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Item 1. Business

2025-03-26 compared with 2024-02-23 · 371 added, 230 removed, 816 unchanged (42% of the section changed)

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Patent Rights and Licensed Technology to, among other things, Develop, have Developed, make, have made, use, sell, import, export and

commercialize TH104 and TH103 and to practice the Licensed Technology in connection with the foregoing, throughout the world.

Developments” below for additional information.

commercialize TH104 and TH103 and to practice the Licensed Technology in connection with the foregoing, throughout the world, each as

defined in the Avior Patent License Agreement.

In February 2023, the U.S.

Food and Drug Administration (“FDA”) approved

an investigational new drug (“IND”) application for TH104.

Food and Drug Administration (“FDA”) approved an

investigational new drug (“IND”) application for TH104.

is a proprietary transmucosal buccal film embedded with the active compound nalmefene onto a thin film which easily adheres inside of

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The molecule has a dual mechanism of action affecting both the µ-opioid

and kappa opioid receptors with emerging data showing inhibition of interleukin-17, a pro-inflammatory cytokine.

These well-known opioid

receptors when stimulated and/or inhibited by the body’s endogenous ligands have been shown to be involved in the body’s

itch circuitry for certain conditions, including cholestatic or dysregulated bile acid-related liver conditions.

to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, primary biliary

cholangitis (“PBC”), is a chronic disease where the bile ducts in the liver eventually become dysfunctional and cause the

buildup of bile which causes liver damage.

The disease, believed to be an autoimmune condition, affects an estimated 58 out of every

women and about 15 out of every 100,000 U.S.

Pruritus is one of the most common symptoms associated with PBC affecting

up to 75% of individuals at some point during their disease course.

It has a negative impact on health-related quality of life with limited

treatment options.

Published survey data of PBC respondents suffering from pruritus described their itch as “bugs crawling under

More than 65% of patients reported that the itch was worse at night, known as nocturnal pruritus, a high unmet need.

are also developing an early-stage pipeline of novel therapeutic candidates targeting validated high value immune-oncology (“IO”)

and kappa opioid receptors.

These well-known opioid receptors when stimulated and/or inhibited by the body’s endogenous ligands

have been shown to be involved in the body’s itch circuitry for certain conditions, including cholestatic or dysregulated bile

acid-related liver conditions.

has a dual mechanism of action by affecting multiple receptors, known to suppress chronic, debilitating pruritus or “uncontrollable

itching” With respect to TH104, we intend to first seek approval for the treatment of moderate-to-severe chronic pruritus in patients

with primary biliary cholangitis (“PBC”), an orphan rare form of liver disease with no known cure in which more than 70%

of patients suffer from debilitating chronic pruritus.

A Phase 2 proof-of-concept (“POC”) trial with TH104

is ready to be initiated and the Company intends to conduct a hepatic impairment trial prior and expects to develop TH103 and potentially file an IND at some point in the future, depending on discussions with the FDA.

TH104, administered via a

transmucosal buccal delivery system applied to the inside of the mouth by adhering to the cheek, is anticipated to demonstrate a favorable

safety profile in a dedicated hepatic impairment study.

This expectation is supported by data from nalmefene tablets (Selincro ® ),

a product available in Europe and not in the United States with relevant pharmacokinetic considerations.

Selincro studies, using a single

18.06 mg dose, revealed that patients with mild hepatic impairment experienced a 1.5-fold increase in exposure (AUC) and a 35% decrease

in oral clearance compared to healthy subjects.

In patients with moderate hepatic impairment, the impact was even more pronounced:

(AUC) increased 2.9-fold, Cmax increased 1.7-fold, and oral clearance was reduced by approximately 60%.

Critically, despite these significant

changes in exposure and clearance, no clinically relevant alterations were observed in either Cmax or the elimination half-life in either

the mild or moderate hepatic impairment groups.

This data provides a potential foundation for predicting TH104 behavior and we intend

to acknowledge that pharmacokinetic data for nalmefene in patients with severe hepatic impairment is not yet available, and that there

are existing contraindications and precautions.

Therefore, while the nalmefene data suggests a reduced risk profile for TH104, we planto

begin a hepatic impairment study in 2025 to fully evaluate the pharmacokinetic profile and safety in certain stages of liver impairment,

beginning with mild and moderate, and potentially severe impairment prior to launching the phase 2 study to ensure we have potential suitable

precautions in place if necessary.

September 11, 2024, we entered into a Patent License Agreement (the “Intract Agreement”) with Intract Pharma Limited (“Intract”),

pursuant to which, we exclusively licensed INT-023/TH023, an oral anti-Tumor Necrosis Factor-alpha (TNF-a) monoclonal antibody infliximab.

Infliximab is a purified recombinant DNA-derived chimeric IgG monocloncal antibody protein that contains both murine and human components

that inhibit tumor TNF-a.

Under the terms of the Intract Agreement, we licensed global development and commercialization rights (outside

of South Korea) to Intract’s Soteria® and Phloral® delivery platform along with an existing supply agreement for infliximab

to be used in the oral product development program.

are also developing an early-stage pipeline of novel therapeutic candidates targeting validated high value immuno-oncology (“IO”)

targets including human epidermal growth factor (“EGF”) receptor 2 (“HER2”), human EGF receptor 3 (“HER3”)

and programmed cell death protein (“PD-1”).

We are developing antibodies including bispecific antibodies, antibody drug conjugates

(“ADCs”) and small molecular weight bovine- derived Picobodies™ or antibody “knob” domains which have the

potential to target and bind more tightly to “undruggable” epitopes better than full sized antibodies.

We are advancing TH3215,

a bispecific against both HER2 and HER3 antibody which targets a novel “bridging epitope” encompassing multiple domains of

the HER2 extracellular domain (“ECD”) as well as ligand-dependent and independent blocking of the ECD of HER3 into IND-enabling

studies in 2024.

In addition, we anticipate that TH0059, a HER2/HER3 bispecific ADC (“bsADC”), and TH1940, a PD-1 Picobody,

will progress into IND-enabling studies in 2025.

and programmed cell death protein (“PD-1”) and vascular endothelial growth factor (“VEGF”).

We are developing

antibodies including bispecific antibodies, antibody drug conjugates (“ADCs”) and small molecular weight bovine- derived

“knob” domains which have the potential to target and bind more tightly to “undruggable” epitopes with conceivably

improved characteristics compared to full sized antibodies.

We are developing HS1940, a novel multispecific biologic targeting both

PD-1 and VEGF.

We are advancing HS3215, a bispecific against both HER2 and HER3 antibody which targets a novel “bridging epitope”

encompassing multiple domains of the HER2 extracellular domain (“ECD”) as well as ligand-dependent and independent blocking

of the ECD of HER3.

is an immunosuppressive checkpoint and seen in macrophages, B lymphocytes, dendritic cells, monocytes, tumor-specific activated T cells,

myeloid cells and natural killer cells in circumstances of chronic antigen contact.

PD-L1 is one of the PD-1 ligands.

PD-L1 expression

has been shown to be a valuable biomarker for the prognosis and prediction of the sensitivity of PD-1/PD-L1 inhibitors.

The expression

of PD-L1 is mainly expressed in tumor cells, tumor-infiltrating cells and antigen-presenting cells in many cancers.

Despite the noteworthy

efficacy of PD-1/PD-L1 immune checkpoint inhibitors (“ICI”) in the treatment of tumors, some problems remain such as drug

resistance and adverse events.

Acquired drug resistance may present despite resuming or continuing treatment with anti-PD-1/PD-L1 immunotherapy.

The presence of drug resistance significantly reduces the efficacy of anti-PD-1/PD-L1 immunotherapy.

We believe exploring the mechanisms

of PD-1/PD-L1 ICI resistance may assist with the discovery of new immunotherapeutic strategies to control disease progression and provide

a more sustainable survival benefit for patients.

As such, we aim to further improve on PD-1 as a breakthrough technology by developing,

HS1940, a proprietary PD-1 Picobody with unique binding affinity differently than currently available PD-1 drugs.

We believe this unique

binding difference allows for novel therapeutic possibilities both as a stand-alone agent and in combination and that our tumor immunotherapy

based on PD-1 inhibition may become a future strategy for human cancers.

EGF subset known as the epidermal growth factor receptor (“ErbB”) family of receptors are a validated set of targets preferentially

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to EGFR inhibitors.

We believe combining anti-HER2 with an anti-HER3 strategy as a bispecific multifunctional agent without a toxin (TH3215)

as well as with a toxin (TH0059) could capitalize on some of the findings described in the literature to take advantage of precise tumor-killing

We believe combining anti-HER2 with an anti-HER3 strategy as a bispecific multifunctional agent without a toxin (HS3215)

as well as with a toxin (HS0059) could capitalize on some of the findings described in the literature to take advantage of precise tumor-killing

through two important targets with different mechanisms of action.

is an immunosuppressive checkpoint and seen in macrophages, B lymphocytes, dendritic cells, monocytes, tumor-specific activated T cells,

myeloid cells and natural killer cells in circumstances of chronic antigen contact.

PD-L1 is one of the PD-1 ligands.

PD-L1 expression

has been shown to be a valuable biomarker for the prognosis and prediction of the sensitivity of PD-1/PD-L1 inhibitors.

The expression

of PD-L1 is mainly expressed in tumor cells, tumor-infiltrating cells and antigen-presenting cells in many cancers.

Despite the noteworthy

efficacy of PD-1/PD-L1 immune checkpoint inhibitors (“ICI”) in the treatment of tumors, some problems remain such as drug

resistance and adverse events.

Acquired drug resistance may present despite resuming or continuing treatment with anti-PD-1/PD-L1 immunotherapy.

The presence of drug resistance significantly reduces the efficacy of anti-PD-1/PD-L1 immunotherapy.

We believe exploring the mechanisms

of PD-1/PD-L1 ICI resistance may assist with the discovery of new immunotherapeutic strategies to control disease progression and provide

a more sustainable survival benefit for patients.

As such, we aim to further improve on PD-1 as a breakthrough technology by developing,

TH1940, a proprietary PD-1 Picobody with unique binding affinity differently than currently available PD-1 drugs.

We believe this unique

binding difference allows for novel therapeutic possibilities both as a stand-alone agent and in combination and that our tumor immunotherapy

based on PD-1 inhibition may become a future strategy for human cancers.

have deprioritized our previous preclinical candidate, HSB-1216, due to a strategic reprioritization to focus on therapeutics in high

unmet need cancers focused on novel epitopes of certain antitumor drug targets.

currently have an IND-approved transmucosal film product, TH104 in Phase 1 clinical development, two bispecific candidates and a Picobody

candidate in pre-clinical development.

currently have an IND-approved transmucosal film product, TH104, a Phase 2 ready clinical candidate and an oral biologic as well as

two bispecific biologics in pre-clinical development.

The following table summarizes our development candidate pipeline:

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Our business strategy comprises the following components:

TH104 as a transmucosal buccal film product for the treatment of chronic pruritis in PBC and other inflammatory diseases.

to advance TH3215 as an anti-HER2/HER3 BspAb for multiple tumor types including high unmet need cancers.

create a strategy to develop TH0059 as a bispecific monoclonal ADC specifically targeted to both HER2 and HER3 receptors in high

unmet need standard-of-care resistant tumors with a high capacity to metastasize.

a preclinical and clinical path forward for our third product candidate, TH1940, a unique PD-1 Picobody with unique binding differentiation

compared to full length antibodies for IO vulnerable tumors.

the discovery and development of next generation multi-specific (bi- and tri) antibodies with binding capabilities to novel epitopes

of combinations of HER2, HER3, PD-1, PD-L1, TROP2 and other validated targets with and without toxin delivery capacity to multiple

high unmet need rare cancers.

strategic collaboration opportunities to maximize the value of our pipeline to bring novel therapies to patients suffering from high

unmet need conditions.

and moderate-to-severe chronic pruritis

Develop TH104 as a transmucosal buccal film product for the treatment

of chronic pruritus in PBC and other inflammatory diseases.

Develop TH023 by optimizing the CMC pathway and planning

a Phase 1 first-in-human clinical trial through feedback from a non-US regulatory authority

Create a preclinical and clinical path forward for our early stage product candidate, HS1940, a novel PD-1/VEGF with binding differentiation compared to full length antibodies for IO vulnerable tumors.

Hasten the discovery and development of next generation multi-specific (bi- and tri) antibodies with binding capabilities to novel epitopes of combinations of HER2, HER3, PD-1 and other validated targets with and without toxin delivery capacity to multiple high unmet need rare cancers.

Pursue strategic collaboration opportunities to maximize the value of our

pipeline to bring novel therapies to patients suffering from high unmet need conditions.

and moderate-to-severe chronic pruritus

to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, PBC, is a

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an on-line survey focusing on certain features of patients’ itch respondents described their itch as “bugs crawling”

as well as more than 65% of participants reporting that the itch was worse at night, known as nocturnal pruritis.

Ladder for Pruritis in Primary Biliary Cholangitis

as well as more than 65% of participants reporting that the itch was worse at night, known as nocturnal pruritus.

Ladder for Pruritus in Primary Biliary Cholangitis

Hegade VS, Bolier R, Oude Elferink RPJ, et.

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LT, liver transplantation

current treatment ladder in pruritis for PBC shown above is the paradigm of therapy and if there is no response with one category of

current treatment ladder in pruritus for PBC shown above is the paradigm of therapy and if there is no response with one category of

drugs, typically patients “move up” the ladder.

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Bergasa N et.

Oral nalmefene therapy reduces scratching activity due to the pruritis of cholestasis:

Oral nalmefene therapy reduces scratching activity due to the pruritus of cholestasis:

a controlled study J Am Acad Dermatol 1999;41:431-4

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the itch circuitry is imbalanced in diseased conditions, pharmacological intervention can help suppress this phenomenon which occurs

in patients suffering from chronic pruritis.

in patients suffering from chronic pruritus.

Nalmefene crosses into the circulation via a proprietary buccal delivery by adhering the

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the marketed tablet in the literature including mild dizziness, headache and somnolence, nausea and vomiting.

second phase 1 study was a single-dose, single-center, open-label, parallel group design with 2 treatment groups of 2 different formulations

of TH104 with variable pH in sixteen normal healthy volunteers under fasting conditions.

The primary outcome measure was to determine

the effect of pH in the transmucosal buccal film on drug absorption profile evaluated from serial blood sample collections.

this study, the evaluation of TH104 transmucosal film given as an equal-labelled dose in 2 different pH formulations delivered buccally

to normal healthy volunteers under fasting conditions, had an insignificant effect on the performance of the film as measured by drug

concentrations in human plasma.

The low impact on pH shows that variations of oral pH due to inter-patient variability in future studies

would have a low impact on predictable drug absorption with regards to speed of delivery and drug action once absorbed into the systemic

were no new adverse events in these studies with events correlated with the previous phase 1 study and a safety profile consistent with

the literature.

launched a phase 1 pharmacokinetic trial for TH104 in early 2024 and intend to complete the study with a topline readout in 2Q24.

clinical data package is strengthened by the phase 1 clinical trials previously conducted outside of the U.S., which showed reliable

bioavailability of the active ingredient in TH104 via transmucosal film technology in healthy volunteers.

We intend to provide topline

data in 2024 for a phase 1 pharmacokinetic bridging study in the United States designed as a single-dose, single-center, open-label,

randomized 2-way crossover study of TH104 transmucosal buccal film and an intravenous dose of drug administered under fasting conditions,

with a 7 to 11-day washout period between doses.

Sixteen normal healthy volunteers will participate in the study.

The primary objective

is to evaluate the absolute bioavailability of TH104 as well as assess safety and tolerability of the formulation.

intend to complete a bridging pharmacokinetic phase 1 trial and a phase 2 proof-of-concept in PBC patients over approximately 12 months

after aligning with FDA on trial design.

We believe the completed phase 1 data coupled with the ongoing phase 1 pharmacokinetic bridging

study in the United States may complement a phase 2a efficacy study to be initiated in 3Q24 in moderate-to-severe chronic pruritis in

PBC as we begin engaging regulatory authorities in both the US and European Regulatory Authorities.

The phase 2a trial is planned as

a multiple ascending dose trial to assess the safety and tolerability of TH104 and will also evaluate the change from baseline in a validated

endpoint for itch intensity in pruritis studies.

Based on this data package, the Company expects to be able to initiate a registrational

trial in 2025 pending an FDA discussion on phase 2 results.

launched a phase 1 pharmacokinetic trial for TH104 in early 2024 and completed the study with a topline readout in 2Q24.

data package is strengthened by the phase 1 clinical trials previously conducted outside of the U.S., which showed reliable bioavailability

of the active ingredient in TH104 via transmucosal film technology in healthy volunteers.

Phase 1 trial was a single-dose, single-center, open-label, randomized 2-way crossover study comparing 16mg of TH104 with 1mg intravenous

nalmefene administered under fasting conditions, with a 7-day washout period between doses.

Twenty healthy subjects were enrolled to

complete both doses of the crossover design.

All 20 subjects completed TH104 buccal dosing, while 19 of 20 subjects also completed the

intravenous dosing.

The primary objective was to evaluate the absolute bioavailability of TH104, as well as to assess safety and tolerability.

from the study indicate that the primary endpoint of the absolute bioavailability (F) of TH104, or fraction (or percentage) of the administered

dose absorbed into the systemic circulation compared to an equivalent intravenous dose of nalmefene, was 0.459 (45.9%).

The median time

to maximum concentration (C max ) of TH104 was 2.0 hours, with rising concentrations beginning within minutes of dosing.

mean half-life (T 1/2 ) as measured in the blood of subjects was 14 hours after a single buccal administration of TH104, compared

to 9 hours for the 1mg intravenous dose of nalmefene.

data are consistent and within range of published findings of population PK data of nine Phase 1 studies of 243 subjects with extensive

blood sampling.

Furthermore, in the same analysis, receptor occupancy of oral dosing of nalmefene using a robust PK model

for nalmefene was developed where a single 20mg dose showed μ-opioid receptor occupancy was simulated to be within or above 60-90%

for up to 22-24 hours.

Company believes PK results from this Phase 1 trial show proportional kinetics consistent with published findings of oral and intravenous

formulations of nalmefene including F, C max , T 1/2 and potential receptor occupancy time, suggest TH104 could be

developed for once-daily dosing in a target population of moderate-to-severe chronic pruritus in PBC patients.

on the Phase 1 data, Type C meeting feedback from the U.S.

Food and Drug Administration (FDA) was received and reported by the

Company in June of 2024 for its planned Phase 2 clinical trial with TH104.

The feedback received as Type C feedback from the FDA

confirmed the Company’s plan to pursue a 505(b)(2) approval pathway for TH104, which permits inclusion of data from external

studies when the active ingredient is already approved in the United States.

The FDA also agreed that the nonclinical studies

submitted to the FDA in advance of the meeting appear sufficient to support the proposed Phase 2 clinical trial.

In addition, the

FDA provided feedback on study design and certain recommendations regarding PBC patient inclusion, the primary endpoint to assess

pruritus in these patients, and considerations for monitoring for adverse events in this patient population.

Based on this

interaction, we plan to conduct a hepatic impairment study in 2025 to fully evaluate the pharmacokinetic profile and safety in

certain stages of liver impairment, beginning with mild and moderate, and potentially severe impairment.

We also began some start up

activities for the Phase 2 trial with TH104 in moderate-to-severe chronic pruritus in PBC patients in early 2025 and have

incorporated feedback from the FDA into its clinical protocol.

The Company also received

positive feedback from a Scientific Advice meeting with the European Medicines Agency (EMA) that included guidance on the planned

Phase 2 trial to advance TH104.

The EMA interactions specifically focused on both the Phase 2 and Phase 3 clinical program of TH104.

Overall, the Agency noted that using Article 10(3), hybrid application, is acceptable and could enable referring to non-clinical and

some safety data from the approved products.

Regarding non-clinical information provided, the Agency endorsed the strategy presented

by the Company and noted that there is no need to conduct additional animal studies and considered human exposure to be adequate to

move forward.

The Agency found the design and main features of the proposed Phase 2 study overall acceptable with some comments

which were addressed by the Company subsequently.

The Agency also provided general guidance for the design of a future Phase 3

to the Centers for Disease control and Prevention Summary Health Statistics National Health Survey, more than 4 million patients suffer

from liver disease in the U.S.

and about 1.7 million suffer from pruritis, where PBC has the highest rate of prevalence.

and about 1.7 million suffer from pruritus, where PBC has the highest rate of prevalence.

We believe TH104

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and non-liver related diseases including fatty and alcoholic liver, non-alcoholic liver disease and certain types of hepatitis.

pruritis is significant in liver diseases (40% chronic pruritis;

pruritus is significant in liver diseases (40% chronic pruritus;

1.7 million patients affected) as well as chronic kidney diseases (24%

chronic pruritis;

1.3 million patients affected), hemodialysis as well as atopic dermatitis (40% pruritis;

chronic pruritus;

1.3 million patients affected), hemodialysis as well as atopic dermatitis (40% pruritus;

2.7 million patients affected).

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liver disease and certain types of hepatitis.

Chronic pruritis is significant in liver diseases as well as chronic kidney diseases, hemodialysis

Chronic pruritus is significant in liver diseases as well as chronic kidney diseases, hemodialysis

and atopic dermatitis.

pre-clinical, current lead product candidate, TH3215, is an anti-HER2/HER3 bispecific antibody candidate.

The ErbB or HER family of cell

surface proteins are some of the most well-known and validated oncology drug targets including ErbB2 or HER2 and Erb3 or HER3.

Our antibodies

against HER2 and HER3 bind to different domains of the extracellular portion of the proteins or epitopes with trastuzumab primarily binding

the ECD IV of HER2.

HER2 is a validated tumor antigen for antibody drug conjugates to treat HER2 positive cancers with two approved antibodies,

Roche/Genentech’s KADCYLA® and Daiichi Sankyo/AstraZeneca’s ENHERTU®.

Areas of interest for the development of TH3215

are as a treatment of solid tumors in which HER2 is overexpressed including breast cancer, colorectal cancer, endometrial cancer and

gastroesophageal cancer.

INT-023/TH023,

is an oral anti-tumor necrosis factor-alpha (TNF-α) monoclonal antibody, infliximab.

The product uses Intract Pharma’s Soteria ®

and Phloral ® delivery platform to deleiver infliximab as an oral product.

is a purified, recombinant DNA-derived chimeric IgG monoclonal antibody protein that contains both murine and human components that inhibit

Tumor necrosis factor-alpha is a signaling protein involved in acute phase reactions and systemic inflammation.

is sold by Janssen Biotech under the Remicade ® brand for numerous indications including Crohn’s disease, ulcerative

colitis, rheumatoid diseases and plaque psoriasis.

Traditionally administered through intravenous infusions, oral delivery of antibodies

such as infliximab is challenging due to the complexity of navigating such large molecules through the gastrointestinal tract.

aims to overcome these challenges using Intract’s delivery platform, making it possible to administer infliximab in a pill form.

TH023 enables the targeted delivery of infliximab directly to the colon or small intestine and the Company intends to pursue the CMC

plan in 2025;

subsequent to adequate formulation development analyses the Company intends to begin planning a human phase 1 trial to

be conducted outside the United States as an initial proof-of-concept.

early-stage lead product candidate, HS1940, is a proprietary IO biologic, in development targeting PD-1 and VEGF.

On November 21, 2022,

we entered into a research collaboration and product license agreement with Minotaur and a commercial license agreement with Taurus for

use of certain technology, including OmniAb antibodies, to advance Picobodies against novel, unreachable and undruggable epitopes in

high-value validated targets starting with PD-1.

The research and collaboration agreement and product license agreement are for the development

of proprietary targeted biologics, including TH 1940, against PD-1 and VEGF.

It is anticipated that we will collaborate with Minotaur

under the license from Taurus to discover, develop and advance biotherapeutics against high-value validated IO targets starting with

We extended this agreement in July of 2023 with an additional target (HER3) and an oncology target.

are bovine-derived antibody “knob” domains comprised of cysteine-rich ultralong complementary determining region H3 sequences

of 30-40 amino acids weighing ~3-4 KDa, which have the potential to access challenging undruggable epitopes better than full size antibodies

By extending the half-life of knobs to create HS1940, we believe we can more efficiently target novel epitopes with greater binding

affinity than approved anti-PD-1 antibodies.

We further believe that the development of HS1940 is a step toward enabling us to enter

the rapidly growing IO market with additional targets thereafter.

Proceedings of the National Academy of Sciences of the United States of America “The smallest functional antibody fragment:

CDR H3 antibody knob regions potently neutralize SARS-CoV-2”

is an anti-HER2/HER3 bispecific antibody candidate.

The ErbB or HER family of cell surface proteins are some of the most well-known and

validated oncology drug targets including ErbB2 or HER2 and Erb3 or HER3.

Our antibodies against HER2 and HER3 bind to different domains

of the extracellular portion of the proteins or epitopes with trastuzumab primarily binding the ECD IV of HER2.

HER2 is a validated tumor

antigen for antibody drug conjugates to treat HER2 positive cancers with two approved antibodies, Roche/Genentech’s KADCYLA®

and Daiichi Sankyo/AstraZeneca’s ENHERTU®.

Areas of interest for the development of HS3215 are as a treatment of solid tumors

in which HER2 is overexpressed including breast cancer, colorectal cancer, endometrial cancer and gastroesophageal cancer.

ErbB family of receptor tyrosine kinases, also known as Human Epidermal Growth Factor Receptor (“HER”) family, comprises

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the ABSI Know-How to Exploit the ABSI Products for the treatment, diagnosis, prediction, detection or prevention of disease in humans

and animals worldwide (as defined in the ABSI Agreement).

Pursuant to the ABSI Agreement, the parties shall form a committee to manage

the preclinical, investigational new drug enabling studies and such other activities as shall lead to the initiation of a Phase 1 clinical

trial of the ABSI Product.

The parties will collaborate on a Target-by-Target basis to identify and evaluate ABSI Products directed against

such Target with a view to identifying or generating suitable Products (as defined in the ABSI Agreement) for our Company to Exploit.

Upon completion of the Discovery Timeline (as defined in the ABSI Agreement) for a Target, subject to the terms and conditions of ABSI

Agreement, we shall exclusively own any ABSI Products against such Target.

In the event the committee determines that the discovery activities

are unsuccessful with respect to a Target, we may propose an additional target, which, upon approval by ABSI, shall replace a failed

The antibodies from ABSI we are licensing are intended to be developed as unique from the currently approved anti-HER2 antibodies

and may be incorporated into proprietary multi-format biologics (bi- and tri-specific antibodies, ADCs, CAR-T and CAR-NKs) against drug

resistant cancers including HER2-positive metastatic breast cancer, gastric cancer, lung cancer and ovarian cancer.

and animals worldwide (the “Territory”).

Pursuant to the ABSI Agreement, the parties shall form a committee to manage the

preclinical, IND-enabling studies and such other activities as shall lead to the initiation of a Phase 1 clinical trial of the ABSI Product.

The parties will collaborate on a Target-by-Target basis to identify and evaluate ABSI Products directed against such Target with a view

to identifying or generating suitable Products for our Company to Exploit.

“Target” means ErB2 (Her2) and ErB3.

Upon completion

of the Discovery Timeline for a Target, subject to the terms and conditions of ABSI Agreement, we shall exclusively own any ABSI Products

against such Target.

In the event the committee determines that the discovery activities are unsuccessful with respect to a Target, we

may propose an additional target, which, upon approval by ABSI, shall replace a failed Target, each such capitalized term as defined

in the BASI Agreement.

part of the ABSI Agreement, on July 26, 2023, we issued 1,674 shares of our common stock with a per share value of $149.34, representing

total compensation expense of $250,000.

March 11, 2024, we entered into an addendum to the ABSI Agreement to fund research services with quarterly payments of $50,000 beginning

March 18, 2024 with subsequent payments due on the 18 th of each calendar quarter.

the past decade, cancer therapy has seen significant innovations, and one class of therapeutics gaining significant attention is bispecific

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and antibody-dependent cellular phagocytosis.

second product candidate, TH0059, is a bispecific anti-HER2/anti-HER3 monoclonal ADC candidate.

Research studies elucidating the biology

of HER3 reveal that triggering of HER3 signaling stimulates tumor progression via augmentation of metastatic potential and induces treatment

failure in human tumors.

Mounting evidence supports HER3 as an important target and its activation is considered to be required to overcome

therapeutic resistance, enhance efficacy, and increase patient survival.

To date, to our knowledge, there is no FDA-approved HER3-targeted

therapy for cancer treatment.

Targeting both HER2 and HER3 with a blocking antibody is a strategy we intend to explore as we progress

our pipeline.

third product candidate, TH1940, is a proprietary IO biologic, in development targeting PD-1.

On November 21, 2022, we entered into a

research collaboration and product license agreement with Minotaur and a commercial license agreement with Taurus for use of certain

technology, including OmniAb antibodies, to advance Picobodies against novel, unreachable and undruggable epitopes in high-value validated

targets starting with PD-1.

The research and collaboration agreement and product license agreement are for the development of proprietary

targeted biologics, including TH 1940, against PD-1.

It is anticipated that we will collaborate with Minotaur under the license from

Taurus to discover, develop and advance biotherapeutics against high-value validated IO targets starting with PD-1.

We extended this

agreement in July of 2023 with an additional target (HER3) and an oncology target.

are bovine-derived antibody “knob” domains comprised of cysteine-rich ultralong complementary determining region H3 sequences

of 30-40 amino acids weighing ~3-4 KDa, which have the potential to access challenging undruggable epitopes better than full size antibodies

By extending the half-life of knobs to create TH1940, we believe we can more efficiently target novel epitopes with greater binding

affinity than approved anti-PD-1 antibodies.

We further believe that the development of TH1940 is a step toward enabling us to enter

the rapidly growing IO market with additional targets thereafter.

Proceedings of the National Academy of Sciences of the United States of America “The smallest functional antibody fragment:

CDR H3 antibody knob regions potently neutralize SARS-CoV-2”

Other Product Candidates

is a bispecific anti-HER2/anti-HER3 monoclonal ADC candidate.

Research studies elucidating the biology of HER3 reveal that triggering

of HER3 signaling stimulates tumor progression via augmentation of metastatic potential and induces treatment failure in human tumors.

Mounting evidence supports HER3 as an important target and its activation is considered to be required to overcome therapeutic resistance,

enhance efficacy, and increase patient survival.

To date, to our knowledge, there is no FDA-approved HER3-targeted therapy for cancer

Targeting both HER2 and HER3 with a blocking antibody is a strategy we intend to explore as we progress our pipeline.

intend to further develop our pipeline with novel bispecific monoclonal antibodies.

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occurring antibodies typically only target one epitope on one antigen.

the Avior Effective Date, we entered into the Avior Patent License Agreement with Avior pursuant to which we received an exclusive sublicensable

right and license to Licensed Patent Rights and Licensed Technology to, among other things, Develop, have Developed, make, have made,

use, sell, import, export and commercialize TH104 and TH103 and to practice the Licensed Technology in connection with the foregoing,

throughout the world.

Pursuant to the Avior Patent License Agreement, we shall pay Avior a mid six digit up front license fee within

ten days of the Avior Effective Date and an additional mid six digit license fee which shall be paid in four equal installments within

ten days of the end of each fiscal quarter following the Avior Effective Date.

In addition, we shall pay Avior a high single digit percentage

of any upfront payments received by us as a result of the grant of any sublicenses with respect to AV104.

We shall also pay Avior milestone

payments in the aggregate amount of $24,250,000 upon the occurrence of various development milestones.

Furthermore, we shall pay Avior

certain fees based upon sales milestones.

The payments for such sales milestones range from the low seven digits to the low eight digits

with higher sales being subject to higher fees.

Finally, we shall pay Avior royalties based on net sales.

Such royalties range from low

single digit percentages to mid single digit percentages with higher sales being subject to lower percentages.

The Avior Patent License

Agreement shall expire upon the expiration of the final payment obligation due to Avior as set forth in such agreement.

Upon the expiration

of the Avior Patent License Agreement, we shall have a fully paid, irrevocable, freely transferable and sublicensable worldwide license

to the Licensed Patent Rights and Licensed Technology to Develop, have Developed, make, have made, use, have used, sell, offer for sale,

have sold, import, have imported, export, have exported, commercialize or have commercialized any and all Licensed Products and to practice

the Licensed Technology worldwide.

Pursuant to the Avior Patent License Agreement, we may terminate the agreement at any time without

cause, upon 30 days’ prior written notice to Avior along with payment of the next unpaid Development Milestone Payment, if any.

Furthermore, either we or Avior may terminate the Avior Patent License Agreement (i) on written notice to the other party if the other

party materially breaches any provision of the Avior Patent License Agreement and fails to cure such breach within 30 days after the

breaching party receives written notice thereof or (ii) on written notice in the event that either party (A) becomes insolvent or admits

its inability to pay its debts generally as they become due;

(B) becomes subject, voluntarily or involuntarily, to any proceeding under

any domestic or foreign bankruptcy or insolvency law, which is not fully dismissed or vacated within 60 days;

or takes any corporate action for such purpose;

(D) makes a general assignment for the benefit of creditors;

or (E) has a receiver, trustee,

custodian or similar agent appointed by order of any court of competent jurisdiction to take charge of or sell any material portion of

its property or business.

Upon termination of the Avior Patent License Agreement, the license granted pursuant to such agreement shall

terminate and all rights in the Licensed Patent Rights and Licensed Products shall revert back to Avior.

June 17, 2024, we entered into a securities purchase agreement with certain accredited investors for the issuance and sale in a private

placement (the “June PIPE Offering”), consisting of an offering of shares of our common stock and/or pre-funded warrants

to acquire shares of our common stock and warrants to acquire shares of our common stock, with net proceeds of approximately $1.8 million.

See Note 3 to the consolidated financial statements included elsewhere in this Annual Report on Form 10-K for details regarding

these offerings.

signed a manufacturing agreement for clinical trial supply with regards to TH104 and the upcoming Phase 2 clinical trial on July 25,

2024 with a contract manufacturing organization located in North Carolina.

The development work includes both TH104 active product and

corresponding placebo batches expected to be released for clinical packaging by the end of the year.

September 30, 2024, we entered into a nonbinding, exclusive letter of intent (the “LOI”) with Intract pursuant to which we

will acquire all outstanding shares of common stock of the privately-held Intract for newly issued restricted common stock.

a biopharmaceutical company incorporated in England and Wales developing disruptive delivery solutions for oral biologics.

terms of the LOI, following the execution of a definitive agreement and the closing of the merger, Intract shareholders will own 49%

of the total equity in the combined entity, which will be named Tharimmune, Inc., with Intract becoming a wholly owned subsidiary.

believed the merger and business combination will form a best-in-class, transformative oral biologics company and the synergies between

our clinical-stage assets and Intract’s delivery platform will drive pipeline growth.

During the year ended December 31, 2024,

we paid $0.3 million in fees pursuant to the LOI agreement prior to cancellation.

November 30, 2024, the Company provided notice to Intract that it has terminated the non-binding, exclusive LOI to merge with Intract.

December 5, 2024, we entered into a securities purchase agreement with certain accredited investors for the issuance and sale in a

private placement (the “December PIPE Offering”), consisting of an offering of shares of our common stock and/or

pre-funded warrants to acquire shares of our common stock and warrants to acquire shares of our common stock, with gross proceeds of

approximately $2.02 million and net proceeds of approximately $1.83 million.

See Note 3 to the consolidated financial

statements included elsewhere in this Annual Report on Form 10-K for details regarding these offerings.

pharmaceutical and biotechnology industries are characterized by rapidly advancing technologies, intense competition, and a strong emphasis

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advance Picobodies against novel, unreachable and undruggable epitopes in high-value validated targets starting with PD-1.

and collaboration agreement and product license agreement are for the development of proprietary targeted biologics, including TH1940,

and collaboration agreement and product license agreement are for the development of proprietary targeted biologics, including HS1940,

against PD-1.

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epitopes better than full size antibodies can.

combining non-proprietary half-life extending methods which are linked to a PD-1 Picobody ™ to create TH1940, we believe

combining non-proprietary half-life extending methods which are linked to a PD-1 Picobody ™ to create HS1940, we believe

we could more efficiently target novel epitopes with greater binding affinity than currently approved anti-PD-1 antibodies.

believe that the development of TH1940 is a step toward enabling us to enter the rapidly growing immune-oncology market with additional

believe that the development of HS1940 is a step toward enabling us to enter the rapidly growing immune-oncology market with additional

targets thereafter.

Biomedical Research Institute Option Agreement

July 5, 2023, the ABSI Effective Date, we entered into the ABSI Agreement with ABSI pursuant to which ABSI granted us an exclusive royalty-bearing,

sublicensable license to the ABSI Patents and a non-exclusive, royalty-bearing, sublicensable license to the ABSI Know-How to Exploit

the ABSI Products for the treatment, diagnosis, prediction, detection or prevention of disease in humans and animals worldwide (each

as defined in the ABSI Agreement).

Pursuant to the ABSI Agreement, the parties shall form a committee to manage the preclinical, IND-

enabling studies and such other activities as shall lead to the initiation of a Phase 1 clinical trial of the ABSI Product.

will collaborate on a Target-by-Target basis to identify and evaluate ABSI Products directed against such Target with a view to identifying

or generating suitable Products (as defined in the ABSI Agreement) for our Company to Exploit.

“Target” means ErB2 (Her2)

and ErbB3 (HER3).

Upon completion of the Discovery Timeline (as defined in the ABSI Agreement) for a Target, subject to the terms and

conditions of ABSI Agreement, we shall exclusively own any ABSI Products against such Target.

In the event the committee determines that

the discovery activities are unsuccessful with respect to a Target, we may propose an additional target, which, upon approval by ABSI,

shall replace a failed Target.

Biomedical Research Institute Research and Development Collaboration and License Agreement

July 5, 2023 (the “ABSI Effective Date”), we entered into a Research and Development Collaboration and License Agreement

(the “ABSI Agreement”) with Applied Biomedical Science Institute (“ABSI”) pursuant to which ABSI granted us an

exclusive royalty-bearing, sublicensable license to the ABSI Patents and a non-exclusive, royalty-bearing, sublicensable license to the

ABSI Know-How to Exploit the ABSI Products for the treatment, diagnosis, prediction, detection or prevention of disease in humans and

animals worldwide (the “Territory”).

Pursuant to the ABSI Agreement, the parties shall form a committee to manage the preclinical,

IND- enabling studies and such other activities as shall lead to the initiation of a Phase 1 clinical trial of the ABSI Product.

parties will collaborate on a Target-by-Target basis to identify and evaluate ABSI Products directed against such Target with a view

to identifying or generating suitable Products for our Company to Exploit.

“Target” means ErB2 (Her2) and ErbB3.

Upon completion

of the Discovery Timeline for a Target, subject to the terms and conditions of ABSI Agreement, we shall exclusively own any ABSI Products

against such Target.

In the event the committee determines that the discovery activities are unsuccessful with respect to a Target, we

may propose an additional target, which, upon approval by ABSI, shall replace a failed Target, each capitalized term as defined in the

ABSI Agreement.

part of the ABSI Agreement, on July 26, 2023, we issued 1,674 shares of our common stock with a per share value of $149.34, representing

total compensation expense of $250,000.

March 11, 2024, we entered into an addendum to the ABSI Agreement to fund research services with quarterly payments of $50,000 beginning

March 18, 2024 with subsequent payments due on the 18 th of each calendar quarter.

Patent License Agreement

November 3, 2023 (the “Avior Effective Date”), we entered into the Avior Patent License Agreement with Avior pursuant to

which we received an exclusive sublicensable right and license to Licensed Patent Rights and Licensed Technology to, among other

things, develop, have developed, make, have made, use, sell, import, export and commercialize TH104 and TH103 and to practice the

Licensed Technology in connection with the foregoing throughout the world.

Pursuant to the Avior Patent License Agreement, we paid

Avior an up front license fee of $400,000 within ten days of the Avior Effective Date and an additional mid-six digit license fee

which shall be paid in four equal installments within ten days of the end of each fiscal quarter following the Avior Effective Date.

In addition, we shall pay Avior a high single digit percentage of any upfront payments received by us as a result of the grant of

any sublicenses with respect to TH104.

We shall also pay Avior milestone payments in the aggregate amount of $24.25 million upon the

occurrence of various development milestones (the “Development Milestone Payments”).

Furthermore, we shall pay Avior

certain fees based upon sales milestones.

The payments for such sales milestones range from the low seven digits to the low eight

digits with higher sales being subject to higher fees.

Finally, we shall pay Avior royalties based on net sales.

Such royalties

range from low single digit percentages to mid-single digit percentages with higher sales being subject to lower percentages.

Avior Patent License Agreement shall expire upon the expiration of the final payment obligation due to Avior as set forth in such

Upon the expiration of the Avior Patent License Agreement, we shall have a fully paid-up, irrevocable, freely

transferable and sublicensable worldwide license to the Licensed Patent Rights and Licensed Technology to Develop, have Developed,

make, have made, use, have used sell, offer for sale, have sold, import, have imported, export, have exported, commercialize or have

commercialized any and all Licensed Products and to practice the Licensed Technology worldwide.

Pursuant to the Avior Patent License

Agreement, we may terminate the agreement at any time without cause, upon 30 days’ prior written notice to Avior along with

payment of the next unpaid Development Milestone Payment, if any.

Furthermore, either we or Avior may terminate the Avior Patent

License Agreement (i) on written notice to the other party if the other party materially breaches any provision of the Avior Patent

License Agreement and fails to cure such breach within 30 days after the breaching party receives written notice thereof or (ii) on

written notice in the event that either party (A) becomes insolvent or admits its inability to pay its debts generally as they

(B) becomes subject, voluntarily or involuntarily, to any proceeding under any domestic or foreign bankruptcy or

insolvency law, which is not fully dismissed or vacated within 60 days;

for such purpose;

(D) makes a general assignment for the benefit of creditors;

or (E) has a receiver, trustee, custodian or similar

agent appointed by order of any court of competent jurisdiction to take charge of or sell any material portion of its property or

Upon termination of the Avior Patent License Agreement, the license granted pursuant to such agreement shall terminate and

all rights in the Licensed Patent Rights and Licensed Products shall revert back to Avior.

License Agreement

June 17, 2024 (the “Enkefalos Effective Date”), we signed a letter of intent (the “Enkefelos LOI”) to enter into

the Enkefalos License Agreement with Enkefalos Biosciences Inc.

pursuant to which we are licensing the global rights in all fields of

use for the products related to the compounds knows as cyclotides to deliver HER2 antibodies across the blood-brain barrier and all associated

know-how, technology, intellectual property and related information and constructs, and any associated authorized generic rights and

all related assets (collectively, the “Products” referred to in this letter as ENBI-01) from Enkefalos Biosciences, Inc.

Pursuant to the Enkefalos License Agreement, we paid Enkefalos an upfront license fee of $150,000 upon signing of the Enkefalos LOI and

an additional $150,000 license fee to be paid 6 months after the Enkefalos Effective Date.

In addition, we shall pay Enkefalos a $50,000

annual license fee and milestone payments in the aggregate amount of up to $8,500,000 upon the occurrence of various development milestones

(the “Enkefalos Development Milestone Payments”).

Furthermore, we shall pay Enkefalos royalties based on net sales.

royalties range from low-single digit percentages to mid-single digit percentages with higher sales being subject to lower percentages.

The Enkefalos License Agreement shall expire upon the expiration of the final payment obligation due to Enkefalos as set forth in such

Upon the expiration of the Enkefalos Patent License Agreement, we shall have a fully paid, irrevocable, freely transferable

and sublicensable worldwide license to the Licensed Patent Rights and Licensed Technology to Develop, have Developed, make, have made,

use, have used sell, offer for sale, have sold, import, have imported, export, have exported, commercialize or have commercialized any

and all Licensed Products and to practice the Licensed Technology worldwide.

Pursuant to the Enkefalos License Agreement, either the

Company or Enkefalos may terminate the Enkefalos License Agreement on written notice to the other party.

Upon termination of the Enkefalos

License Agreement, the license granted pursuant to such agreement shall terminate and all rights in the Licensed Patent Rights and Licensed

Products shall revert back to Enkefalos.

Patent License Agreement

September 11, 2024 (the “Intract Effective Date”), we entered into a Patent License Agreement (the “Intract

Agreement”) with Intract Pharma Limited, (“Intract”), pursuant to which the Company exclusively licensed

INT-023/TH023, an oral anti-Tumor Necrosis Factor-alpha (TNF-α) monoclonal antibody infliximab.

Under the terms of the Intract

Agreement, we licensed global development and commercialization rights (outside of South Korea) to Intract’s Soteria® and

Phloral® delivery platform along with an existing supply agreement for infliximab to be used in the oral product development

Pursuant to the Intract Agreement, Intract recieved an upfront license fee of $400,000 and is eligible to receive

additional payments upon an equity financing of the Company and for future development, regulatory and commercial

milestones, as well as mid-single digit royalties based on net product sales.

Under the terms of the Intract Agreement, we retain a

right of first refusal to continue development and commercialization after a Phase 2 clinical trial and have the option to exercise

the license to Intract’s platform for up to four additional targets.

The term of the Intract Agreement expires upon the final

payment obligation of the Company under the Intract Agreement.

In addition, the Intract Agreement may be terminated by us at any

time upon 90 days written notice to Intract.

Either party may terminate the Intract Agreement if the other party materially breaches

any provision of the Intract Agreement and fails to cure such breach within thirty (30) days after the breaching party receives

written notice thereof.

In addition, either party may terminate the Intract Agreement on written notice in the event that either

party declare:

(a) becomes insolvent or admits inability to pay its debts generally as they become due;

(b) becomes subject,

voluntarily or involuntarily, to any proceeding under any domestic or foreign bankruptcy or insolvency law, which is not fully

dismissed or vacated within sixty (60) days;

makes a general assignment for the benefit of creditors;

or (e) has a receiver, trustee, custodian or similar agent appointed by

order of any court of competent jurisdiction to take charge of or sell any material portion of its property or business.

authorities in the U.S.

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to the extent that our product is sold in a foreign country, we may be subject to similar foreign laws.

of February 20, 2024, we employed 2 full-time employees and 1 part-time employee.

of March 1, 2025, we employed 2 full-time employees and 1 part-time employee.

We are not a party to any collective bargaining agreements,

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effective as of September 25, 2023.

On November 17, 2023, we

filed a Certificate of Amendment to our Certificate of Incorporation, as amended, with the Delaware Secretary of State to effectuate a

1-for-25 reverse stock split of our issued and outstanding shares of common stock.

The reverse stock split became effective at 4:01 p.m.

November 17, 2023, we filed a Certificate of Amendment to our Certificate of Incorporation, as amended, with the Delaware Secretary of

State to effectuate a 1-for-25 reverse stock split of our issued and outstanding shares of common stock.

The reverse stock split became

effective at 4:01 p.m.

Eastern time on November 20, 2023.

All share data, per share data, and related information contained in this Annual Report on Form 10-K

has been retrospectively adjusted to reflect the effect of the reverse stock split.

December 31, 2023, the Company had one wholly-owned subsidiary, HB Pharma Corp.

All share data, per share data, and related information contained in this Annual

Report on Form 10-K has been retrospectively adjusted to reflect the effect of the reverse stock split.

May 22, 2024, we filed a Certificate of Amendment to our Certificate of Incorporation, as amended, with the Delaware Secretary of State

to effectuate a 1-for-15 reverse stock split of our issued and outstanding shares of common stock.

The reverse stock split became effective

Eastern time on May 24, 2024.

All share data, per share data, and related information contained in this Annual Report on

Form 10-K has been retrospectively adjusted to reflect the effect of the reverse stock split.

of December 31, 2024, the Company had one wholly-owned subsidiary, HB Pharma Corp.

website address is www.tharimmune.com .

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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