;72(3):140-151.

MaassenVanDenBrink A, et al.

Trends Pharmacol Sci.

37(9):779-788.

is based on Tonix’s patented intranasal potentiated oxytocin formulation, or TNX-1900, but being developed for Prader-Willi

Tonix licensed technology using oxytocin-based therapeutics for the treatment of Prader-Willi syndrome and non-organic

failure to thrive disease from the French National Institute of Health and Medical Research (Inserm).

The licensing agreement

has been negotiated and signed by Inserm Transfert, the private subsidiary of Inserm, on behalf of Inserm (the French National

Institute of Health and Medical Research), Aix-Marseille Université and Centre Hospitalier Universitaire of Toulouse.

syndrome is recognized as the most common genetic cause of life-threatening childhood obesity and affects males and females with

equal frequency and all races and ethnicities.

There is currently no approved treatment for either the suckling deficit in infants

or the obesity and hyperphagia in older children associated with Prader-Willi syndrome.

Since Prader-Willi syndrome is an orphan

disease that occurs in approximately one in 15,000 births, Tonix has been granted Orphan Drug Designation for TNX-2900 by the

2022, Tonix entered into a research collaboration with Inserm involving in vitro and in vivo animal studies designed

to validate and characterize the role of oxytocin in suckling and in the maturation of feeding behavior during infancy in order

to support an intranasal therapeutic approach to restore a normal nutritive suckling.

The studies will include mice that have

been engineered to precisely recapitulate the genetic issue underlying Prader-Willi in humans.

The mechanisms involved in suckling

activity required for normal feeding and the role of oxytocin system in this process will be investigated.

The results of this

work are expected to be useful in the clinical care of infants requiring support to achieve efficient suckling behavior.

oxytocin has previously been shown to improve suckling in newborn animals and suppress feeding behaviors in adult animal models.

preclinical pipeline of drugs and biologic candidates includes TNX-801, a smallpox vaccine, TNX-3500, a COVID-19 antiviral;

a COVID-19 therapeutic platform;

TNX-3700, a COVID-19 vaccine;

TNX-701, a drug candidate for radioprotection;

TNX-1700 a preclinical

candidate for cancers of the gastrointestinal system and TNX-1600, a preclinical candidate for PTSD, ADHD and depression.

CR is a novel oral formulation of tianeptine oxalate designed for once-daily daytime dosing that is currently in development for

the treatment of major depressive disorder (MDD), but may also be developed for PTSD and neurocognitive disorder from corticosteroids.

Tianeptine sodium (amorphous) immediate release was first marketed for depression in France in 1989 and has been available for

decades in Europe, Russia, Asia, and Latin America for the treatment of depression.

Tianeptine sodium has an established safety

profile from decades of use in these jurisdictions.

Currently there is no tianeptine-containing product approved in the U.S.

no controlled-release tianeptine product approved in any jurisdiction.

Tonix discovered a novel oxalate salt of tianeptine that

may provide improved stability, consistency, and manufacturability compared to known forms of tianeptine.

Tianeptine is believed

to work in depression as a modulator of the glutamatergic system.

Tianeptine modulates the glutamatergic system indirectly since

it does not directly bind to NMDA, AMPA or kainate receptors.

In animals, tianeptine has been shown to reverse the adverse neuroplastic

changes that are observed during periods of stress and elevated corticosteroid exposure.

Tianeptine and its MC5 metabolite are

weak µ-opioid receptor agonists.

Tonix has added naloxone to the TNX-601 CR tablet to mitigate potential for parenteral

abuse as tianeptine has been linked to illicit misuse at much higher doses than the reported therapeutic dose in the treatment

Neither tianeptine nor MC5 have been shown to bind other neurotransmitter receptors.

Tianeptine’s reported pro-cognitive

and anxiolytic effects as well as its ability to attenuate the neuropathological effects of excessive stress responses suggest

that it may also be used to treat post-traumatic stress disorder by a different mechanism of action than TNX-102 SL.

intend to develop TNX-601 CR under Section 505(b)(2) of the FDCA.

Tonix completed a Phase 1 clinical trial for formulation development

outside of the U.S in 2019.

Based on this study, the final formulation of TNX-601 CR to be used in Phase 2 testing will be 39.4

mg tianeptine oxalate and 1 mg naloxone for once daily treatment of MDD.

Naloxone is included in the formulation to mitigate the

potential for high dose parenteral abuse.

Tianeptine has weak off-target activity at the µ-opioid receptor that presents

the potential for parenteral abuse with doses on the order of eight to 80 times the therapeutic daily dose for depression.

on official minutes from a pre-IND meeting with the FDA, we expect to initiate a pharmacokinetic study,

in the third quarter of 2022, and a Phase 2 study in the first quarter of 2023.

Phase 2 study, expected to start in the first quarter of 2023, is expected to be a randomized, double-blind, placebo-controlled,

parallel group study to evaluate the efficacy and safety of TNX-601 CR monotherapy compared to placebo in MDD.

Treatment duration

will be six weeks, preceded by up to five weeks in screening and followed by a two-week safety follow-up period (total up to 13

weeks of participation).

We plan to randomize approximately 260 individuals with MDD at a 1:1 ratio to two arms of 130 each for

drug and placebo at approximately 25-30 U.S.

The primary efficacy endpoint will be the change from baseline to Week 6 in

the Montgomery-Åsberg Depression Rating Scale (MADRS) total score.

– Potential Smallpox and Monkeypox Vaccine

is a novel potential smallpox-preventing vaccine based on a synthetic version of live horsepox virus, grown in cell culture.

ER – Depression, PTSD, Neurocognitive Dysfunction from Corticosteroids

announced the development of TNX-601 ER in July 2022, a potential abuse deterrent, extended-release formulation of tianeptine

TNX-601 ER is designed for once-daily daytime dosing and is being developed as a treatment for major depressive

disorder (MDD), posttraumatic stress disorder, and neurocognitive dysfunction associated with corticosteroid use.

represents a novel approach to treating depression in the U.S., since the active ingredient tianeptine induces a neuroprotective and

resilient phenotype in both neurons and microglia under conditions of stress in animals.

The dramatic and unique effects of

tianeptine are illustrated in animal models by the restoration of dendritic arborization of pyramidal neurons of CA3 region of

hippocampus and the dentate gyrus region new neuron formation and integration into hippocampal networks.

antidepressants that are marketed in the U.S.

act by modulating the levels or receptor binding of neurotransmitters in the synapse.

Tianeptine sodium (amorphous) immediate release (IR) tablets have been available in Europe and many countries in Asia and Latin

America for the treatment of MDD over the more than three decades since it was first marketed in France in 1989.

tianeptine-containing product has been approved by the FDA.

The proposed mechanism of action of TNX-601 ER is distinct from

traditional monoaminergic antidepressants in the U.S.

In addition to its glutamatergic properties central to its antidepressant

effect, tianeptine has weak µ-opioid receptor agonist properties and has been linked to illicit misuse at much higher doses

than those reported to be effective in the treatment of MDD (reported to be used daily at 8-80 times the antidepressant daily dose).

Previously, we were developing a naloxone-containing tablet, TNX-601 CR (tianeptine oxalate and naloxone controlled-release) for MDD,

that was designed to mitigate the risk of parenteral abuse.

We intend to develop TNX-601 ER under Section 505(b)(1) of the Federal

Food, Drug, and Cosmetic Act (FDCA).

Tonix completed a Phase 1 clinical trial for formulation development outside of the U.S in 2019.

Based on this study, the final formulation of TNX-601 ER to be used in Phase 2 testing will be 39.4 mg tianeptine hemioxalate for once

daily treatment of MDD (which is equivalent in tianeptine content to three 12.5 mg doses of tianeptine sodium).

Based on the clearance

of IND 152371 by the FDA, we expect to initiate a Phase 2 study in the first quarter of 2023.

The Phase 2 study is planned to be a randomized, double-blind, placebo-controlled,

parallel group study to evaluate the efficacy and safety of TNX-601 ER monotherapy compared to placebo in MDD.

Treatment duration will

be six weeks, preceded by up to five weeks in screening and followed by a two-week safety follow-up period (total up to 13 weeks of participation).

We plan to randomize approximately 300 individuals with MDD at a 1:1 ratio to two arms of 150 each for drug and placebo at approximately

The primary efficacy endpoint will be the change from baseline to Week 6 in the Montgomery-Åsberg Depression Rating

Scale (MADRS) total score.

An IA will be conducted once the first 50 percent of the sample has completed the study, estimated to occur

in the fourth quarter of 2023.

– Cocaine Intoxication

(T172R/G173Q double-mutant cocaine esterase 200 mg, i.v.

solution) is being developed for the treatment of cocaine intoxication.

is a recombinant protein enzyme produced through rDNA technology in a non-disease-producing strain of E.

coli bacteria.

Cocaine Esterase

(CocE) was identified in bacteria (Rhodococcus) that use cocaine as the sole source of carbon and nitrogen and that grow in soil surrounding

The gene encoding CocE was identified and the protein was extensively characterized.

CocE catalyzes the breakdown of cocaine

into metabolite ecgonine methyl ester and benzoic acid.

Wild-type CocE is unstable at body temperature, so targeted mutations were introduced

in the CocE gene and resulted in the T172R/G173Q double-mutant CocE, which is active for approximately 6 hours at body temperature.

there is no specific pharmacotherapy indicated for cocaine intoxication, a state characterized by acute agitation, hyperthermia, tachycardia,

arrhythmias, and hypertension, with the potential life-threatening sequalae of myocardial infarction, cerebrovascular accident, rhabdomyolysis,

respiratory failure, and seizures.

Patients are currently managed only by supportive care for the adverse effects of cocaine overdose

on the cardiovascular and central nervous systems.

By targeting the cause of cocaine intoxication, rather than the symptoms like other

medicines in emergency usage, we believe TNX-1300 may offer significant advantages to the current standard of care for cocaine overdose.

TNX-1300 was developed by Columbia University, University of Kentucky and University of Michigan, and in-licensed by Tonix from Columbia

University in 2019.

a Phase 2 randomized, double-blind, placebo-controlled clinical study, TNX-1300 at 100 mg or 200 mg i.v.

doses was well tolerated and

interrupted cocaine effects after cocaine 50 mg i.v.

In August 2022, we announced that we received a Cooperative Agreement grant

from the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), to support development of TNX-1300.

The Company expects to initiate a new Phase 2 clinical study of TNX-1300 for the treatment of cocaine intoxication in the second quarter

of 2023, pending agreement on protocol design with the U.S.

Food and Drug Administration (FDA).

The Phase 2 trial is a single-blind, open-label,

placebo-controlled, randomized study comparing the safety of a single 200 mg dose of TNX-1300 to standard of care alone in approximately

60 emergency department patients presenting with cocaine intoxication.

A positive Phase 2a study of volunteer cocaine users in a controlled

laboratory setting has been previously completed.

TNX-1300 has been granted Breakthrough Therapy designation by the FDA.

As a biologic and new molecular entity, TNX-1300 is eligible for 12 years

market exclusivity upon approval by the FDA, in addition to expected patent protection through 2029.

Since in-licensing, Tonix

has requalified existing inventory, developed a lyophilized drug product to facilitate enhanced stability and handling conditions applicable

for an ER treatment, updated the process and analytical methods to current standards and is in the process of manufacturing Phase 2/3

drug product clinical supply.

– Prader-Willi Syndrome

is based on our patented intranasal potentiated oxytocin formulation, or TNX-1900, but being developed for Prader-Willi syndrome.

licensed technology using oxytocin-based therapeutics for the treatment of Prader-Willi syndrome and non-organic failure to thrive disease

from the French National Institute of Health and Medical Research (Inserm).

The licensing agreement has been negotiated and signed by

Inserm Transfert, the private subsidiary of Inserm, on behalf of Inserm (the French National Institute of Health and Medical Research),

Aix-Marseille Université and Centre Hospitalier Universitaire of Toulouse.

Prader-Willi syndrome is recognized as the most common

genetic cause of life-threatening childhood obesity and affects males and females with equal frequency and all races and ethnicities.

There is currently no approved treatment for either the suckling deficit in infants or the obesity and hyperphagia in older children associated

with Prader-Willi syndrome.

Since Prader-Willi syndrome is an orphan disease that occurs in approximately one in 15,000 births, Tonix

has been granted Orphan Drug Designation for TNX-2900 by the FDA.

Tonix completed a pre-IND meeting with the FDA in November 2022 to discuss

the most efficient and appropriate investigational plan to establish the safety and effectiveness evidence to support the approval of

2022, Tonix entered into a research collaboration with Inserm involving in vitro and in vivo animal studies designed to validate and characterize

the role of oxytocin in suckling and in the maturation of feeding behavior during infancy in order to support an intranasal therapeutic

approach to restore a normal nutritive suckling.

The studies will include mice that have been engineered to precisely recapitulate the

genetic issue underlying Prader-Willi in humans.

mechanisms involved in suckling activity required for normal feeding and the role of oxytocin system in this process will be investigated.

The results of this work are expected to be useful in the clinical care of infants requiring support to achieve efficient suckling behavior.

Intranasal oxytocin has previously been shown to improve suckling in newborn animals and suppress feeding behaviors in adult animal models.

– Organ Transplant Rejection/Autoimmune Conditions

TNX-1500 is a humanized mAb directed against CD40-ligand, or CD40L (also

known as CD154), engineered to modulate binding to Fc receptors, that is being developed to prevent and treat organ transplant rejection

as well as to treat autoimmune conditions.

TNX-1500 incorporates the antigen binding fragment (Fab) region of hu5c8, which has been extensively

characterized including at the atomic level in complex with CD40-ligand.

In experiments at the Massachusetts General Hospital, a teaching hospital

of Harvard Medical School, TNX-1500 is being studied as monotherapy or in combination with immunosuppressive drugs in heart and kidney

organ transplants in non-human primates.

Preliminary results from ongoing animal experiments in kidney and heart allogeneic transplants

indicate that TNX-1500 appears to have comparable efficacy to historical experiments using the chimeric mouse/primate version of the anti-CD40L

mAb 5c8, but to date has not shown evidence of the thromboembolic adverse events associated with the first generation mAb directed against

is a protein expressed on the surface of activated T lymphocytes that mediates T cell helper function.

CD40-ligand is also known as CD154,

the T cell-B cell activating molecule (T-BAM), TRAP and gp39.

CD154 is a member of the Tumor Necrosis Factor (TNF) Super Family.

against CD154 has been approved for commercial use anywhere in the world.

Other TNF Super Family members have been successfully targeted

by antagonist mAbs.

Approved mAbs against TNFα include:

infliximab (Remicade®), adalimumab (Humira®), certolizumab pegol

(Cimzia®), and golimumab (Simponi®) for the treatment of certain autoimmune conditions.

Also, etanercept (Enbrel®) is a

TNFα antagonist receptor fusion protein.

An approved mAb against RANKL (CD254) is denosumab (Prolia® or Xgeva®) for the

treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.

January 2021, the World Intellectual Property Organization published a patent application filed under the Patent Cooperation Treaty covering

TNX-1500, a humanized mAb directed against CD40-ligand, which is also known as CD154.

The patent application is titled “Anti-CD154

Antibodies and Uses Thereof” and published under International Publication No.

WO 2021/001458 A1.

The application entered national

phase in December 2021.

The patent applications include claims related to proprietary anti-human CD40-ligand mAbs that were engineered

to have modified effector function, including TNX-1500, which have reduced potential for Fc binding to FcγRII.

The patent applications

also claim uses of TNX-1500 for preventing and treating conditions, such as organ transplant rejection and autoimmune disorders.

are granted, a patent issuing from a national stage of this application could potentially provide U.S.

patent coverage for the TNX-1500

composition of matter through 2040 excluding possible patent term extensions or patent term adjustments.

We also have filed a PCT patent

application, PCT/US2022/011404, in January 2022, entitled “Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies.”

It claims methods of inducing immune tolerance in transplant recipients using anti-CD154 antibodies having modified effector functions.

Tonix completed a pre-IND meeting with the FDA in October 2022 to discuss the most efficient and appropriate investigational plan to establish

the safety and effectiveness evidence to support the licensure of TNX-1500.

We expect to start a Phase 1 study of TNX-1500 in the second

quarter of 2023.

and Simponi® are trademarks of Janssen;

Humira® is a trademark of AbbVie Inc.;

Cimzia® is a trademark of UCB S.

Prolia® and Xgeva® are trademarks of Amgen Inc.

– Potential Smallpox and Mpox Vaccine

TNX-801 is a novel

potential smallpox- and mpox-preventing vaccine based on a synthetic version of live horsepox virus, grown in cell culture.

it shares structural characteristics with vaccinia-based vaccines, TNX-801 has unique properties that we believe indicate potential

1 unchanged sentence

such as myopericarditis in some individuals.

Emergent BioSolutions’ ACAM2000 ® is the only replicating

vaccinia virus vaccine currently approved by the FDA to protect against smallpox.

We believe replicating virus vaccines have potential

efficacy advantages over non-replicating vaccines, relating to the stimulation of cell mediated immunity.

Bavarian Nordic’s

Jynneos ® is the only non-replicating virus vaccine currently approved by the FDA to protect against smallpox and

We believe TNX-801 has the potential to have improved tolerability relative to replicating vaccinia vaccines and the

potential to have improved efficacy relative to non-replicating vaccinia vaccines.

was eradicated by a World Health Organization program that vaccinated individuals with live replicating vaccinia vaccines wherever

smallpox appeared.

Emergent BioSolutions’ ACAM2000® is the only replicating vaccinia

virus vaccine currently approved by the FDA to protect against smallpox.

We believe replicating virus vaccines have potential efficacy

advantages over non-replicating vaccines, relating to the stimulation of cell mediated immunity.

Bavarian Nordic’s Jynneos®

is the only non-replicating virus vaccine currently approved by the FDA to protect against smallpox and mpox.

We believe TNX-801

has the potential to have improved tolerability relative to replicating vaccinia vaccines and the potential to have improved efficacy

relative to non-replicating vaccinia vaccines.

Smallpox was eradicated

by a World Health Organization program that vaccinated individuals with live replicating vaccinia vaccines wherever smallpox appeared.

In the 1970s, vaccination of civilians to protect against smallpox was discontinued in the U.S.;

however, smallpox

remains a material threat to national security and a proportion of military personnel, including members of the Global Response

Force, continue to be vaccinated.

We are developing TNX-801 as a potential smallpox-preventing vaccine for the U.S.

national stockpile and for potential widespread immunization in the event of malicious reintroduction of variola, the virus that

causes smallpox.

however, smallpox remains a material

threat to national security and a proportion of military personnel, including members of the Global Response Force, continue to

be vaccinated.

We are developing TNX-801 as a potential smallpox- and mpox-preventing vaccine for the U.S.

strategic national stockpile

and for potential widespread immunization in the event of malicious reintroduction of variola, the virus that causes smallpox.

is a growing problem in certain regions of Africa.

Some cases of monkeypox have been reported outside of Africa in patients who

had been infected while in Africa.

January 2020 at the American Society of Microbiology Biothreats conference, we reported the results of experiments on TNX-801

that were performed in collaboration with Southern Research, that showed TNX-801 vaccinated macaques were protected against monkeypox

Starting in May of 2022, cases of mpox have been reported outside of Africa in patients

who had not been infected while in Africa.

More than 30,000 cases in the U.S.

have been reported according to the U.S.

Centers for Disease

Control and Prevention.

January 2020 at the American Society of Microbiology Biothreats conference, we reported the results of experiments on TNX-801 that were

performed in collaboration with Southern Research, that showed TNX-801 vaccinated macaques were protected against monkeypox challenge.

The TNX-801 vaccinated macaques showed no overt clinical signs after monkeypox challenge.

Furthermore, eight of eight

animals vaccinated with two different doses of TNX-801 showed no lesions after monkeypox challenge.

have filed a patent application to protect the TNX-801 vaccine candidate.

In addition, we expect that TNX-801 will be eligible for

12 years of non-patent-based exclusivity under the Patient Protection and Affordable Care Act, or PPACA.

Following the passage of

the 21st Century Cures Act, a law designed to help accelerate medical product development, we believe TNX-801 will qualify as a

medical countermeasure and would therefore be eligible for a Priority Review Voucher upon receiving FDA approval.

Priority Review Voucher program provision of the 21st Century Cures Act is set to expire in 2023.

If TNX-801 does not receive FDA

approval by 2023, we may not be able to capitalize on the incentives contained in the 21st Century Cures Act unless the provision

allowing for the Priority Review Voucher Program is extended until such time as TNX-801 is approved by the FDA.

intend to meet with the FDA to discuss the most efficient and appropriate investigational plan for TNX-801, to establish the safety

and effectiveness evidence to support the licensure TNX-801.

We are currently working to develop a vaccine that meets cGMP quality

to support a clinical study.

and TNX-1850 – Potential COVID-19 Vaccines

Furthermore, eight of eight animals vaccinated

with two different doses of TNX-801 showed no lesions after monkeypox challenge.

Those studies were published as an article in the peer

reviewed journal, Viruses in 2023.

Patent for TNX-801 smallpox and mpox vaccine and Recombinant Pox Virus (RPV) platform technology.

This patent is expected

to provide Tonix with U.S.

market exclusivity until 2037, excluding any possible patent term extensions or patent term adjustments.

addition, we expect that TNX-801 will be eligible for 12 years of non-patent-based exclusivity under the Patient Protection and Affordable

Care Act, or PPACA.

intend to meet with the FDA to discuss the most efficient and appropriate investigational plan for TNX-801, to establish the safety and

effectiveness evidence to support the licensure TNX-801.

We are currently working to develop a vaccine that meets cGMP quality to support

a clinical study.

A Phase 1 study of TNX-801 is expected to be initiated in the second half of 2023.

– Potential COVID-19 Vaccine

infectious disease portfolio includes a platform for vaccines for COVID-19.

TNX-1800 is live virus vaccine based on Tonix’s

RPV platform that expresses the SARS-CoV-2 spike protein from the ancestral Wuhan strain.

Because the subsequent omicron variant

has out-competed the ancestral Wuhan strain, we are now planning new versions of this vaccine, TNX-1840 and TNX-1850, that express

spike protein from the omicron variant and from the BA.2 variant, respectively.

Each of these RPV vaccines is being developed

to protect against COVID-19 primarily by eliciting T cell responses.

The COVID-19 vaccines that are approved for use, or have

emergency use authorization, or EUA, in the U.S.

have provided significant health benefits to the vaccinated population;

they are showing limitations in the durability of protection conferred and in their ability to block forward transmission.

virus vaccines that protect against other viral diseases by eliciting T cell responses have shown durability of protection that

lasts years to decades and some live virus vaccines have significantly inhibited forward transmission.

reported positive efficacy data for the TNX-1800 (spike from Wuhan strain) from animal challenge studies using live SARS-CoV-2

in the first quarter of 2021.

In this study, TNX-1800 vaccinated, SARS-CoV-2 challenged animals had undetectable SARS-CoV-2 in

the upper airways, which we believe relates to potential inhibition of forward transmission of this respiratory pathogen.

study of non-human primates compared TNX-1800 (modified horsepox virus encoding CoV-2 spike protein) to TNX-801 (horsepox virus,

live vaccine) at two doses.

TNX-1800 is live virus vaccine based on our RPV platform that

expresses the SARS-CoV-2 spike protein from the ancestral Wuhan strain.

Because the subsequent omicron variant has out-competed the ancestral

Wuhan strain, we are now planning new versions of this vaccine, TNX-1840 and TNX-1850, that are designed to express spike protein from

the omicron variant and from the BA.2 variant, respectively.

Each of these RPV vaccines is being developed to protect against COVID-19

primarily by eliciting T cell responses.

COVID-19 vaccines that are approved for use, or have emergency use authorization, or EUA, in the U.S.

have provided significant health

benefits to the vaccinated population;

however, they are showing limitations in the durability of protection conferred and in their ability

to block forward transmission.

Live virus vaccines that protect against other viral diseases by eliciting T cell responses have shown

durability of protection that lasts years to decades and some live virus vaccines have significantly inhibited forward transmission.

We reported positive efficacy data for the TNX-1800 (spike from Wuhan strain)

from animal challenge studies using live SARS-CoV-2 in the first quarter of 2021.

In this study, TNX-1800 vaccinated, SARS-CoV-2 challenged

animals had undetectable SARS-CoV-2 in the upper airways, which we believe relates to potential inhibition of forward transmission of

this respiratory pathogen.

This study of non-human primates compared TNX-1800 (modified horsepox virus encoding CoV-2 spike protein) to

TNX-801 (horsepox virus, live vaccine) at two doses.

A control group received a placebo.

Each of these five groups (TNX-1800 high and low dose;

high and low dose and placebo) included four animals.

At day 41 after vaccination (or placebo), each animal was exposed to SARS-COV-2

by intra-tracheal (1 x 10 6 TCID50) and intra-nasal (1 x 10 6 TCID50) administration.

Upper airway virus was

studied by oropharyngeal swabs and lower airway virus by tracheal lavage using qRT-PCR to determine the number of genome copies

of SARS-CoV-2 present in the samples.

Six days after challenge, no (0/8) samples taken from animals vaccinated with TNX-1800 showed

infection (more than 1,000 genome copies of SARS CoV-2) in either upper or lower airway samples.

In contrast, all (8/8) animals

vaccinated with the control vaccine TNX-801 showed infection in either the upper or lower airway samples as did all (4/4) monkeys

vaccinated with vehicle control.

At day 14 after a single vaccination, all eight of the TNX-1800 vaccinated animals made anti-CoV-2

neutralizing antibodies (≥1:40 titer) and, as expected, none of the eight TNX-801 vaccinated control animals, or any of the

four animals in the placebo group made anti-CoV-2 neutralizing antibodies (≤1:10 titer).

At 6 days after CoV-2 challenge, TNX-1800

vaccinated animals showed neutralizing antibody titers of (≥1:1280 titer).

The level of neutralizing anti-CoV-2 antibody production

was similar between the low and high dose TNX-1800 groups (1 x 10 6 Plaque Forming Units [PFU] and 3 x 10 6

PFU, (respectively).

For unvaccinated animals challenged with SARS-CoV-2, neutralizing antibodies were measurable after vaccination

(≥1:40 titer) that were lower and appeared later than neutralizing antibodies in TNX-1800 vaccinated animals.

TNX-801 were well tolerated at both doses.

Further, as an expected additional outcome, all 16 animals vaccinated with either dose

of TNX-1800 or the control TNX-801 manifested a “take”, or cutaneous response, signaling that the horsepox vector

elicits a strong T cell immune response.

These results support the expectation that TNX-1800 at the low dose of 1 x 10 6

PFU is an appropriate dose for a one-shot vaccine in humans and indicate that 100 doses per vial is the target format for commercialization,

which is well suited to manufacturing and distribution at large scale.

Together, these data show that

TNX-1800 induces protection against SARS-COV-2 infection in non-human primates.

These data confirm that “take” is a biomarker

of protection of upper and lower airways from SARS-CoV-2 challenge, and a biomarker of immunological response to TNX-1800’s cargo

COVID-19 antigen, which is the CoV-2 spike protein.

Tonix completed a pre-IND meeting with the FDA to discuss the most efficient and appropriate

investigational plan to establish the safety and effectiveness evidence to support the licensure of TNX-1800.

We believe that the animal

data and manufacturing process information that we have developed for TNX-1800 will facilitate expedited development of TNX-1840 and TNX-1850.

In addition, we believe the RPV platform can be engineered to express relevant protein antigens from different infectious diseases to

make a variety of vaccines.

In June 2020, we announced

a partnership with FUJIFILM Diosynth Biotechnologies (FDBT) to provide contract manufacturing and development services to support the

manufacturing of our COVID-19 vaccine candidate at the time, TNX-1800, for clinical trial supply.

In February 2022, this contract ended.

We continue to work with other third party CMOs for the manufacturing and development of TNX-1800, TNX-1840 and TNX-1850, in addition

Each of these five groups (TNX-1800 high and

TNX-801 high and low dose and placebo) included four animals.

At day 41 after vaccination (or placebo), each animal was exposed

to SARS-COV-2 by intra-tracheal (1 x 10 6 TCID50) and intra-nasal (1 x 10 6 TCID50) administration.

Upper airway virus

was studied by oropharyngeal swabs and lower airway virus by tracheal lavage using qRT-PCR to determine the number of genome copies of

SARS-CoV-2 present in the samples.

Six days after challenge, no (0/8) samples taken from animals vaccinated with TNX-1800 showed infection

(more than 1,000 genome copies of SARS CoV-2) in either upper or lower airway samples.

In contrast, all (8/8) animals vaccinated with

the control vaccine TNX-801 showed infection in either the upper or lower airway samples as did all (4/4) monkeys vaccinated with vehicle

At day 14 after a single vaccination, all eight of the TNX-1800 vaccinated animals made anti-CoV-2 neutralizing antibodies (≥1:40

titer) and, as expected, none of the eight TNX-801 vaccinated control animals, or any of the four animals in the placebo group made anti-CoV-2

neutralizing antibodies (≤1:10 titer).

At 6 days after CoV-2 challenge, TNX-1800 vaccinated animals showed neutralizing antibody

titers of (≥1:1280 titer).

The level of neutralizing anti-CoV-2 antibody production was similar between the low and high dose TNX-1800

groups (1 x 10 6 Plaque Forming Units [PFU] and 3 x 10 6 PFU, (respectively).

For unvaccinated animals challenged

with SARS-CoV-2, neutralizing antibodies were measurable after vaccination (≥1:40 titer) that were lower and appeared later than

neutralizing antibodies in TNX-1800 vaccinated animals.

TNX-1800 and TNX-801 were well tolerated at both doses.

Further, as an expected

additional outcome, all 16 animals vaccinated with either dose of TNX-1800 or the control TNX-801 manifested a “take”, or

cutaneous response, signaling that the horsepox vector elicits a strong T cell immune response.

These results support the expectation

that TNX-1800 at the low dose of 1 x 10 6 PFU is an appropriate dose for a one-shot vaccine in humans and indicate that 100

doses per vial is the target format for commercialization, which is well suited to manufacturing and distribution at large scale.

these data show that TNX-1800 induces protection against SARS-COV-2 infection in non-human primates.

These data confirm that “take”

is a biomarker of protection of upper and lower airways from SARS-CoV-2 challenge, and a biomarker of immunological response to TNX-1800’s

cargo COVID-19 antigen, which is the CoV-2 spike protein.

Tonix completed a pre-IND meeting with the FDA to discuss the most efficient

and appropriate investigational plan to establish the safety and effectiveness evidence to support the licensure of TNX-1800.

that the animal data and manufacturing process information that we have developed for TNX-1800 will facilitate expedited development of

TNX-1840 and TNX-1850.

In addition, we believe the RPV platform can be engineered to express relevant protein antigens from different

infectious diseases to make a variety of vaccines.

June 2020, we announced a partnership with FUJIFILM Diosynth Biotechnologies (FDBT) to provide contract manufacturing and development

services to support the manufacturing of our COVID-19 vaccine candidate at the time, TNX-1800, for clinical trial supply.

2022, this contract ended.

We continue to work with other third party CMOs for the manufacturing and development of TNX-1850, in addition

to ultimately planning to utilize our in-house manufacturing capabilities which are currently in development.

We have filed patent

applications on the COVID-19 vaccines TNX-1800, TNX-1840 and TNX-1850 and also expect 12 years of non-patent-based exclusivity under PPACA.

TNX-2100 is a diagnostic product candidate (a COVID skin test) comprising

three different mixtures of synthetic peptides (TNX-2110, -2120 and -2130), which are designed to represent different protein components

of the SARS-CoV-2 virus.

TNX-2110 (SARS-CoV-2 multi-antigen peptides) represents epitopes of multiple proteins from SARS-CoV-2.

(SARS-CoV-2 spike peptides) represents only the spike protein.

TNX-2130 (SARS-CoV-2 non-spike peptides) represents non-spike proteins.

Each of these three synthetic peptide mixtures is expected to be administered as part of the same procedure, at separate locations on

the forearm, and each is expected to elicit a DTH response after approximately 48 hours in individuals with pre-existing T cell immunity

to peptides in that mixture.

Individuals who have been infected by or exposed to SARS-CoV-2 would be expected to respond to all three

In contrast, a successfully vaccinated individual who has not been exposed or infected by SARS-CoV-2 would be expected to respond

only to TNX-2120 (SARS-CoV-2 spike peptides), since the currently available vaccines only encode spike protein.

In the clinical protocol

for testing TNX-2100, positive skin test controls are being used to confirm that study participants have intact T cell immunity and are

not immunodeficient.

test is designed to be administered in the same manner as skin tests for tuberculosis, or TB, sold as Tubersol® or Aplisol®

or generically as the Mantoux tuberculin purified protein derivative (PPD) test.

A thin gauge needle is used to apply each of

the three separate TNX-2100 peptide mixtures into the skin, or intradermally, on the inner surface of the forearm between the

wrist and the elbow.

In a typical positive test, the skin surrounding the injection site is expected to become red, raised and

hardened, or “indurated”, after approximately 48 hours.

Induration above a threshold level would signify a positive

result and the diameter of the induration would indicate the amount of T cell immunity to the test peptides.

DTH skin test responses

are believed to reflect functional in vivo immunity.

Clinical trials are expected to correlate skin test results with clinical

history and laboratory findings to inform estimates about the sensitivity and specificity of the test as a marker of T cell immunity

in individuals who are pre- and post-COVID-19 vaccination, recovered from COVID-19, or exposed but asymptomatic.

in 1882 by Robert Koch, the DTH reaction has been used for more than a century as a clinical test for T cell-mediated immune reactions 1 .

In the 1940s, Landsteiner and Chase demonstrated that the reaction was mediated by the cellular and not the antibody arm of the

immune system 2 .

The DTH reaction has been shown to be dependent on the presence of memory T cells.

Both the CD4+ and

CD8+ T cells have been shown to participate in this response.

DTH skin tests have been commonly used to detect T cell responses

to tuberculosis, fungal pathogens, and mumps virus.

has the potential to serve as:

(i) a biomarker for T cell protective immunity and durability of vaccine protection;

(ii) a personalized

approach for vaccine boosters;

(ii) a method to stratify participants in COVID-19 vaccine trials with a more complete picture

of immune status;

(iv) an endpoint in COVID-19 vaccine trials for vaccines that elicit T cell immunity, and (v) public health

surveillance.

Tonix received IND clearance in the fourth quarter of 2021 and initiated enrollment in a first-in-human study of

TNX-2100 in the first quarter of 2022.

We expect topline data from this study in the first half of 2022.

Delayed type hypersensitivity:

current theories with an historic perspective.

Dermatol Online J.

Landsteiner K, Chase MW.

Studies on the sensitization of animals with simple chemical compounds:

Skin sensitization

by intraperitoneal injections.

is a trademark of Sanfi Pasteur.

is a trademark of Par Pharmaceutical, Inc.

announced the issuance of U.S.

Patent for TNX-801 smallpox and mpox vaccine and Recombinant Pox Virus (RPV) platform technology.

patent is expected to provide Tonix with U.S.

market exclusivity until 2037, excluding any possible patent term extensions or patent term

adjustments, and also expect 12 years of non-patent-based exclusivity under PPACA.

preclinical pipeline of drugs and biologic candidates also includes TNX-1600, a preclinical candidate for PTSD, ADHD and depression;

a preclinical candidate for cancers of the gastrointestinal system;

TNX-2300, a live-virus vaccine based on bovine parainfluenza virus

for COVID-19;

TNX-3600, a COVID-19 therapeutic platform;

TNX-3700, a COVID-19 vaccine;

TNX-3800, a COVID-19 Therapeutic/Preventative.

Facilities Overview

to our COVID-19 and other infectious disease development programs, we are developing the resources necessary to enable internal

research, development and manufacturing capabilities necessary to meet the goal of producing new vaccine candidates within 100

days and new diagnostics within weeks of obtaining sequence information.

As articulated in the American Pandemic Preparedness

Plan, or AP3 released by the U.S.

Office of Science and Technology Policy, this 100-day goal for vaccines is a key component of

preparedness for future pandemics.

We are establishing the infrastructure necessary to support the pandemic preparedness goals

established in the AP3, specifically with respect to our RPV vaccine and skin test platforms and potentially to other vaccine,

diagnostic and therapeutic platforms.

Infectious Disease Research & Development Center (RDC)

We acquired the infectious disease RDC in Frederick, Maryland consisting

of two buildings totaling approximately 48,000 square feet.

The acquisition closed in October 2021 and was operational at closing, but

as of December 31, 2021, the facility was not ready for its intended use.

It is our intention to have the facility ready for use in the

first half of 2022.

The RDC facility will focus on our development of vaccines and antiviral drugs against COVID-19, its variants, and

other infectious diseases.

The RDC facility is currently biosafety level 2 (BSL-2) but we intend to upgrade components to BSL-3.

capacity, the RDC can employ 80-100 scientists and technical support staff.

Relating to our COVID-19

and other infectious disease development programs, we are developing the resources necessary to enable internal research, development

and manufacturing capabilities necessary to meet the goal of producing new vaccine candidates within 100 days and new diagnostics

within weeks of obtaining sequence information of a novel pathogen.

We seek to be a leader in the movement to re-build domestic

research, development and manufacturing capabilities.

Because this movement follows a protracted period when domestic research,

development and manufacturing were moved out of the U.S., or “off-shore” by other companies to save on labor and other

costs, the movement to reverse that trend has been described as “on-shoring” or “re-domestication”.

COVID-19 pandemic taught that national borders may close during a health emergency.

Therefore, domestic capabilities are essential

for the health security of the U.S., which has also been described as pandemic preparedness and biodefense.

As articulated in the

American Pandemic Preparedness Plan, or AP3 released by the U.S.

Office of Science and Technology Policy, this 100-day goal for

vaccines is a key component of preparedness for future pandemics.

We are establishing the infrastructure necessary to support the

pandemic preparedness goals established in the AP3, specifically with respect to our RPV vaccine platform and potentially to other

vaccine and therapeutic platforms.

Research & Development Center (RDC)

We own the approximately

48,000 square foot RDC facility in Frederick, Maryland.

The RDC facility is operational and focuses on our development of vaccines and

antiviral drugs against COVID-19, its variants, and other infectious diseases.

The RDC also conducts research on CNS and immunology drugs.

The RDC facility is biosafety level 2 (BSL-2) with BSL-3 components.

The RDC currently employs 26 staff.

At full capacity, the RDC can

employ 80-100 scientists and technical support staff.

Advanced Development Center (ADC)

are in the process of a substantial renovation of the ADC located in the New Bedford business park in Dartmouth, Massachusetts.

This facility is intended to accelerate development and clinical scale manufacturing of live-virus vaccines to support Phase 1

and Phase 2 clinical trials.

Plans for the ADC include single-use bioreactors and purification suites with equipment for Good

Manufacturing Practice (GMP) production of vaccines for clinical trials, including when fully operational, the capability of producing

sterile vaccines in glass bottles.

ADC is currently being constructed and will be an approximately 45,000 square foot BSL-2 facility, once completed.

At full capacity,

the facility can employ up to 70 researchers, scientists, manufacturing, and technical support staff.

It is expected to be partially

operational in the first half of 2022.

ADC located in the New Bedford business park in Dartmouth, Massachusetts is operational and intended to accelerate development and clinical

scale manufacturing of live-virus vaccines and biologics to support Phase 1 and Phase 2 clinical trials.

ADC includes single-use bioreactors

and purification suites with equipment for Good Manufacturing Practice (GMP) production of vaccines for and biologics clinical trials,

including the capability of producing sterile vaccines in glass bottles.

ADC is an approximately 45,000 square foot BSL-2 facility that currently employs 35 staff.

At full capacity, the facility can employ up

to 70 researchers, scientists, manufacturing, and technical support staff.

Commercial Manufacturing Center (CMC)

intend to build the CMC in Hamilton, Montana where we purchased approximately 44 acres of land.

The site is on land designated

by Ravalli County as a Target Economic Development District.

The CMC will focus on developing and manufacturing Phase 3 and commercial

scale live-virus vaccines and is also intended to be BSL-2.

Site enabling work is expected to be initiated for the CMC in 2022.

Our industry is highly competitive

and subject to rapid and significant technological change.

Our potential competitors include large pharmaceutical and biotechnology companies,

specialty pharmaceutical and generic drug companies, academic institutions, government agencies and research institutions.

that key competitive factors that will affect the development and commercial success of our product candidates are efficacy, safety, tolerability,

reliability, price and reimbursement level.

Many of our potential competitors, including many of the organizations named below, have substantially

greater financial, technical, and human resources than we do and significantly greater experience in the discovery and development of

product candidates, obtaining the FDA’s and other regulatory approvals of products and the commercialization of those products.

Accordingly, our competitors may be more successful than we may be in obtaining FDA approval for drugs and achieving widespread market

Our competitors’ drugs may be more effective, or more effectively marketed and sold, than any drug we may commercialize

and may render our product candidates obsolete or non-competitive before we can recover the expenses of developing and commercializing

any of our product candidates.

We anticipate that we will face intense and increasing competition as new drugs enter the market and advanced

technologies become available.

Further, the development of new treatment methods for the conditions we are targeting could render our

drugs non-competitive or obsolete.

Summarized below is the competitive landscape for the indications in which Tonix has product candidates

in or nearing the clinical stages of development.

Anti-CD40-ligand mAbs

Tonix is aware of several companies

developing biologics that target CD40-L or CD40, including UCB S.A., Belgium/Biogen Inc., Eledon Pharmaceuticals, Inc., Horizon Therapeutics

and Sanofi S.A.

Furthermore, Tonix is aware of several companies developing antagonistic anti-CD40 mAbs including Novartis, Boehringer

Ingelheim, Kiniska Pharmaceuticals, and Boston Immune Technologies.

The site is on land designated by Ravalli

County as a Target Economic Development District.

The CMC will focus on developing and manufacturing Phase 3 and commercial scale live-virus

vaccines and biologics and is also intended to be BSL-2.

We have constructed a field office on the site to direct construction.

industry is highly competitive and subject to rapid and significant technological change.

Our potential competitors include large pharmaceutical

and biotechnology companies, specialty pharmaceutical and generic drug companies, academic institutions, government agencies and research

institutions.

We believe that key competitive factors that will affect the development and commercial success of our product candidates

are efficacy, safety, tolerability, reliability, price and reimbursement level.

Many of our potential competitors, including many of the

organizations named below, have substantially greater financial, technical, and human resources than we do and significantly greater experience

in the discovery and development of product candidates, obtaining the FDA’s and other regulatory approvals of products and the commercialization

of those products.

Accordingly, our competitors may be more successful than we may be in obtaining FDA approval for drugs and achieving

widespread market acceptance.

Our competitors’ drugs may be more effective, or more effectively marketed and sold, than any drug

we may commercialize and may render our product candidates obsolete or non-competitive before we can recover the expenses of developing

and commercializing any of our product candidates.

We anticipate that we will face intense and increasing competition as new drugs enter

the market and advanced technologies become available.

Further, the development of new treatment methods for the conditions we are targeting

could render our drugs non-competitive or obsolete.

Summarized below is the competitive landscape for the indications in which Tonix has

product candidates in or nearing the clinical stages of development.

Products approved for the

treatment of fibromyalgia include Lyrica® (pregabalin), marketed by Pfizer;

Cymbalta® (duloxetine), marketed by Eli Lilly;

(milnacipran), marketed by Allergan (acquired by AbbVie).

Tonix is aware of several other companies developing treatments for fibromyalgia

including Virios Therapeutics, Axsome Therapeutics, Tryp Therapeutics, Biomind Labs, Cortene, and Sorrento Therapeutics.

Episodic Migraine Prophylaxis

Currently there are several classes of drugs that are approved for the

prophylactic treatment of chronic or episodic migraine, including generic beta blockers (propranolol, timolol), and anticonvulsants (divalproex,

Other drug classes that are used off-label to treat migraine prophylaxis, include tricyclic antidepressants (e.g., amitriptyline).

Also, Allergan markets Botox® (onabotulinumtoxinA).

More recently, several products have received FDA approval including Aimovig®

(erenumab), which is marketed by Amgen/Novartis;

Ajovy® (fremanezumab), which is marketed by Teva Pharmaceuticals;

(galcanezumab) which is marketed by Eli Lilly;

and Yvepti® (eptinezumab), which is marketed by Lundbeck.

Also, Nurtec ODT® (Rimegepant)

was more recently approved as both a preventive and an acute treatment for episodic migraine, marketed by Pfizer;

and Qulipta® (atogepant)

was approved for prevention of episodic migraine, marketed by AbbVie.

We are aware of other companies working to develop therapeutics

for the treatment or prophylaxis of migraine including Astrocyte Pharmaceuticals, Protox, Kallyope, Crystec Pharma, Pulmatrix, and Epalex.

Major Depressive

Many antidepressant medications

are beyond their patent life and are generally produced by generic drug companies, including several compounds in the tricyclic class

(e.g., amitriptyline), the serotonin-selective reuptake inhibitor class (e.g, fluoxetine, paroxetine and sertraline), the serotonin-norepinephrine

reuptake inhibitor class (e.g., venlafaxine), as well as the norepinephrine-dopamine reuptake inhibitor, bupropion.

Recently, Auvelity,

developed by Axsome Therapeutics, and Vraylar, developed by Allergan, received FDA approval.

Tonix is aware of several companies developing

novel prescription medicines for depression including Janssen, Neumora Therapeutics (formerly BlackThorn Therapeutics), Sage Therapeutics,

Relmada Therapeutics, Clexio Biosciences Ltd., Otsuka, Seelos Therapeutics, Biomind Labs, FSD Pharma, Bright Minds Bioscienes, Vistagen,

Alto Neuroscience, Addex Therapeutics, and BetterLife Pharma.

(Post-Acute Sequelae of SARS-CoV-2 Infection or PASC)

There currently are no approved

products for the treatment of long COVID/PASC.

Tonix is aware of several other companies developing therapeutics for long COVID including

Direct Biologics, American CryoStem, HopeBiosciences, Axcella Health Inc., Ampio Pharmaceuticals, Pieris Pharmaceuticals, Resolve Therapeutics,

PaxMedia, GeNeuro, Organicell, Ampio Pharmaceuticals, Lyramid, Virios Therapeutics, Berlin Cures, and Statera Biopharma.

Products approved for

the treatment of PTSD include Paxil® (paroxetine), marketed by GlaxoSmithKline and Zoloft® (sertraline), marketed by

Tonix is aware of other companies working to develop therapeutics for the treatment of PTSD including Bionomics, Otsuka/Lundbeck,

Nobilis Therapeutics, Bright Minds Biosciences, Alto Neuroscience, Addex Therapeutics, Ophidion, Artelo Biosciences, Roche, Boehringer

Ingelheim, NRx Pharmaceuticals, Nanomerics, Seelos Therapeutics, and the Multidisciplinary Association of Psychedelic Studies (MAPS).

Acadia Pharmaceuticals is testing Nuplazid® (pimavanserin) for the treatment of insomnia in veterans with PTSD.

Cocaine Intoxication

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for the treatment of cocaine intoxication.

approved for the treatment of fibromyalgia include Lyrica® (pregabalin), marketed by Pfizer;

Cymbalta (duloxetine), marketed by Eli

and Savella (milnacipran), marketed by Allergan (acquired by AbbVie).

Tonix is aware of several other companies developing

treatments for fibromyalgia, including Aptinyx, Virios Therapeutics, Teva Pharmaceuticals, and Axsome Therapeutics.

Long COVID (Post-Acute Sequelae

of COVID-19 or PASC)

There currently are no approved

products for the treatment of Long COVID/PASC.

Tonix is aware of several other companies developing therapeutics for Long COVID, including

PureTech Health, Direct Biologics, American CryoStem, HopeBiosciences, Axcella Health Inc., Ampio Pharmaceuticals, CytoDyn, Pieris Pharmaceuticals,

Resolve Therapeutics, PaxMedia, GeNeuro and Organicell.

Products approved for the treatment

of PTSD include Paxil ® (paroxetine), marketed by GlaxoSmithKline and Zoloft ® (sertraline), marketed by Pfizer.

Tonix is aware of other companies working to develop therapeutics for the treatment of PTSD including Bionomics, Otsuka/Lundbeck, Aptinyx,

Nobilis Therapeutics, the Multidisciplinary Association of Psychedelic Studies (MAPS) and Tryp Therapeutics.

Chronic or Episodic Migraine

Currently there are several classes

of drugs that are approved for the prophylactic treatment of chronic or episodic migraine, including generic beta blockers (propranolol,

timolol), and anticonvulsants (divalproex, topiramate).

Other drug classes that are used off-label to treat migraine prophylaxis, include

tricyclic antidepressants (e.g., amitriptyline).

Also, Allergan markets Botox ® (onabotulinumtoxinA).

More recently, several

products have received FDA approval for the treatment of migraine, including Aimovig ® (erenumab), which is marketed by

Amgen/Novartis;

Ajovy ® (fremanezumab), which is marketed by Teva Pharmaceuticals;

Emgality ® (galcanezumab)

which is marketed by Eli Lilly;

and Yvepti ® (eptinezumab), which is marketed by Lundbeck.

Other therapies are approved

as abortive treatment for acute migraine.

Prader-Willi Syndrome

There are no FDA approved therapies

Anti-CD40-ligand

Monoclonal Antibodies

Tonix is aware of several

companies developing biologics that target the CD40L molecule and block its interaction with CD40 including UCB/Biogen, Eledon

Pharmaceuticals, Horizon Therapeutics Plc.

(which is being acquired by Amgen), Lundbeck (in partnership with Aprilbio), and Sanofi.

Furthermore, Tonix is aware of several companies developing antagonistic anti-CD40 mAbs including Novartis, Boehringer

Ingelheim, Kiniska Pharmaceuticals, Boston Immune Therapies, and NapaJen Pharma, Inc.

There are no approved products

for the treatment of Prader-Willi syndrome.

1 unchanged sentence

Tonix is aware

of several companies developing treatments for Prader-Willi syndrome including Aadvark Therapeutics, Radius, Levo Therapeutics, ConSynance

Therapeutics, Soleno Therapeutics, Lipidio Pharma, Helsinn, Inversago Pharma, Saniona, 9 Meters Biopharma, Neuren Pharmaceuticals, Neuracle

Science, Harmony Biosciences, Notitia Biotechnologies, and Taysha Gene Therapies.

Major Depressive Disorder

Many antidepressant medications

are beyond their patent life and are generally produced by generic drug companies, including several compounds in the tricyclic class

(e.g., amitriptyline), the serotonin-selective reuptake inhibitor class (e.g, fluoxetine, paroxetine and sertraline), the serotonin-norepinephrine

reuptake inhibitor class (e.g., venlafaxine, duloxetine), as well as the norepinephrine-dopamine reuptake inhibitor, bupropion.

of companies are marketing prescription drugs for depression, including Johnson & Johnson’s Janssen division.

aware of several companies developing novel prescription medicines for depression including Axsome Therapeutics, Janssen, Neumora Therapeutics

(formerly BlackThorn Therapeutics), Sage Therapeutics, Relmada Therapeutics, Clexio Biosciences Ltd., Allergan (acquired by AbbVie) and

vaccines and antivirals

approved for the treatment of smallpox include ACAM2000, marketed by Emergent BioSolutions and JYNNEOS ® , marketed

by Bavarian Nordic.

Approved antivirals include TPOXX ® , marketed by SIGA and TEMBEXA ® , marketed

Tonix is aware of other companies developing treatments for smallpox including EpiVax, HK inno.N, and BioFactura.

environment for developing vaccines for COVID-19 is competitive and includes over 150 companies and academic institutions in various

stages of development.

Vaccines granted full FDA regulatory approval include Comirnaty (BNT162b2), marketed by Pfizer-BioNTech,

and Spikevax (mRNA-1273), marketed by Moderna.

Ad.26.COV2S, developed by Janssen, has received emergency use authorization (EUA)

from the FDA.

of two companies developing a therapeutic for Prader Willi Syndrome including Acadia (which purchased Levo Therapeutics in 2022) and OT4B.

Several other companies are developing treatments for Prader-Willi syndrome including Aadvark Therapeutics, ConSynance Therapeutics, Soleno

Therapeutics, Lipidio Pharma, Helsinn, Inversago Pharma, Saniona, 9 Meters Biopharma, Neuren Pharmaceuticals, Neuracle Science, Harmony

Biosciences, and Notitia Biotechnologies.

Colorectal Cancer

Tonix is developing a small peptide/biologic

for the treatment of gastric and colorectal cancer.

Tonix is aware of several other companies developing biologics for the treatment of

gastric and colorectal cancer including Bexion Pharmaceuticals Inc., Faeth Therapeutics Inc., PDS Biotechnology Corp, and F-star Alpha

Vaccines granted full

FDA regulatory approval include Comirnaty® (BNT162b2), marketed by Pfizer-BioNTech and Spikevax® (mRNA-1273), marketed

Ad.26.COV2S, developed by Janssen, has FDA approval for limited use.

Covovax® (NVX-CoV2373), developed by Novavax,

has received EUA from the FDA.

Other vaccines have received EUA in international markets.

Tonix is aware of 120 vaccines currently in clinical

trials, and more than 75 vaccines in preclinical development.

Test for COVID-19 (measure of T cell immune response)

currently is no standardized laboratory test available to measure T cell immune responses to SARS-CoV-2, however the FDA granted

EUA to T-Detect™ COVID test by Adaptive Biotechnologies Corporation in March 2021.

The only other currently available methods

to detect T cell immunity to SARS-CoV-2 require several tubes of blood from the test subject, a multi-step sample preparation

process including isolation of peripheral blood mononuclear cells, tissue culture with in vitro T cell stimulation in highly

specialized laboratories that have fluorescent activated cells sorting (FACS) flow cytometry technology, methodologies that have

not been amenable to standardization or scalability for commercial clinical services.

Tonix is aware of other companies developing

diagnostics to identify T cell immune response to SARS-CoV-2 , including Biovaxys.

believe that we have an extensive patent portfolio and substantial know-how relating to TNX-1800, TNX-801, TNX-102 SL and our

other product candidates.

Our patent portfolio, described more fully below, includes claims directed to various compositions and

methods of use related to our product candidates.

As of March 8, 2022, the patents we are either the owner of record of or own

the contractual right to include 31 issued U.S.

and Mpox Vaccines and Antivirals

Vaccines approved for

the prevention of smallpox include ACAM2000®, marketed by Emergent BioSolutions and JYNNEOS®, marketed by Bavarian Nordic.

JYNNEOS® is also approved for the prevention of mpox.

Approved antivirals for smallpox include TPOXX®, marketed by SIGA

and TEMBEXA®, marketed by Chimerix.

These antivirals are not FDA approved for the treatment of mpox.

Tonix is aware of other

companies developing treatments for smallpox and mpox including EpiVax, HK inno.N, BioFactura, Blue Water Vaccines, NightHawk Biosciences,

Ascletis, and Hyundai Biosciences.

Intellectual Property

We believe that we have an

extensive patent portfolio and substantial know-how relating to TNX-102 SL, TNX-1300, TNX-1500, TNX-601 ER, TNX-801 and our other product

Our patent portfolio, described more fully below, includes claims directed to various compositions and methods of use related

to our product candidates.

As of March 8, 2023, the patents we are either the owner of record of or own the contractual right to include

34 issued U.S.

patents and 271 issued non-U.S.

We are actively pursuing an additional

patent applications, of which 4 are provisional and 27 are non-provisional, 13 international patent applications, and

218 non-U.S./non-international patent applications.

strive to protect the proprietary technology that we believe is important to our business, including our proprietary technology

platform, our product candidates, and our processes.

We are actively pursuing an additional 32 U.S.

patent applications, of which

7 are provisional and 25 are non-provisional, 11 international patent applications, and 247 non-U.S./non-international patent applications.

We strive to protect the proprietary

technology that we believe is important to our business, including our proprietary technology platform, our product candidates, and our

We seek patent protection in the U.S.

and internationally for our products,

their methods of use and processes of manufacture, and any other technology to which we have rights, where available and when

We also rely on trade secrets that may be important to the development of our business.

success will depend on 1) the ability to obtain and maintain patent and other proprietary rights in commercially important technology,

inventions and know-how related to our business, 2) the validity and enforceability of our patents, 3) the continued confidentiality

of our trade secrets, and 4) our ability to operate without infringing the valid and enforceable patents and proprietary rights

of third parties.

We also rely on continuing technological innovation and in-licensing opportunities to develop and maintain our

proprietary position.

cannot be certain that patents will be granted with respect to any of our pending patent applications or with respect to any patent

applications we may own or license in the future, nor can we be certain that any of our existing patents or any patents we may

own or license in the future will be useful in protecting our technology.

For this and more comprehensive risks related to our

intellectual property, please see “Risk Factors — Risks Relating to Our Intellectual Property.”

term of individual patents depends upon the legal term of the patents in the countries in which they are obtained.

In most countries

in which we file, the patent term is 20 years from the date of filing the first non-provisional priority application.

In the United

States, a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays

by the PTO in granting a patent or may be shortened if a patent is terminally disclaimed over another patent.

term of a U.S.

patent that covers a drug approved by the FDA or methods of making or using that drug may also be eligible for

patent term extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory

review process.

The Drug Price Competition and Patent Term Restoration Act, also known as the Hatch-Waxman Act, is a federal law

that encourages new drug research by restoring patent term lost to regulatory delays by permitting a patent term extension of

up to five years beyond the statutory 20-year term of the patent for the approved product or its methods of manufacture or use

if the active ingredient has not been previously approved in the U.S.

The length of the patent term extension is related to the

length of time the drug is under regulatory review.

A patent term extension cannot extend the remaining term of a patent beyond

a total of 14 years from the date of product approval and only one patent applicable to an approved drug may be extended.

provisions are available in Europe and some other foreign jurisdictions to extend the term of a patent that covers an approved

When possible, depending upon the length of clinical trials and other factors involved in the filing of an NDA, we expect

to apply for patent term extensions for patents covering our product candidates and their methods of use.

patent portfolios for our proprietary technology platform and our five most advanced product candidates as of March 8, 2022 are

summarized below.

— anti-CD40L Therapeutics

are collaborating with Harvard Medical School to develop TNX-1500, a humanized mAb that targets CD40L for

the prevention and treatment of organ transplant rejection.

In this regard, we filed International Application No.

PCT/EP2020/068589,

entitled “Anti-CD154 antibodies and uses thereof” on July 1, 2020 (nationalized in 15 countries).

We also filed International

Patent Application No.

PCT/US2020/028002 on April 13, 2020, entitled “Inhibitors of CD40-CD154 Binding” (nationalized

in Canada, European Patent Office and Japan).

We also filed International Patent Application No.

PCT/US2022/011404, entitled “Methods

of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies” on January 6, 2022.

— Cocaine Intoxication Treatment

have licensed rights from The Trustees of Columbia University in the City of New York, The Regents of the University of Michigan,

and University of Kentucky Research Foundation to develop a potential product, TNX-1300, for the treatment of cocaine intoxication.

The licensed patents are directed to mutant cocaine esterase polypeptides and methods of using these polypeptides as anti-cocaine

therapeutics.

They include U.S.

8,318,156 and 9,200,265, entitled “Anti-Cocaine Compositions and Treatment”

and various counterpart patents outside of the U.S (e.g., European Patent 2046368).

These patents provide TNX-1300 with US market

exclusivity until February 2029, and market exclusivity outside of the U.S.

until July 10, 2027, subject to any patent term extensions.

and internationally for our products, their methods of use and processes of manufacture,

and any other technology to which we have rights, where available and when appropriate.

We also rely on trade secrets that may be important

to the development of our business.

Our success will depend on 1)

the ability to obtain and maintain patent and other proprietary rights in commercially important technology, inventions and know-how related

to our business, 2) the validity and enforceability of our patents, 3) the continued confidentiality of our trade secrets, and 4) our

ability to operate without infringing the valid and enforceable patents and proprietary rights of third parties.

We also rely on continuing

technological innovation and in-licensing opportunities to develop and maintain our proprietary position.

We cannot be certain that patents

will be granted with respect to any of our pending patent applications or with respect to any patent applications we may own or license

in the future, nor can we be certain that any of our existing patents or any patents we may own or license in the future will be useful

in protecting our technology.

For this and more comprehensive risks related to our intellectual property, please see “Risk Factors — Risks

Relating to Our Intellectual Property.”

The term of individual patents

depends upon the legal term of the patents in the countries in which they are obtained.

In most countries in which we file, the patent

term is 20 years from the date of filing the first non-provisional priority application.

In the United States, a patent’s term may

be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the PTO in granting a patent or may

be shortened if a patent is terminally disclaimed over another patent.

The term of a U.S.

covers a drug approved by the FDA or methods of making or using that drug may also be eligible for patent term extension, which permits

patent term restoration as compensation for the patent term lost during the FDA regulatory review process.

The Drug Price Competition

and Patent Term Restoration Act, also known as the Hatch-Waxman Act, is a federal law that encourages new drug research by restoring patent

term lost to regulatory delays by permitting a patent term extension of up to five years beyond the statutory 20-year term of the patent

for the approved product or its methods of manufacture or use if the active ingredient has not been previously approved in the U.S.

length of the patent term extension is related to the length of time the drug is under regulatory review.

A patent term extension cannot

extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only one patent applicable to an

approved drug may be extended.

Similar provisions are available in Europe and some other foreign jurisdictions to extend the term of a

patent that covers an approved drug.

When possible, depending upon

the length of clinical trials and other factors involved in the filing of an NDA, we expect to apply for patent term extensions for patents

covering our product candidates and their methods of use.

The patent portfolios for our

proprietary technology platform and our most advanced product candidates as of March 8, 2023 are summarized below.

SL — Central Nervous System Conditions

patent portfolio for TNX-102 SL includes patent applications directed to compositions of matter of CBP, formulations containing

CBP, and methods for treating CNS conditions, such as TNX-102 SL for PTSD, for acute stress disorder, for sleep disturbances in

fibromyalgia, for alcohol abuse, for disordered sleep, for sexual dysfunction, for depression in fibromyalgia and for agitation

in neurodegenerative conditions, e.g., AAD, utilizing these compositions and formulations.

eutectic compositions were discovered by development partners and are termed the “Eutectic Technology.” The patent

portfolio for TNX-102 SL relating to the Eutectic Technology includes patent applications directed to eutectic compositions containing

CBP, eutectic CBP formulations, methods for treating PTSD and other CNS conditions utilizing eutectic CBP compositions and formulations,

and methods of manufacturing eutectic CBP compositions.

patent portfolio for TNX-102 SL includes patent applications directed to compositions of matter of CBP, formulations containing CBP, and

methods for treating CNS conditions, such as TNX-102 SL for PTSD, for acute stress disorder, for sleep disturbances in fibromyalgia, for

alcohol abuse, for disordered sleep, for sexual dysfunction, for depression in fibromyalgia, fatigue, e.g., CAP rates, post-acute sequelae

of SARS-CoV-2 infection, and for agitation in neurodegenerative conditions, e.g., AAD, utilizing these compositions and formulations.

eutectic compositions were discovered by development partners and are termed the “Eutectic Technology.” The patent portfolio

for TNX-102 SL relating to the Eutectic Technology includes patent applications directed to eutectic compositions containing CBP, eutectic

CBP formulations, methods for treating PTSD and other CNS conditions utilizing eutectic CBP compositions and formulations, and methods

of manufacturing eutectic CBP compositions.

The Eutectic Technology patent portfolio includes U.S.

patents, such as

patents, such as U.S.

9,956,188, U.S.

1 unchanged sentence

10,357,465, U.S.

patents claiming priority from those applications issue, those patents would expire in 2034

or 2035, excluding any patent term adjustments or extensions.

10,864,175, and U.S.

patents claiming priority from those applications issue, those patents would expire in 2034 or 2035, excluding any

patent term adjustments or extensions.

unique pharmacokinetic profile of TNX-102 SL, or the PK Technology, was discovered by Tonix and its development partners.

patent portfolio for TNX-102 SL relating to the PK Technology includes patent applications directed to compositions of matter

of CBP, formulations containing CBP, methods for treating PTSD, agitation in neurodegenerative conditions, and other CNS conditions

utilizing these compositions and formulations.

The patent portfolio

for TNX-102 SL relating to the PK Technology includes patent applications directed to compositions of matter of CBP, formulations containing

CBP, methods for treating PTSD, agitation in neurodegenerative conditions, and other CNS conditions utilizing these compositions and formulations.

The PK Technology patent portfolio includes U.S.

Patent Application No.

patents claiming priority from those applications issue, those patents would expire in 2033, excluding any

patent term adjustments or extensions.

patents claiming priority from

those applications issue, those patents would expire in 2033, excluding any patent term adjustments or extensions.

May 2, 2017, U.S.

9,636,408 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline

Hydrochloride”, issued.

9,636,408 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”,

The patent claims recite pharmaceutical compositions comprising the eutectic.

The patent claims

also recite methods of manufacturing the eutectic.

September 13, 2017, European patent 2,501,234, entitled “Methods and Compositions for Treating Symptoms Associated with

PTSD Using Cyclobenzaprine”, issued.

This patent recites the use of CBP for the treatment of PTSD, which covers the use

of TNX-102 SL for the treatment of PTSD, since the active ingredient in TNX-102 SL is CBP and provides TNX-102 SL with European

market exclusivity until 2030 and may be extended based on the timing of the European marketing authorization of TNX-102 SL for

In response to an opposition filed in June 2018 by a German law firm, the European Patent Office’s Opposition

Division in October 2019 upheld the patent in unamended form.

The patent claims also recite methods of manufacturing

the eutectic.

September 13, 2017, European patent 2,501,234, entitled “Methods and Compositions for Treating Symptoms Associated with PTSD Using

Cyclobenzaprine”, issued.

This patent recites the use of CBP for the treatment of PTSD, which covers the use of TNX-102 SL for the

treatment of PTSD, since the active ingredient in TNX-102 SL is CBP and provides TNX-102 SL with European market exclusivity until 2030

and may be extended based on the timing of the European marketing authorization of TNX-102 SL for PTSD.

In response to an opposition

filed in June 2018 by a German law firm, the European Patent Office’s Opposition Division in October 2019 upheld the patent in unamended

Opponent has appealed.

The Technical Board of the European Patent Office has canceled the April 27, 2023 Oral Proceedings

pending the decision of the Enlarged Board of Appeal in G 2/21 (plausibility), which seeks to clarify whether a technical effect can be

relied on when proof for the effect rests solely in post-published evidence and what role, if any, plausibility should play in this assessment.

December 15, 2017, Japanese Patent No.

1 unchanged sentence

These claims relate to the pharmacokinetic profile of TNX-102 SL.

August 3, 2022, European Patent No.

2861223, entitled “Compositions and Methods for Transmucosal Absorption,” issued.

These claims relate to the pharmacokinetic profile of TNX-102 SL.

March 20, 2018, U.S.

9,918,948 entitled “Methods and Compositions for Treating Symptoms Associated with PTSD

Using Cyclobenzaprine”, issued.

The claims recite a method of using TNX-102 SL’s active ingredient cyclobenzaprine

to treat PTSD and provides TNX-102 SL with US market exclusivity until 2030, excluding any patent term extensions.

9,918,948 entitled “Methods and Compositions for Treating Symptoms Associated with PTSD Using Cyclobenzaprine,”

The claims recite a method of using TNX-102 SL’s active ingredient cyclobenzaprine to treat PTSD and provides TNX-102 SL

with US market exclusivity until 2030, excluding any patent term extensions.

March 23, 2018, Japanese Patent No.

6310542 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline

Hydrochloride”, issued.

The claims recite pharmaceutical compositions comprising the eutectics and methods of manufacturing

these eutectic formulations.

6310542 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”,

The claims recite pharmaceutical compositions comprising the eutectics and methods of manufacturing these eutectic formulations.

May 1, 2018, U.S.

9,956,188, entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline

Hydrochloride”, issued.

The claims recite a eutectic of cyclobenzaprine hydrochloride and mannitol and methods of making

those eutectics.

9,956,188, entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”,

The claims recite a eutectic of cyclobenzaprine hydrochloride and mannitol and methods of making those eutectics.

November 6, 2018, U.S.

1 unchanged sentence

Hydrochloride”, issued.

The claims recite pharmaceutical compositions of eutectics of cyclobenzaprine hydrochloride and

mannitol and methods of making those compositions.

The claims recite pharmaceutical compositions of eutectics of cyclobenzaprine hydrochloride and mannitol

and methods of making those compositions.

April 16, 2019, Chinese Patent No.

ZL 201480024011.1 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and

Amitriptyline Hydrochloride”, issued.

The claims recite pharmaceutical compositions comprising eutectics of cyclobenzaprine

hydrochloride and mannitol and methods of making those compositions.

ZL 201480024011.1 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline

Hydrochloride”, issued.

The claims recite pharmaceutical compositions comprising eutectics of cyclobenzaprine hydrochloride and

mannitol and methods of making those compositions.

July 23, 2019, U.S.

10,357,465 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride”, issued.

The claims recite pharmaceutical compositions comprising eutectics of cyclobenzaprine hydrochloride and mannitol and methods of

making those compositions.

recite pharmaceutical compositions comprising eutectics of cyclobenzaprine hydrochloride and mannitol and methods of making those compositions.

December 11, 2019, European patent 2968992, entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride”, issued.

This patent recites pharmaceutical compositions comprising a eutectic of mannitol and Cyclobenzaprine HCl and methods of making

In response to an opposition filed in September 2020 by Hexal AG, the European Patent Office’s Opposition Division

upheld the patent in unamended form in the January 2022 oral proceedings.

patent recites pharmaceutical compositions comprising a eutectic of mannitol and Cyclobenzaprine HCl and methods of making the same.

response to an opposition filed in September 2020 by Hexal AG, the European Patent Office’s Opposition Division upheld the patent

in unamended form in the January 2022 oral proceedings.

The written decision is pending.

1 unchanged sentence

The claims recite the use of CBP for the treatment of depression in a FM patient.

This patent provides TNX-102 SL

with European market exclusivity until March 2032 and may be extended based on the timing of the European marketing authorization

of TNX-102 SL for depression in a FM patient.

This patent provides TNX-102 SL with European

market exclusivity until March 2032 and may be extended based on the timing of the European marketing authorization of TNX-102 SL for

depression in a FM patient.

In September 2020, Hexal AG filed an opposition against this patent.

Patent Office’s Opposition Division upheld the patent claims in unamended form at the February 2022 oral proceedings.

written decision is pending.

The European Patent Office’s Opposition

Division upheld the patent claims in unamended form at the February 2022 oral proceedings.

The written decision is pending.

December 15, 2020, U.S.

5 unchanged sentences

17/226,058 and International Patent Application No.

PCT/US2021/026492

were filed, entitled “Cyclobenzaprine Treatment for Sexual Dysfunction”.

The claims are directed to methods using

pharmaceutical compositions and combinations for treating sexual dysfunction with cyclobenzaprine or pharmaceutically acceptable

salts of cyclobenzaprine.

PCT/US2021/026492, entitled

“Cyclobenzaprine Treatment for Sexual Dysfunction” were filed.

The PCT application is now nationalized in Australia, Canada,

China, European Patent Office and Japan.

On October 5, 2022, International Patent Application No.

PCT/US2022/045791, entitled “Cyclobenzaprine

Treatment for Sexual Dysfunction” was filed.

The claims of these applications are directed to methods using pharmaceutical compositions

and combinations for treating sexual dysfunction with cyclobenzaprine or pharmaceutically acceptable salts of cyclobenzaprine.

October 25, 2016 and July 28, 2020, U.S.

2 unchanged sentences

for Treating Fatigue Associated with Disordered Sleep Using Very Low Dose Cyclobenzaprine”, issued, respectively.

are directed to a method for monitoring the effectiveness of cyclobenzaprine treatment for disordered sleep and method for reducing

CAP rates A2 or A3 by treating a subject with a pharmaceutical composition comprising cyclobenzaprine.

The claims are

directed to a method for monitoring the effectiveness of cyclobenzaprine treatment for disordered sleep and method for reducing CAP rates

A2 or A3 by treating a subject with a pharmaceutical composition comprising cyclobenzaprine.

December 11, 2018, U.S.

non-provisional Patent Application No.

16/215,952 and International Patent Application No.

PCT/IB2018/001509,

entitled “Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions,”

The PCT application is now nationalized in 16 countries.

The claims are directed to methods for treating or preventing agitation,

cognitive decline, psychosis, and associated symptoms thereof using pharmaceutical compositions and combinations with cyclobenzaprine

or pharmaceutically acceptable salts of cyclobenzaprine.

August 20, 2019, International Patent Application No.

PCT/IB2019/000940, entitled “Methods of Treating Acute Stress Disorder and

Posttraumatic Stress Disorder,” was filed.

The PCT application is now nationalized in 18 countries.

The claims are directed to methods

of treating acute stress disorder or post-traumatic stress disorder in a subject who has experienced a traumatic event using pharmaceutical

compositions with cyclobenzaprine, amitriptyline or pharmaceutically acceptable salts of cyclobenzaprine or amitriptyline.

November 19, 2021, International Patent Application No.

PCT/US2021/060011, entitled “Cyclobenzaprine Treatment for Alcohol Use Disorder,”

The claims are directed to methods for treating alcohol use disorder and associated symptoms using pharmaceutical compositions

with cyclobenzaprine or pharmaceutically acceptable salts of cyclobenzaprine.

December 7, 2021, International Patent Application No.

PCT/US2021/062244, entitled, “Cyclobenzaprine Treatment for Fibromyalgia,”

The claims are directed to methods for treating fibromyalgia and its associated symptoms of pain, sleep disturbance and/or

fatigue by transmucosally administering a eutectic with cyclobenzaprine hydrochloride and mannitol in dosage units with a basifying agent.

— Oxytocin-based treatments for Migraine, Pain, Insulin Resistance, Diabetes and Obesity

have acquired the migraine and pain treatment technologies of Trigemina, Inc., and have assumed its license rights to related

technologies from The Board of Trustees of the Leland Stanford Junior University.

TNX-1900, an enhanced formulation of nasal oxytocin,

has demonstrated activity in several non-clinical studies in pain, including migraine.

As part of our acquisition, we acquired

International Patent Application No.

PCT/US2016/012512, filed on January 7, 2016, entitled “Magnesium-Containing Oxytocin

Formulations and Methods of Use” (nationalized in 13 countries).

have acquired the migraine and pain treatment technologies of Trigemina, Inc., and have assumed its license rights to related technologies

from The Board of Trustees of the Leland Stanford Junior University.

TNX-1900, an enhanced formulation of nasal oxytocin, has demonstrated

activity in several non-clinical studies in pain, including migraine.

part of our acquisition, we acquired International Patent Application No.

PCT/US2016/012512, filed on January 7, 2016, entitled “Magnesium-Containing

Oxytocin Formulations and Methods of Use” (nationalized in 13 countries).

We also acquired U.S.

9,629,894, entitled “Magnesium-Containing

Oxytocin Formulations and Methods of Use”, which will expire in January 2036, excluding any patent term extensions.

have rights to International Patent Application No.

PCT/US2019/020419, filed on April 12, 2017, entitled “Labeled Oxytocin

and Method of Manufacture and Use” (nationalized in the U.S., European Patent Office and Japan).

have entered into an exclusive license to the University of Geneva’s technology for using oxytocin to treat insulin resistance

and related syndromes, including obesity.

This license expands our intranasal potentiated oxytocin development program, TNX-1900,

into cardiometabolic syndromes.

9,629,894 and 11,389,473,

entitled “Magnesium-Containing Oxytocin Formulations and Methods of Use”, which will expire in January 2036, excluding any

patent term extensions.

We also have rights to International Patent Application No.

PCT/US2019/020419, filed on April 12, 2017, entitled

“Labeled Oxytocin and Method of Manufacture and Use” (nationalized in the U.S., European Patent Office and Japan).

have entered into an exclusive license to the University of Geneva’s technology for using oxytocin to treat insulin resistance and

related syndromes, including obesity.

This license expands our intranasal potentiated oxytocin development program, TNX-1900, into cardiometabolic

Under the license, we have rights to European Patent No.

EP2571511B1, entitled “New Uses

of Oxytocin-like Molecules and Related Methods”.

We also have rights to U.S.

9,101,569, entitled “Methods

for the Treatment of Insulin Resistance”.

patents expire in May 2031, excluding any patent term adjustments

or extensions.

— Oxytocin-based therapeutics for Prader-Willi syndrome

have licensed technology using oxytocin-based therapeutics for the treatment of Prader-Willi syndrome and non-organic failure

to thrive disease from the French National Institute of Health and Medical Research (INSERM).

The co-exclusive license relates

to TNX-2900, an intranasal potentiated oxytocin, for the treatment of Prader-Willi syndrome and other feeding disorders.

the license, we have rights to European Patent No.

EP2575853B1, entitled “Methods and Pharmaceutical Composition for the

Treatment of a Feeding Disorder with Early-Onset in a Patient”;

8,853,158, entitled “Methods for the

Treatment of a Feeding Disorder with Onset During Neonate Development Using an Agonist of the Oxytocin Receptor”;

9,125,862, entitled “Methods for the Treatment of Prader-Willi-like Syndrome or Non-Organic Failure to Thrive

(NOFITT) Feeding Disorder Using an Agonist of the Oxytocin Receptor”.

patents expire in May 2031,

excluding any patent term extensions.

— Depression, Posttraumatic Stress Disorder, Neurocognitive Dysfunction

EP2571511B1, entitled “New Uses of Oxytocin-like Molecules and

Related Methods.” We also have rights to U.S.

9,101,569, entitled “Methods for the Treatment of Insulin Resistance.”

patents expire in May 2031, excluding any patent term adjustments or extensions.

— Oxytocin-based therapeutics treatments for Prader-Willi syndrome

have licensed technology using oxytocin-based therapeutics for the treatment of Prader-Willi syndrome and non-organic failure to thrive

disease from the French National Institute of Health and Medical Research (INSERM).

The co-exclusive license relates to TNX-2900, an intranasal

potentiated oxytocin, for the treatment of Prader-Willi syndrome and other feeding disorders.

Under the license, we have rights to European

EP2575853B1, entitled “Methods and Pharmaceutical Composition for the Treatment of a Feeding Disorder with Early-Onset

in a Patient”;

8,853,158, entitled “Methods for the Treatment of a Feeding Disorder with Onset During Neonate

Development Using an Agonist of the Oxytocin Receptor”;

9,125,862, entitled “Methods for the Treatment

of Prader-Willi-like Syndrome or Non-Organic Failure to Thrive (NOFITT) Feeding Disorder Using an Agonist of the Oxytocin Receptor.”

patents expire in May 2031, excluding any patent term extensions.

and TNX-601 ER— Depression, Posttraumatic Stress Disorder, Neurocognitive Dysfunction

patent portfolio for tianeptine oxalate includes U.S.

2 unchanged sentences

for Treating Neurocognitive Dysfunction”, which issued on April 29, 2016 and July 26, 2017, respectively.

patent recites pharmaceutical compositions comprising various compounds (which include tianeptine) and uses thereof.

patent provides TNX-601 with European market exclusivity until April 2029 and may be extended based on the timing of the European

marketing authorization of TNX-601 for neurocognitive side effects associated with the use of corticosteroids.

patent claims methods of treating cognitive impairment associated with corticosteroid treatment using compounds, including tianeptine,

excluding patent term extensions, the patent provides TNX-601 with US marketing exclusivity until 2028.

The ’822 patent

recites pharmaceutical compositions comprising various compounds (which include tianeptine) and uses thereof.

This patent provides

TNX-601 with European market exclusivity until April 2029 and may be extended based on the timing of the European marketing authorization

of TNX-601 for neurocognitive side effects associated with the use of corticosteroids.

The ‘469 patent claims methods of treating

cognitive impairment associated with corticosteroid treatment using compounds, including tianeptine, excluding patent term extensions,

the patent provides TNX-601 with US marketing exclusivity until 2028.

February 27, 2019, European Patent No.

3,246,031 entitled “Method for Treating Neurodegenerative Dysfunction,” issued.

The claims recite the use of TNX-601, or tianeptine oxalate and other salts, for treating neurocognitive dysfunction associated

with corticosteroid treatment.

This patent provides TNX-601 with European market exclusivity until April 2029 and may be extended

based on the timing of the European market authorization of TNX-601 for neurocognitive disfunction associated with corticosteroid

claims recite the use of TNX-601, or tianeptine oxalate and other salts, for treating neurocognitive dysfunction associated with corticosteroid

This patent provides TNX-601 with European market exclusivity until April 2029 and may be extended based on the timing of the

European market authorization of TNX-601 for neurocognitive disfunction associated with corticosteroid treatment.

October 22, 2019, U.S.

10,449,203 issued.

The claims recite anhydrous crystalline oxalate salts of tianeptine

and provides TNX-601 with US market exclusivity until 2037, excluding any patent term extensions.

The claims recite anhydrous crystalline oxalate salts of tianeptine and provides

TNX-601 with US market exclusivity until 2037, excluding any patent term extensions.

March 16, 2021, U.S.

10,946,027 issued.

The claims recite pharmaceutical compositions of anhydrous crystalline oxalate

salts of tianeptine and provides TNX-601 with US market exclusivity until 2037, excluding any patent term extensions.

The claims recite pharmaceutical compositions of anhydrous crystalline oxalate salts

of tianeptine and provides TNX-601 with US market exclusivity until 2037, excluding any patent term extensions.

patent portfolio for TNX-601 also includes International Patent Application PCT/IB2017/001709 (now nationalized in 16 countries).

It includes claims directed to crystalline tianeptine oxalate and compositions of those crystal forms, and disclosures directed

to methods of using those crystalline forms and their compositions.

— Live Horsepox Vaccine for Prevention of Smallpox and Monkeypox

own the rights to develop a potential biodefense technology, TNX-801, a live horsepox that is being developed as a new smallpox

and monkeypox preventing vaccine, we have filed patent applications directed to synthetic chimeric poxviruses and methods of using

these poxviruses to protect individuals against smallpox.

claims directed to crystalline tianeptine oxalate and compositions of those crystal forms, and disclosures directed to methods of using

those crystalline forms and their compositions.

patent portfolio for TNX-601 CR includes International Patent Application No.

PCT/US2022/020406, entitled “Tianeptine Oxalate and

Naloxone Treatment for Major Depressive Disorder,” was filed March 15, 2022.

It includes claims directed to compositions with tianeptine

and naloxone or pharmaceutically acceptable salts of tianeptine and naloxone and methods of preventing or treating major depressive disorder

using the compositions.

— Cocaine Intoxication Treatment

have licensed rights from The Trustees of Columbia University in the City of New York, The Regents of the University of Michigan, and

University of Kentucky Research Foundation to develop a potential product, TNX-1300, for the treatment of cocaine intoxication.

The licensed patents are directed to mutant cocaine esterase polypeptides and methods of using these polypeptides as anti-cocaine therapeutics.

They include U.S.

8,318,156 and 9,200,265, entitled “Anti-Cocaine Compositions and Treatment” and various counterpart

patents outside of the U.S (e.g., European Patent 2046368).

These patents provide TNX-1300 with US market exclusivity until February 2029,

and market exclusivity outside of the U.S.

until July 10, 2027, subject to any patent term extensions.

— anti-CD40L Therapeutics

are developing TNX-1500, a humanized mAb that targets CD40L for the prevention and treatment of organ transplant rejection.

regard, we filed International Application No.

PCT/EP2020/068589, entitled “Anti-CD154 antibodies and uses thereof” on July

1, 2020 (nationalized in 15 countries).

We also filed International Patent Application No.

PCT/US2020/028002 on April 13, 2020, entitled

“Inhibitors of CD40-CD154 Binding” (nationalized in U.S., Canada, China, European Patent Office and Japan).

We also filed

International Patent Application No.

PCT/US2022/011404, entitled “Methods of Inducing Immune Tolerance with Modified Anti-CD154

Antibodies” on January 6, 2022.

— Live Horsepox Vaccine for Prevention of Smallpox and Mpox

own the rights to develop a potential biodefense technology, TNX-801, a live horsepox that is being developed as a new smallpox and mpox

preventing vaccine, we have filed patent applications directed to synthetic chimeric poxviruses and methods of using these poxviruses

to protect individuals against smallpox.

These applications include U.S.

non-provisional Patent Application No.

15/802,189 and International Patent Application No.

PCT/US2017/059782 (nationalized in 15 countries and filed in 4 non-PCT countries).

We also own the rights to develop other vaccine candidates against smallpox.

With respect to these vaccine candidates, we

15/802,189 and International

Patent Application No.

14/207,727 and International Patent Application No.

PCT/US2019/030486 and the non-convention and

national phase applications related thereto (nationalized in 17 countries and filed in 2 non-PCT countries).

The smallpox vaccine

technologies relate to proprietary forms of live horsepox and vaccinia vaccines which may be safer than ACAM2000, the only currently

available replication competent, live vaccinia vaccine to protect against smallpox disease.

We believe that this technology, after

further development, may be of interest to biodefense agencies in the U.S.

PCT/US2017/059782 (nationalized in 15 countries and filed in 4 non-PCT countries).

We also own the rights to develop

other vaccine candidates against smallpox.

With respect to these vaccine candidates, we own International Patent Application No.

PCT/US2019/030486 and the non-convention and national phase applications related thereto (nationalized in 17 countries and filed in 2

non-PCT countries).

The smallpox vaccine technologies relate to proprietary forms of live horsepox and vaccinia vaccines which may be

safer than ACAM2000, the only currently available replication competent, live vaccinia vaccine to protect against smallpox disease.

believe that this technology, after further development, may be of interest to biodefense agencies in the U.S.

and other countries.

— Live HPXV Vaccine for Prevention of COVID-19

May 31, 2022, U.S.

11,345,896 was issued.

The claims recite a synthetic chimeric orthopoxvirus (scOPV), a synthetic chimeric

horsepox virus (scHPXV), methods of generating the scOPV and scHPXV, and compositions comprising the scOPV or scHPXV.

— Live Modified Horsepox Vaccine for Prevention of COVID-19

are developing TNX-1850, a live HPXV that is being developed as a new COVID-19 preventing vaccine.

On February 26, 2021, we filed

International Patent Application No.

PCT/US2021/020119 (as well as applications in 2 non-PCT countries) and U.S.

On February 26, 2021, we filed International

Patent Application No.

PCT/US2021/020119, entitled “Recombinant Poxvirus Based Vaccine Against SARS-CoV-2.” On the same date,

we also filed applications in Argentina and Taiwan and we filed U.S.

Application No.

17/187,678, entitled “Recombinant Poxvirus Based Vaccine Against SARS-CoV-2”.

These applications are directed to synthetic

poxviruses comprising a SARS-CoV-2 protein, poxvirus delivery vectors for SARS-CoV-2 proteins and methods of using these modified

poxviruses to protect individuals against COVID-19.

The PCT application is not nationalized

in 18 countries.

These applications are directed to synthetic poxviruses comprising a SARS-CoV-2 protein, poxvirus delivery vectors for

SARS-CoV-2 proteins and methods of using these modified poxviruses to protect individuals against COVID-19.

— Recombinant Trefoil Family Factor 2 (rTFF2) to Treat Gastric and Pancreatic Cancers

have licensed rights from The Trustees of Columbia University in the City of New York to develop a potential product, TNX-1700,

for the treatment of gastric and pancreatic cancers.

The licensed patents are directed to TFF2 compositions and methods

of treatment.

have licensed rights from The Trustees of Columbia University in the City of New York to develop a potential product, TNX-1700, for the

treatment of gastric and pancreatic cancers.

The licensed patents are directed to TFF2 compositions and methods of treatment.

The licensed patents U.S.

10,124,037 and U.S.

The licensed patents

provide TNX-1700 with US market exclusivity until April 2033, subject to any patent term extensions.

On August 27, 2020, we filed

International Patent Application No.

PCT/IB2020/000699 entitled “Modified TFF2 Polypeptides” (being nationalized in

11 countries).

The licensed patents provide TNX-1700 with

US market exclusivity until April 2033, subject to any patent term extensions.

On August 27, 2020, we filed International Patent Application

PCT/IB2020/000699 entitled “Modified TFF2 Polypeptides.” The PCT application is now nationalized in 12 countries.

— Triple Reuptake Inhibitor to Treat PTSD

have licensed rights from Wayne State University to develop a potential product, TNX-1600, for PTSD treatment.

patents directed to pyran-based derivatives and analogues.

They include U.S.

7,915,433, 8,017,791, 8,519,159,

8,841,464, and 8,937,189, entitled “Tri-substituted 2-benzhydryl 5-benzlamino-tetrahydro-pyran-4-OL and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-OL

analogues, and novel 3,6 disubstituted pyran derivatives” and U.S.

9,458,124, entitled “Substituted Pyran

Derivatives”.

These patents provide TNX-1600 with US market exclusivity between April 2024 and February 2034, respectively,

subject to any patent term extensions.

The licensed patents

directed to pyran-based derivatives and analogues.

7,915,433, 8,017,791, 8,519,159, 8,841,464, and 8,937,189, entitled “Tri-substituted 2-benzhydryl 5-benzlamino-tetrahydro-pyran-4-OL

and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-OL analogues, and novel 3,6 disubstituted pyran derivatives” and U.S.

9,458,124, entitled “Substituted Pyran Derivatives”.

These patents provide TNX-1600 with US market exclusivity between

April 2024 and February 2034, respectively, subject to any patent term extensions.

— Radioprotection Biodefense Technology

own the rights to develop a potential biodefense technology, which is a potential radioprotective therapy.

For protection of our

intellectual property, we have not disclosed the identity of the new development candidate.

On May 7, 2021, we filed International

Patent Application No.

PCT/US2021/031441 and U.S.

For protection of our intellectual

property, we have not disclosed the identity of the new development candidate.

May 7, 2021, we filed International Patent Application No.

PCT/US2021/031441, entitled “Radio-and Chemo-Protective Compounds,”

non-provisional Patent Application No.

They claim compounds, compositions

and methods of use in radioprotection.

17/315,258, entitled “Radio-Protective and Chemo-Protective Substituted Thiols.”

The PCT application is now nationalized in 10 countries.

The applications claim compounds, compositions and methods of use in radioprotection.

January 31, 2023, U.S.

11,566,032 issued.

The claims recite compounds of a formula I or a pharmaceutically acceptable salt

thereof or stereoisomer thereof and a pharmaceutical composition comprising a compound of formula I.

— Smallpox Vaccine Technology

own the rights to develop a potential biodefense technology, TNX-1200, a live vaccinia virus that is being developed as a new

smallpox preventing vaccine, we have patent applications directed to synthetic chimeric poxviruses and methods of using these

poxviruses to protect individuals against smallpox.

These applications include U.S.

non-provisional Patent Application No.

own the rights to develop a potential biodefense technology, TNX-1200, a live vaccinia virus that is being developed as a new smallpox

preventing vaccine, we have patent applications directed to synthetic chimeric poxviruses and methods of using these poxviruses to protect

individuals against smallpox.

These applications, entitled “Synthetic Chimeric Vaccinia Virus,” include U.S.

non-provisional

Patent Application No.

17/050,946 and International Patent Application No.

PCT/US2019/030486 (nationalized in 16 countries and filed in 3 non-PCT countries).

believe that this technology, after further development, may be of interest to biodefense agencies in the U.S.

PCT/US2019/030486 (now nationalized in 16 countries) and applications

filed in Argentina, Taiwan and Venezuela.

We believe that this technology, after further development, may be of interest to biodefense

agencies in the U.S.

and other countries.

— Sangivamycin for Treatment of COVID

have entered into an exclusive license to OyaGen, Inc.’s antiviral technology for use in treating coronavirus infections

(including SARS-CoV-2), Ebola virus, arenaviridae infections and poxviridae infections.

This license expands our pipeline for

developing a potential treatment, TNX-3500, for COVID-19 and emerging variants.

Under the license, we have rights to U.S.

non-provisional

TNX-2300 — Bovine Parainfluenza 3 Virus vaccine

We have an exclusive field-of-use

option agreement with Kansas State University Research Foundation to develop TNX-2300, a bovine parainfluenza virus vaccine, as a new

COVID-19 preventing vaccine or treatment.

The patent applications in this agreement include International Patent Application No.

PCT/US2020/070725,

entitled “Broadly Protective Bovine Parainfluenza 3 Virus and Bovine Viral Diarrhea Virus Vaccine” (nationalized in U.S.

as Patent Application No.

17/755,359), and International Patent Application No.

PCT/US2022/072433, entitled “SARS-Coronavirus 2

(SARS-CoV-2) Spike Protein Subunit Vaccines.”

TNX-3700 — Zinc Nanoparticle mRNA vaccine

We have an exclusive field-of-use

option agreement with Kansas State University Research Foundation to develop TNX-3700, a zinc nanoparticle mRNA vaccine, as a new COVID-19

preventing vaccine or treatment.

The patent applications in this agreement include International Patent Application No.

PCT/US2022/070739,

entitled “RNA Stabilizing Nanoparticles,” and International Patent Application No.

PCT/US2022/075944, entitled “mRNA

Vaccine Formulations and Methods of Using the Same.”

TNX-3900 — antiviral drugs

We have acquired the intellectual

property rights of Healion Bio, Inc.

to develop antiviral drugs.

These rights include International Patent Application No.

PCT/US2021/032461

(nationalized in 4 countries) and U.S.

Patent Application No.

16/851,047 and International Patent Application Nos.

PCT/US2020/028567 and PCT/US2021/016472, entitled

“Methods for Treating Coronavirus Infections”.

We also have rights to U.S.

non-provisional Patent Application No.

16/348,867 and European Patent Application No.

17869003.8, entitled “Methods of Treating and Inhibiting Ebola Virus Infection”.

We also have rights to International Patent Application Nos.

PCT/US2021/027352 and PCT/US2021/027354, entitled “Method for

Treating Arenaviridae Infections” and “Method for Treating Poxviridae Infection,” respectively.

18/055,596, both entitled “Compositions and Methods for Increasing

Efficacy of a Drug,” as well as International Patent Application No.

PCT/US2021/052664, entitled “Methods and Compositions

for the Treatment of Viral Diseases.”

TNX-4100 — murine anti-SARS-CoV-2 antibodies

We have exercised the option to

obtain an exclusive license from Columbia University to develop, TNX-4100, a series of murine and humanized anti-SARS-CoV-2 mAbs as new

COVID-19 preventatives or treatments.

addition to patents, we rely on trade secrets and know-how to develop and maintain our competitive position.

1 unchanged sentence

aspects of our proprietary technology platform are based on unpatented trade secrets and know-how.

Trade secrets and know-how

can be difficult to protect.

We seek to protect our proprietary technology and processes, in part, by confidentiality agreements

and invention assignment agreements with our employees, consultants, scientific advisors, contractors, and commercial partners.

These agreements are designed to protect our proprietary information and, in the case of the invention assignment agreements,

to grant us ownership of technologies that are developed through a relationship with a third party.

We also seek to preserve the

integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and

electronic security of our information technology systems.

While we have confidence in these individuals, organizations and systems,

agreements or security measures may be breached, and we may not have adequate remedies for any breach.

In addition, our trade

secrets may otherwise become known or be independently discovered by competitors.

To the extent that our contractors use intellectual

property owned by others in their work for us, disputes may arise as to rights in related or resulting inventions and know-how.

Trade secrets and know-how can be difficult

We seek to protect our proprietary technology and processes, in part, by confidentiality agreements and invention assignment

agreements with our employees, consultants, scientific advisors, contractors, and commercial partners.

These agreements are designed to

protect our proprietary information and, in the case of the invention assignment agreements, to grant us ownership of technologies that

are developed through a relationship with a third party.

We also seek to preserve the integrity and confidentiality of our data and trade

secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems.

we have confidence in these individuals, organizations and systems, agreements or security measures may be breached, and we may not have

adequate remedies for any breach.

In addition, our trade secrets may otherwise become known or be independently discovered by competitors.

To the extent that our contractors use intellectual property owned by others in their work for us, disputes may arise as to rights in

related or resulting inventions and know-how.

current patents owned or licensed include:

Compositions and Treatment

Anti-Cocaine Compositions and Treatment

February 14, 2029

Anti-Cocaine Compositions and Treatment

December 30, 2027

Anti-Cocaine Compositions and Treatment

July 10, 2027

Anti-Cocaine Compositions and Treatment

July 10, 2027

Anti-Cocaine Compositions and Treatment

July 10, 2027

Anti-Cocaine Compositions and Treatment

July 10, 2027

2046368 (602007045044.6 in Germany;

502016000056543 in Italy)

Compositions and Treatment

– (Germany, Spain, France, United Kingdom, and Italy)

Compositions and Treatment

Anti-Cocaine Compositions and Treatment

Europe – (Germany, Spain,

France, United Kingdom, and Italy)

July 10, 2027

Anti-Cocaine Compositions and Treatment

July 10, 2027

Anti-Cocaine Compositions and Treatment

July 10, 2027

Anti-Cocaine Compositions and Treatment

July 10, 2027

CBP/Amitriptyline

and Methods for Transmucosal Absorption

and Compositions for Treating Depression Using Cyclobenzaprine

Patent Office – Albania, Austria, Belgium, Bulgaria, Switzerland, Cyprus, Czechia, Germany, Denmark, Estonia, Spain,

Finland, France, United Kingdom, Greece, Croatia, Hungary, Ireland, Iceland, Italy, Lithuania, Luxembourg, Latvia, Monaco,

Republic of North Macedonia, Malta, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Sweden, Slovenia, Slovakia, San

Marino, and Turkey

and Compositions for Treating Symptoms Associated with Post-Traumatic Stress Disorder Using Cyclobenzaprine

Compositions and Methods for Transmucosal

June 14, 2033

Compositions and Methods for Transmucosal

June 14, 2033

Compositions and Methods for Transmucosal

Taiwan R.O.C.

June 14, 2033

Compositions and Methods for Transmucosal

June 14, 2033

Compositions and Methods for Transmucosal

Taiwan R.O.C.

June 14, 2033

Compositions and Methods for Transmucosal

June 14, 2033

Compositions and Methods for Transmucosal

Taiwan R.O.C.

June 14, 2033

Compositions and Methods for Transmucosal

June 14, 2033

Compositions and Methods for Transmucosal

June 14, 2033

Compositions and Methods for Transmucosal

June 14, 2033

Compositions and Methods for Transmucosal

June 14, 2033

Compositions and Methods for Transmucosal

European Patent Office – Italy,

Albania, Austria, Belgium, Bulgaria, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Latvia,

Lithuania, Luxembourg, Malta, Monaco, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland,

United Kingdom, San Marino, Serbia, Croatia, North Macedonia and Turkey

June 14, 2033

Compositions for Transmucosal Delivery

and Uses Thereof

June 14, 2033

Compositions and Methods for Transmucosal

June 14, 2033

BR112014031394-6

Compositions and Methods for Transmucosal

June 14, 2033

Compositions and Methods for Transmucosal

June 14, 2033

Compositions and Methods for Transmucosal

June 14, 2033

Compositions and Methods for Transmucosal

June 14, 2033

Compositions and Methods for Transmucosal

June 14, 2033

Methods and Compositions for Treating

Depression Using Cyclobenzaprine

March 6, 2032

Methods and Compositions for Treating

Depression Using Cyclobenzaprine

March 6, 2032

Methods and Compositions for Treating

Depression Using Cyclobenzaprine

March 6, 2032

Methods and Compositions for Treating

Depression Using Cyclobenzaprine

March 6, 2032

Methods and Compositions for Treating

Depression Using Cyclobenzaprine

March 6, 2032

Compositions for Treating Depression Using Cyclobenzaprine

March 6, 2032

Methods and Compositions for Treating

Depression Using Cyclobenzaprine

March 6, 2032

Compositions for Treating Depression Using Cyclobenzaprine

European Patent Office – Albania,

Austria, Belgium, Bulgaria, Switzerland, Cyprus, Czechia, Germany, Denmark, Estonia, Spain, Finland, France, United Kingdom, Greece, Croatia,

Hungary, Ireland, Iceland, Italy, Lithuania, Luxembourg, Latvia, Monaco, Republic of North Macedonia, Malta, Netherlands, Norway, Poland,

Portugal, Romania, Serbia, Sweden, Slovenia, Slovakia, San Marino, and Turkey

March 6, 2032

Methods and Compositions for Treating

Symptoms Associated with Post-Traumatic Stress Disorder Using Cyclobenzaprine

November 18, 2030

602010045270.0 in Germany;

1 unchanged sentence

502017000142469 in Italy;

MK/P/17/000807 in Republic of North

56634 in Serbia;

MK/P/17/000807 in Republic of North Macedonia;

SM-T-201700578 in San Marino;

201717905 in Turkey)

and Compositions for Treating Symptoms Associated with Post-Traumatic Stress Disorder Using Cyclobenzaprine

Patent Office – Albania, Austria, Belgium, Bulgaria, Switzerland, Cyprus, Czechia, Germany, Denmark, Estonia, Spain,

Finland, France, United Kingdom, Greece, Croatia, Hungary, Ireland, Iceland, Italy, Lithuania, Luxembourg, Latvia, Monaco,

Republic of North Macedonia, Malta, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Sweden, Slovenia, Slovakia, San

Marino, Turkey

and Compositions for Treating Symptoms Associated with Post-Traumatic Stress Disorder Using Cyclobenzaprine

and Compositions for Treating Fatigue Associated with Disordered Sleep Using Very Low Dose Cyclobenzaprine

Methods and Compositions for Treating

Symptoms Associated with Post-Traumatic Stress Disorder Using Cyclobenzaprine

European Patent Office – Albania,

Austria, Belgium, Bulgaria, Switzerland, Cyprus, Czechia, Germany, Denmark, Estonia, Spain, Finland, France, United Kingdom, Greece, Croatia,

Hungary, Ireland, Iceland, Italy, Lithuania, Luxembourg, Latvia, Monaco, Republic of North Macedonia, Malta, Netherlands, Norway, Poland,

Portugal, Romania, Serbia, Sweden, Slovenia, Slovakia, San Marino, Turkey

November 16, 2030

Methods and Compositions for Treating

Symptoms Associated with Post-Traumatic Stress Disorder Using Cyclobenzaprine

November 16, 2030

Methods and Compositions for Treating

Fatigue Associated with Disordered Sleep Using Very Low Dose Cyclobenzaprine

Methods and Compositions for Treating

Fatigue Associated with Disordered Sleep Using Very Low Dose Cyclobenzaprine

CBP/Amitriptyline

Eutectic Formulations

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline

Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline

Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

September 18, 2035

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

September 18, 2035

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine Hydrochloride

September 18, 2035

Eutectic Formulations of Cyclobenzaprine Hydrochloride

September 18, 2035

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

ZL201480024011.1

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

ZL.201580050140.2

Formulations of Cyclobenzaprine Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

in Austria, CZ2014-762323 in Czechia, 602014058260.5 in Germany, E018723 in Estonia, P20200055 in Croatia, 201361792757

P in Ireland, 2020.67 in Monaco, P-2020/0094 in Serbia, 201431487 in Slovenia, 33269 in Slovakia, 2020000045 in San Marino)

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Patent Office -Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Republic

of North Macedonia, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands,

Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Methods of Producing Same

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

September 18, 2035

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

September 18, 2035

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

Taiwan R.O.C.

March 14, 2034

Eutectic Formulations

of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Taiwan R.O.C.

March 14, 2034

Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline

Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine Hydrochloride

September 18, 2035

Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline

Hydrochloride

March 14, 2034

Austria, CZ2014-762323 in Czechia, 602014058260.5 in Germany, E018723 in Estonia, P20200055 in Croatia, 201361792757 P in Ireland, 2020.67

in Monaco, P-2020/0094 in Serbia, 201431487 in Slovenia, 33269 in Slovakia, 2020000045 in San Marino, AL/P/2019/906 in Albania, MK/P/2020/67

in Republic of North Macedonia, 3102655 in Greece, 502020000007756 in Italy)

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

European Patent Office -Albania,

Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Republic of North Macedonia, Germany, Greece,

Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, Norway, Poland, Portugal, Romania, San Marino,

Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Methods of Producing Same

September 18, 2035

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Methods of Producing Same

September 18, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

September 18, 2035

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

September 18, 2035

BR112015022095-9

Pharmaceutical

Composition, Method of Fabrication, Eutectic Composition and Use of Compositions Containing Cyclobenzaprine HCl and Mannitol

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

and Pharmaceutical Composition for the Treatment of a Feeding Disorder with Early-Onset in a Patient

– (Spain, France, and United Kingdom)

for the Treatment of a Feeding Disorder with Onset During Neonate Development Using an Agonist of the Oxytocin Receptor

for the Treatment of Prader-Willi-like Syndrome or Non-Organic Failure to Thrive (NOFITT) Feeding Disorder Using an Agonist

of the Oxytocin Receptor

Uses of Oxytocin-like Molecules and Related Methods

– (Switzerland, Spain, France, United Kingdom, and Ireland)

for the Treatment of Insulin Resistance

Pharmaceutical Composition, Method

of Fabrication, Eutectic Composition and Use of Compositions Containing Cyclobenzaprine HCl and Mannitol

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

March 14, 2034

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

September 18, 2035

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

September 18, 2035

Magnesium-Containing Oxytocin Formulations

and Methods of Use

January 7, 2036

Magnesium-Containing Oxytocin Formulations

and Methods of Use

January 7, 2036

Magnesium-Containing Oxytocin Formulations

and Methods of Use

January 7, 2036

Magnesium-Containing Oxytocin Formulations

and Methods of Use

January 7, 2036

Magnesium-Containing Oxytocin Formulations

and Methods of Use

January 7, 2036

Magnesium-Containing Oxytocin Formulations

and Methods of Use

January 7, 2036

ZL201680013809.5

Magnesium-Containing Oxytocin Formulations

and Methods of Use

January 7, 2036

Magnesium-Containing Oxytocin Formulations

and Methods of Use

April 12, 2037

Methods and Pharmaceutical Composition

for the Treatment of a Feeding Disorder with Early-Onset in a Patient

Europe – (Spain, France, and

United Kingdom)

Methods for the Treatment of a Feeding

Disorder with Onset During Neonate Development Using an Agonist of the Oxytocin Receptor

Methods for the Treatment of Prader-Willi-like

Syndrome or Non-Organic Failure to Thrive (NOFITT) Feeding Disorder Using an Agonist of the Oxytocin Receptor

New Uses of Oxytocin-like Molecules

and Related Methods

Europe – (Switzerland, Spain,

France, United Kingdom, and Ireland)

Methods for the Treatment of Insulin

June 22, 2031

Nociceptin/Orphanin

FQ therapeutics

for treatment of pain

201080042858.4

for treatment of pain

Methods for treatment of pain

August 11, 2031

Methods for treatment of pain

October 12, 2030

Methods for treatment of pain

July 27, 2030

ZL 201080042858.4

Methods for treatment of pain

July 27, 2030

2459183 (602010028120.5 in Germany)

for treatment of pain

– (Switzerland, Germany, Denmark, France, and United Kingdom)

for treatment of pain

Oxalate – Salts and Crystalline Forms

Oxalate Salts and Polymorphs

Methods for treatment of pain

Europe – (Switzerland, Germany,

Denmark, France, and United Kingdom)

July 27, 2030

Methods for treatment of pain

July 27, 2030

Methods for treatment of pain

July 27, 2030

Methods for treatment of pain

July 27, 2030

Methods for treatment of pain

July 27, 2030

Methods for treatment of pain

July 27, 2030

Methods for treatment of pain

July 27, 2030

Methods for treatment of pain

July 27, 2030

Hemioxalate – Salts and Crystalline Forms

Tianeptine Oxalate Salts and Polymorphs

December 28, 2037

Tianeptine Oxalate Salts and Polymorphs

December 28, 2037

Tianeptine Oxalate Salts and Polymorphs

December 28, 2037

Tianeptine Oxalate Salts and Polymorphs

December 28, 2037

Tianeptine Oxalate Salts and Polymorphs

December 28, 2037

Tianeptine Oxalate Salts and Polymorphs

December 28, 2037

– Neurocognitive Dysfunction

for Treating Neurocognitive Dysfunction

for Treating Neurodegenerative Dysfunction

Method for Treating Neurocognitive

September 24, 2030

Method for Treating Neurodegenerative

April 30, 2029

2299822 (602009047361.1 in Germany

for Treating Neurodegenerative Dysfunction

– Austria, Belgium, Switzerland, Germany, Spain, France, United Kingdom, Ireland, Luxembourg, Monaco, Portugal

and E911827 in Austria)

Method for Treating Neurodegenerative

European Patent Office – Austria,

Belgium, Switzerland, Germany, Spain, France, United Kingdom, Ireland, Luxembourg, Monaco, Portugal

April 30, 2029

3246031 (602009057284.9 in Germany)

for Treating Neurocognitive Dysfunction

– Austria, Belgium, Switzerland, Germany, Spain, France, United Kingdom, Ireland, Luxembourg, Monaco, Portugal

Method for Treating Neurocognitive

European Patent Office – Austria,

Belgium, Switzerland, Germany, Spain, France, United Kingdom, Ireland, Luxembourg, Monaco, Portugal

April 30, 2029

reuptake inhibitor therapeutics

Tri-substituted

2-benzhydryl 5-benzlamino-tetrahydro-pyran-4-OL and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-OL analogues, and novel

3,6 disubstituted pyran derivatives

Tri-substituted

2-benzhydryl 5-benzlamino-tetrahydro-pyran-4-OL and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-OL analogues, and novel

3,6 disubstituted pyran derivatives

Tri-substituted

2-benzhydryl 5-benzlamino-tetrahydro-pyran-4-OL and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-OL analogues, and novel

3,6 disubstituted pyran derivatives

Tri-substituted

2-benzhydryl 5-benzlamino-tetrahydro-pyran-4-OL and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-OL analogues, and novel

3,6 disubstituted pyran derivatives

Tri-substituted

2-benzhydryl 5-benzlamino-tetrahydro-pyran-4-OL and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-OL analogues, and novel

3,6 disubstituted pyran derivatives

Pyran Derivatives

family factor proteins and uses thereof

Tri-substituted 2-benzhydryl 5-benzlamino-tetrahydro-pyran-4-OL

and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-OL analogues, and novel 3,6 disubstituted pyran derivatives

Tri-substituted 2-benzhydryl 5-benzlamino-tetrahydro-pyran-4-OL

and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-OL analogues, and novel 3,6 disubstituted pyran derivatives

April 14, 2024

Tri-substituted 2-benzhydryl 5-benzlamino-tetrahydro-pyran-4-OL

and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-OL analogues, and novel 3,6 disubstituted pyran derivatives

December 7, 2025

Tri-substituted 2-benzhydryl 5-benzlamino-tetrahydro-pyran-4-OL

and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-OL analogues, and novel 3,6 disubstituted pyran derivatives

April 15, 2025

Tri-substituted 2-benzhydryl 5-benzlamino-tetrahydro-pyran-4-OL

and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-OL analogues, and novel 3,6 disubstituted pyran derivatives

January 12, 2027

Substituted Pyran Derivatives

February 6, 2034

Trefoil family factor proteins and

April 2, 2033

Trefoil family factor proteins and

April 2, 2033

Chimeric Poxviruses

Synthetic Chimeric Poxviruses

November 2, 2037

Synthetic Chimeric Poxviruses

November 2, 2037

Synthetic Chimeric Poxviruses

November 2, 2037

Radioprotection

Radio-Protective and Chemo-Protective

Substituted Thiols

Patent Applications

current pending patent applications are as follows:

and CD154 Therapeutics

antibodies and uses thereof

and anti-CD154 Therapeutics

Anti-CD154 antibodies and uses thereof

BR112021026410-8

antibodies and uses thereof

Patent Office

antibodies and uses thereof

Anti-CD154 antibodies and uses thereof

202080059891.1

Anti-CD154 antibodies and uses thereof

European Patent Office

Anti-CD154 antibodies and uses thereof

antibodies and uses thereof

Anti-CD154 antibodies and uses thereof

PI 2021007835

Anti-CD154 antibodies and uses thereof

MX/a/2022/000133

antibodies and uses thereof

Anti-CD154 antibodies and uses thereof

62022063693.5

Anti-CD154 antibodies and uses thereof

62022062573.0

Anti-CD154 antibodies and uses thereof

PCT/US2022/011404

of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies

of CD40-CD154 Binding

Patent Office

of CD40-CD154 Binding

Methods of Inducing Immune Tolerance

with Modified Anti-CD154 Antibodies

Inhibitors of CD40-CD154 Binding

European Patent Office

Inhibitors of CD40-CD154 Binding

202080033531.4

Inhibitors of CD40-CD154 Binding

CBP/Amitriptyline

Eutectic Formulations

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride (Allowed)

BR112017005231-8

Formulations of Cyclobenzaprine Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

BR122020020968-2

Formulations of Cyclobenzaprine Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

201910263541.6

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

202011576351.9

Formulations of Cyclobenzaprine Hydrochloride

Patent Office

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Patent Office

Formulations of Cyclobenzaprine Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

European Patent Office

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

European Patent Office

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

42020003105.2

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Eutectic Formulations

of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

42020019748.1

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

42021036749.6

Formulations of Cyclobenzaprine Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Methods of Producing Same (Allowed)

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

3392/KOLNP/2015

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride

Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

PI 2015703142

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

PI 20233000078

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride

Eutectic Formulations

of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride

Eutectic Formulations

of Cyclobenzaprine Hydrochloride

Eutectic Formulations of Cyclobenzaprine

Hydrochloride and Amitriptyline Hydrochloride

CBP/Amitriptyline

and Methods for Transmucosal Absorption

BR112014031394-6

and Methods for Transmucosal Absorption

Compositions and Methods for Transmucosal

Not Yet Assigned

Compositions and Methods for Transmucosal

BR122019024508-8

and Methods for Transmucosal Absorption

Compositions and Methods for Transmucosal

202010024102.2

and Methods for Transmucosal Absorption

Patent Office

and Methods for Transmucosal Absorption

Cooperation Council

Compositions and Methods for Transmucosal

and Methods for Transmucosal Absorption

Cooperation Council

and Methods for Transmucosal Absorption

Gulf Cooperation

Compositions and Methods for Transmucosal

Gulf Cooperation Council

42020020336.2

and Methods for Transmucosal Absorption

and Methods for Transmucosal Absorption (Allowed)

and Methods for Transmucosal Absorption

MX/a/2021/005317

and Methods for Transmucosal Absorption

and Methods for Transmucosal Absorption (Allowed)

and Compositions for Treating Symptoms Associated with Post-Traumatic Stress Disorder Using Cyclobenzaprine

Compositions and Methods for Transmucosal

P-00 2021 01421

Compositions and Methods for Transmucosal

Methods and Compositions for Treating

Symptoms Associated with Post-Traumatic Stress Disorder Using Cyclobenzaprine

Clinical Response – PTSD

PCT/US2022/015327

Improved Method of Assessing Clinical Response in the Treatment of PTSD Symptoms

and Compositions for Treating Fatigue Associated with Disordered Sleep Using Very Low Dose Cyclobenzaprine

An Improved Method of Assessing

Clinical Response in the Treatment of PTSD Symptoms

Methods and Compositions for Treating

Fatigue Associated with Disordered Sleep Using Very Low Dose Cyclobenzaprine

– Agitation in Neurodegenerative Condition

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment

for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

BR112020011345-0

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

201880079917.1

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Patent Office

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

European Patent Office

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

MX/a/2020/006140

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

62021029558.5

Cyclobenzaprine

Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

and Compositions for Treating Depression Using Cyclobenzaprine

and Compositions for Treating Depression Using Cyclobenzaprine (Allowed)

and Compositions for Treating Depression Using Cyclobenzaprine

Patent Office

Cyclobenzaprine Treatment for Agitation,

Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions

Methods and Compositions for Treating

Depression Using Cyclobenzaprine

Methods and Compositions for Treating Depression Using Cyclobenzaprine

European Patent Office

201880050758.2

of Cyclobenzaprine and Amitryptilene

Patent Office

of Cyclobenzaprine and Amitryptilene

Cyclobenzaprine and Amitriptyline

European Patent

Analogs of Cyclobenzaprine and Amitriptyline

– ASD and PTSD

of Treating Acute Stress Disorder and Posttraumatic Stress Disorder

Cooperation Council

of Treating Acute Stress Disorder and Posttraumatic Stress Disorder

– Fibromyalgia

PCT/US2021/062244

Cyclobenzaprine

Treatment for Fibromyalgia

– Alcohol Use Disorder

PCT/US2021/060011

Cyclobenzaprine

Treatment for Alcohol Use Disorder

CBP/Amitriptyline

– Single Nucleotide Polymorphisms as Predictive Markers

Nucleotide Polymorphisms (SNPs) as Predictive Markers for Treatment with Cyclobenzaprine or Amitriptyline

Cyclobenzaprine

or Amitriptyline Containing Compositions for Use in Treating Stress Disorders

of Treating Acute Stress Disorder and Posttraumatic Stress Disorder

Application No.

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

Gulf Cooperation Council

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

Taiwan R.O.C.

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

BR112021003107-3

of Treating Acute Stress Disorder and Posttraumatic Stress Disorder

MX/a/2021/002012

of Treating Acute Stress Disorder and Posttraumatic Stress Disorder

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

201980062283.3

of Treating Acute Stress Disorder and Posttraumatic Stress Disorder

Patent Office

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

European Patent Office

62021045278.0

of Treating Acute Stress Disorder and Posttraumatic Stress Disorder

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

62022046260.5

of Treating Acute Stress Disorder and Posttraumatic Stress Disorder

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

Cyclobenzaprine or Amitriptyline

Containing Compositions for Use in Treating Stress Disorders

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

MX/a/2021/002012

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

Methods of Treating Acute Stress

Disorder and Posttraumatic Stress Disorder

– Fibromyalgia

PCT/US2021/062244

Cyclobenzaprine Treatment for Fibromyalgia

– Alcohol Use Disorder

PCT/US2021/060011

Cyclobenzaprine Treatment for Alcohol

– Sexual dysfunction

PCT/US2022/045791

Cyclobenzaprine

Treatment for Sexual Dysfunction

Cyclobenzaprine

Treatment for Sexual Dysfunction

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

BR1120170145456

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Cyclobenzaprine Treatment for Sexual

202180040673.8

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Patent Office

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use (Allowed)

Magnesium-Containing

Oxytocin Formulations and Methods of Use (Allowed)

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Oxytocin and Method of Manufacture and Use

Patent Office

Oxytocin and Method of Manufacture and Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Patent Office

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Cyclobenzaprine Treatment for Sexual

European Patent Office

Cyclobenzaprine Treatment for Sexual

– Post-Acute Sequelae of SARS-CoV-2 (PASC)

Cyclobenzaprine Treatment for Post-Acute

Sequelae of (SARS)-CoV-2 Infection (PASC)

Magnesium-Containing Oxytocin Formulations

and Methods of Use

BR1120170145456

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Magnesium-Containing Oxytocin Formulations

and Methods of Use

European Patent Office

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Republic of Korea

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Magnesium-Containing Oxytocin Formulations

and Methods of Use (Allowed)

Labeled Oxytocin and Method of Manufacture

European Patent Office

Labeled Oxytocin and Method of Manufacture

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Magnesium-Containing Oxytocin Formulations

and Methods of Use (Allowed)

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Magnesium-Containing Oxytocin Formulations

and Methods of Use

European Patent Office

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Magnesium-Containing Oxytocin Formulations

and Methods of Use

MX/a/2018/012351

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Magnesium-Containing

Oxytocin Formulations and Methods of Use

Oxytocin Peptide Analogs

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Magnesium-Containing Oxytocin Formulations

and Methods of Use

Nociceptin/Orphanin

1 unchanged sentence

BR122021007932-3

for Treatment of Pain

for Treatment of Pain (Allowed)

1614/CHENP/2012

for Treatment of Pain

Oxalate – Salts and Crystalline Forms

Oxalate Salts and Polymorphs (Allowed)

Methods for Treatment of Pain

Hemioxalate – Salts and Crystalline Forms

BR112019013244-9

Oxalate Salts and Polymorphs

Tianeptine Oxalate Salts and Polymorphs

201780085697.9

Oxalate Salts and Polymorphs

Patent Office

Tianeptine Oxalate Salts and Polymorphs

European Patent Office

62020006380.3

Oxalate Salts and Polymorphs

Tianeptine Oxalate Salts and Polymorphs

62020006381.1

Oxalate Salts and Polymorphs

Oxalate Salts and Polymorphs, Compositions Comprising Same and Uses Thereof

Oxalate Salts and Polymorphs

Tianeptine Oxalate Salts and Polymorphs

Tianeptine Oxalate Salts and Polymorphs,

Compositions Comprising Same and Uses Thereof

Tianeptine Oxalate Salts and Polymorphs

MX/a/2019/007891

5 unchanged sentences

Oxalate Salts and Polymorphs

Neurocognitive Dysfunction

for Treating Neurocognitive Dysfunction

and Naloxone – Major Depressive Disorder

Oxalate and Naloxone Treatment for Major Depressive Disorder

Smallpox Vaccines

Chimeric Poxviruses

Cooperation Council

Chimeric Poxviruses

Cooperation Council

Chimeric Poxviruses

PCT/US2022/020406

Tianeptine Oxalate and Naloxone

Treatment for Major Depressive Disorder

Chimeric Poxviruses

Synthetic Chimeric Poxviruses

P 20170103043

Synthetic Chimeric Poxviruses

Gulf Cooperation Council

Synthetic Chimeric Poxviruses

Gulf Cooperation Council

Synthetic Chimeric Poxviruses

Taiwan R.O.C.

Synthetic Chimeric Poxviruses

BR112019008781-8

Chimeric Poxviruses

Synthetic Chimeric Poxviruses

BR122023000373-0

Synthetic Chimeric Poxviruses

201780078546.0

Chimeric Poxviruses

Patent Office

Chimeric Poxviruses

Synthetic Chimeric Poxviruses

European Patent Office

Chimeric Poxviruses

MX/a/2019/005102

Chimeric Poxviruses

1 unchanged sentence

Chimeric Poxviruses

Synthetic Chimeric Poxviruses

Chimeric Poxviruses

Synthetic Chimeric Poxviruses

62020003684.1

Chimeric Poxviruses

Synthetic Chimeric Poxviruses

62020003675.9

Chimeric Poxviruses

Synthetic Chimeric Poxviruses

Vaccinia Virus

Chimeric Vaccinia Virus

Cooperation Council

Chimeric Vaccinia Virus

Cooperation Council

Chimeric Vaccinia Virus

Synthetic Chimeric Vaccinia Virus

Gulf Cooperation Council

Synthetic Chimeric Vaccinia Virus

Gulf Cooperation Council

Synthetic Chimeric Vaccinia Virus

Taiwan R.O.C.

Synthetic Chimeric Vaccinia Virus

BR112020022181-3

Chimeric Vaccinia Virus

Synthetic Chimeric Vaccinia Virus

201980029677.9

Chimeric Vaccinia Virus

Patent Office

Chimeric Vaccinia Virus

Synthetic Chimeric Vaccinia Virus

European Patent Office

Synthetic Chimeric Vaccinia Virus

PI 2020005696

Synthetic Chimeric Vaccinia Virus

MX/a/2020/011586

Chimeric Vaccinia Virus

Synthetic Chimeric Vaccinia Virus

62021036744.2

Chimeric Vaccinia Virus

Synthetic Chimeric Vaccinia Virus

62021038254.0

Chimeric Vaccinia Virus

Synthetic Chimeric Vaccinia Virus

cells-scPV treatment

Cells Comprising Synthetic Chimeric Vaccinia Virus and Methods of Using Them

Cooperation Council

Cells Comprising Synthetic Chimeric Vaccinia Virus and Methods of Using Them

Cooperation Council

Cells Comprising Synthetic Chimeric Vaccinia Virus and Methods of Using Them

Stem Cells Comprising Synthetic

Chimeric Vaccinia Virus and Methods of Using Them

Gulf Cooperation Council

Stem Cells Comprising Synthetic

Chimeric Vaccinia Virus and Methods of Using Them

Gulf Cooperation Council

Stem Cells Comprising Synthetic

Chimeric Vaccinia Virus and Methods of Using Them

Stem Cells Comprising Synthetic

Chimeric Vaccinia Virus and Methods of Using Them

Taiwan R.O.C.

Stem Cells Comprising Synthetic

Chimeric Vaccinia Virus and Methods of Using Them

Stem Cells Comprising Synthetic

Chimeric Vaccinia Virus and Methods of Using Them

Stem Cells Comprising

Synthetic Chimeric Vaccinia Virus and Methods of Using Them

201980029672.6

Cells Comprising Synthetic Chimeric Vaccinia Virus and Methods of Using Them

Patent Office

Cells Comprising Synthetic Chimeric Vaccinia Virus and Methods of Using Them

Stem Cells Comprising Synthetic

Chimeric Vaccinia Virus and Methods of Using Them

Stem Cells Comprising Synthetic

Chimeric Vaccinia Virus and Methods of Using Them

European Patent Office

Stem Cells Comprising Synthetic

Chimeric Vaccinia Virus and Methods of Using Them

Stem Cells Comprising Synthetic

Chimeric Vaccinia Virus and Methods of Using Them

62021038255.7

Cells Comprising Synthetic Chimeric Vaccinia Virus and Methods of Using Them

Stem Cells Comprising Synthetic

Chimeric Vaccinia Virus and Methods of Using Them

62021031667.0

Cells Comprising Synthetic Chimeric Vaccinia Virus and Methods of Using Them

Stem Cells Comprising Synthetic

Chimeric Vaccinia Virus and Methods of Using Them

vaccine against COVID-19

PCT/US2021/020119

Poxvirus Based Vaccine against SARS-CoV-2 virus

Recombinant Poxvirus Based Vaccine against SARS-CoV-2

African Intellectual Property Organization

AP/P/2022/014318

Recombinant Poxvirus Based Vaccine against SARS-CoV-2

African Regional Intellectual Property Organization

Recombinant Poxvirus Based Vaccine against SARS-CoV-2

BR112022016992-2

Recombinant Poxvirus Based Vaccine against SARS-CoV-2

202180027983.6

Recombinant Poxvirus Based Vaccine against SARS-CoV-2

Eurasian Patent Office

Recombinant Poxvirus Based Vaccine against SARS-CoV-2

European Patent Office

Recombinant Poxvirus Based Vaccine against SARS-CoV-2

PI 2022004613

Recombinant Poxvirus Based Vaccine against SARS-CoV-2

MX/a/2022/010588

Recombinant Poxvirus Based Vaccine against SARS-CoV-2

10-2022-7033014

Recombinant Poxvirus Based Vaccine against SARS-CoV-2

Republic of Korea

Recombinant Poxvirus Based Vaccine against SARS-CoV-2

of glutathione

forms of S-(N, N-diethylcarbamolyl) glutathione

Salt forms of S-(N, N-diethylcarbamolyl)

202080034626.8

forms of S-(N, N-diethylcarbamolyl) glutathione

Patent Office

forms of S-(N, N-diethylcarbamolyl) glutathione

TFF2 polypeptides

Patent Office

TFF2 polypeptides

Salt forms of S-(N, N-diethylcarbamolyl)

European Patent Office

Salt forms of S-(N, N-diethylcarbamolyl)

62022054457.6

Salt forms of S-(N, N-diethylcarbamolyl)

62022057646.1

Salt forms of S-(N, N-diethylcarbamolyl)

Modified TFF2 polypeptides

202080071768.1

Modified TFF2 polypeptides

European Patent Office

Modified TFF2 polypeptides

MX/a/2022/002337

TFF2 polypeptides

Modified TFF2 polypeptides

62023066535.3

Modified TFF2 polypeptides

62023066928.0

Modified TFF2 polypeptides

Radioprotection

PCT/US2021/031441

and Chemo-Protective Compounds

Radio-Protective

and Chemo-Protective Substituted Thiols

PCT/US2021/042102

Testing for Detection of Cell-Mediated Immune Responses to SARS-CoV-2

Radio-Protective and Chemo-Protective

Substituted Thiols

Radio-and Chemo-Protective Compounds

Not Yet Assigned

Radio-and Chemo-Protective

Radio-and Chemo-Protective Compounds

European Patent Office

Radio-and Chemo-Protective Compounds

data statistical analysis

PCT/US2021/056213

Randomization

Honoring Methods to Assess the Significance of Interventions on Outcomes in Disorders

Randomization

Honoring Methods to Assess the Significance of Interventions on Outcomes in Disorders

and nucleoside analogs – Ebola virus

of Treating and Inhibiting Ebola Virus Infection

Patent Office

and nucleoside analogs – Coronavirus

Randomization Honoring Methods to

Assess the Significance of Interventions on Outcomes in Disorders

Randomization Honoring Methods to

Assess the Significance of Interventions on Outcomes in Disorders

Antibodies – anti-SARS-CoV-2 Spike

Anti-SARS-CoV-2-Spike Monoclonal

Antibodies and Antigen-Binding Fragments Thereof and Use in Treating SARS-CoV-2 Infection

Anti-SARS-CoV-2-Spike Monoclonal

Antibodies and Antigen-Binding Fragments Thereof and Use in Treating SARS-CoV-2 Infection

Anti-SARS-CoV-2-Spike Monoclonal

Antibodies and Antigen-Binding Fragments Thereof and Use in Treating SARS-CoV-2 Infection

Nanoparticles

– T cell Immune Response

Nanoparticles for Inducing a TH1

T Cell Immune Response

Nanoparticles –

Application No.

Country / Region

PCT/US2022/070739

for Treating Coronavirus Infections

RNA Stabilizing Nanoparticles

PCT/US2022/075944

for Treating Coronavirus Infections

and nucleoside analogs – Arenaviridae

mRNA Vaccine Formulations and Methods of Using the Same

Virus Vaccine –

Bovine Parainfluenza Virus Vaccine

Application No.

Country / Region

Broadly Protective Bovine Parainfluenza 3 Virus and Bovine Viral Diarrhea Virus Vaccine

PCT/US2022/072433

for Treating Arenaviridae Infections

and nucleoside analogs – Poxviridae

SARS-Coronavirus 2 (SARS-CoV-2) Spike Protein Subunit Vaccines

Drugs – Cathepsin Inhibitors

Therapeutic Agents and Combinations

for Treating Viral Diseases

Compositions and Methods for Increasing

Efficacy of a Drug

Compositions and Methods for Increasing

Efficacy of a Drug

Compositions and Methods for Increasing

Efficacy of a Drug

European Patent Office

Compositions and Methods for Increasing

Efficacy of a Drug

Compositions and Methods for Increasing

Efficacy of a Drug

PCT/US2021/052664

for Treating Poxviridae Infections

Methods and Compositions for the

Treatment of Viral Diseases

and Service Marks

4 unchanged sentences

4656463, issued December 16, 2014).

2014) and TONMYA (Reg.

4868328, issued December 8, 2015).

are the owner of the following marks for which applications for U.S.

federal registration are currently pending:

FYMRALIN (Serial

88/064191, filed August 3, 2018), MODALTIN (Serial No.

88/196892, filed November 16, 2018), RAPONTIS (Serial No.

88/196897, filed November 16, 2018), PROTECTIC (Serial No.

88/196912, filed November 16, 2018), TONIX PHARMACEUTICALS (Serial

88/896150, filed April 30, 2020), and ANGSTRO-TECHNOLOGY (Serial No.

88/690384, filed November 13, 2019) and TONMYA (Serial

FYMRALIN (Serial No.

97/458017, filed June 14, 2022), MODALTIN (Serial No.

97/424052, filed May 23, 2022), RAPONTIS (Serial No.

97/424058, filed

May 23, 2022), PROTECTIC (Serial No.

97/424071, filed May 23, 2022), TONIX PHARMACEUTICALS (Serial No.

88/896150, filed April 30, 2020),

and ANGSTRO-TECHNOLOGY (Serial No.

88/690384, filed November 13, 2019) and TONMYA (Serial No.

97/185424, filed December 22, 2021).

and Development

We have approximately 52 employees dedicated to research and development.

Our research and development operations are located in Chatham, NJ, Dartmouth, MA, Frederick, Maryland, San Diego, CA, Dublin, Ireland

and Montreal, Canada.

We have used, and expect to continue to use, third parties to conduct our nonclinical and clinical studies.

acquired the infectious disease RDC in Frederick, Maryland consisting of two buildings totaling approximately 48,000 square feet.

acquisition closed in October 2021 and was operational at closing, but as of December 31, 2021, the facility was not ready for its intended

It is our intention to have the facility ready for use in the first half of 2022.

have approximately 94 employees dedicated to research and development.

Our research and development operations are located in Chatham,

NJ, Dartmouth, MA, Frederick, Maryland, San Diego, CA, Dublin, Ireland and Montreal, Canada.

We have used, and expect to continue to use,

third parties to conduct our nonclinical and clinical studies.

We acquired the RDC in Frederick, Maryland consisting of two

buildings totaling approximately 48,000 square feet.

The acquisition closed in October 2021 and is operational.

Manufacturing

have contracted with a third-party cGMP-compliant contract manufacturer organization, or CMOs, for the manufacture of TNX-102

SL drug substances and drug products for investigational purposes, including nonclinical and clinical testing.

For TNX-102 SL,

we have engaged a cGMP facility for manufacturing of to-be-marketed product for Phase 3 clinical and commercial.

Our manufacturing

operations are managed and controlled in Dublin, Ireland.

of our small molecules drug candidates are synthesized using industry standard processes, and our drug products are formulated

using commercially available pharmaceutical grade excipients.

smallpox-preventing vaccine candidate is a biologic and uses live form of horsepox.

Both the drug substance (HPVX and the cell

bank) and the drug product (vaccine) will be manufactured by contract cGMP-compliant facilities capable of manufacturing for nonclinical/clinical

have contracted with a third-party cGMP-compliant contract manufacturer organization, or CMOs, for the manufacture of TNX-102 SL drug

substances and drug products for investigational purposes, including nonclinical and clinical testing.

For TNX-102 SL, we have engaged

a cGMP facility for manufacturing of to-be-marketed product for Phase 3 clinical and commercial.

Our manufacturing operations are managed

and controlled in Dublin, Ireland.

of our small molecules drug candidates are synthesized using industry standard processes, and our drug products are formulated using commercially

available pharmaceutical grade excipients.

Our smallpox- and mpox-preventing vaccine candidate is a biologic and employs a live form of horsepox.

Both the drug substance (HPVX and the cell bank)

and the drug product (vaccine) will be manufactured by contract cGMP-compliant facilities capable of manufacturing for nonclinical/clinical

testing and licensed product.

On September 28, 2020, we completed

the purchase of our 40,000 square foot facility in Massachusetts, to house our new Advanced Development Center for accelerated development

and manufacturing of vaccines.

As of December 31, 2021, the facility was not ready for its intended use.

On December 23, 2020, we completed

the purchase of our approximately 44-acre site in Hamilton, Montana, for the construction of a vaccine development and commercial scale

manufacturing facility.

On September 28, 2020,

we completed the purchase of our 45,000 square foot facility in Massachusetts, to house our new Advanced Development Center for

accelerated development and manufacturing of vaccines and biologics.

As of October 1, 2022, the facility was ready for its intended

use and is operational.

December 23, 2020, we completed the purchase of our approximately 44-acre site in Hamilton, Montana, for the construction of a vaccine

development and commercial scale manufacturing facility.

As of December 31, 2022, the facility was not ready for its intended use.

On March 5, 2021, the Company

announced that it entered into a $2.9 million non-binding Purchase and Sale Agreement in connection with a property in Massachusetts,

which is expected to close in the second quarter of 2022.

The Property is intended for process development activities.

FDA and other federal, state, local and foreign regulatory agencies impose substantial requirements upon the clinical development,

approval, labeling, manufacture, marketing and distribution of drug products.

These agencies regulate, among other things, research

and development activities and the testing, approval, manufacture, quality control, safety, effectiveness, labeling, storage,

record keeping, advertising and promotion of our product candidates.

The regulatory approval process is generally lengthy and

expensive, with no guarantee of a positive result.

Moreover, failure to comply with applicable requirements by the FDA or other

requirements may result in civil or criminal penalties, recall or seizure of products, injunctive relief including partial or

total suspension of production, or withdrawal of a product from the market.

FDA and other federal, state, local and foreign regulatory agencies impose substantial requirements upon the clinical development, approval,

labeling, manufacture, marketing and distribution of drug products.

These agencies regulate, among other things, research and development

activities and the testing, approval, manufacture, quality control, safety, effectiveness, labeling, storage, record keeping, advertising

and promotion of our product candidates.

The regulatory approval process is generally lengthy and expensive, with no guarantee of a positive

Moreover, failure to comply with applicable requirements by the FDA or other requirements may result in civil or criminal penalties,

recall or seizure of products, injunctive relief including partial or total suspension of production, or withdrawal of a product from

FDA regulates, among other things, the research, manufacture, promotion and distribution of drugs in the U.S.

under the FDCA and

other statutes and implementing regulations.

The process required by the FDA before prescription drug product candidates may be

marketed in the U.S.

under the FDCA and other

statutes and implementing regulations.

The process required by the FDA before prescription drug product candidates may be marketed in

generally involves the following:

of extensive nonclinical laboratory tests, animal studies and formulation studies, all performed in accordance with the FDA’s

Good Laboratory Practice regulations;

to the FDA of an IND, which must become effective before human clinical trials may begin;

of adequate and well-controlled human clinical trials in accordance with the FDA’s regulations, including Good Clinical

Practices, to establish the safety and efficacy of the product candidate for each proposed indication;

to the FDA of an NDA for drug products, or a Biologics License Application, or BLA, for biologic products;

completion of a preapproval inspection by the FDA of the manufacturing facilities at which the product is produced to assess

compliance with cGMP regulations;

FDA’s review and approval of the NDA or BLA prior to any commercial marketing, sale or shipment of the drug.

testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals

for our product candidates will be granted on a timely basis, if at all.

tests include laboratory evaluations of product chemistry, formulation and stability, as well as studies to evaluate toxicity

in animals and other animal studies.

The results of nonclinical tests, together with manufacturing information and analytical

data, are submitted as part of an IND to the FDA.

completion of extensive nonclinical

laboratory tests, animal studies and formulation studies, all performed in accordance with the FDA’s Good Laboratory Practice regulations;

submission to the FDA of an IND,

which must become effective before human clinical trials may begin;

performance of adequate and well-controlled

human clinical trials in accordance with the FDA’s regulations, including Good Clinical Practices, to establish the safety and efficacy

of the product candidate for each proposed indication;

submission to the FDA of an NDA

for drug products, or a Biologics License Application, or BLA, for biologic products;

satisfactory completion of a preapproval

inspection by the FDA of the manufacturing facilities at which the product is produced to assess compliance with cGMP regulations;

the FDA’s review and approval

of the NDA or BLA prior to any commercial marketing, sale or shipment of the drug.

testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals for

our product candidates will be granted on a timely basis, if at all.

tests include laboratory evaluations of product chemistry, formulation and stability, as well as studies to evaluate toxicity in animals

and other animal studies.

The results of nonclinical tests, together with manufacturing information and analytical data, are submitted

as part of an IND to the FDA.

Some nonclinical testing may continue even after an IND is submitted.

also includes one or more protocols for the initial clinical trial or trials and an investigator’s brochure.

An IND automatically

becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises concerns or questions

relating to the proposed clinical trials as outlined in the IND and places the clinical trial on a clinical hold.

In such cases,

the IND sponsor and the FDA must resolve any outstanding concerns or questions before any clinical trials can begin.

trial holds also may be imposed at any time before or during studies due to safety concerns or non-compliance with regulatory

requirements.

An independent Institutional Review Board, or IRB, at each of the clinical centers proposing to conduct the clinical

trial must review and approve the plan for any clinical trial before it commences at that center.

An IRB considers, among other

things, whether the risks to individuals participating in the trials are minimized and are reasonable in relation to anticipated

The IRB also approves the consent form signed by the trial participants and must monitor the study until completed.

The IND also includes one or more

protocols for the initial clinical trial or trials and an investigator’s brochure.

An IND automatically becomes effective 30 days

after receipt by the FDA, unless the FDA, within the 30-day time period, raises concerns or questions relating to the proposed clinical

trials as outlined in the IND and places the clinical trial on a clinical hold.

In such cases, the IND sponsor and the FDA must resolve

any outstanding concerns or questions before any clinical trials can begin.

Clinical trial holds also may be imposed at any time before

or during studies due to safety concerns or non-compliance with regulatory requirements.

An independent Institutional Review Board, or

IRB, at each of the clinical centers proposing to conduct the clinical trial must review and approve the plan for any clinical trial before

it commences at that center.

An IRB considers, among other things, whether the risks to individuals participating in the trials are minimized

and are reasonable in relation to anticipated benefits.

The IRB also approves the consent form signed by the trial participants and must

monitor the study until completed.

trials involve the administration of the product candidate to human subjects under the supervision of qualified medical investigators

2 unchanged sentences

Each protocol for a U.S.

study is submitted to the FDA as part of

study is submitted to the FDA as part of the IND.

clinical trials are typically conducted in three sequential phases, but the phases may overlap, or be combined.

1 clinical trials typically involve the initial introduction of the product candidate into healthy human volunteers.

1 clinical trials, the product candidate is typically tested for safety, dosage tolerance, absorption, metabolism, distribution,

excretion and pharmacodynamics.

2 clinical trials are generally conducted in a limited patient population to gather evidence about the efficacy of the product

candidate for specific, targeted indications;

Phase 1 clinical trials typically

involve the initial introduction of the product candidate into healthy human volunteers.

In Phase 1 clinical trials, the product candidate

is typically tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and pharmacodynamics.

Phase 2 clinical trials are generally

conducted in a limited patient population to gather evidence about the efficacy of the product candidate for specific, targeted indications;

to determine dosage tolerance and optimal dosage;

and to identify possible adverse

effects and safety risks.

Phase 2 clinical trials, in particular Phase 2b trials, can be undertaken to evaluate clinical efficacy

and to test for safety in an expanded patient population at geographically dispersed clinical trial sites.

3 clinical trials are undertaken to evaluate clinical efficacy and to test for safety in an expanded patient population at

geographically dispersed clinical trial sites.

The size of Phase 3 clinical trials depends upon clinical and statistical considerations

for the product candidate and disease.

Phase 3 clinical trials are intended to establish the overall risk-benefit ratio of

the product candidate and provide an adequate basis for product labeling.

and to identify possible adverse effects and safety risks.

Phase 2 clinical trials,

in particular Phase 2b trials, can be undertaken to evaluate clinical efficacy and to test for safety in an expanded patient population

at geographically dispersed clinical trial sites.

Phase 3 clinical trials are undertaken

to evaluate clinical efficacy and to test for safety in an expanded patient population at geographically dispersed clinical trial sites.

The size of Phase 3 clinical trials depends upon clinical and statistical considerations for the product candidate and disease.

3 clinical trials are intended to establish the overall risk-benefit ratio of the product candidate and provide an adequate basis for

product labeling.

Post-approval

clinical trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial approval.

These clinical trials

are used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for

long-term safety follow-up.

These clinical trials are

used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety

testing must satisfy the extensive regulations of the FDA.

Reports detailing the results of the clinical trials must be submitted

at least annually to the FDA and safety reports must be submitted for serious and unexpected adverse events.

Success in early-stage

clinical trials does not assure success in later-stage clinical trials.

The FDA, an IRB or we may suspend a clinical trial at

any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health

Reports detailing the results of the clinical trials must be submitted at least

annually to the FDA and safety reports must be submitted for serious and unexpected adverse events.

Success in early-stage clinical trials

does not assure success in later-stage clinical trials.

The FDA, an IRB or we may suspend a clinical trial at any time on various grounds,

including a finding that the research subjects or patients are being exposed to an unacceptable health risk.

Drug Applications

successful completion of the required clinical trials, the results of product development, nonclinical studies and clinical trials

are submitted to the FDA as part of an NDA (or BLA, in the case of a biologic product).

An NDA or BLA also must contain extensive

manufacturing information, as well as proposed labeling for the finished product.

An NDA or BLA applicant must develop information

about the chemistry and physical characteristics of the drug and finalize a process for manufacturing the product in accordance

The manufacturing process must be capable of consistently producing quality product within specifications approved

The manufacturer must develop methods for testing the quality, purity and potency of the final product.

appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product does

not undergo unacceptable deterioration over its shelf life.

Prior to approval, the FDA will conduct an inspection of the manufacturing

facilities to assess compliance with cGMP.

successful completion of the required clinical trials, the results of product development, nonclinical studies and clinical trials are

submitted to the FDA as part of an NDA (or BLA, in the case of a biologic product).

An NDA or BLA also must contain extensive manufacturing

information, as well as proposed labeling for the finished product.

An NDA or BLA applicant must develop information about the chemistry

and physical characteristics of the drug and finalize a process for manufacturing the product in accordance with cGMP.

The manufacturing

process must be capable of consistently producing quality product within specifications approved by the FDA.

The manufacturer must develop

methods for testing the quality, purity and potency of the final product.

In addition, appropriate packaging must be selected and tested,

and stability studies must be conducted to demonstrate that the product does not undergo unacceptable deterioration over its shelf life.

Prior to approval, the FDA will conduct an inspection of the manufacturing facilities to assess compliance with cGMP.

FDA reviews all NDAs and BLAs submitted before it accepts them for filing.

The FDA may request additional information rather than

accept an NDA for filing.

In this event, the NDA or BLA must be resubmitted with the additional information and is subject to

review before the FDA accepts it for filing.

After an application is filed, the FDA may refer the NDA or BLA to an advisory committee

for review, evaluation and recommendation as to whether the application should be approved and under what conditions.

is not bound by the recommendations of an advisory committee, but it considers them carefully when making decisions.

deny approval of an NDA or BLA if the applicable regulatory criteria are not satisfied.

Data obtained from clinical trials are

not always conclusive and the FDA may interpret data differently than we interpret the same data.

The FDA may issue a complete

response letter, which may require additional clinical or other data or impose other conditions that must be met in order to secure

final approval of the NDA or BLA.

If a product receives regulatory approval, the approval may be significantly limited to specific

diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product.

In addition, the FDA may require us to conduct Phase 4 testing which involves clinical trials designed to further assess a drug’s

safety and effectiveness after NDA or BLA approval, and may require surveillance programs to monitor the safety of approved products

which have been commercialized.

The FDA may request additional information rather than accept

an NDA for filing.

In this event, the NDA or BLA must be resubmitted with the additional information and is subject to review before the

FDA accepts it for filing.

After an application is filed, the FDA may refer the NDA or BLA to an advisory committee for review, evaluation

and recommendation as to whether the application should be approved and under what conditions.

The FDA is not bound by the recommendations

of an advisory committee, but it considers them carefully when making decisions.

The FDA may deny approval of an NDA or BLA if the applicable

regulatory criteria are not satisfied.

Data obtained from clinical trials are not always conclusive and the FDA may interpret data differently

than we interpret the same data.

FDA may issue a complete response letter, which may require additional clinical or other data or impose other conditions that must be

met in order to secure final approval of the NDA or BLA.

If a product receives regulatory approval, the approval may be significantly

limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value

of the product.

In addition, the FDA may require us to conduct Phase 4 testing which involves clinical trials designed to further assess

a drug’s safety and effectiveness after NDA or BLA approval, and may require surveillance programs to monitor the safety of approved

products which have been commercialized.

Once issued, the FDA may withdraw product approval if ongoing regulatory requirements are not

met or if safety or efficacy questions are raised after the product reaches the market.

are two types of NDAs:

the Section 505(b)(1) NDA, or full NDA, and the Section 505(b)(2) NDA.

We intend to file Section 505(b)(2)

NDAs for TNX-102 SL for FM and PTSD, and for certain other products, that might, if accepted by the FDA, save time and expense

in the development and testing of our product candidates.

We may need to file a Section 505(b)(1) NDA for certain other products

in the future.

A full NDA is submitted under Section 505(b)(1) of the FDCA, and must contain full reports of investigations conducted

by the applicant to demonstrate the safety and effectiveness of the drug.

A Section 505(b)(2) NDA may be submitted for a drug

for which one or more of the investigations relied upon by the applicant was not conducted by or for the applicant and for which

the applicant has no right of reference from the person by or for whom the investigations were conducted.

A Section 505(b)(2)

NDA may be submitted based in whole or in part on published literature or on the FDA’s finding of safety and efficacy of

one or more previously approved drugs, which are known as reference drugs.

Thus, the filing of a Section 505(b)(2) NDA may result

in approval of a drug based on fewer clinical or nonclinical studies than would be required under a full NDA.

The number and size

of studies that need to be conducted by the sponsor depends on the amount and quality of data pertaining to the reference drug

that are publicly available, and on the similarity of and differences between the applicant’s drug and the reference drug.

In some cases, extensive, time-consuming, and costly clinical and nonclinical studies may still be required for approval of a

Section 505(b)(2) NDA.

drug approval strategy for our new formulations of approved chemical entities is to submit Section 505(b)(2) NDAs to the FDA.

As such, we plan to submit an NDA under Section 505(b)(2) for TNX-102 SL for FM, PTSD and Long COVID;

TNX-1900, TNX-2900 and TNX-601

The FDA may not agree that these product candidates are approvable as a Section 505(b)(2) NDA.

If the FDA determines that

a Section 505(b)(2) NDA is not appropriate and that a full NDA is required, the time and financial resources required to obtain

FDA approval could substantially and materially increase, and be less likely to be approved.

If the FDA requires a full NDA, or

requires more extensive testing and development for some other reason, our ability to compete with alternative products that arrive

on the market more quickly than our product candidates would be adversely impacted.

If reference listed products are withdrawn

from the market by the FDA for a safety reason, we may not be able to reference such products to support our anticipated 505(b)(2)

NDAs, and we may be required to follow the requirements of Section 505(b)(1).

applicant submitting a Section 505(b)(2) NDA must certify to the FDA with respect to the patent status of the reference drug upon

which the applicant relies in support of approval of its drug.

With respect to every patent listed in the FDA’s Orange Book,

which is the FDA’s list of approved drug products, as claiming the reference drug or an approved method of use of the reference

drug, the Section 505(b)(2) applicant must certify that:

(1) there is no patent information listed in the orange book for the

reference drug;

There are two types of NDAs:

Section 505(b)(1) NDA, or full NDA, and the Section 505(b)(2) NDA.

We intend to file Section 505(b)(2) NDAs for TNX-102 SL for FM, Long

COVID and PTSD, for TNX-1900 for chronic migraine and TNX-2900 for Prader Willi Syndrome and for certain other products, that might, if

accepted by the FDA, save time and expense in the development and testing of our product candidates.

We may need to file a Section 505(b)(1)

NDA for certain other products in the future.

A full NDA is submitted under Section 505(b)(1) of the FDCA, and must contain full reports

of investigations conducted by the applicant to demonstrate the safety and effectiveness of the drug.

A Section 505(b)(2) NDA may be submitted

for a drug for which one or more of the investigations relied upon by the applicant was not conducted by or for the applicant and for

which the applicant has no right of reference from the person by or for whom the investigations were conducted.

A Section 505(b)(2) NDA

may be submitted based in whole or in part on published literature or on the FDA’s finding of safety and efficacy of one or more

previously approved drugs, which are known as reference drugs.

Thus, the filing of a Section 505(b)(2) NDA may result in approval of a

drug based on fewer clinical or nonclinical studies than would be required under a full NDA.

The number and size of studies that need

to be conducted by the sponsor depends on the amount and quality of data pertaining to the reference drug that are publicly available,

and on the similarity of and differences between the applicant’s drug and the reference drug.

In some cases, extensive, time-consuming,

and costly clinical and nonclinical studies may still be required for approval of a Section 505(b)(2) NDA.

Our drug approval strategy for

our new formulations of approved chemical entities is to submit Section 505(b)(2) NDAs to the FDA.

As such, we plan to submit an NDA under

Section 505(b)(2) for TNX-102 SL for FM, Long COVID and PTSD;

TNX-1900 for chronic migraine, and TNX-2900 for Prader Willi Syndrome.

FDA may not agree that these product candidates are approvable as a Section 505(b)(2) NDA.

If the FDA determines that a Section 505(b)(2)

NDA is not appropriate and that a full NDA is required, the time and financial resources required to obtain FDA approval could substantially

and materially increase and be less likely to be approved.

If the FDA requires a full NDA or requires more extensive testing and development

for some other reason, our ability to compete with alternative products that arrive on the market more quickly than our product candidates

would be adversely impacted.

If reference listed products are withdrawn from the market by the FDA for a safety reason, we may not be

able to reference such products to support our anticipated 505(b)(2) NDAs, and we may be required to follow the requirements of Section

applicant submitting a Section 505(b)(2) NDA must certify to the FDA with respect to the patent status of the reference drug upon which

the applicant relies in support of approval of its drug.

With respect to every patent listed in the FDA’s Orange Book, which is

the FDA’s list of approved drug products, as claiming the reference drug or an approved method of use of the reference drug, the

Section 505(b)(2) applicant must certify that:

(1) there is no patent information listed in the orange book for the reference drug;

the listed patent has expired;

(3) the listed patent has not expired, but will expire on a particular date;

(4) the listed patent is invalid or will not be infringed by the manufacture, use, or sale of the product in the Section 505(b)(2)

or (5) if the patent is a use patent, that the applicant does not seek approval for a use claimed by the patent.

If the applicant

files a certification to the effect of clause (1), (2) or (5), FDA approval of the Section 505(b)(2) NDA may be made effective

immediately upon successful FDA review of the application, in the absence of marketing exclusivity delays, which are discussed

If the applicant files a certification to the effect of clause (3), the Section 505(b)(2) NDA approval may not be made

effective until the expiration of the relevant patent and the expiration of any marketing exclusivity delays.

(4) the listed patent is invalid

or will not be infringed by the manufacture, use, or sale of the product in the Section 505(b)(2) NDA;

or (5) if the patent is a use patent,

that the applicant does not seek approval for a use claimed by the patent.

If the applicant files a certification to the effect of clause

(1), (2) or (5), FDA approval of the Section 505(b)(2) NDA may be made effective immediately upon successful FDA review of the application,

in the absence of marketing exclusivity delays, which are discussed below.

If the applicant files a certification to the effect of clause

(3), the Section 505(b)(2) NDA approval may not be made effective until the expiration of the relevant patent and the expiration of any

marketing exclusivity delays.

the Section 505(b)(2) NDA applicant provides a certification to the effect of clause (4), referred to as a paragraph IV certification,

the applicant also must send notice of the certification to the patent owner and the holder of the NDA for the reference drug.

The filing of a patent infringement lawsuit within 45 days of the receipt of the notification may prevent the FDA from approving

the Section 505(b)(2) NDA for 30 months from the date of the receipt of the notification unless the court determines that a longer

or shorter period is appropriate because either party to the action failed to reasonably cooperate in expediting the action.

the FDA may approve the Section 505(b)(2) NDA before the 30 months have expired if a court decides that the patent is invalid

or not infringed, or if a court enters a settlement order or consent decree stating the patent is invalid or not infringed.

of a patent infringement lawsuit within 45 days of the receipt of the notification may prevent the FDA from approving the Section 505(b)(2)

NDA for 30 months from the date of the receipt of the notification unless the court determines that a longer or shorter period is appropriate

because either party to the action failed to reasonably cooperate in expediting the action.

However, the FDA may approve the Section 505(b)(2)

NDA before the 30 months have expired if a court decides that the patent is invalid or not infringed, or if a court enters a settlement

order or consent decree stating the patent is invalid or not infringed.

Notwithstanding

the approval of many products by the FDA pursuant to Section 505(b)(2), over the last few years certain brand-name pharmaceutical

companies and others have objected to the FDA’s interpretation of Section 505(b)(2).

If the FDA’s interpretation of

Section 505(b)(2) is successfully challenged in court, the FDA may be required to change its interpretation of Section 505(b)(2)

which could delay or even prevent the FDA from approving any Section 505(b)(2) NDA that we submit.

The pharmaceutical industry

is highly competitive, and it is not uncommon for a manufacturer of an approved product to file a citizen petition with the FDA

seeking to delay approval of, or impose additional approval requirements for, pending competing products.

If successful, such

petitions can significantly delay, or even prevent, the approval of the new product.

Moreover, even if the FDA ultimately denies

such a petition, the FDA may substantially delay approval while it considers and responds to the petition.

exclusivity provisions under the FDCA can delay the submission or the approval of Section 505(b)(2) NDAs, thereby delaying a Section

505(b)(2) product from entering the market.

The FDCA provides five-year marketing exclusivity to the first applicant to gain approval

of an NDA for an NCE, meaning that the FDA has not previously approved any other drug containing the same active moiety.

exclusivity prohibits the submission of a Section 505(b)(2) NDA for any drug product containing the active ingredient during the

five-year exclusivity period.

However, submission of a Section 505(b)(2) NDA that certifies that a listed patent is invalid, unenforceable,

or will not be infringed, as discussed above, is permitted after four years, but if a patent infringement lawsuit is brought within

45 days after such certification, FDA approval of the Section 505(b)(2) NDA may automatically be stayed until 7½ years

after the NCE approval date.

The FDCA also provides three years of marketing exclusivity for the approval of new and supplemental

NDAs for product changes, including, among other things, new indications, dosage forms, routes of administration or strengths

of an existing drug, or for a new use, if new clinical investigations, other than bioavailability studies, that were conducted

or sponsored by the applicant are deemed by FDA to be essential to the approval of the application.

Five-year and three-year exclusivity

will not delay the submission or approval of another full NDA;

however, as discussed above, an applicant submitting a full NDA

under Section 505(b)(1) would be required to conduct or obtain a right of reference to all of the nonclinical and adequate and

well-controlled clinical trials necessary to demonstrate safety and effectiveness.

the approval of many products by the FDA pursuant to Section 505(b)(2), over the last few years certain brand-name pharmaceutical companies

and others have objected to the FDA’s interpretation of Section 505(b)(2).

If the FDA’s interpretation of Section 505(b)(2)

is successfully challenged in court, the FDA may be required to change its interpretation of Section 505(b)(2) which could delay or even

prevent the FDA from approving any Section 505(b)(2) NDA that we submit.

The pharmaceutical industry is highly competitive, and it is

not uncommon for a manufacturer of an approved product to file a citizen petition with the FDA seeking to delay approval of, or impose

additional approval requirements for, pending competing products.

If successful, such petitions can significantly delay, or even prevent,

the approval of the new product.

Moreover, even if the FDA ultimately denies such a petition, the FDA may substantially delay approval

while it considers and responds to the petition.

exclusivity provisions under the FDCA can delay the submission or the approval of Section 505(b)(2) NDAs, thereby delaying a Section 505(b)(2)

product from entering the market.

The FDCA provides five-year marketing exclusivity to the first applicant to gain approval of an NDA

for an NCE, meaning that the FDA has not previously approved any other drug containing the same active moiety.

This exclusivity prohibits

the submission of a Section 505(b)(2) NDA for any drug product containing the active ingredient during the five-year exclusivity period.

However, submission of a Section 505(b)(2) NDA that certifies that a listed patent is invalid, unenforceable, or will not be infringed,

as discussed above, is permitted after four years, but if a patent infringement lawsuit is brought within 45 days after such certification,

FDA approval of the Section 505(b)(2) NDA may automatically be stayed until 7½ years after the NCE approval date.

The FDCA also provides

three years of marketing exclusivity for the approval of new and supplemental NDAs for product changes, including, among other things,

new indications, dosage forms, routes of administration or strengths of an existing drug, or for a new use, if new clinical investigations,

other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by FDA to be essential to the approval

of the application.

and three-year exclusivity will not delay the submission or approval of another full NDA;

however, as discussed above, an applicant submitting

a full NDA under Section 505(b)(1) would be required to conduct or obtain a right of reference to all of the nonclinical and adequate

and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

types of exclusivity in the United States include orphan drug exclusivity and pediatric exclusivity.

The FDA may grant orphan

drug designation to a drug intended to treat a rare disease or condition, which is generally a disease or condition that affects

fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States and for which there

is no reasonable expectation that the cost of developing and making available in the United States a drug for this type of disease

or condition will be recovered from sales in the United States for that drug.

Seven-year orphan drug exclusivity is available

to a product that has orphan drug designation and that receives the first FDA approval for the indication for which the drug has

such designation.

Orphan drug exclusivity prevents approval of another application for the same drug for the same orphan indication,

for a period of seven years, regardless of whether the application is a full NDA or a Section 505(b)(2) NDA, except in limited

circumstances, such as a showing of clinical superiority to the product with orphan exclusivity.

Pediatric exclusivity, if granted,

provides an additional six months to an existing exclusivity or statutory delay in approval resulting from a patent certification.

This six-month exclusivity, which runs from the end of other exclusivity protection or patent delay, may be granted based on the

voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request” for such a study.

505(b)(2) NDAs are similar to full NDAs filed under Section 505(b)(1) in that they are entitled to any of these forms of exclusivity

if they meet the qualifying criteria.

They also are entitled to the patent protections described above, based on patents that

are listed in the FDA’s Orange Book in the same manner as patents claiming drugs and uses approved for NDAs submitted as

The FDA may grant orphan drug designation

to a drug intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals

in the United States, or more than 200,000 individuals in the United States and for which there is no reasonable expectation that the

cost of developing and making available in the United States a drug for this type of disease or condition will be recovered from sales

in the United States for that drug.

Seven-year orphan drug exclusivity is available to a product that has orphan drug designation and

that receives the first FDA approval for the indication for which the drug has such designation.

Orphan drug exclusivity prevents approval

of another application for the same drug for the same orphan indication, for a period of seven years, regardless of whether the application

is a full NDA or a Section 505(b)(2) NDA, except in limited circumstances, such as a showing of clinical superiority to the product with

orphan exclusivity.

Pediatric exclusivity, if granted, provides an additional six months to an existing exclusivity or statutory delay

in approval resulting from a patent certification.

This six-month exclusivity, which runs from the end of other exclusivity protection

or patent delay, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written

Request” for such a study.

505(b)(2) NDAs are similar to full NDAs filed under Section 505(b)(1) in that they are entitled to any of these forms of exclusivity if

they meet the qualifying criteria.

They also are entitled to the patent protections described above, based on patents that are listed

in the FDA’s Orange Book in the same manner as patents claiming drugs and uses approved for NDAs submitted as full NDAs.

Therapy Designation

Food and Drug Administration Safety and Innovation Act, or FDASIA, Section 902 provides for Breakthrough Therapy designation.

A Breakthrough Therapy is a drug:

alone or in combination with one or more other drugs to treat a serious or life-threatening disease or condition;

clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically

significant endpoints, such as substantial treatment effects observed early in clinical development.

A Breakthrough

Therapy is a drug:

intended alone or in combination

with one or more other drugs to treat a serious or life-threatening disease or condition;

preliminary clinical evidence indicates

that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as

substantial treatment effects observed early in clinical development.

Track Designation

Fast Track is a designation by the FDA of an investigational drug which:

alone or in combination with one or more other drugs to treat a serious or life-threatening disease or condition;

or clinical data demonstrate the potential to address an unmet medical need

track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill

an unmet medical need.

The benefits of a Fast Track designation include rolling submission of portions of the NDA for the drug

candidate and eligibility for priority review of the NDA.

Additionally, more frequent meetings and written communication with

the FDA regarding the development plan and trial design for the drug candidate are encouraged throughout the entire drug development

and review process, with the goal of having earlier drug approval and access for patients.

intended alone or in combination

with one or more other drugs to treat a serious or life-threatening disease or condition;

non-clinical or clinical data demonstrate

the potential to address an unmet medical need

track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet

medical need.

The benefits of a Fast Track designation include rolling submission of portions of the NDA for the drug candidate and eligibility

for priority review of the NDA.

Additionally, more frequent meetings and written communication with the FDA regarding the development

plan and trial design for the drug candidate are encouraged throughout the entire drug development and review process, with the goal of

having earlier drug approval and access for patients.

Threat Medical Countermeasures

2016, the 21 st Century Cures Act, or Act, was signed into law to support ongoing biomedical innovation.

the Act, Section 3086, is aimed at “Encouraging Treatments for Agents that Present a National Security Threat.” The

Act created a new priority review voucher program for approved “material threat medical countermeasure applications.”

The Act defines such countermeasures as drug or biological products, including vaccines intended to treat biological, chemical,

radiological, or nuclear agents that present a national security threat or to treat harm from a condition that may be caused by

administering a drug or biological product against such an agent.

The Department of Homeland Security has identified 13 such threats,

including anthrax, smallpox, Ebola/Marburg, tularemia, botulinum toxin, and pandemic influenza, which includes the SARS coronavirus

2, known as SARS-CoV-2.

A priority review voucher can be applied to any other product application;

it shortens the FDA review

timeline for a new application from 10-12 months to 6 months.

The recipient of a priority review voucher may transfer it.

to seek a priority review voucher if and when a TNX-801 Biologics License Application is approved as a material threat medical

countermeasure.

However, the Priority Review Voucher program provision of the 21st Century Cures Act is set to expire in 2023.

If TNX-801 does not receive FDA licensure by 2023, we may not be able to capitalize on the incentives contained in the 21st Century

Cures Act unless the provision allowing for the Priority Review Voucher Program is extended until such time as TNX-801 is licensed.

In 2016, the 21 st Century

Cures Act, or Act, was signed into law to support ongoing biomedical innovation.

One part of the Act, Section 3086, is aimed at “Encouraging

Treatments for Agents that Present a National Security Threat.” The Act created a new priority review voucher program for approved

“material threat medical countermeasure applications.” The Act defines such countermeasures as drug or biological products,

including vaccines intended to treat biological, chemical, radiological, or nuclear agents that present a national security threat or

to treat harm from a condition that may be caused by administering a drug or biological product against such an agent.

The Department

of Homeland Security has identified 13 such threats, including anthrax, smallpox, Ebola/Marburg, tularemia, botulinum toxin, and pandemic

influenza, which includes the SARS coronavirus 2, known as SARS-CoV-2.

Regulatory Requirements

substantial compliance with appropriate federal, state and local statutes and regulations requires the expenditure of substantial

time and financial resources.

Drug manufacturers are required to register their establishments with the FDA and certain state

agencies, and after approval, the FDA and these state agencies conduct periodic unannounced inspections to ensure continued compliance

with ongoing regulatory requirements, including cGMPs.

In addition, after approval, some types of changes to the approved product,

such as adding new indications, manufacturing changes and additional labeling claims, are subject to further FDA review and approval.

The FDA may require post-approval testing and surveillance programs to monitor safety and the effectiveness of approved products

that have been commercialized.

Any drug products manufactured or distributed by us pursuant to FDA approvals are subject to continuing

regulation by the FDA, including:

record-keeping

requirements;

of adverse experiences with the drug;

the FDA with updated safety and efficacy information;

on advertisements and promotional labeling;

sampling and distribution requirements;

with electronic record and signature requirements.

addition, the FDA strictly regulates labeling, advertising, promotion and other types of information on products that are placed

on the market.

There are numerous regulations and policies that govern various means for disseminating information to health-care

professionals as well as consumers, including to industry sponsored scientific and educational activities, information provided

to the media and information provided over the Internet.

Drugs may be promoted only for the approved indications and in accordance

with the provisions of the approved label.

substantial compliance with appropriate federal, state and local statutes and regulations requires the expenditure of substantial time

and financial resources.

Drug manufacturers are required to register their establishments with the FDA and certain state agencies, and

after approval, the FDA and these state agencies conduct periodic unannounced inspections to ensure continued compliance with ongoing

regulatory requirements, including cGMPs.

In addition, after approval, some types of changes to the approved product, such as adding new

indications, manufacturing changes and additional labeling claims, are subject to further FDA review and approval.

The FDA may require

post-approval testing and surveillance programs to monitor safety and the effectiveness of approved products that have been commercialized.

Any drug products manufactured or distributed by us pursuant to FDA approvals are subject to continuing regulation by the FDA, including:

record-keeping requirements;

reporting of adverse experiences

with the drug;

providing the FDA with updated safety

and efficacy information;

reporting on advertisements and

promotional labeling;

drug sampling and distribution requirements;

complying with electronic record

and signature requirements.

addition, the FDA strictly regulates labeling, advertising, promotion and other types of information on products that are placed on the

There are numerous regulations and policies that govern various means for disseminating information to health-care professionals

as well as consumers, including to industry sponsored scientific and educational activities, information provided to the media and information

provided over the Internet.

Drugs may be promoted only for the approved indications and in accordance with the provisions of the approved

FDA has very broad enforcement authority and the failure to comply with applicable regulatory requirements can result in administrative

or judicial sanctions being imposed on us or on the manufacturers and distributors of our approved products, including warning

letters, refusals of government contracts, clinical holds, civil penalties, injunctions, restitution and disgorgement of profits,

recall or seizure of products, total or partial suspension of production or distribution, withdrawal of approvals, refusal to

approve pending applications, and criminal prosecution resulting in fines and incarceration.

The FDA and other agencies actively

enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted

off-label uses may be subject to significant liability.

In addition, even after regulatory approval is obtained, later discovery

of previously unknown problems with a product may result in restrictions on the product or even complete withdrawal of the product

from the market.

or judicial sanctions being imposed on us or on the manufacturers and distributors of our approved products, including warning letters,

refusals of government contracts, clinical holds, civil penalties, injunctions, restitution and disgorgement of profits, recall or seizure

of products, total or partial suspension of production or distribution, withdrawal of approvals, refusal to approve pending applications,

and criminal prosecution resulting in fines and incarceration.

The FDA and other agencies actively enforce the laws and regulations prohibiting

the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant

In addition, even after regulatory approval is obtained, later discovery of previously unknown problems with a product may

result in restrictions on the product or even complete withdrawal of the product from the market.

and Reimbursement

of our product candidates, if approved, will depend, in part, on the extent to which such products will be covered by third-party

payors, such as government health care programs, commercial insurance and managed healthcare organizations.

These third-party

payors are increasingly limiting coverage or reducing reimbursements for medical products and services.

of our product candidates, if approved, will depend, in part, on the extent to which such products will be covered by third-party payors,

such as government health care programs, commercial insurance and managed healthcare organizations.

These third-party payors are increasingly

limiting coverage or reducing reimbursements for medical products and services.

In addition, the U.S.

government, state legislatures and foreign governments have continued implementing cost-containment programs, including price

controls, restrictions on reimbursement and requirements for substitution of generic products.

Third-party payors decide which

therapies they will pay for and establish reimbursement levels.

Third-party payors often rely upon Medicare coverage policy and

payment limitations in setting their own coverage and reimbursement policies.

However, decisions regarding the extent of coverage

and amount of reimbursement to be provided for any drug candidates that we develop will be made on a payor-by-payor basis.

Each payor determines whether or not it will provide coverage for a therapy, what amount it will pay the manufacturer for the

therapy, and on what tier of its formulary it will be placed.

The position on a payor’s list of covered drugs, or formulary,

generally determines the co-payment that a patient will need to make to obtain the therapy and can strongly influence

the adoption of such therapy by patients and physicians.

Adoption of price controls and cost-containment measures, and adoption

of more restrictive policies in jurisdictions with existing controls and measures, could further limit our net revenue and results.

government, state legislatures and

foreign governments have continued implementing cost-containment programs, including price controls, restrictions on reimbursement and

requirements for substitution of generic products.

Third-party payors decide which therapies they will pay for and establish reimbursement

Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own coverage and reimbursement

However, decisions regarding the extent of coverage and amount of reimbursement to be provided for any drug candidates that

we develop will be made on a payor-by-payor basis.

Each payor determines whether or not it will provide coverage for a therapy,

what amount it will pay the manufacturer for the therapy, and on what tier of its formulary it will be placed.

The position on a payor’s

list of covered drugs, or formulary, generally determines the co-payment that a patient will need to make to obtain the therapy

and can strongly influence the adoption of such therapy by patients and physicians.

Adoption of price controls and cost-containment measures,

and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit our net revenue and

Decreases in third-party reimbursement for our product candidates or a decision by a third-party payor to not cover our product

candidates could reduce physician usage of our product candidates, once approved, and have a material adverse effect on our sales,

results of operations and financial condition.

candidates could reduce physician usage of our product candidates, once approved, and have a material adverse effect on our sales, results

of operations and financial condition.

Healthcare Laws

of our current and future arrangements with healthcare professionals, principal investigators, consultants, customers and third-party

payors, we will also be subject to healthcare regulation and enforcement by the federal government and the states and foreign

governments in which we will conduct our business, including our clinical research, proposed sales, marketing and educational

Failure to comply with these laws, where applicable, can result in the imposition of significant civil penalties, criminal

penalties, or both.

payors, we will also be subject to healthcare regulation and enforcement by the federal government and the states and foreign governments

in which we will conduct our business, including our clinical research, proposed sales, marketing and educational programs.

comply with these laws, where applicable, can result in the imposition of significant civil penalties, criminal penalties, or both.

laws that may affect our ability to operate, among others, include:

the federal Health Insurance

Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical

Health Act, which governs the conduct of certain electronic healthcare transactions and protects the security and privacy of protected

health information;

certain state laws governing the privacy and security of health information in certain circumstances, some

of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same

effect, thus complicating compliance efforts;

the federal healthcare programs’ Anti-Kickback Statute, which prohibits, among

other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly,

in exchange for or to induce either the referral of an individual for, or the purchase, order or recommendation of, any good or

service for which payment may be made under federal healthcare programs such as the Medicare and Medicaid programs;

federal false

claims laws which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented,

claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent;

federal criminal laws that

prohibit executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

the federal Health Insurance Portability and Accountability Act

of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, which governs the conduct of

certain electronic healthcare transactions and protects the security and privacy of protected health information;

certain state laws governing

the privacy and security of health information in certain circumstances, some of which are more stringent than HIPAA and many of which

differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts;

the federal healthcare

programs’ Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving,

offering or paying remuneration, directly or indirectly, in exchange for or to induce either the referral of an individual for, or the

purchase, order or recommendation of, any good or service for which payment may be made under federal healthcare programs such as the

Medicare and Medicaid programs;

federal false claims laws which prohibit, among other things, individuals or entities from knowingly presenting,

or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent;

criminal laws that prohibit executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare

the Physician Payments Sunshine Act, which requires manufacturers of drugs, devices, biologics, and medical supplies to report

1 unchanged sentence

Department of Health and Human Services information related to payments and other transfers of value to physicians

(defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, and ownership and

investment interests held by physicians and their immediate family members;

and state law equivalents of each of the above federal

laws, such as anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including

commercial insurers.

addition, many states have similar laws and regulations, such as anti-kickback and false claims laws that may be broader in scope

and may apply regardless of payor, in addition to items and services reimbursed under Medicaid and other state programs.

Additionally,

to the extent that our product is sold in a foreign country, we may be subject to similar foreign laws.

(defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, and ownership and investment

interests held by physicians and their immediate family members;

and state law equivalents of each of the above federal laws, such as

anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers.

addition, many states have similar laws and regulations, such as anti-kickback and false claims laws that may be broader in scope and

may apply regardless of payor, in addition to items and services reimbursed under Medicaid and other state programs.

Additionally, to

the extent that our product is sold in a foreign country, we may be subject to similar foreign laws.

Impact of New Legislation and Amendments to Existing Laws

FDCA is subject to routine legislative amendments with a broad range of downstream effects.

In addition to new legislation, such

as the FDA Reauthorization Act of 2017 or the FDASIA in 2012, Congress introduces amendments to reauthorize drug user fees and

address emerging concerns every five years.

We cannot predict the impact of these new legislative acts and their implementing

regulations on our business.

The programs established or to be established under the legislation may have adverse effects upon

us, including increased regulation of our industry.

Compliance with such regulation may increase our costs and limit our ability

to pursue business opportunities.

In addition, the FDA’s regulations, policies and guidance are often revised or reinterpreted

by the agency or the courts in ways that may significantly affect our business and our products.

expect that additional federal and state, as well as foreign, healthcare reform measures will be adopted in the future, any of

which could result in reduced demand for our products or additional pricing pressure.

In addition to new legislation, such as

the FDA Reauthorization Act of 2017 or the FDASIA in 2012, Congress introduces amendments to reauthorize drug user fees and address

emerging concerns every five years.

We cannot predict the impact of these new legislative acts and their implementation of regulations

on our business.

The programs established or to be established under the legislation may have adverse effects upon us, including

increased regulation of our industry.

Compliance with such regulation may increase our costs and limit our ability to pursue

business opportunities.

In addition, the FDA’s regulations, policies and guidance are often revised or reinterpreted by the

agency or the courts in ways that may significantly affect our business and our products.

expect that additional federal and state, as well as foreign, healthcare reform measures will be adopted in the future, any of which could

result in reduced demand for our products or additional pricing pressure.

Capital Resources

As of March 14, 2022, we had 73 full-time employees, of whom 12 hold M.D.

We have 52 employees dedicated to research and development.

None of our employees are represented by a collective bargaining

We believe that the skills, experience and industry knowledge of our key employees significantly benefit our operations and

Our research and development operations are located in Chatham, NJ, San Diego, CA, Dartmouth, MA, Frederick, Maryland, Dublin,

Ireland and Montreal, Canada.

We have used, and expect to continue to use, third parties to conduct our nonclinical and clinical studies

as well as part-time employees.

of March 13, 2023, we had 117 full-time employees, of whom 19 hold M.D.

We have 94 employees dedicated to research and

None of our employees are represented by a collective bargaining agreement.

We believe that the skills, experience and industry

knowledge of our key employees significantly benefit our operations and performance.

Our research and development operations are located

in Chatham, NJ, San Diego, CA, Dartmouth, MA, Frederick, Maryland, Dublin, Ireland and Montreal, Canada.

We have used, and expect to continue

to use, third parties to conduct our nonclinical and clinical studies as well as part-time employees.

health and safety in the workplace is one of our core values.

The COVID-19 pandemic has underscored for us the importance of keeping

our employees safe and healthy.

In response to the pandemic, we have taken actions aligned with the World Health Organization

and the Centers for Disease Control and Prevention in an effort to protect our workforce so they can more safely and effectively

perform their work.

The COVID-19 pandemic has underscored for us the importance of keeping our

employees safe and healthy.

In response to the pandemic, we have taken actions aligned with the World Health Organization and the Centers

for Disease Control and Prevention in an effort to protect our workforce so they can more safely and effectively perform their work.

levels are managed to align with the pace of business and management believes it has sufficient human capital to operate its business

successfully.

lease the space for our principal executive offices, which are located at 26 Main Street, Suite 101, Chatham, New Jersey 07928,

and our telephone number is (862) 799 8599.

Our website addresses are www.tonixpharma.com, www.tonix.com, and www.krele.com.

do not incorporate the information on our websites into this annual report, and you should not consider such information part

of this annual report.

We lease the space for our principal executive offices, which are located

at 26 Main Street, Suite 101, Chatham, New Jersey 07928, and our telephone number is (862) 799 8599.

Our website address is www.tonixpharma.com.

We do not incorporate the information on our websites into this annual report, and you should not consider such information part of this

annual report.

were incorporated on November 16, 2007 under the laws of the State of Nevada as Tamandare Explorations Inc.

On October 11, 2011,

we changed our name to Tonix Pharmaceuticals Holding Corp.

On October 11, 2011, we changed

our name to Tonix Pharmaceuticals Holding Corp.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business