Tonix Pharmaceuticals Holding Corp. 10-K

ITEM 1 – BUSINESS This 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. Although 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). We 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. Forward-looking statements include, but are not necessarily limited to, those relating to: ● Our prospects are dependent on the success of TNX 102-SL for the management of Fibromyalgia (“FM”) and progressing our pipeline through development stages. To the extent regulatory approval of TNX-102 SL is delayed or not granted or, if approved, TNX-102 SL is not commercially successful, our business, financial condition and results of operations may be materially adversely affected and the price of our common stock may decline. ● The commercial success and market acceptance of our products, including the coverage of our products by payors and pharmacy benefit managers; our ability to successfully develop and execute our sales, marketing and non-personal and digital promotion strategies, including developing and maintaining relationships with customers, physicians, payors and other constituencies, the entry of other products competitive with our commercial products; ● Our ability to successfully execute business development, strategic partnerships, and investment opportunities to build and grow for the future; ● Our ability to achieve the expected financial performance from our marketed products Tosymra® and Zembrace® Symtouch®, as well as delays, challenges and expenses, and unexpected costs associated with integrating and operating this commercial business; ● The ability of our third-party manufacturers to manufacture adequate quantities of commercially saleable inventory and active pharmaceutical ingredients for each of our products, and our ability to maintain our supply chain; ● Our ability to raise additional capital, if necessary; 3 ● The timing and results of any future research and development efforts including potential clinical studies relating to any future product candidates; ● Our common stock maintaining compliance with Nasdaq’s minimum closing bid requirement of at least $1.00 per share. Business Overview Tonix Pharmaceuticals (“Tonix” or the “Company”) is a fully-integrated biopharmaceutical company developing and commercializing therapeutics to treat, and vaccines to prevent, disease and alleviate suffering. Tonix’s primary focus is to obtain U.S. marketing authorization for TNX-102 SL (cyclobenzaprine HCl sublingual tablet) 5.6 mg (2 x 2.8 mg tablets) for the management of fibromyalgia (“FM”) from the U.S. Food and Drug Administration (“FDA”). The FDA assigned a prescription drug user fee act (“PDUFA”) goal date of August 15, 2025, for a decision on marketing authorization for TNX-102 SL. In addition, we market two FDA-approved, prescription products for the treatment of acute migraine, and we are developing a robust pipeline of potential new products. Our pipeline has been generated from internal discovery, as well as licenses, acquisitions and collaborations with academic institutions and non-profit organizations. Our development portfolio is focused on central nervous system (“CNS”), disorders, but also consists of immunology, infectious disease and rare disease, product candidates. The CNS portfolio includes small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions and includes TNX-1300 which is in Phase 2 clinical development to treat cocaine intoxication partially funded by the U.S. National Institute on Drug Abuse (NIDA). Our immunology portfolio includes TNX-1500 (anti-CD40L monoclonal antibody, or mAb), a biologic which has shown encouraging results in Phase 1, which we plan to study to prevent organ transplant rejection and treat autoimmune diseases. Our infectious disease portfolio includes TNX-801 (horsepox, live virus vaccine) a vaccine in development to prevent smallpox and mpox (formerly known as monkeypox) and TNX-4200, which is a discovery program for broad spectrum antiviral drugs funded by a U.S Department of Defense contract for up to $34 million over five years. TNX-4200 is being developed at our R&D facility located in Frederick, Maryland, (“RDC”), which has biosafety level 2 (BSL-2) with BSL-3 components. Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication. Central Nervous System (CNS) Pipeline In October 2024, Tonix submitted a New Drug Application (“NDA”) to the FDA for TNX-102 SL 5.6 mg for the management of FM, a proprietary sublingual tablet formulation of cyclobenzaprine (“CBP”) designed for bedtime administration, and in December 2024, the FDA assigned a PDUFA goal date of August 15, 2025, for a decision on marketing authorization for TNX-102 SL. FM is a chronic pain disorder characterized by widespread pain, non-restorative sleep, fatigue and impaired cognition. TNX-102 SL is a centrally-acting, non-opioid analgesic designed for long-term bedtime use and has been studied in three Phase 3 trials using TNX-102 SL 5.6 mg, two studies reported statistically significant results. The FDA granted TNX-102 SL Fast Track designation in July 2024. We are preparing for a commercial launch of TNX-102 SL in the fourth quarter of 2025, conditional on FDA approval. In March 2024, Tonix announced it selected two contract manufacturing organizations (CMOs), one of which is Almac Pharma Services, a member of the privately owned Almac Group, as dual supply sources for the potential launch and commercialization of TNX-102 SL in the U.S. 4 TNX-102 SL also is being developed also as a treatment for acute stress reaction (“ASR”) and to prevent acute stress disorder (“ASD”) and posttraumatic stress disorder (“PTSD”) under a physician-initiated Investigational New Drug Application (“IND”) in partnership with the University of North Carolina (“UNC”) Institute for Trauma Recovery. In addition, TNX-102 SL has active INDs for the treatment of PTSD, agitation in Alzheimer’s disease (“AAD”), alcohol use disorder (“AUD”) and the management of multi-site pain associated with Long COVID (also known as Post-Acute SARS-CoV-2 or PASC). TNX-102 SL for AAD has been granted Fast Track designation by the FDA. We are currently not actively studying TNX-102 SL in PTSD, AAD or AUD. Tonix is continuously evaluating further indications for which TNX-102 SL could potentially provide benefit. Another CNS candidate in development is TNX-1300 (double-mutant cocaine esterase) which is in Phase 2 for the treatment of cocaine intoxication. TNX-1300 has been granted Breakthrough Therapy designation by the 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 (i.v.) cocaine. In August of 2022, we received a Federal Grant from the U.S. National Institute on Drug Abuse (“NIDA”) a part of the U.S. National Institutes of Health (“NIH”) to advance the development of TNX-1300 as a treatment for cocaine intoxication. Finally, we are developing TNX-1900 (intranasal potentiated oxytocin) for several CNS disorders through investigator-initiated studies. TNX-1900 is in development through investigator-initiated studies at Massachusetts General Hospital (“MGH”) for the treatment of binge eating disorder (“BED”), adolescent obesity, and bone health in pediatric autism. TNX-1900 is in development through an investigator-initiated study at the University of Washington for the treatment of social anxiety disorder. Immunology Pipeline Our lead candidate in the immunology pipeline is TNX-1500, an Fc-modified humanized monoclonal antibody (“mAb”), directed against CD40-ligand (CD40L, also known as CD154). TNX-1500 was engineered to modulate binding to Fc receptors with the goal of maintaining the activity of first-generation mAbs, yet with reduced risk of thrombotic complications. TNX-1500 is being developed to prevent organ transplant rejection as well as to treat autoimmune conditions. Topline results from a Phase 1 single ascending dose escalation study at 3 mg/kg, 10 mg/kg and 30 mg/kg of TNX-1500 in healthy volunteers was reported in the first quarter of 2025. 5 TNX-1500 has also been studied in combination with other immunosuppressive agents in allogeneic transplants in non-human primates at MGH. In experiments at MGH, 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. Results from 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. TNX-1500 also is being studied in combination with other immunosuppressive agents in xenogeneic organ transplants in non-human primates at MGH. In some of these studies, genetically engineered (“GE”) pigs in baboon transplants were treated with cold perfused ischemia minimization and a novel co-stimulation-based immunosuppressive regimen including TNX-1500. The results of these preclinical studies were encouraging and demonstrated the potential of GE pig hearts in the context of a clinically applicable regimen. The multi-GE pigs were provided by eGenesis and Revivicor. Revivicor is a subsidiary of United Therapeutics. Some results from the collaboration with MGH and eGenesis were published in the peer-reviewed journal, Nature in 2023. In March of 2024, MGH announced the first GE pig kidney transplant into a living recipient supported in part by the pre-clinical work with TNX-1500. Subsequently, several other GE pig kidney transplants have been performed. TNX-1500 treatment has not been used in any human transplant recipient. Our immunology pipeline also includes TNX-1700, a recombinant Trefoil Factor Family 2 (“hTFF2-HSA”) fusion protein that was licensed from Columbia University in 2019. TNX-1700 consists of TFF2 fused to human serum albumin 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. We presented data that show a murine version of TNX-1700 consisting of a fusion protein with murine serum albumin 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. We plan to request an INTERACT meeting with the FDA in 2025 to seek early guidance on program development. Infectious Disease Pipeline Our infectious disease portfolio includes vaccines based on our live virus vaccine or recombinant pox vaccine (“RPV”) platform. Live virus 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 minimally replicative vaccine based on synthesized horsepox, is in the pre-IND stage of development to protect against smallpox and mpox. In 2022 the WHO determined that the upsurge of mpox Clade IIb constituted a public health emergency of international concern (PHEIC). Mpox Clade IIB subsequently has become endemic in the U.S. mostly in populations of men who have sex with men. In August 2024, the WHO determined that the upsurge of mpox clade Ib in a growing number of countries in Africa constituted a PHEIC. The WHO reaffirmed the PHEIC status of mpox clade Ib in February of 2025. Mpox cases of the new clade Ib mpox have been detected in the United States and many other countries outside of Africa. Non-human primates vaccinated with TNX-801 were protected from mpox clade Ia in studies reported in the first quarter of 2020 and published in the peer-reviewed journal Vaccines in 2023. In September 2024, at the DoD’s MHSRS conference and in October 2024 at the World Vaccine Congress in Barcelona, Spain, Tonix presented new data on a potential mpox vaccine, TNX-801, demonstrating tolerability and no evidence of spreading to blood or tissues, even at high doses, in immunocompromised animals. After a single-dose vaccination, TNX-801 prevented clinical disease and lesions, and also decreased shedding in the mouth and lungs of animals after a lethal challenge with clade Ia monkeypox. These findings are consistent with TNX-801 inducing mucosal immunity and suggest TNX-801 may block forward transmission. In September 2024, the Company also announced that the WHO’s preferred target product profile (“TPP”) aligns with the characteristics of TNX-801. Key elements of the WHO draft TPP include single-dose, durable protection, administration without special equipment, and stability at ambient temperature. Other potential beneficial characteristics include the ability to limit forward transmission, use in case-contact vaccination strategies and suitability for use in immunocompromised individuals. 6 In October 2023, at the World Vaccine Congress - Europe, we reported that the TNX-801 vaccine was shown to be greater than 10 to 1,000-fold more minimally replicative than older vaccinia-based smallpox vaccines in both human primary cell lines and immunocompromised mice. In October 2024, at the World Vaccine Congress - Europe, we highlighted positive preclinical efficacy data of TNX-801, demonstrating tolerability in immunocompromised animals and showed that TNX-801 is unable to spread in blood or tissues in these animals, even at an approximately 100-fold higher dose than 20th century vaccinia vaccines in immune-comprised mice. These data were published in the peer-reviewed journal mSphere in 2024. TNX-801 also 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. The company’s Good Manufacturing Practice (“GMP”)-capable advanced manufacturing facility in Dartmouth, MA was purpose-built to manufacture TNX-801. The GMP suites are currently decommissioned but are ready to be reactivated in case of a national or international emergency. TNX-1800 is a live virus vaccine on the RPV platform that expresses the SARS-CoV-2 spike protein from the ancestral Wuhan strain, which has shown encouraging results in non-human primates. In June 2024, the Company announced preclinical data, demonstrating immunity and tolerability, during an oral keynote talk at the Vaccine Congress 2024. Like TNX-801, TNX-1800 is a live minimally replicative vaccine based on horsepox that is believed to provide immune protection with better tolerability than modern vaccinia viruses. TNX-1800 was selected by the NIH’s Project NextGen for inclusion in clinical trials as part of a select group of next generation COVID-19 vaccine candidates with the intent to identify promising vaccine platforms. If Tonix is able to provide TNX-1800 to NIH, they would conduct a Phase 1 trial and cover the full cost. However, Tonix has not prioritized the production of TNX-1800, so it is uncertain whether or how quickly this project will progress. The COVID-19 vaccines approved for use 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. 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. These data were published in the peer-reviewed journal Vaccines in 2023. 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. Tonix is developing potential broad-spectrum antiviral drugs in three programs: CD45-targeted therapeutics (TNX-4200), cathepsin inhibitors (TNX-3900) and viral glycan-targeted engineered biologics (TNX-4000). The DoD announced in December 2022 a plan to move beyond a ‘one bug, one drug’ approach and are seeking broad-spectrum drugs since it may be hard to predict which or how many viruses may be deployed on the battlefield. In July 2024 Tonix was awarded a contract with a potential for up to $34 million over five years by the Defense Threat Reduction Agency (DTRA), an agency within the DoD. The objective of the contract is to develop small molecule broad-spectrum antiviral agents for the prevention or treatment of infections to improve the medical readiness of military personnel in biological threat environments. Tonix’s program will focus on optimization and development of its TNX-4200 program, to develop an orally available CD45 antagonist with broad-spectrum efficacy against a range of viral families through preclinical evaluation. The program is expected to establish physicochemical properties, pharmacokinetics, and safety attributes to support an IND submission and to fund a first-in-human Phase 1 clinical study. Tonix plans to leverage previous research on phosphatase inhibitors, specifically compounds that target CD45, to optimize lead compounds for therapeutic intervention of biothreat agents and provide the government with a complete and cost-effective solution for a broad-spectrum medical countermeasure. Tonix’s premise is that partial inhibition of CD45 will provide optimal antiviral protection while requiring lower plasma drug concentrations, a lower dose, and a better safety profile. Tonix will utilize its state-of-the-art research laboratory capabilities, including a Biosafety Level 3 (BSL-3) lab and an Animal Biosafety Level 3 (ABSL-3) facility at the RDC, as well as experienced personnel in-house. 7 Rare Disease Pipeline Our rare disease portfolio consists of TNX-2900 (intranasal potentiated oxytocin) for Prader-Willi syndrome (“PWS”), a genetic disorder characterized by complex symptoms. The formulation technology for TNX-2900 was acquired from Trigemina, Inc. and licensed from Stanford University in 2020. The potentiated formulation includes magnesium, which has been shown in animal studies to potentiate binding of oxytocin to the oxytocin receptor. The therapeutic technology was licensed from Inserm, the French National Institute of Health and Medical Research. TNX-2900 was granted Orphan-Drug Designation by the FDA in the second half of 2023 and the IND was cleared by the FDA in the fourth quarter of 2023 and received Rare Pediatric Disease Designation on March 21, 2024. 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 PWS gene mutations. Marketed Medicines Our commercial portfolio consists of two FDA-approved prescription products for the treatment of migraine: Zembrace SymTouch (sumatriptan injection) 3 mg and Tosymra (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are both indicated for the treatment of acute migraine with or without aura in adults. Zembrace SymTouch is the only branded sumatriptan autoinjector professionally promoted in the United States and is designed for ease of use and favorable tolerability with a low 3 mg dose. Tosymra is a novel intranasal sumatriptan product formulated with a permeation enhancer that provides rapid and efficient absorption of sumatriptan. Tosymra was approved on the basis of bioequivalence to subcutaneous ( s.c. ) sumatriptan. Tonix Medicines is the only manufacturer with both a branded injectable and nasal spray indicated for the acute treatment of migraine with or without aura in adults. In September 2024, Tonix announced that the United States Patent and Trademark Office (USPTO) issued U.S. Patent No. 12,097,183 to the Company, claiming use of a pre-filled autoinjector comprising a composition of Zembrace® SymTouch® for treating migraines via subcutaneous administration. This patent, excluding possible patent term extensions, is expected to fortify protection and market exclusivity into 2036. Additionally, Tonix announced that the USPTO issued U.S. Patent No. 12,090,139 to the Company, claiming a pharmaceutical composition, a method of treating migraine via intranasal administration, and an intranasal delivery system for Tosymra®. This patent is expected to fortify protection and market exclusivity into 2030. In June 2024, the Company presented data at the 66th Annual Scientific Meeting of the American Headache Society (AHS) comparing real-world data with real-world usage of non-oral migraine products with the most recent AHS consensus statement. This data stressed the need for customizing treatment of migraine headaches to the needs of patients. Thus far, real world data show that conformity with the guidelines and the consensus statement have yet to be achieved but has the potential to be increased. The data show the use of non-oral drugs for treating an acute migraine attack was only 7% in 2012 and has decreased to below 4% in 2023, when the potential need for such drugs is anticipated to be a more substantial percentage of migraineurs based on epidemiological data. In 2024, Tonix Medicines launched a national educational campaign focusing on the link between migraine, gastroparesis, and the need for non-oral acute migraine therapies. Facilities Relating to our development programs, we own and operate the RDC in Frederick, Maryland consisting of one building totaling approximately 48,000 square feet. The RDC conducts research on CNS, immunology, and infectious disease candidates. The RDC facility is mostly biosafety level 2 (BSL-2), with some components designated BSL-3. We also own an Advanced Development Center (“ADC”) located in the New Bedford business park in Dartmouth, Massachusetts. This approximately 45,000 square foot BSL-2 facility is intended to accelerate development, clinical and commercial scale manufacturing of live-virus vaccines and biologics to support clinical trials. This facility was decommissioned in 2024 but Tonix has the ability to reactivate it should we choose to do so. 8 We are led by a management team with significant industry experience in commercialization and drug development. We complement our management team with a network of scientific, clinical, and regulatory advisors that includes recognized experts in their respective fields. Our Strategy Our strategy is to use our integrated development and marketing capabilities to advance innovative programs across multiple therapeutic areas through the drug development process, with the ultimate objectives of FDA approval and commercialization. The principal components of our strategy are to: ● Pursue CNS, rare disease, immunology, and infectious disease indications with high unmet medical need and significant commercial potential. We are pursuing multiple indications that are underserved with limited, effective treatment options. Our latest stage product candidate is TNX-102 SL for the management of FM, a condition which affects between 6-12 million adults in the U.S. Fewer than half of those treated for FM receive relief from the three FDA-approved drugs. 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 ASR, ASD, AAD and AUD, all of which are underserved by currently approved medications or have no approved treatment. Within CNS, Tonix is also developing TNX-1300 to treat cocaine intoxication and TNX-1900 to treat binge eating disorder, adolescent obesity, social anxiety disorder and improvement in bone health in autism. 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 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. 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 the acquisition of our two FDA-approved, marketed products for the treatment of acute migraine (Zembrace SymTouch and Tosymra) positions Tonix to build out commercial capability to market the migraine products and to launch TNX-102 SL for fibromyalgia. 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 will seek to enter into collaborations with pharmaceutical or biotechnology companies for commercialization. In preparation for the launch of TNX-102 SL, we have added to our team of professionals to market and distribute our products. Our commercial team is engaged in marketing and distributing our products and is also engaged in planning the launch of TNX-102 SL contingent on FDA approval. ● 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-1800, 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. We have filed patent applications for TNX-1500. We plan to opportunistically apply for new patents to protect our product candidates. 9 ● Pursue additional indications and commercial opportunities for our product candidates. We plan 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, and insulin resistance. Finally, our live virus platform using our RPV technology may be developed as vaccines for future pandemics, infectious diseases generally, in addition to smallpox and mpox, and for oncology applications. Disease and Market Overview Our 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 of development is set forth below. Central Nervous System Fibromyalgia (FM) Fibromyalgia is a common chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system, called central sensitization. Brain imaging studies have localized the functional disorder to the brain’s insular and anterior cingulate cortex. Fibromyalgia afflicts more than 10 million adults in the U.S., the majority of whom are women. Symptoms of fibromyalgia include chronic widespread pain, non-restorative sleep, fatigue, and brain fog (or cognitive dysfunction). Other associated symptoms include mood disturbances, including depression, anxiety, headaches, and abdominal pain or cramps. Individuals suffering from fibromyalgia often struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products. Fibromyalgia is now recognized as the prototypic nociplastic syndrome. Nociplastic pain is the third primary type of pain in addition to nociceptive pain and neuropathic pain. Many patients present with pain syndromes that are combinations of the three primary types of pain. Nociplastic syndromes can involve components of both central and peripheral sensitization. Fibromyalgia can occur without any identifiable precipitating event. However, many fibromyalgia cases follow one or more precipitating event(s) including: chronic nociceptive or neuropathic pain states; recovery from an infectious illness; a cancer diagnosis or cancer treatment; a metabolic or endocrine stress; or a traumatic event. In the cases of recovery from an infectious illness, fibromyalgia is considered an Infection-Associated Chronic Condition. In addition to fibromyalgia cases associated with other conditions or stressors, the U.S. National Academies of Sciences, Engineering, and Medicine, has concluded that fibromyalgia is a diagnosable condition that occurs after recovery from COVID-19 in the context of Long COVID. Fibromyalgia is also recognized as a Chronic Overlapping Pain Condition, due to shared symptoms with chronic fatigue syndrome/myalgic encephalomyelitis, irritable bowel syndrome, endometriosis, low back pain, post-concussive syndrome (also known as mild traumatic brain injury), chronic Lyme disease, chronic diabetic neuropathy and chronic post-herpetic neuralgia. We believe that diagnosing fibromyalgia in Long COVID patients will increase the potential market for TNX-102 SL as compared to market estimates from before the COVID-19 pandemic. Tonix has previously presented its analysis of real-world evidence from the TriNetX claims database suggesting that over 40% of Long COVID patients present with a constellation of symptoms that overlap with fibromyalgia. According to reports by Frost and Sullivan and Eversana 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, based on U.S. claims data, approximately 50% of patients diagnosed with FM are prescribed opioids within 18 months of diagnosis, despite the lack of evidence for their effectiveness and the risk of addiction and toxicity, including overdose. 10 Cocaine Intoxication 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. There are approximately 505,000 emergency room visits for cocaine abuse each year in the U.S., of which 61,000 require detoxification services. 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. Acute Stress Disorder (ASD) ASD is a mental health condition that can occur within the first month of experiencing a traumatic event. The symptoms are similar to those of PTSD and can affect both civilian and military populations. According to the National Center for PTSD, in the U.S. about 60% of men and 50% of women experience at least one trauma in their lives. In the U.S. alone, one-third of emergency department visits (40-50 million patients per year) involve evaluation after trauma exposures, and in a 2014 study involving U.S. veterans, 87% reported exposure to at least one potentially traumatic event during their service. No medications are currently available at or near the point of care to treat patients suffering from acute traumatic events and to support long-term health. 11 Immunology 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. 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. Gastric 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 36.4%. According to 2018-2021 data, approximately 0.8 percent of men and women will be diagnosed with stomach cancer during their lifetime. In 2021, there were an estimated 130,263 people living with stomach cancer in the U.S. As of 2024, there were approximately 26,890 new cases with 10,880 deaths. 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, malignancy begins in the mucosal layer and spreads outwards. The 5-year relative survival rate with colorectal cancer is 65.0%, per the National Cancer Institute. Based on 2018-2021 data, approximately 4.0 percent of men and women will be diagnosed with colorectal cancer during their lifetime. In 2021, there were an estimated 1,392,445 people living with colorectal cancer in the United States. As of 2024, there were approximately 152,810 new cases with 53,010 deaths. It is the 3 rd leading cause of cancer death in women, and 2 nd in men. Infectious Diseases Smallpox and Mpox 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. Mpox is an 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 Africa. Until 2022, only a few cases of mpox had been reported outside of Africa in patients who had been infected while in Africa. Starting in May of 2022, mpox clade II cases spread rapidly in the U.S. and other countries. The Clade II mpox affects mostly men who have sex with men in the U.S., where it has become endemic. In August 2024, the World Health Organization (“WHO”) declared mpox Clade Ib to be a public health emergency of international concern (PHEIC) due to an outbreak in the Democratic Republic of the Congo that spread globally, including to the United States. Clade Ib affects children as well as adults. The WHO reaffirmed the PHEIC status of mpox clade Ib in February of 2025. 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. Vaccines for 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. The U.S. National Academy of Sciences has recently issued a consensus report raising concerns about the state of new mpox vaccines in development. 12 COVID-19 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. New variants continue to sweep across the world in successive 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 protection. Rare Disease 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 morbidity and mortality. PWS is an orphan disease that occurs in approximately one in 15,000 births. There is currently no approved treatment for obesity and hyperphagia in adults and older children associated with PWS. Tonix’s Marketed Migraine Products Zembrace SymTouch and Tosymra – Acute Migraine in Adults In June 2023, we acquired two FDA-approved, marketed products from Upsher-Smith: Zembrace SymTouch (sumatriptan injection) 3 mg and Tosymra (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are both indicated for the treatment of acute migraine with or without aura in adults. Zembrace SymTouch is the only actively promoted brand of sumatriptan autoinjector in the United States. It has a unique low dose and has demonstrated onset of migraine pain relief in as few as 10 minutes (17% of patients vs. 5% for placebo). Zembrace SymTouch also demonstrated migraine pain freedom for 46% of patients (vs 27% for placebo) at 2 hours in a single-attack, double-blind study (N=230). Zembrace SymTouch currently has patent protection to 2036. Tosymra employs Intravail® permeation enhancer technology and is pharmacokinetically equivalent to 4 mg subcutaneous sumatriptan. Tosymra delivers migraine pain relief in as little as 10 minutes with just one spray for some patients (13% vs. 5% for placebo). Tosymra® currently has patent protection to 2031. 13 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 later stage product candidates that are in or nearing the clinic: Product Candidate Indication Stage of Development TNX-102 SL Fibromyalgia NDA submitted and accepted by FDA for review; PDUFA goal date of August 15, 2025 TNX-102 SL Acute Stress Reaction Phase 2 ready* – investigator-initiated IND TNX-1300 Cocaine Intoxication Mid-Phase 2 TNX-1900 Adolescent Obesity, Binge Eating Disorder, and Bone Health in Pediatric Autism; Social Anxiety Disorder Phase 2 currently enrolling* Phase 2 clinical phase completed* TNX-1500 Kidney Transplant Rejection Phase 1 topline reported 1Q’25 TNX-801 Smallpox and Mpox vaccine Preclinical, pre-IND TNX-1800 COVID-19 vaccine Preclinical, pre-IND TNX-2900 Prader-Willi Syndrome Phase 2 ready TNX-4200 Treatment or Prevention of Viral Disease Preclinical, pre-IND TNX-1700 Gastric and colorectal Cancer Preclinical, pre-IND *Investigator Initiated Studies TNX-102 SL Overview TNX-102 SL is a proprietary sublingual tablet formulation of cyclobenzaprine (“CBP”) that efficiently delivers CBP across the oral mucosal membrane into the systemic circulation. We have active IND’s for TNX-102 SL as a bedtime treatment for fibromyalgia, PTSD, of multi-site pain associated with Long COVID, AAD and AUD. The University of North Carolina has an investigator-initiated IND for ASD that references our INDs. 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 transmucosal absorption of CBP. The current TNX-102 SL sublingual tablets each contain 2.8 mg of CBP. 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. The active ingredient in TNX-102 SL is CBP, a multi-functional drug that blocks the serotonin-2A, alpha-1 adrenergic, muscarinic M1 and histaminergic H1 receptors. CBP is a tertiary amine tricyclic, that is the listed 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 or ER 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 (ER) CBP capsules taken once a day mimic, and flatten, the pharmacokinetic profile of three times per day CBP IR tablets. 14 Both the IR and ER tablet formulations of CBP result in accumulation of the persistent metabolite norcyclobenzaprine (“norCBP”) to blood levels that exceed the levels of CBP. NorCBP is a secondary amine tricyclic with a relatively stronger inhibitory activity of the norepinephrine transporter (NET) than the parent CBP. We believe that the accumulation of norCBP is undesirable in a medicine to be taken chronically at bedtime because norCBP accumulates over weeks, potentially interfering with the dynamic receptor effects of CBP and also may interrupt sleep quality by inhibiting the NET. We 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 pharmacokinetic 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 bypasses the “first pass” hepatic metabolism that swallowed medications undergo, results in a higher plasma level of CBP relative to norcyclobenzaprine during sleeping hours when taken at bedtime. We believe the dynamic changes in CBP after TNX-102 SL administration at steady state during chronic use contribute to its activity in treating fibromyalgia. We believe this is the first drug designed to increase the activity of the tertiary amine tricyclic parent and decrease the activity of the secondary amine tricyclic metabolite. 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. The most common adverse event was transient numbness in the mouth after TNX-102 SL administration. In September 2024, at the 11th Global Conference on Pharmaceutics and Novel Drug Delivery Systems (PDDS 2024), the Company announced data highlighting the proprietary formulation technology and pharmacokinetic properties of TNX-102 SL, including composition and methods patents based on the proprietary eutectic formulation of TNX-102 SL that are expected to provide market exclusivity until at least 2034 in the U.S., EU, Japan, China and other jurisdictions. The eutectic protects cyclobenzaprine HCl from interacting with the basifying agent that is also part of the formulation and required for efficient transmucosal absorption. The formulation of TNX-102 SL was designed specifically for sublingual administration and transmucosal absorption for bedtime dosing to target disturbed sleep, improve pain and other fibromyalgia symptoms, while reducing the risk of daytime somnolence. 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 (“FDCA”) with Amrix as the listed drug. We believe that TNX-102 SL has the potential to provide clinical benefit in fibromyalgia and PTSD and possibly other CNS indications that are underserved by currently marketed products or have no approved treatment. We have also successfully completed a bridging pharmacokinetic study in ethnic Japanese and Chinese volunteers that shows similar characteristics to our historical data in Caucasian volunteers. We believe this will satisfy one of the criteria for approval in Japan and China and will allow us to reference the U.S. efficacy data to support marketing applications in those countries. TNX-102 SL (cyclobenzaprine HCl sublingual tablets) – FM program We are developing TNX-102 SL as a bedtime treatment for FM. Clinical Development Plan NDA Acceptance and PDUFA Goal Date In October 2024, Tonix submitted its NDA to the FDA for TNX-102 SL 5.6 mg for the management of fibromyalgia and in December 2024, the FDA assigned a PDUFA goal date of August 15, 2025, for a decision on marketing authorization for TNX-102 SL. We are preparing for a commercial launch of TNX-102 SL in the fourth quarter of 2025, conditional on FDA approval. 15 Pre-NDA Meetings and Fast Track Designation In July 2024, Tonix was granted Fast Track designation by the FDA for TNX-102 SL for FM. The designation validates that FM is a serious condition and that TNX-102 SL has the potential to address this unmet medical need. Tonix previously announced alignment with the FDA regarding the content of its proposed NDA submission, following completion of the Company’s pre-NDA meetings. During the second quarter of 2024, Tonix successfully completed two positive pre-NDA meetings with the FDA for TNX-102 SL for the management of fibromyalgia. The first, with minutes announced in June 2024, was a Type B Chemistry, Manufacturing, and Controls (CMC) meeting to seek alignment and agreement with the FDA on key CMC topics to support the planned NDA submission for TNX-102 SL. Based on formal meeting minutes, the Company believes it is aligned with the FDA on proposed drug substance and drug product commercial specifications, shelf life assignment, manufacturing and commercial drug packaging. At the second pre-NDA meeting announced in July 2024, the Company and the FDA aligned on nonclinical, clinical pharmacology and clinical matters and agreed that the proposed data package is sufficient to support the NDA submission. Completed Phase 3 RESILIENT Study (F307) with Statistically Significant Improvement in Primary Endpoint of Pain Reduction The first patient was enrolled in the pivotal Phase 3 RESILIENT study in April 2022. The RESILIENT study was 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 enrolled 457 participants in the U.S. 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 RESILIENT study achieved statistical significance on the pre-specified 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]: -1.8 [0.12] units) versus placebo (-1.2 [0.12] units), analyzed by mixed model repeated measures with multiple imputation (LS mean [SE] difference: -0.7 [0.16] units, p=0.00005). In addition, all pre-specified sensitivity analyses of the primary endpoint were statistically significant (p≤0.001). We observed reduction in pain across all weeks of the 14-week study, with nominal p<0.01 for every week. The rapid onset of action with separation from placebo at Week 1 was sustained throughout all weeks of dosing. TNX-102 SL was well tolerated and consistent with prior trials, with no new safety signals observed. Among participants randomized to the TNX-102 SL and placebo arms, 81.0% and 79.2%, respectively, completed the 14-week dosing period. As expected, based on prior TNX-102 SL studies, administration site reactions were the most commonly reported adverse events and were higher in the TNX-102 SL treatment group. Hypoaesthesia oral and paraesthesia oral, or tongue and mouth numbness or tingling, product taste abnormal (typically a bitter aftertaste upon dosing), and tongue discomfort were local effects nearly always temporally related to dose administration and transiently expressed (<60 minutes) in most occurrences. The only treatment-emergent adverse events that occurred at a rate of 3.0% or greater in either arm were these four oral adverse events, along with COVID-19, somnolence, and headache. Adverse events resulted in premature study discontinuation in 6.1% of those who received TNX-102 SL compared with 3.5% of placebo recipients. There were a total of seven serious adverse events in five patients, five of which were experienced by three patients in the placebo arm, and two of which were in the TNX-102 SL arm. Of the two in the TNX-102 SL arm, one was renal cancer, deemed unrelated to study drug, and the other was acute pancreatitis with onset 14 days after dosing was completed, reported as possibly related to study drug, and was resolved before the final study visit. 16 Completed Phase 3 RALLY Study (F306) 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 designed to enroll approximately 670 patients across approximately 40 U.S. sites. 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. 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. 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 (~80% higher in each), which we believe may have been impacted by conducting the study in the period of highest mortality across the U.S. from the COVID-19 pandemic (September 2020 through March 2021 for the interim analysis sample). Completed Phase 3 RELIEF Study (F304) with Statistically Significant Improvement in Primary Endpoint of Pain Reduction In 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 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; odds ratio [95% CI]: 1.67 [1.16, 2.40]; p=0.006, uncorrected). 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; p<0.001). For the PROMIS Sleep Disturbance instrument, TNX-102 SL was also nominally significant over placebo on T-scores (LS mean difference: -2.9 [0.82] units; p<0.001). The effect sizes on the diary sleep quality 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 prior 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 studies, administration site reactions are the most commonly reported adverse events and were higher in the TNX-102 SL treatment group, including rates of hypoaesthesia oral (17.3% vs. 0.8%), oral pain/discomfort (11.7% v. 2.0%), product taste abnormal (6.5% vs. 0.4%), and paraesthesia oral (5.6% v. 0.4%). Hypoaesthesia or paraesthesia oral and product taste abnormal were local administration site effects nearly always temporally related to dose administration and transiently expressed (<60 minutes) in most 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 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 case of pneumonia secondary to an infection. 17 Global NDA Requirements 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 new chemical entity (NCE). In 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. 18 The F108 Phase 1 study was initiated in March 2022 and the clinical phase was completed in May 2022. Since the similarity in PK profile between people of Japanese and Chinese descent was confirmed, the PK data from the two ethnic groups were pooled as for Asian data (n=20) and compared retrospectively with the Caucasian study data from Study TNX-CY-F110 (n=16). The Asian/Caucasian geometric mean ratios of cyclobenzaprine Cmax, AUC 0-T and AUC 0-∞ were between 0.9 and 1.11 after both the 5.6 mg dose and the 2.8 mg dose. The 90% CI of Asian/Caucasian geometric mean ratios for Cmax, AUC 0-T and AUC 0-∞ , were all within the formal narrow equivalence limit of 0.8 to 1.25 after both the 5.6 mg dose and 2.8 mg dose, respectively. These results support similarity in cyclobenzaprine PK between Asian (pooled Japanese and Chinese) and Caucasian samples. Long-Term Safety Exposure Study for TNX-102 SL In 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 open-label extension studies of the PTSD program. Based on the FDA’s guidance, the long-term safety exposure studies in PTSD was used to support the NDA for the management of fibromyalgia. Manufacturing of TNX-102 SL 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 fibromyalgia market. During the second quarter of 2024, Tonix successfully completed a pre-NDA meeting with the FDA for TNX-102 SL for a Type B Chemistry, Manufacturing, and Controls (CMC) meeting to seek alignment and agreement with the FDA on key CMC topics to support the planned NDA submission for TNX-102 SL. Based on formal meeting minutes, the Company believes it is aligned with the FDA on proposed drug substance and drug product commercial specifications, shelf life assignment, manufacturing and commercial drug packaging. In March 2024, Tonix announced it selected two contract manufacturing organizations (CMOs), one of which is Almac Pharma Services, a member of the privately owned Almac Group, as dual supply sources for the potential launch and commercialization of TNX-102 SL in the U.S. TNX-102 SL – Acute Stress Disorder Program TNX-102 SL is being developed as a bedtime treatment for ASR in collaboration with the University of North Carolina under an investigator-initiated IND. Phase 2 OASIS Study This investigator-initiated study will be conducted by the University of North Carolina Institute for Trauma Recovery. The University of North Carolina has been awarded a $3 million grant from the DoD to investigate the potential of Tonix’s TNX-102 SL to reduce the frequency and severity of adverse effects of acute trauma. The proposed Optimizing Acute Stress reaction Interventions with TNX-102 SL (OASIS) trial will examine the safety and efficacy of TNX-102 SL to reduce adverse posttraumatic neuropsychiatric sequelae among patients presenting to the emergency department (“ED”) after a motor vehicle collision. The trial will enroll approximately 180 individuals who acutely experienced trauma at ED study sites across the U.S. and participants will be randomized in the ED to receive a two-week course of either TNX-102 SL or placebo. We expect enrollment in the OASIS study to begin in the first half of 2025. The OASIS trial will examine the safety and efficacy of TNX-102 SL to reduce adverse posttraumatic neuropsychiatric sequelae among patients in the ED after a motor vehicle collision. A fourteen day course of bedtime TNX-102 SL will be tested in the immediate aftermath of motor vehicle collision trauma. The study will test the potential for TNX-102 SL to target trauma-related sleep disturbance and its ability to facilitate recovery from ASR and to prevent PTSD. The results may ultimately provide military personnel with a new treatment option that, when administered in the early aftermath of a traumatic event to individuals with ASR symptoms, improves warfighter function. The OASIS trial will build upon a foundation of knowledge and infrastructure developed through the University of North Carolina-led, $40 million AURORA initiative. The AURORA study is a major national research initiative to improve the understanding, prevention, and recovery of individuals who have experienced a traumatic event. AURORA is supported by funding from the NIH, leading brain health nonprofit One Mind, private foundations, and partnerships with leading tech companies such as Mindstrong Health and Verily Life Sciences, the health care arm of Google’s parent company Alphabet. 19 Initiation of patient enrollment in the proposed investigator sponsored OASIS trial is anticipated in the first half of 2025. The FDA granted IND clearance in the first quarter of 2024. In August 2024 at the DoD’s MHSRS conference, the Company presented clinical data and rationale supporting the potential for TNX-102 SL to be studied for the treatment of ASR and prevention of PTSD. Prior studies showed that treatment with TNX-102 SL showed effects on sleep and PTSD symptoms in PTSD patients at two and four weeks. This supportive data on the effects of TNX-102 SL on reducing PTSD symptoms suggest early intervention immediately after trauma using TNX-102 SL has the potential to reduce ASR/ASD symptoms which are similar to those of PTSD. Data from these trials support testing of TNX-102 SL within 24 hours of index trauma for effects on ASR symptoms and the subsequent incidence of newly developed PTSD. TNX-1300 – Cocaine Intoxication 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. 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. 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. 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 50 mg i.v . challenge. In August 2022, we announced that we received a Cooperative Agreement grant from NIDA, part of NIH, to support development of TNX-1300. 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 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 manufactured Phase 2 drug product clinical supply. We initiated a Phase 2 clinical trial, CATALYST, of TNX-1300 in the third quarter of 2024. The Phase 2 trial is a single-blind, placebo-controlled, proof-of-concept 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. Because of the challenges of recruiting eligible patients into this study, we are not guiding to a timeline for completion of enrollment or topline data. TNX-1900 –Adolescent Obesity, Binge Eating Disorder. Social Anxiety and Bone Health in Autism TNX-1900 (intranasal potentiated oxytocin) is a proprietary formulation of oxytocin primarily in development under investigator-initiated INDs for the treatment of adolescent obesity, binge eating disorder, bone health in pediatric autism, and social anxiety disorder. 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. 20 Oxytocin 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 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. With 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. There are three ongoing Phase 2 investigator-initiated studies enrolling at MGH: the POWER study for the treatment of adolescent obesity, the STROBE study for the treatment of BED, and the BOX study for the treatment of bone health in pediatric autism. In addition to the studies at MGH, University of Washington is conducting an investigator-initiated study of TNX-1900 in SAD using functional MRI, in which the clinical phase has been completed, and data analyses are in progress. TNX-1500 – 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. CD40-ligand 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. No mAb 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. TNX-1500 was engineered to modulate binding to Fc receptors with the goal of maintaining the activity of first-generation monoclonal antibodies (mAbs), yet with reduced risk of thrombotic complications. TNX-1500 is being developed as a prophylaxis against organ transplant rejection as well as to treat autoimmune conditions. The IND was cleared for the prevention of kidney transplant, and a Phase 1 single ascending dose escalation study at 3 mg/kg, 10 mg/kg and 30 mg/kg of TNX-1500 in healthy volunteers was initiated in the second quarter of 2023. The objectives of the Phase 1 trial were to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenous TNX-1500, as well as to support dosing in a planned Phase 2 trial in kidney transplant recipients. We reported positive topline data related to the Phase 1 in February of 2025. TNX-1500 showed suppression of the primary and secondary antibody responses to KLH antigen challenges for the 10 and 30 mg/kg doses. Additionally, preliminary pharmacokinetic results showed mean half-life (t 1/2 ) for the 10 mg/kg and 30 mg/kg dose groups of 34-38 days, consistent with monthly dosing. In healthy volunteers, TNX-1500 was generally well-tolerated with a favorable safety profile. Anti-CD40L has multiple potential indications in addition to solid organ and bone marrow transplantation including autoimmune diseases: potential pipeline in a product. Tonix plans to discuss these results with the FDA in an End-of-Phase 1 meeting. Pending alignment with the FDA, a Phase 2 study of TNX-1500 in kidney transplant recipients will be pursued. TNX-1500 has also been studied in combination with other immunosuppressive agents in allogeneic transplants in non-human primates at MGH. In experiments at MGH, 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. Results from 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. Some results from this collaboration were published in the peer-reviewed journal, American Journal of Transplantation in 2023. In June 2024, at the American Transplant Congress 2024, Tonix announced data demonstrating the combined use of TNX-1500 and anti-CD28 monoclonal antibody, VEL-101 is associated with durable protection and graft survival and function in a nonhuman primate model. Further data demonstrated that TNX-1500 has promise to prevent rejection of 9-, or 10-gene-edited (GE) pig hearts. All research has been directed by the faculty of the Center for Transplantation Sciences at Massachusetts General Hospital. 21 TNX-1500 also is being studied in combination with other immunosuppressive agents in xenogeneic organ transplants in non-human primates at MGH. In some of these studies, genetically engineered (“GE”) pigs in baboon transplants were treated with cold perfused ischemia minimization and a novel costimulation-based immunosuppressive regimen including TNX-1500. The results of these preclinical studies were encouraging and demonstrated the potential of genetically engineered pig hearts in the context of a clinically applicable regimen. The multi-GE pigs were provided by eGenesis and Revivicor. Revivicor is a subsidiary of United Therapeutics. Some results from the collaboration with MGH and eGenesis were published in the peer-reviewed journal, Nature in 2023. In March of 2024, MGH announced the first GE pig kidney transplant into a living recipient supported in part by the pre-clinical work with TNX-1500. TNX-1500 therapy was not used in the human transplant recipient. In pre-clinical experiments at MGH, TNX-1500 is being studied as monotherapy or in combination with immunosuppressive drugs in heart and kidney organ transplants in animals. The data demonstrates that TNX-1500 showed activity in preventing organ rejection and was well tolerated in animals. Blockade of CD40L with TNX-1500 monotherapy consistently prevented pathologic alloimmunity in animal models of cardiac and kidney allograft model without evidence of clinical thrombosis. In 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. 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. Remicade® and Simponi® are trademarks of Janssen; Humira® is a trademark of AbbVie Inc.; Cimzia® is a trademark of UCB S. A.; Enbrel®, Prolia® and Xgeva® are trademarks of Amgen Inc. TNX-1700 — Gastric and Colorectal Cancers TNX-1700 is a recombinant Trefoil Family Factor 2 (hTFF2-HSA) fusion protein in development to treat gastric and colorectal cancers. We 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 colorectal cancers. The licensed patents are directed to TFF2 compositions and methods of treatment. The licensed patents U.S. Patent No. 10,124,037 and U.S. Patent No. 11,167,010. 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.” The PCT application is now nationalized in 12 countries. 22 Preclinical data has shown that mTFF2-CTP augmented the efficacy of mAb anti-PD-1 therapy. Anti-PD-1 in combination with mTFF2-CTP showed greater anti-tumor activity in PD-L1-overexpressing mice. The mechanism of action is to suppress myeloid-derived suppressor cells and activate anti-cancer CD8+ T cells, which is different from checkpoint inhibitors. There is potential synergy with anti-PD-1 or anti-PD-L1 mAbs. TNX-801 –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. Though it shares structural characteristics with vaccinia-based vaccines, TNX-801 has unique properties that we believe indicate potential safety advantages over existing live replicating vaccinia virus vaccines, which have been associated with adverse side effects 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 and mpox. 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®, the only non-replicating virus vaccine, is currently approved by the FDA to protect against smallpox and mpox. Jynneos® requires two-doses, with an efficacy of approximately 35% after one dose. During the most recent mpox outbreak in the United States, dropout between doses was 24%. 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. We also believe that TNX-801 would require only one dose. 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. The Bipartisan Commission on Biodefense (2024) noted that “Smallpox and other orthopoxviruses pose significant threats to the United States and the world due to their potential for weaponization, accidental release, and vulnerability of populations who stopped routinely vaccinating against smallpox in the 1970s” (Bipartisan Commission on Biodefense). 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. Mpox has become endemic in the U.S. since it spread in the U.S. and other countries outside of Africa, mostly in populations of gay men. In August 2024, the WHO determined that the upsurge of mpox in a growing number of countries in Africa constitutes a public health emergency of international concern (PHEIC), the second such declaration in the past two years in response to transmission of the virus. Mpox cases of the new clade Ib mpox have since also been detected in multiple countries outside of Africa, including the U.S.. Animals vaccinated with TNX-801 were protected from mpox in studies reported in the first quarter of 2020. These data were published in the peer-reviewed journal Vaccines in 2023. In November 2024, Tonix announced that it has entered into a sponsored research agreement with the Kenya Medical Research Institute (KEMRI) to design, plan and seek regulatory approval for a Phase 1 clinical study in Kenya to test the safety, tolerability, and immunogenicity of TNX-801 as a vaccine to prevent mpox and smallpox. Tonix will be the sponsor and KEMRI will lead the execution of the proposed clinical trial. In September 2024, at the DoD’s MHSRS conference and in October 2024 at the World Vaccine Congress in Barcelona, Spain, Tonix presented new data on potential mpox vaccine, TNX-801, demonstrating tolerability and no evidence of spreading to blood or tissues, even at high doses, in immunocompromised animals. After a single-dose vaccination, TNX-801 prevented clinical disease and lesions, and also decreased shedding in the mouth and lungs of animals after a lethal challenge with clade Ia monkeypox. These findings are consistent with TNX-801 inducing mucosal immunity and suggest TNX-801 has the ability to block forward transmission. In September 2024, the Company also announced that the WHO’s preferred TPP aligns with the characteristics of TNX-801. Key elements of the WHO draft TPP include single-dose, durable protection, administration without special equipment, and stability at ambient temperature. Other potential beneficial characteristics include the ability to limit forward transmission, use in case-contact vaccination strategies and suitability for use in immunocompromised individuals. 23 In August 2024, Tonix and Bilthoven Biologicals, part of the world’s largest vaccine manufacturer the Cyrus Poonawalla Group, which includes the Serum Institute of India, announced a collaboration to advance TNX-801. In October 2023, at the World Vaccine Congress - Europe, we reported that the TNX-801 vaccine was shown to be greater than 10 to 1,000-fold more minimally replicative than older vaccinia-based smallpox vaccines in both human primary cell lines and immunocompromised mice. Similar data was also published in the peer-reviewed journal mSphere which presented data demonstrating that TNX-801 is less virulent than 20th Century vaccinia vaccines in immune-compromised mice. In August 2023 we received pre-IND meeting written responses from the FDA. Tonix believes the FDA feedback provides a path to agreement on the design of a Phase 1/2 study and the overall clinical development plan. The Phase 1/2 clinical trial will assess the safety, tolerability, and immunogenicity of TNX-801, following the submission and clearance of an IND. We are actively working to develop a vaccine meeting cGMP quality to support a clinical study. In 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. These results were published in the peer-reviewed journal Viruses in 2023. We hold a U.S. 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. 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. TNX-801 also 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. The company’s Good Manufacturing Practice (GMP)-capable advanced manufacturing facility in Dartmouth, MA was purpose-built to manufacture TNX-801 and the GMP suites are ready to be reactivated in case of a national or international emergency. TNX-1800 – COVID-19 Vaccine TNX-1800 is a minimally replicative, live virus vaccine based on our RPV platform that expresses the SARS-CoV-2 spike protein from the ancestral Wuhan strain. TNX-1800 is being further developed to rapidly address new variants as they emerge. The vaccine platform itself can carry a payload of genes. The vaccine protects against COVID-19 by eliciting a durable T cell, humoral and mucosal immune response. It is delivered in only one dose. In November 2023, Tonix announced that the NIAID, a part of the NIH, will conduct a Phase 1 clinical trial with TNX-1800 as part of the Project NextGen Covid-19 Vaccine initiative. This NIAID/NIH program is funded to take selected NextGen vaccine candidates into Phase 1 and Phase 2 trials. Because of extensive reviews of NIH programs, the future of this program is uncertain. 24 The COVID-19 vaccines that are approved for use 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 limited ability to block the spread of infection (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 (e.g. smallpox). The TNX-1800 vaccine development plan is wholly consistent with priority vaccine attributes advanced by the White House Office of Science and Technology Policy’s Pandemic Preparedness Plan from September 2021, the National Biodefense Science Board report from August 2023, and the BARDA Strategic Plan 2022-2026. Tonix believes its RPV platform can address a wide variety of disease targets of public health interest. The results of an animal study data showing the protective effect of TNX-1800 vaccine was published in the peer-reviewed journal Vaccines in 2023 and show that TNX-1800 induces complete protection against SARS-CoV-2 infection as well as evidence that indicates an impact on spread of infection. These data also 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 has also began undertaking studies to show attenuation of the RPV platform itself in order to evaluate the potential use of the live vaccine platform in the immunocompromised host by the use of mouse model system. These data (detailed below) demonstrate that the RPV vaccine platform that is used for TNX-1800 is >10- to 1,000-fold more minimally replicative than older VACV-based smallpox vaccines in human primary cell lines and immunocompromised mice. We received pre-IND meeting written responses from the FDA in 2021 regarding our investigational plan to establish the safety and effectiveness evidence in support of the licensure of TNX-1800. We believe that the FDA feedback provides a clear pathway forward towards utilizing its underlying RPV platform for a COVID-19 vaccine. We announced the issuance of U.S. Patent for TNX-801 smallpox and mpox vaccine and 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, and also expect 12 years of non-patent-based exclusivity under PPACA. At the World Vaccine Congress in October 2023, Tonix presented its positive, published non-human primate data for the TNX-1800 (spike from Wuhan strain) from animal challenge studies using live SARS-CoV- 2. 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. 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-dose vaccine in humans. These data were published in the peer-reviewed journal Vaccines in 2023. Additional studies have been undertaken to show attenuation of the RPV platform alone (TNX-801) in order to evaluate the potential use of this live vaccine in the immunocompromised host. These data demonstrate that the RPV platform used with TNX-1800 is >10- to 1,000-fold more minimally replicative than older VACV-based smallpox vaccines in human primary cell lines and immunocompromised mice. TNX-4200 – Broad-Spectrum Antiviral Tonix is developing CD45-targeted therapeutics (TNX-4200). In July 2024 Tonix was awarded a contract with a potential for up to $34 million over five years by DTRA. The objective of the contract is to develop small molecule broad-spectrum antiviral agents for the prevention or treatment of infections to improve the medical readiness of military personnel in biological threat environments. Tonix’s program will focus on optimization and development of its TNX-4200 program, to develop an orally available CD45 antagonist, with broad-spectrum efficacy against a range of viral families through preclinical evaluation. The program is expected to establish physicochemical properties, pharmacokinetics, and safety attributes to support an IND submission and to fund a first-in-human Phase 1 clinical study. Tonix plans to leverage previous research on phosphatase inhibitors, specifically compounds that target CD45, to optimize lead compounds for therapeutic intervention of biothreat agents and provide the government with a complete and cost-effective solution for a broad-spectrum medical countermeasure. Tonix’s hypothesis is that partial inhibition of CD45 will provide optimal antiviral protection while requiring lower plasma drug concentrations, a lower dose, and a better safety profile. 25 TNX-2900 – Prader-Willi Syndrome (PWS) TNX-2900 is based on our patented intranasal potentiated oxytocin formulation, or TNX-1900, but being developed for PWS. Tonix licensed technology using oxytocin-based therapeutics for the treatment of PWS and non-organic failure to thrive disease from Inserm. The licensing agreement has been negotiated and signed by Inserm Transfert, the private subsidiary of Inserm, on behalf of Inserm, Aix-Marseille Université and Centre Hospitalier Universitaire of Toulouse. 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. There is currently no approved treatment for either the suckling deficit in infants or the obesity and hyperphagia in older children associated with PWS. Since PWS is an orphan disease that occurs in approximately one in 15,000 births, TNX-2900 for PWS has been granted Orphan Drug Designation and Rare Pediatric Disease Designation 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 TNX-2900, and Tonix has received IND clearance. In 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 PWS 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. Intranasal oxytocin has previously been shown to improve suckling in newborn animals and suppress feeding behaviors in adult animal models. Tonix’s Facilities Overview The 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 is the principal site for the research on TNX-4200, a broad-spectrum antiviral targeting CD45 funded by the U.S. Department of Defense, Defense Threat Agency contract. The RDC also conducts research on CNS and immunology drugs. The RDC facility is biosafety level 2 (BSL-2) with BSL-3 components. The Advanced Development Center (ADC) The ADC located in the New Bedford business park in Dartmouth, Massachusetts is intended to accelerate development, clinical and commercial scale manufacturing of live-virus vaccines and biologics. ADC includes single-use bioreactors and purification suites with equipment for Good Manufacturing Practice (GMP) production of vaccines and biologics for clinical trials, including the capability of producing sterile vaccines in glass vials. The ADC is an approximately 45,000 square foot BSL-2 facility which can employ up to 70 researchers, scientists, manufacturing, and technical support staff. This facility was decommissioned in May 2024 but Tonix has the ability to reactivate it should we choose to do so. 26 Marketing, Sales and Distribution Marketing activity for Zembrace Symtouch and Tosymra in the United States is conducted by our wholly-owned subsidiary, Tonix Medicines, Inc. We focus our sales and marketing efforts on physicians in private practice and in public treatment systems. We employ standard pharmaceutical marketing practices to promote our products, encompassing advertisements, professional symposia, sales initiatives, and educational outreach aimed at physicians, nurses, social workers, counselors, and other stakeholders involved in treating acute migraine in adults. We have established contracts with third-party vendors to handle logistics, offer customer services, and manage other related aspects for our products. These services include managing product-specific websites, conducting insurance research, processing orders, and handling delivery and fulfillment services. Zembrace Symtouch and Tosymra are primarily sold to pharmaceutical wholesalers, pharmacies, and specialty distributors. We intend to implement patient access programs and expand distribution channels in our marketing efforts for our migraine drugs. In 2024, Tonix engaged EVERSANA to support the launch strategy and commercial planning of TNX-102 SL for the management of fibromyalgia. Specifically, EVERSANA worked with Tonix to assess the fibromyalgia landscape and help plan an efficient go-to-market strategy. In 2024, Tonix hired a new head of Commercial Operations as well as Vice Presidents to run Medical Affairs and Marketing, each with decades of experience successfully launching and commercializing new CNS products. In January 2025, Tonix announced the appointment of a vice president to oversee Market Access. In 2025, we will continue to build out our commercial team and capabilities as we look forward to a targeted launch of TNX-102 SL in the fourth quarter of 2025, contingent on FDA approval. Competition Our sector faces intense competition and experiences rapid, substantial technological advancements both domestically and internationally. Our potential competitors encompass major pharmaceutical and biotechnology firms, specialty pharmaceutical and generic drug manufacturers, academic institutions, government agencies, and research organizations. We consider efficacy, safety, tolerability, reliability, pricing, and reimbursement levels as crucial competitive factors influencing the development and commercial success of our product candidates. Numerous potential competitors, including some of the organizations listed below, possess considerably larger financial, technical, and human resources, as well as extensive experience in discovering and developing product candidates, securing FDA and other regulatory approvals, and commercializing those products, far surpassing our own capabilities. Hence, our competitors might achieve greater success in securing FDA approval for drugs and gaining widespread market acceptance compared to us. The drugs offered by our competitors may prove to be more effective or better marketed and sold than any product we bring to market, potentially rendering our product candidates obsolete or non-competitive before we can recoup the expenses incurred in their development and commercialization. We expect to encounter heightened competition as the market sees the introduction of new drugs and the emergence of advanced technologies. Additionally, the evolution of novel treatment approaches for the conditions we are focusing on may potentially diminish the competitiveness or relevance of our drugs. Below, we provide an overview of the competitive landscape for the indications where Tonix has product candidates either in or nearing the clinical stages of development. Migraine Zembrace Symtouch and Tosymra are indicated for the treatment of acute migraine and compete with generic versions of sumatriptan. Zembrace is an autoinjector formulation of sumatriptan and competes with generic subcutaneous products. Tosymra is an intranasal formulation of sumatriptan and competes with generic intranasal products. Zembrace and Tosymra also compete with the new molecular entities including oral migraine therapies such as Nurtec® (Rimegepant) from Pfizer Inc. and Ubrelvy® (Ubrogepant) and QULIPTA® (atogepant) from AbbVie Inc. and intranasal migraine therapies such as Zavzpret™ (vazegepant) by Pfizer, Inc. Most recently, Axsome Therapeutics announced FDA approval of SYMBRAVO® (meloxicam and rizatriptan) for the acute treatment of migraine with or without aura in adults. We also note that the PDUFA goal date for Shin Nippon Biomedical Laboratories, Ltd and Satsuma Pharmaceuticals is April 30, 2025 for their intranasal asset STS101 (dihydroergotamine) for the treatment of migraine headaches. 27 Fibromyalgia We are currently awaiting an FDA decision on marketing authorization for TNX-102 SL for the management of fibromyalgia. There are 3 products approved for the treatment of fibromyalgia which include Lyrica® (pregabalin), developed by Pfizer, Inc., Cymbalta® (duloxetine), developed by Eli Lilly and Company, and Savella® (milnacipran) marketed by AbbVie. Pregabalin and duloxetine are available as generics, while Savella is still on patent. There has not been a new product approved for this indication in 15 years. Tonix is aware of multiple companies actively developing treatments for fibromyalgia. Axsome Therapeutics Inc. expects to submit an NDA for AXS-14 (esreboxetine) for the management of fibromyalgia to the FDA for AXS-14 in Q1 2025. Virios Therapeutics, Inc. announced the initiation of a Phase 3 trial in the U.S. for IMC-1 for the treatment of fibromyalgia. IMC-1 is a fixed dose combination of famciclovir + celecoxib, is a 505(b)(2) and has been granted Fast Track Designation by the FDA. Tonix is also focused on developments for fibromyalgia outside of the U.S. and keeps abreast of the progress made by Australian company Tryptamine Therapeutics Ltd who announced positive data from a Phase IIa clinical trial of TRP-8802 for fibromyalgia which was presented in an abstract at the International Association for the Study of Pain (IASP) 2024 World Congress on August 9, 2024. Long COVID (Post-Acute Sequelae of SARS-CoV-2 Infection or PASC) As of now, there are no specific drugs approved by the FDA solely for the treatment of Long COVID (formerly known as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)). Tonix is aware of several companies developing therapeutics for the treatment of Long COVID including, but not limited to, Direct Biologics, LLC (Phase III for DB-001 was completed in the fourth quarter of 2024 and American CryoStem Corporation. Other developments include Organicell Regenerative Medicine, Inc. is conducting a Phase 2 for Zofin as a potential therapeutic for Long COVID. PaxMedica, Inc. is developing PAX-101 for the treatment of Long COVID and currently conducting a Phase1b in South Africa. In October 2024, Resolve Therapeutics, LLC, announced the results from its Phase II Long COVID study of RSLV-132. Furthermore, GeNeuro announced the data from Phase II GNC-501 clinical trial in patients suffering from Long COVID, testing temelimab against placebo. Finally, in June 2024, Berlin Cures Holding AG announced that it is preparing for a Phase III study in Long COVID and Statera BioPharma, Inc. is comparing STAT-205 with placebo for reducing fatigue in Long COVID. Acute Stress Reaction/Acute Stress Disorder (ASR/ASD) There are no approved drugs for treating ASR or for the prevention of ASD or PTSD. In October 2024, BioXcel Therapeutics announced a Phase IIa efficacy and safety trial of BXCL501 in patients experiencing ASD resulting from motor vehicle collisions to begin in the first half of 2025. BXCL501 is an orally dissolvable film formulation of the α2A adrenergic receptor agonist dexmedetomidine that is FDA approved as IGALMI® for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. Cocaine Intoxication There are no approved antidotes for the treatment of cocaine intoxication. Patients generally receive supportive care. We are not aware of any drugs in development for the treatment of cocaine intoxication. We are aware of companies that are targeting cocaine use disorder and we monitor their progress. Embera NeuroTherapeutics currently lists EMB-001 in Phase II development for the treatment of cocaine use disorder in its pipeline. 28 Transplantation Rejection and Autoimmune Treatments with Anti-CD40-ligand Monoclonal Antibodies We are aware of multiple companies advancing the development of biologics targeting the CD40L molecule including Sanofi, UCB, Eledon Pharmaceuticals, and Amgen Inc. Eledon Pharmaceuticals revealed promising results from the Phase I/II trial of tegoprubart, aimed at preventing islet transplant rejection in individuals with type 1 diabetes. The trial showed that the first human cases of insulin independence were achieved using an anti-CD40L monoclonal antibody therapy, without relying on tacrolimus, the current standard treatment for preventing transplant rejection. Sanofi’s SAR441344 (Frexalimab), a second-generation anti-CD40L monoclonal antibody, is being tested in multiple sclerosis. In a Phase II trial involving participants with relapsing multiple sclerosis (NCT04879628), frexalimab demonstrated effectiveness in quickly reducing the number of new gadolinium-enhancing T1-lesions at week 12. Amgen Inc. is currently conducting a Phase III trial to test Dazodalibep for Sjogren’s Syndrome (NCT06104124) with an estimated completion date for the first half of 2026. H. Lundbeck is testing Lu AG22515 for Thyroid Eye Disease (TED) and plans to report results from the Phase Ib TED study in the second half of 2026. In 2024, UCB and Biogen announced positive results from a Phase III trial testing Dapirolizumab Pegol for Systemic Lupus Erythematosus. In November 2024, UCB and Biogen announced the initiation of their potentially confirmatory Phase III trial to test Dapirolizumab Pegol for Systemic Lupus Erythematosus (NCT06617325). These are a few key highlights that underscore the focus of major pharmaceutical companies in this area and we monitor the activity of other companies in the process of developing antagonistic anti-CD40 mAbs, including Novartis, Boehringer Ingelheim GmbH, Kiniska Pharmaceuticals, Boston Immune Therapies, and NapaJen Pharma Inc. Prader Willi Syndrome Somatropin, which targets the Growth Hormone Receptor is approved in the U.S. and marketed by Pfizer Inc. and Novo Nordisk. Novartis AG markets Omnitrope® in Europe. There are no approved products for the treatment of hyperphagia or over-eating in PWS. Patients generally receive care to best manage individual symptom presentation. ACADIA Pharmaceuticals Inc. currently have ACP-101 (intranasal carbetocin) (acquired Levo Therapeutics in June 2022) in a Phase 3, randomized, double-blind, placebo-controlled, 8-week clinical study to assess the efficacy, safety, and tolerability, of ACP-101 in PWS with long term follow-up. Acadia anticipates the enrollment of the final patient in by the fourth quarter of 2025, with top-line results expected to be announced in the first half of 2026. Soleno is developing diazoxide chloride controlled release (DCCR) which had positive results in a randomized withdrawal study of PWS. The PDUFA goal date for a decision on marketing authorization is in March 2025. Carmot Therapeutics Inc. announced that they plan to release Phase I single ascending dose (SAD)/MAD data for CT-PYY in 2025 for the treatment of PWS. Harmony Biosciences Holdings, Inc. received Orphan Drug Designation for their asset Wakix (pitolisant hydrochloride) for the treatment of PWS. Harmony Biosciences announced initial topline results from its Phase II proof-of-concept study in patients with PWS, which showed a signal on improvement in the primary outcome related to excessive daytime sleepiness in November 2022. At the end of 2024, Neuren Pharmaceuticals Limited announced the suspension of its Phase II open-label study of the safety, tolerability, and pharmacokinetics of oral NNZ-2591 in Prader-Willi syndrome (PWS-001) due to a revised development strategy. Tonix is knowledgeable about several companies dedicated to developing a therapy for the treatment of PWS including, but not limited to, Aardvark Therapeutics, ConSynance Therapeutics, Lipidio Pharma, Helsinn, Inversago Pharma, Saniona, 9 Meters Biopharma, Neuracle Science, Harmony Biosciences Holding Inc., and Notitia Biotechnologies. Gastric and Colorectal Cancer TNX-1700 asset is a recombinant TFF2 (albumin fusion peptide) and has demonstrated that by targeting myeloid derived suppressor cells (MDSCs) using TFF2-MSA fusion protein synergizes well with PD-1 blockade therapy in advanced and metastatic syngeneic mouse models of colorectal cancer. Tonix is aware of several companies that are focused on MDSCs to treat Gastric and Colorectal Cancer. Anbogen announced a drug supply collaboration to evaluate the combination of Anbogen’s ABT-301, with BeiGene’s tislelizumab, in patients with mismatch repair–proficient or microsatellite stable metastatic colorectal cancer (“mCRC”) in a global Phase II trial. Gilead Sciences and Arcus Biosciences announced new data from Cohort B of ARC-9, a Phase Ib/II study evaluating the safety and efficacy of etrumadenant, a dual A2a/b adenosine receptor antagonist, plus anti-PD-1 monoclonal antibody zimberelimab, FOLFOX chemotherapy and bevacizumab (EZFB) in third-line mCRC. In 2023, TriSalus Life Sciences announced it plans to initiate a Phase II trial of SD-101 (Nelitolimod) for colorectal cancer. NextCure, Inc. have NC410 in the clinic for Colorectal Cancer. Faron Pharmaceuticals Oy have Bexmarilimab in the clinic for Colorectal Cancer. Merck & Co., Inc. and Agenus are collaborating on MK-4830 for Colorectal Cancer. 29 Smallpox / Mpox BioNTech SE is conducting a Phase I/II study in the U.S. evaluating the safety, tolerability, reactogenicity and immunogenicity of the investigational RNA-based multivalent vaccine candidate BNT166a for active immunization against mpox. The study is expected to complete in the first quarter of 2026. In 2023, Moderna announced it has mRNA-1769 in preclinical development for the treatment of Mpox. Moderna is conducting a P1/2 study of mpox vaccine in the U.K. Emergent BioSolutions, Inc. has enabled the enrolment of the first patients for the MOSA, a pan-African randomized platform adaptive trial to test Tembexa to treat mpox at Mbandaka Hospital in Equateur Province, Democratic Republic of Congo. A first interim analysis is expected by the end of the first quarter of 2025. Other companies we monitor include GeoVax Labs, Inc., NanoViricides, Inc., EpiVax, Inc., Gylden Pharma Limited. Covid-19 There are many vaccine products in development for the treatment or prevention of Covid-19 globally. Approved products include Pfizer-BioNTech’s (BNT162b2), Moderna’s (mRNA-1273) and Novavax’s (NVX-CoV2373) which are routinely updated to address new variants. CSL and Arcturus announced that the European Commission has granted marketing authorization for KOSTAIVE (ARCT-154), an mRNA COVID-19 vaccine, KOSTAIVE is currently marketed in Japan against COVID-19. Codagenix is developing CoviLiv™ as an intranasal vaccine candidate and in Phase 3 for COVID-19. Other companies working in the area include: Vaxart Inc. which is developing a potentially orally administered vaccine based on the adenovirus serotype 5 (Ad-5) vector to express the spike protein of SARS-CoV-2; CastleVax USA which is developing a potential nasally administered vaccine based on a Newcastle disease virus (NDV) vector to express the Spike protein of SARS-CoV-2. Intellectual Property We believe that we have an extensive patent portfolio and substantial know-how relating to TNX-102 SL, Zembrace®, Tosymra®, TNX-1300, TNX-1500, TNX-2900, TNX-1900, TNX-801, TNX-1800 and TNX-1700, 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 10, 2025, the patents we are either the owner of record of or own the contractual right to include 42 issued U.S. patents and 432 issued non-U.S. patents. We are actively pursuing an additional 23 U.S. non-provisional patent applications, 3 international patent applications, and 244 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 processes. 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 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. 30 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. 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. 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 February 10, 2025 are summarized below. TNX-102 SL — Central Nervous System Conditions Our patent portfolio for TNX-102 SL includes patents and 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 pain, fatigue and sleep disturbances in fibromyalgia, for treating or managing fibromyalgia (early onset response, favorable tolerability, or side effect profile), for alcohol abuse, for disordered sleep, for sexual dysfunction, for depression in fibromyalgia, for fatigue and disordered sleep (e.g., CAP rates), for post-acute sequelae of SARS-CoV-2 infection, for acute stress reaction/acute stress disorder, and for agitation in neurodegenerative conditions, e.g., AD. Certain eutectic compositions were discovered by development partners and are termed the “Eutectic Technology.” The patent portfolio for CBP compositions (e.g., TNX-102 SL) relating to the Eutectic Technology includes patents and 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 U.S. Patent No. 9,636,408, U.S. Patent No. 9,956,188, U.S. Patent No. 10,117,936, U.S. Patent No. 10,357,465, U.S. Patent No. 10,864,175, U.S. Patent No. 11,026,898, and U.S. Patent No. 11,839,594. These U.S. patents and counterpart non-U.S. patents, and any U.S. and non-U.S. patents that issue in the future from this portfolio would expire in 2034 or 2035, excluding any patent term adjustments or extensions. The unique pharmacokinetic profile of TNX-102 SL, or the PK Technology, was discovered by Tonix and its development partners. 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. 13/918,692. If U.S. and non-U.S. patents claiming priority from those applications issue, those patents would expire in 2033, excluding any patent term adjustments or extensions. 31 On May 2, 2017, U.S. Patent No. 9,636,408 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”, issued. The patent claims recite pharmaceutical compositions comprising the eutectic. The patent claims also recite methods of manufacturing the eutectic. On 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. On January 11, 2024, the European Patent Office Technical Board of Appeal reversed the October 2019 decision of the Opposition Division of the European Patent Office maintaining the patent in unamended form and held the patent to be invalid. No appeal may be taken from that decision. On December 15, 2017, Japanese Patent No. 6259452, entitled “Compositions and Methods for Transmucosal Absorption,” issued. These claims relate to the pharmacokinetic profile of TNX-102 SL. On 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. On March 20, 2018, U.S. Patent No. 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 US market exclusivity until 2030, excluding any patent term extensions. On 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. On May 1, 2018, U.S. Patent No. 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. On November 6, 2018, U.S. Patent No. 10,117,936, entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”, issued. The claims recite pharmaceutical compositions of eutectics of cyclobenzaprine hydrochloride and mannitol and methods of making those compositions. On 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. On August 4, 2023, Chinese Patent No. ZL201910263541.6, entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride,” issued. The claims recite a eutectics of cyclobenzaprine hydrochloride and beta-mannitol and methods of making those eutectics. On July 23, 2019, U.S. Patent No. 10,357,465 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride”, issued. The claims recite a eutectic of cyclobenzaprine hydrochloride and mannitol and methods of making those eutectics. On 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 the same. 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 after the January 2022 oral proceedings. Hexal AG did not appeal that decision. 32 On December 25, 2019, European patent 2,683,245, entitled “Methods and Compositions for Treating Depression Using Cyclobenzaprine”, issued. 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. In September 2020, Hexal AG filed an opposition against this patent. The European Patent Office’s Opposition Division upheld the patent claims in unamended form after the February 2022 oral proceedings. Hexal AG did not appeal that decision. On June 4, 2024, U.S. Patent No. 11,998,516, entitled “Methods and Compositions for Treating Depression Using Cyclobenzaprine,” issued. The claims recite methods for treating major depressive disorder in a fibromyalgia patient using a composition comprising cyclobenzaprine or its salts. On December 15, 2020, U.S. Patent No. 10,864,175 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”, issued. The claims recite a eutectic comprising cyclobenzaprine hydrochloride and beta-mannitol. On December 12, 2023, U.S. Patent No. 11,839,594 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”, issued. The claims recite a method of manufacturing a eutectic comprising cyclobenzaprine hydrochloride and beta-mannitol comprising mixing or milling. On February 14, 2024, European Patent No. 3,650,081, entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”, issued. The claims recite a eutectic of mannitol and cyclobenzaprine hydrochloride and methods of manufacturing a eutectic. On April 8, 2021, U.S. non-provisional Patent Application No. 17/226,058 and International Patent Application No. PCT/US2021/026492, entitled “Cyclobenzaprine Treatment for Sexual Dysfunction” were filed. The PCT application is now nationalized in Australia, Canada, China, European Patent Office, Japan, and Hong Kong. On October 5, 2022, International Patent Application No. PCT/US2022/045791, entitled “Cyclobenzaprine Treatment for Sexual Dysfunction,” was filed and is now nationalized in European Patent Office and U.S. (U.S. Patent Application No. 18/698,483). 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. On October 25, 2016 and July 28, 2020, U.S. Patent No. 9,474,728 and U.S. Patent No. 10,722,478, entitled “Methods and Compositions for Treating Fatigue Associated with Disordered Sleep Using Very Low Dose Cyclobenzaprine”, issued, respectively. 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. On December 11, 2018, International Patent Application No. PCT/IB2018/001509, entitled “Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions,” was filed. 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. On November 28, 2023, U.S. Patent No. 11,826,321, entitled “Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions,” issued. The claims are directed to a method for treating or preventing one or more agitation associated symptoms comprising administering a eutectic of cyclobenzaprine HCl and mannitol. On 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. 33 On November 19, 2021, International Patent Application No. PCT/US2021/060011, entitled “Cyclobenzaprine Treatment for Alcohol Use Disorder,” was filed. The PCT application is now nationalized in 13 countries. 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. On December 7, 2021, International Patent Application No. PCT/US2021/062244, entitled, “Cyclobenzaprine Treatment for Fibromyalgia,” was filed. The PCT is now nationalized in 15 countries. 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 of cyclobenzaprine hydrochloride and mannitol in dosage units with a basifying agent. On June 21, 2023, U.S. non-provisional Patent Application No. 18/212,500 and International Patent Application No. PCT/US2023/025895, entitled “Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC),” were filed. The PCT is now nationalized in 9 countries. The claims are directed to methods of treating PASC or one or more associated symptoms comprising administering cyclobenzaprine or a pharmaceutically acceptable salts of cyclobenzaprine. On December 19, 2024, U.S. non-provisional Patent Application No. 18/988,194 and International Patent Application No. PCT/US2024/061125, entitled “Early Onset Response, Favorable Tolerability, and Side Effect Profile in the Treatment of Fibromyalgia,” were filed. The claims are directed to methods for treating or managing fibromyalgia and its associated symptoms in subjects characterized by an early onset of one or more of: (1) a reduction in widespread pain; (2) a reduction in sleep disturbance; (3) a reduction in fatigue; or (4) an improved sleep quality. The claims are also directed to methods for preventing or avoiding clinically meaningful changes in mean weight, in mean systolic blood pressure or mean diastolic blood pressure, or a decline in sexual functioning. On January 23, 2025, International Patent Application No. PCT/US2025/012803, entitled Cyclobenzaprine Treatment for Acute Stress Reaction or Acute Stress Disorder,” was filed. The claims are directed to methods for treating or preventing acute stress reaction (ASR) or acute stress disorder (ASD) and associated symptoms thereof using a composition with cyclobenzaprine or its salts in. TNX-1900 — Oxytocin-Based Treatments for Obesity, Eating Disorders, Pain, Insulin Resistance, and Diabetes We 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). We also acquired U.S. Patent Nos. 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. On October 4, 2023, European Patent No. 3242676, entitled “Magnesium-Containing Oxytocin Formulations and Methods of Use,” issued. We also acquired International Patent Application No. PCT/US2017/027265, filed April 12, 2017, entitled “Magnesium-Containing Oxytocin Formulations and Methods of Use” (nationalized in 9 countries). On December 3, 2024, U.S. Patent No. 12,156,897, entitled “Magnesium-Containing Oxytocin Formulations and Methods of Use,” issued. The patent, which claims methods for treating autism spectrum disorder, social anxiety disorder, or a social communication disorder, will expire in April 2037, 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). On April 30, 2024, U.S. Patent No. 11,970,554, entitled “Labeled Oxytocin and Method of Manufacture and Use,” issued. 34 We 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. 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. Patent No. 9,101,569, entitled “Methods for the Treatment of Insulin Resistance.” The U.S. and non-U.S. patents expire in May 2031, excluding any patent term adjustments or extensions. TNX-2900 — Oxytocin-Based Therapeutics Treatments for Prader-Willi Syndrome (PWS) We have licensed technology using oxytocin-based therapeutics for the treatment of PWS 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 Patent No. EP2575853B1, entitled “Methods and Pharmaceutical Composition for the Treatment of a Feeding Disorder with Early-Onset in a Patient”; U.S. Patent No. 8,853,158, entitled “Methods for the Treatment of a Feeding Disorder with Onset During Neonate Development Using an Agonist of the Oxytocin Receptor”; and U.S. Patent No. 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.” The U.S. and non-U.S. patents expire in May 2031, excluding any patent term extensions. TNX-1300 — Cocaine Intoxication Treatment We 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. Patent Nos. 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. TNX-1500 — anti-CD40L Therapeutics We are developing 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 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 (nationalized in 14 countries). On August 28, 2024, European Patent No. 3993876, entitled “Anti-CD154 Antibodies and Uses Thereof,” issued (validated in 37 countries). The claims recite an isolated antibody that binds CD154, compositions comprising the antibody, and use of the compositions for treating or preventing a transplant rejection. TNX-801 — Live Horsepox Vaccine for Prevention of Smallpox and Mpox We 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 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. We believe that this technology, after further development, may be of interest to biodefense agencies in the U.S. and other countries. 35 On May 31, 2022, U.S. Patent No. 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. TNX-1800 and TNX-1850 — Live Modified Horsepox Vaccine for Prevention of COVID-19 We are developing TNX-1800 and TNX-1850, live minimally replicative modified HPXVs, as a COVID-19 preventing vaccine against different strains of SARS-CoV-2. 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. The PCT application is now nationalized in 19 countries. These applications are directed to synthetic poxviruses comprising a SARS-CoV-2 virus protein, poxvirus delivery vectors for SARS-CoV-2 virus proteins and methods of using these modified poxviruses to protect individuals against COVID-19. TNX-1700 — Recombinant Trefoil Family Factor 2 (rTFF2) to Treat Gastric and Colorectal Cancers We 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 colorectal cancers. The licensed patents are directed to rTFF2 compositions and methods of treatment. The licensed patents U.S. Patent No. 10,124,037 and U.S. Patent No. 11,167,010. 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.” The PCT application is now nationalized in 12 countries. 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 6 countries) and U.S. Patent Application No. 18/055,596, both entitled “Compositions and Methods for Increasing Efficacy of a Drug.” TNX-4300 — Estianeptine for Psychiatric and Neurodegenerative Diseases We are developing TNX-4300, the (S)-isomer of tianeptine, for psychiatric and neurodegenerative diseases. On March 27, 2024, we filed International Patent Application No. PCT/US2024/021799, entitled “(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor.” 36 Zembrace and Tosymra — Sumatriptan We have acquired the intellectual property rights of Zembrace SymTouch and Tosymra and their uses in treating migraine from Upsher-Smith Laboratories, LLC. These rights include U.S. Patent No. 9,211, 282, U.S. Patent No. 9,610,280, U.S. Patent No. 9,974,770, U.S. Patent No. 10,603,305, U.S. Patent No. 11,337,962, U.S. Patent No. 10,537,554, and U.S. Patent No. 11,364, 224. These rights also include International Patent Application No. PCT/US2016/015961, entitled “Pharmaceutical Composition Comprising Sumatriptan for Treating Migraine,” (nationalized in 7 countries, excluding rights in Brazil and China) and International Patent Application No. PCT/IB2010/001708, entitled “Formulations Comprising Triptan Compounds,” (nationalized in 11 countries, excluding rights in Brazil, Russia, India, and China). Trade Secrets In addition to patents, we rely on trade secrets and know-how to develop and maintain our competitive position. For example, significant 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. Issued Patents Our current patents owned or licensed include: Anti-Cocaine Therapeutics Patent No. Title Country / Region Expiration Date 8,318,156 Anti-Cocaine Compositions and Treatment U.S.A. February 14, 2029 9,200,265 Anti-Cocaine Compositions and Treatment U.S.A. December 30, 2027 2007272955 Anti-Cocaine Compositions and Treatment Australia July 10, 2027 2014201653 Anti-Cocaine Compositions and Treatment Australia July 10, 2027 2657246 Anti-Cocaine Compositions and Treatment Canada July 10, 2027 612929 Anti-Cocaine Compositions and Treatment New Zealand July 10, 2027 2046368 (602007045044.6 in Germany; 502016000056543 in Italy) Anti-Cocaine Compositions and Treatment European Patent Office – Germany, Spain, France, United Kingdom, and Italy July 10, 2027 2009/00197 Anti-Cocaine Compositions and Treatment South Africa July 10, 2027 305483 Anti-Cocaine Compositions and Treatment Mexico July 10, 2027 196411 Mutants of Cocaine Esterase (CocE) Polypeptide, Nucleic Acids Encoding Them, Pharmaceutical Compositions Comprising Them and Uses Thereof Israel July 10, 2027 37 Sublingual CBP/Amitriptyline Patent No. Title Country / Region Expiration Date 6259452 Compositions and Methods for Transmucosal Absorption Japan June 14, 2033 631144 Compositions and Methods for Transmucosal Absorption New Zealand June 14, 2033 I590820 Compositions and Methods for Transmucosal Absorption Taiwan R.O.C. June 14, 2033 2013274003 Compositions and Methods for Transmucosal Absorption Australia June 14, 2033 I642429 Compositions and Methods for Transmucosal Absorption Taiwan R.O.C. June 14, 2033 726488 Compositions and Methods for Transmucosal Absorption New Zealand June 14, 2033 I683660 Compositions and Methods for Transmucosal Absorption Taiwan R.O.C. June 14, 2033 2018241128 Compositions and Methods for Transmucosal Absorption Australia June 14, 2033 2876902 Compositions and Methods for Transmucosal Absorption Canada June 14, 2033 IDP000076019 Compositions and Methods for Transmucosal Absorption Indonesia June 14, 2033 382516 Compositions and Methods for Transmucosal Absorption Mexico June 14, 2033 2861223 (AL/P/2022/458 in Albania; P20221325T in Croatia; 602013082236.0 in Germany; 3111421 in Greece; 502022000069474 in Italy; P912561 in North Macedonia; SM-T-202200436 in San Marino; RS63822B1 in Serbia; and 2022-GE-787024 in Turkey) Compositions and Methods for Transmucosal Absorption 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 236268 Compositions for Transmucosal Delivery and Uses Thereof Israel June 14, 2033 2015/00288 Compositions and Methods for Transmucosal Absorption South Africa June 14, 2033 BR112014031394-6 Compositions and Methods for Transmucosal Absorption Brazil June 14, 2033 1209361 Compositions and Methods for Transmucosal Absorption Hong Kong June 14, 2033 398632 Compositions and Methods for Transmucosal Absorption Mexico June 14, 2033 A059897 Compositions and Methods for Transmucosal Absorption Venezuela June 14, 2033 MY-194495-A Compositions and Methods for Transmucosal Absorption Malaysia June 14, 2033 3,118,913 Compositions and Methods for Transmucosal Absorption Canada June 14, 2033 10201605407T Compositions and Methods for Transmucosal Absorption Singapore June 14, 2033 38 CBP – Depression Patent No. Title Country / Region Expiration Date 11,998,516 Methods and Compositions for Treating Depression Using Cyclobenzaprine U.S.A. March 5, 2032 2012225548 Methods and Compositions for Treating Depression Using Cyclobenzaprine Australia March 6, 2032 2016222412 Methods and Compositions for Treating Depression Using Cyclobenzaprine Australia March 6, 2032 2018204633 Methods and Compositions for Treating Depression Using Cyclobenzaprine Australia March 6, 2032 2020203874 Methods and Compositions for Treating Depression Using Cyclobenzaprine Australia March 6, 2032 614725 Methods and Compositions for Treating Depression Using Cyclobenzaprine New Zealand March 6, 2032 714294 Methods and Compositions for Treating Depression Using Cyclobenzaprine New Zealand March 6, 2032 2,829,200 Methods and Compositions for Treating Depression Using Cyclobenzaprine Canada March 6, 2032 2683245 (AL/P/2020/15 in Albania; P20200142 in Croatia; MK/P/2020/68 in North Macedonia; 602012066717.6 in Germany; 3103147 in Greece; HU/E048596 in Hungary; 502020000014740 in Italy; 10476 in North Macedonia; SM-T-202000083 in San Marino; 60240 in Serbia; 2773834 in Spain; and 2020-GE-5216 in Turkey) Methods and 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 39 CBP – PTSD Patent No. Title Country / Region Expiration Date 9,918,948 Methods and Compositions for Treating Symptoms Associated with Post-Traumatic Stress Disorder Using Cyclobenzaprine U.S.A. November 18, 2030 CBP Fatigue Patent No. Title Country / Region Expiration Date 9,474,728 Methods and Compositions for Treating Fatigue Associated with Disordered Sleep Using Very Low Dose Cyclobenzaprine U.S.A. June 9, 2031 10,722,478 Methods and Compositions for Treating Fatigue Associated with Disordered Sleep Using Very Low Dose Cyclobenzaprine U.S.A. June 9, 2031 CBP – Agitation in Neurodegenerative Condition Patent No. Title Country / Region Expiration Date 11,826,321 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions U.S.A. December 11, 2038 275289 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions Israel December 11, 2038 411601 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions Mexico December 11, 2038 3,083,341 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions Canada December 11, 2038 2020/03243 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions South Africa December 11, 2038 MY-207073-A Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions Malaysia December 11, 2038 40 CBP/Amitriptyline Eutectic Formulations Patent No. Title Country / Region Expiration Date 631152 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride New Zealand March 14, 2034 747040 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride New Zealand March 14, 2034 9,636,408 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride U.S.A. March 14, 2034 9,956,188 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride U.S.A. March 14, 2034 10,117,936 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride U.S.A. March 14, 2034 10,322,094 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride U.S.A. March 14, 2034 10,357,465 Eutectic Formulations of Cyclobenzaprine Hydrochloride U.S.A. September 18, 2035 10,736,859 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride U.S.A. March 14, 2034 10,864,175 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride U.S.A. March 14, 2034 10,864,176 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride U.S.A. March 14, 2034 11,026,898 Eutectic Formulations of Cyclobenzaprine Hydrochloride U.S.A. September 18, 2035 11,737,991 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride U.S.A. March 14, 2034 11,839,594 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride U.S.A. March 14, 2034 6310542 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Japan March 14, 2034 6614724 Eutectic Formulations of Cyclobenzaprine Hydrochloride Japan September 18, 2035 6717902 Eutectic Formulations of Cyclobenzaprine Hydrochloride Japan September 18, 2035 6088 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Saudi Arabia March 14, 2034 ZL201480024011.1 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride China March 14, 2034 ZL.201580050140.2 Eutectic Formulations of Cyclobenzaprine Hydrochloride China September 18, 2035 2014233277 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Australia March 14, 2034 2015317336 Eutectic Formulations of Cyclobenzaprine Hydrochloride Australia September 18, 2035 I661825 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Taiwan R.O.C. March 14, 2034 I740136 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Taiwan R.O.C. March 14, 2034 IDP000055516 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Indonesia March 14, 2034 IDP000063221 Eutectic Formulations of Cyclobenzaprine Hydrochloride Indonesia September 18, 2035 IDP000076872 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Indonesia March 14, 2034 2968992 (1211591 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, 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 March 14, 2034 41 3650081 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 March 14, 2034 241353 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Israel March 14, 2034 251218 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Methods of Producing Same Israel September 18, 2035 277814 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Methods of Producing Same Israel September 18, 2034 370021 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Mexico March 14, 2034 387402 Eutectic Formulations of Cyclobenzaprine Hydrochloride Mexico September 18, 2035 388137 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Mexico March 14, 2034 2015/07443 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride South Africa March 14, 2034 42 2017/01637 Eutectic Formulations of Cyclobenzaprine Hydrochloride South Africa September 18, 2035 BR112015022095-9 Pharmaceutical Composition, Method of Fabrication, Eutectic Composition and Use of Compositions Containing Cyclobenzaprine HCl and Mannitol Brazil March 14, 2034 2904812 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Canada March 14, 2034 3119755 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Canada March 14, 2034 HK1218727 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Hong Kong March 14, 2034 MY-186047-A Eutectic Formulations of Cyclobenzaprine Hydrochloride Malaysia September 18, 2035 398845 Eutectic Formulations of Cyclobenzaprine Hydrochloride India September 18, 2035 441374 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride India March 14, 2034 MY-196014-A Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Malaysia March 14, 2034 ZL201910263541.6 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride China March 14, 2034 2020289838 Eutectic Formulations of Cyclobenzaprine Hydrochloride Australia September 18, 2035 HK40047283 Eutectic Formulations of Cyclobenzaprine Hydrochloride Hong Kong September 18, 2035 ZL202011576351.9 Eutectic Formulations of Cyclobenzaprine Hydrochloride China September 18, 2035 730379 Eutectic Formulations of Cyclobenzaprine Hydrochloride New Zealand September 18, 2035 768064 Eutectic Formulations of Cyclobenzaprine Hydrochloride New Zealand September 18, 2035 40013124 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Hong Kong March 14, 2034 40030559 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Hong Kong March 14, 2034 Analogs of CBP Patent No. Title Country / Region Expiration Date 11,517,557 Analogs of Cyclobenzaprine and Amitryptilene U.S.A. July 13, 2038 12,156,864 Analogs of Cyclobenzaprine and Amitryptilene U.S.A. July 13, 2038 7330964 Analogs of Cyclobenzaprine and Amitryptilene Japan July 13, 2038 Oxytocin therapeutics Patent No. Title Country / Region Expiration Date 9,629,894 Magnesium-Containing Oxytocin Formulations and Methods of Use U.S.A. January 7, 2036 11,389,473 Magnesium-Containing Oxytocin Formulations and Methods of Use U.S.A. January 7, 2036 11201705591P Magnesium-Containing Oxytocin Formulations and Methods of Use Singapore January 7, 2036 388286 Magnesium-Containing Oxytocin Formulations and Methods of Use Mexico January 7, 2036 253347 Magnesium-Containing Oxytocin Formulations and Methods of Use Israel January 7, 2036 43 7030517 Magnesium-Containing Oxytocin Formulations and Methods of Use Japan January 7, 2036 ZL201680013809.5 Magnesium-Containing Oxytocin Formulations and Methods of Use China January 7, 2036 3242676 (P20231438 in Croatia; 602016083177.5 in Germany; 3114323 in Greece; HU/E065385 in Hungary; 65034 in Serbia; SM-T-202400020 in San Marino; and 2023-GE-778438 in Turkey) Magnesium-Containing Oxytocin Formulations and Methods of Use Europe – (Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, North Macedonia, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom) January 7, 2036 2017/05176 Magnesium-Containing Oxytocin Formulations and Methods of Use South Africa January 7, 2036 1252942 Magnesium-Containing Oxytocin Formulations and Methods of Use Hong Kong January 7, 2036 2020286221 Magnesium-Containing Oxytocin Formulations and Methods of Use Australia January 7, 2036 734097 Magnesium-Containing Oxytocin Formulations and Methods of Use New Zealand January 7, 2036 771693 Magnesium-Containing Oxytocin Formulations and Methods of Use New Zealand January 7, 2036 10-2677904 Magnesium-Containing Oxytocin Formulations and Methods of Use Republic of Korea January 7, 2036 7455402 Magnesium-Containing Oxytocin Formulations and Methods of Use Japan January 7, 2036 BR112017014545-6 Magnesium-Containing Oxytocin Formulations and Methods of Use Brazil January 7, 2036 11,970,554 Labeled Oxytocin and Method of Manufacture and Use U.S.A. March 1, 2039 7093559 Magnesium-Containing Oxytocin Formulations and Methods of Use Japan April 12, 2037 2017250505 Magnesium-Containing Oxytocin Formulations and Methods of Use Australia April 12, 2037 ZL201780036185.3 Magnesium-Containing Oxytocin Formulations and Methods of Use China April 12, 2037 40005263 Magnesium-Containing Oxytocin Formulations and Methods of Use Hong Kong April 12, 2037 12,156,897 Magnesium-Containing Oxytocin Formulations and Methods of Use U.S.A. April 12, 2037 44 417307 Magnesium-Containing Oxytocin Formulations and Methods of Use Mexico April 12, 2037 3442560 (602017086259.2 in Germany; and SM/T/2025/000041 in San Marino) Magnesium-Containing Oxytocin Formulations and Methods of Use Europe – (Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, North Macedonia, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, and United Kingdom) April 12, 2037 2575853 (2595251 in Spain) Methods and Pharmaceutical Composition for the Treatment of a Feeding Disorder with Early-Onset in a Patient Europe – (Spain, France, and United Kingdom) May 25, 2031 8,853,158 Methods for the Treatment of a Feeding Disorder with Onset During Neonate Development Using an Agonist of the Oxytocin Receptor U.S.A. May 25, 2031 9,125,862 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 U.S.A. May 25, 2031 2571511 (2526672 in Spain) New Uses of Oxytocin-like Molecules and Related Methods Europe – (Switzerland, Spain, France, United Kingdom, and Ireland) May 17, 2031 9,101,569 Methods for the Treatment of Insulin Resistance U.S.A. June 22, 2031 Nociceptin/Orphanin FQ therapeutics Patent No. Title Country / Region Expiration Date 8,551,949 Methods for treatment of pain U.S.A. August 11, 2031 9,238,053 Methods for treatment of pain U.S.A. October 12, 2030 2010281436 Methods for treatment of pain Australia July 27, 2030 ZL 201080042858.4 Methods for treatment of pain China July 27, 2030 2459183 (602010028120.5 in Germany) Methods for treatment of pain Europe – (Switzerland, Germany, Denmark, France, and United Kingdom) July 27, 2030 1169804 Methods for treatment of pain Hong Kong July 27, 2030 329837 Methods for treatment of pain Mexico July 27, 2030 597763 Methods for treatment of pain New Zealand July 27, 2030 10201406930U Methods for treatment of pain Singapore July 27, 2030 201200584 Methods for treatment of pain South Africa July 27, 2030 2,769,347 Methods for treatment of pain Canada July 27, 2030 413642 Methods for treatment of pain India July 27, 2030 45 Tianeptine – Neurocognitive Dysfunction Patent No. Title Country / Region Expiration Date 9,314,469 Method for Treating Neurocognitive Dysfunction U.S.A. September 24, 2030 2723688 Method for Treating Neurodegenerative Dysfunction Canada April 30, 2029 2299822 (602009047361.1 in Germany; 2644511 in Spain; and E911827 in Austria) Method for Treating Neurodegenerative Dysfunction European Patent Office – Austria, Belgium, Switzerland, Germany, Spain, France, United Kingdom, Ireland, Luxembourg, Monaco, and Portugal April 30, 2029 3246031 (602009057284.9 in Germany; 2727851 in Spain; and E1100344 in Austria) Method for Treating Neurocognitive Dysfunction European Patent Office – Austria, Belgium, Switzerland, Germany, Spain, France, United Kingdom, Ireland, Luxembourg, Monaco, and Portugal April 30, 2029 46 TFF2 therapeutics Patent No. Title Country / Region Expiration Date 10,124,037 Trefoil family factor proteins and uses thereof U.S.A April 2, 2033 11,167,010 Trefoil family factor proteins and uses thereof U.S.A April 2, 2033 Synthetic Chimeric Poxviruses Patent No. Title Country / Region Expiration Date 11,345,896 Synthetic Chimeric Poxviruses U.S.A November 2, 2037 397516 Synthetic Chimeric Poxviruses Mexico November 2, 2037 2019/02868 Synthetic Chimeric Poxviruses South Africa November 2, 2037 MY-200354-A Synthetic Chimeric Poxviruses Malaysia November 2, 2037 2017353868 Synthetic Chimeric Poxviruses Australia November 2, 2037 ZL201780078546.0 Synthetic Chimeric Poxviruses China November 2, 2037 40014109 Synthetic Chimeric Poxviruses Hong Kong November 2, 2037 2022/04981 Synthetic Chimeric Poxviruses South Africa November 2, 2037 Triptan Compound – Formulations Patent No. Title Country / Region Expiration Date 9,211,282 Formulations Comprising Triptan Compounds U.S.A July 19, 2031 9,610,280 Formulations Comprising Triptan Compounds U.S.A June 16, 2030 9,974,770 Formulations Comprising Triptan Compounds U.S.A June 16, 2030 10,603,305 Formulations Comprising Triptan Compounds U.S.A June 16, 2030 11,337,962 Formulations Comprising Triptan Compounds U.S.A. June 16, 2030 12,090,139 Formulations Comprising Triptan Compounds U.S.A. June 16, 2030 2010299607 Formulations Comprising Triptan Compounds Australia June 17, 2030 2775404 Formulations Comprising Triptan Compounds Canada June 17, 2030 2480197 (E760080 in Austria; 502016000000073 in Italy; 602010028995.8 in Germany; and 2553862 in Spain) Formulations Comprising Triptan Compounds European Patent Office - Austria, Belgium, Czechia, Denmark, France, Germany, Italy, Spain, Switzerland, and United Kingdom June 17, 2030 5845183 Formulations Comprising Triptan Compounds Japan June 17, 2030 101646079 Formulations Comprising Triptan Compounds Republic of Korea June 17, 2030 338110 Formulations Comprising Triptan Compounds Mexico June 17, 2030 599344 Formulations Comprising Triptan Compounds New Zealand June 17, 2030 2012/02168 Formulations Comprising Triptan Compounds South Africa June 17, 2030 Triptan Compound – Migraine Patent No. Title Country / Region Expiration Date 10,537,554 Pharmaceutical Composition for Treating Migraine U.S.A January 29, 2036 11,364,224 Pharmaceutical Composition for Treating Migraine U.S.A January 29, 2036 12,097,183 Pharmaceutical Composition for Treating Migraine U.S.A January 29, 2036 385725 Pharmaceutical Composition Comprising Sumatriptan for Treating Migraine Mexico February 1, 2036 2994748 Pharmaceutical Composition Comprising Sumatripan for Treating Migraine Canada February 1, 2036 47 CD40 and anti-CD154 Therapeutics Patent No. Title Country / Region Expiration Date 3993876 (E1717312 in Austria; P20241602 in Croatia; 602020036714.4 in Germany; 3116977 in Greece; HU/E069680 in Hungary; 502024000056334 in Italy; 66218 in Serbia; 2994684 in Spain; and SM-T-202400527 in San Marino) Anti-CD154 antibodies and uses thereof Europe – (Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, North Macedonia, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovenia, Slovakia, Spain, Sweden, Switzerland, Turkey, United Kingdom) July 1, 2040 CBP - ASD and PTSD Patent No. Title Country / Region Expiration Date 420368 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder Mexico August 20, 2039 Pending Patent Applications Our current pending patent applications are as follows: CD40 and anti-CD154 Therapeutics Application No. Title Country / Region 17/623,710 Anti-CD154 antibodies and uses thereof U.S.A. 2020300002 Anti-CD154 antibodies and uses thereof Australia BR112021026410-8 Anti-CD154 antibodies and uses thereof Brazil BR122024022801-7 Anti-CD154 antibodies and uses thereof Brazil 3145453 Anti-CD154 antibodies and uses thereof Canada 202080059891.1 Anti-CD154 antibodies and uses thereof (Allowed) China 24195755.4 Anti-CD154 antibodies and uses thereof European Patent Office 202217004870 Anti-CD154 antibodies and uses thereof India P00202200763 Anti-CD154 antibodies and uses thereof Indonesia 289354 Anti-CD154 antibodies and uses thereof Israel 2021-578262 Anti-CD154 antibodies and uses thereof Japan PI 2021007835 Anti-CD154 antibodies and uses thereof Malaysia PI 2024006778 Anti-CD154 antibodies and uses thereof Malaysia MX/a/2022/000133 Anti-CD154 antibodies and uses thereof Mexico 784548 Anti-CD154 antibodies and uses thereof New Zealand 11202114433Y Anti-CD154 antibodies and uses thereof Singapore 2022/01378 Anti-CD154 antibodies and uses thereof South Africa 2024/09160 Anti-CD154 antibodies and uses thereof South Africa 62022063693.5 Anti-CD154 antibodies and uses thereof (Allowed) Hong Kong 62022062573.0 Anti-CD154 antibodies and uses thereof Hong Kong 18/271,098 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies U.S.A. 2022205313 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies Australia BR112023013285-1 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies Brazil 3207098 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies Canada 202280019221.6 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies China 22701768.8 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies European Patent Office P00202307159 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies Indonesia 304253 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies Israel 2023-541043 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies Japan PI 2023003993 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies Malaysia MX/a/2023/008055 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies Mexico 801414 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies New Zealand 11202305000R Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies Singapore 2023/06791 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies South Africa 62024090562.5 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies Hong Kong 62024091450.2 Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies Hong Kong 3136725 Inhibitors of CD40-CD154 Binding Canada 2021-560713 Inhibitors of CD40-CD154 Binding Japan 17/603,260 Inhibitors of CD40-CD154 Binding U.S.A. 202080033531.4 Inhibitors of CD40-CD154 Binding China 48 CBP/Amitriptyline Eutectic Formulations Application No. Title Country / Region 18/385,468 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride U.S.A. BR112017005231-8 Eutectic Formulations of Cyclobenzaprine Hydrochloride Brazil BR122020020968-2 Eutectic Formulations of Cyclobenzaprine Hydrochloride Brazil 2,961,822 Eutectic Formulations of Cyclobenzaprine Hydrochloride Canada 15841528.1 Eutectic Formulations of Cyclobenzaprine Hydrochloride European Patent Office 18101200.4 Eutectic Formulations of Cyclobenzaprine Hydrochloride Hong Kong 2023-188486 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Japan 2023-116057 Eutectic Formulations of Cyclobenzaprine Hydrochloride Japan Application No. Title Country / Region PI 2023000078 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Malaysia 517381123 Eutectic Formulations of Cyclobenzaprine Hydrochloride Saudi Arabia 10201707528W Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Singapore 10201902203V Eutectic Formulations of Cyclobenzaprine Hydrochloride Singapore 2014-000391 Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride Venezuela 49 Sublingual CBP/Amitriptyline Application No. Title Country / Region 13/918,692 Compositions and Methods for Transmucosal Absorption U.S.A. P20130102101 Compositions and Methods for Transmucosal Absorption Argentina 20230100254 Compositions and Methods for Transmucosal Absorption Argentina 202010024102.2 Compositions and Methods for Transmucosal Absorption China 2013/24661 Compositions and Methods for Transmucosal Absorption Gulf Cooperation Council 2013/37088 Compositions and Methods for Transmucosal Absorption Gulf Cooperation Council 2013/40660 Compositions and Methods for Transmucosal Absorption Gulf Cooperation Council 42020020336.2 Compositions and Methods for Transmucosal Absorption Hong Kong P-00 2021 01421 Compositions and Methods for Transmucosal Absorption Indonesia 2024-14696 Compositions and Methods for Transmucosal Absorption Japan 10202401383X Compositions and Methods for Transmucosal Absorption Singapore CBP – Agitation in Neurodegenerative Condition Application No. Title Country / Region 2018383098 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions (Allowed) Australia BR112020011345-0 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions Brazil 201880079917.1 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions China 18847270.8 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions European Patent Office P00202004178 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions Indonesia 202017023747 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions India 2020-531611 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions Japan 62020022462.9 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions Hong Kong 62021029558.5 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions Hong Kong 42024101171.7 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions Hong Kong 10202303446R Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions Singapore 2023-186441 Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions Japan 202410396685.X Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions China 50 Analogs of CBP Application No. Title Country / Region 18/950,382 3069699 201880050758.2 18831505.5 Analogs of Cyclobenzaprine and Amitriptyline Analogs of Cyclobenzaprine and Amitriptyline Analogs of Cyclobenzaprine and Amitriptyline Analogs of Cyclobenzaprine and Amitriptyline U.S.A. Canada China European Patent Office 2024-027046 Analogs of Cyclobenzaprine and Amitriptyline Japan CBP – ASD and PTSD Application No. Title Country / Region 2019/38140 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder Gulf Cooperation Council 108129709 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder Taiwan R.O.C. 17/269,106 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder U.S.A. 2019323764 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder Australia PI2021000802 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder Malaysia 772889 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder New Zealand 813830 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder New Zealand BR112021003107-3 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder Brazil 3109258 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder Canada 201980062283.3 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder China 202510112547.9 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder China 19802247.7 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder European Patent Office 62021045278.0 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder Hong Kong 62022046260.5 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder Hong Kong 202117011223 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder India P00202101716 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder Indonesia 280921 Cyclobenzaprine or Amitriptyline Containing Compositions for Use in Treating Stress Disorders Israel 2021-509201 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder Japan 2025-32822 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder Japan 10-2024-02502Q Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder Singapore 2021/01121 Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder South Africa 51 CBP – Fibromyalgia Application No. Title Country / Region 18/265,525 Cyclobenzaprine Treatment for Fibromyalgia U.S.A. 2021396509 Cyclobenzaprine Treatment for Fibromyalgia Australia 3204202 Cyclobenzaprine Treatment for Fibromyalgia Canada 202180089897.8 Cyclobenzaprine Treatment for Fibromyalgia China 21844438.8 Cyclobenzaprine Treatment for Fibromyalgia European Patent Office 62024089847.3 Cyclobenzaprine Treatment for Fibromyalgia Hong Kong 62024090216.8 Cyclobenzaprine Treatment for Fibromyalgia Hong Kong 202317044026 Cyclobenzaprine Treatment for Fibromyalgia India P00202306147 Cyclobenzaprine Treatment for Fibromyalgia Indonesia 303497 Cyclobenzaprine Treatment for Fibromyalgia Israel 2023-542924 Cyclobenzaprine Treatment for Fibromyalgia Japan PI 2023003286 Cyclobenzaprine Treatment for Fibromyalgia Malaysia MX/a/2023/006720 Cyclobenzaprine Treatment for Fibromyalgia Mexico 800700 Cyclobenzaprine Treatment for Fibromyalgia New Zealand 523441103 Cyclobenzaprine Treatment for Fibromyalgia Saudi Arabia 524462219 Cyclobenzaprine Treatment for Fibromyalgia Saudi Arabia 10202403823V Cyclobenzaprine Treatment for Fibromyalgia Singapore 2023/06139 Cyclobenzaprine Treatment for Fibromyalgia South Africa CBP – Fibromyalgia (Early Onset Response, Favorable Tolerability, and Side Effect Profile) Application No. Title Country / Region PCT/US2024/061125 Early Onset Response, Favorable Tolerability, and Side Effect Profile in the Treatment of Fibromyalgia PCT 18/988,194 Early Onset Response, Favorable Tolerability, and Side Effect Profile in the Treatment of Fibromyalgia U.S.A. CBP – Acute Stress Reaction or Acute Stress Disorder Application No. Title Country / Region PCT/US2025/012803 Cyclobenzaprine Treatment for Acute Stress Reaction or Acute Stress Disorder PCT CBP – Alcohol Use Disorder Application No. Title Country / Region 18/037,815 Cyclobenzaprine Treatment for Alcohol Use Disorder U.S.A. 2021382668 Cyclobenzaprine Treatment for Alcohol Use Disorder Australia 112023009731-2 Cyclobenzaprine Treatment for Alcohol Use Disorder Brazil 3202722 Cyclobenzaprine Treatment for Alcohol Use Disorder Canada 202180088339.X Cyclobenzaprine Treatment for Alcohol Use Disorder China 21827298.7 Cyclobenzaprine Treatment for Alcohol Use Disorder European Patent Office 62024087606.5 Cyclobenzaprine Treatment for Alcohol Use Disorder Hong Kong 62024089500.8 Cyclobenzaprine Treatment for Alcohol Use Disorder Hong Kong 202317038485 Cyclobenzaprine Treatment for Alcohol Use Disorder India 303050 Cyclobenzaprine Treatment for Alcohol Use Disorder Israel 2023-530204 Cyclobenzaprine Treatment for Alcohol Use Disorder Japan MX/a/2023/005899 Cyclobenzaprine Treatment for Alcohol Use Disorder Mexico 800112 Cyclobenzaprine Treatment for Alcohol Use Disorder New Zealand 11202303835Y Cyclobenzaprine Treatment for Alcohol Use Disorder Singapore 2023/05747 Cyclobenzaprine Treatment for Alcohol Use Disorder South Africa 52 CBP – Sexual dysfunction Application No. Title Country / Region 17/226,058 Cyclobenzaprine Treatment for Sexual Dysfunction U.S.A 2021253592 Cyclobenzaprine Treatment for Sexual Dysfunction Australia 3179754 Cyclobenzaprine Treatment for Sexual Dysfunction Canada 202180040673.8 Cyclobenzaprine Treatment for Sexual Dysfunction (Allowed) China 21721779.3 Cyclobenzaprine Treatment for Sexual Dysfunction European Patent Office 2022-562023 Cyclobenzaprine Treatment for Sexual Dysfunction Japan 62023077251.4 Cyclobenzaprine Treatment for Sexual Dysfunction Hong Kong 62023078964.1 Cyclobenzaprine Treatment for Sexual Dysfunction Hong Kong 62025103395.2 Cyclobenzaprine Treatment for Sexual Dysfunction Hong Kong 18/698,483 Cyclobenzaprine for Treatment or Prevention of Sexual Dysfunction Associated with Mental Health Conditions in Female Patients U.S.A. 22800445.3 Cyclobenzaprine for Treatment or Prevention of Sexual Dysfunction Associated with Mental Health Conditions in Female Patients European Patent Office CBP – Post-Acute Sequelae of SARS-CoV-2 (PASC) Application No. Title Country / Region 18/212,500 Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC) U.S.A. 2023286504 Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC) Australia 36260042 Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC) Canada Not Yet Assigned Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC) China 23744274.4 Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC) European Patent Office 317836 Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC) Israel 2024-575083 Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC) Japan MX/a/2025/000142 Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC) Mexico 817589 Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC) New Zealand 2025/00293 Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC) South Africa Oxytocin therapeutics Application No. Title Country / Region 2024203428 Magnesium-Containing Oxytocin Formulations and Methods of Use Australia BR122024008322-1 Magnesium-Containing Oxytocin Formulations and Methods of Use Brazil 2972975 Magnesium-Containing Oxytocin Formulations and Methods of Use Canada 42024096348.8 Magnesium-Containing Oxytocin Formulations and Methods of Use Hong Kong 23201255.9 Magnesium-Containing Oxytocin Formulations and Methods of Use European Patent Office 2024-33983 Magnesium-Containing Oxytocin Formulations and Methods of Use Japan 18/621,985 Labeled Oxytocin and Method of Manufacture and Use U.S.A. 19710979.6 Labeled Oxytocin and Method of Manufacture and Use European Patent Office 2020-545532 Labeled Oxytocin and Method of Manufacture and Use Japan 2024-9405 Labeled Oxytocin and Method of Manufacture and Use Japan 18/921,777 Magnesium-Containing Oxytocin Formulations and Methods of Use U.S.A. 3,020,179 Magnesium-Containing Oxytocin Formulations and Methods of Use (Allowed) Canada 2023100344997 Magnesium-Containing Oxytocin Formulations and Methods of Use China 24214056.4 Magnesium-Containing Oxytocin Formulations and Methods of Use European Patent Office 2024-196703 Magnesium-Containing Oxytocin Formulations and Methods of Use Japan 747221 Magnesium-Containing Oxytocin Formulations and Methods of Use New Zealand 787097 Magnesium-Containing Oxytocin Formulations and Methods of Use New Zealand 2023203831 Magnesium-Containing Oxytocin Formulations and Methods of Use Australia 42023079422.4 Magnesium-Containing Oxytocin Formulations and Methods of Use Hong Kong MX/a/2023/008840 Magnesium-Containing Oxytocin Formulations and Methods of Use Mexico 53 Nociceptin/Orphanin FQ therapeutics Application No. Title Country / Region BR122021007932-3 Methods for Treatment of Pain Brazil Synthetic Chimeric Poxviruses Application No. Title Country / Region 17/827,320 Synthetic Chimeric Poxviruses U.S.A. P 20170103043 Synthetic Chimeric Poxviruses Argentina 2017/34209 Synthetic Chimeric Poxviruses Gulf Cooperation Council 2017/41626 Synthetic Chimeric Poxviruses Gulf Cooperation Council 106137976 Synthetic Chimeric Poxviruses (Allowed) Taiwan R.O.C. BR112019008781-8 Synthetic Chimeric Poxviruses Brazil 3,042,694 Synthetic Chimeric Poxviruses Canada 17868045.0 Synthetic Chimeric Poxviruses European Patent Office 201917021814 PID201904682 Synthetic Chimeric Poxviruses Synthetic Chimeric Poxviruses India Indonesia 266399 2019-545700 Synthetic Chimeric Poxviruses (Allowed) Synthetic Chimeric Poxviruses Israel Japan 2024-93677 Synthetic Chimeric Poxviruses Japan 752893 11201903893P Synthetic Chimeric Poxviruses Synthetic Chimeric Poxviruses New Zealand Singapore 2024/03393 Synthetic Chimeric Poxviruses South Africa 2017-000418 Synthetic Chimeric Poxviruses Venezuela 62020003684.1 Synthetic Chimeric Poxviruses Hong Kong 792675 Synthetic Chimeric Poxviruses New Zealand P00202402600 Synthetic Chimeric Poxviruses Indonesia 113144133 Synthetic Chimeric Poxviruses Taiwan 54 Synthetic Vaccinia Virus Application No. Title Country / Region 2019/37492 Synthetic Chimeric Vaccinia Virus Gulf Cooperation Council 2019/41458 Synthetic Chimeric Vaccinia Virus Gulf Cooperation Council 20190101165 Synthetic Chimeric Vaccinia Virus Argentina 108115290 Synthetic Chimeric Vaccinia Virus Taiwan R.O.C. 17/050,946 Synthetic Chimeric Vaccinia Virus U.S.A. 2019262149 Synthetic Chimeric Vaccinia Virus Australia BR112020022181-3 Synthetic Chimeric Vaccinia Virus Brazil 3099330 Synthetic Chimeric Vaccinia Virus Canada 201980029677.9 Synthetic Chimeric Vaccinia Virus China 19796145.1 Synthetic Chimeric Vaccinia Virus European Patent Office 202017052398 Synthetic Chimeric Vaccinia Virus India P00202008694 Synthetic Chimeric Vaccinia Virus Indonesia 278419 Synthetic Chimeric Vaccinia Virus Israel 2024-28557 Synthetic Chimeric Vaccinia Virus Japan PI 2020005696 Synthetic Chimeric Vaccinia Virus Malaysia MX/a/2020/011586 Synthetic Chimeric Vaccinia Virus Mexico 768999 Synthetic Chimeric Vaccinia Virus New Zealand 10202401171Y Synthetic Chimeric Vaccinia Virus Singapore 2020/06350 Synthetic Chimeric Vaccinia Virus South Africa 62021036744.2 Synthetic Chimeric Vaccinia Virus Hong Kong 62021038254.0 Synthetic Chimeric Vaccinia Virus Hong Kong PI 2024003859 Synthetic Chimeric Vaccinia Virus Malaysia 810669 Synthetic Chimeric Vaccinia Virus New Zealand Poxvirus vaccine against COVID-19 Application No. Title Country / Region 17/187,678 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus U.S.A. 110107179 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Taiwan 20210100512 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Argentina 1202200348 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus African Intellectual Property Organization AP/P/2022/014318 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus African Regional Intellectual Property Organization 2021226592 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Australia BR112022016992-2 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Brazil 3173996 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Canada 202180027983.6 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus China 202292431 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Eurasian Patent Office 21715007.7 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus European Patent Office 202217053476 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus India P00202210244 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Indonesia 295925 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Israel 2022-551297 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Japan PI 2022004613 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Malaysia MX/a/2022/010588 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Mexico 791924 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus New Zealand 10-2022-7033014 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Republic of Korea 522440323 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Saudi Arabia 2022/09895 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus South Africa 523451920 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Saudi Arabia 62023075022.1 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Hong Kong 62023083678.0 Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus Hong Kong 55 TFF2 therapeutics Application No. Title Country / Region 17/638,761 Modified TFF2 polypeptides U.S.A. 2020338947 Modified TFF2 polypeptides Australia 3152665 Modified TFF2 polypeptides Canada 202080071768.1 Modified TFF2 polypeptides China 20781063.1 Modified TFF2 polypeptides European Patent Office 202217016249 Modified TFF2 polypeptides India 290910 Modified TFF2 polypeptides Israel 2022-513154 Modified TFF2 polypeptides Japan MX/a/2022/002337 Modified TFF2 polypeptides Mexico 786004 Modified TFF2 polypeptides New Zealand 2022/03355 Modified TFF2 polypeptides South Africa 62023066535.3 Modified TFF2 polypeptides Hong Kong 62023066928.0 Modified TFF2 polypeptides Hong Kong Antiviral Drugs – Cathepsin Inhibitors Application No. Title Country / Region 18/055,596 Compositions and Methods for Increasing Efficacy of a Drug U.S.A. 2022-569505 Compositions and Methods for Increasing Efficacy of a Drug Japan 202217072271 Compositions and Methods for Increasing Efficacy of a Drug India 62023079383.3 Compositions and Methods for Increasing Efficacy of a Drug Hong Kong Triptan Compound – Formulations Application No. Title Country / Region 18/782,922 Formulations Comprising Triptan Compounds U.S.A. Triptan Compound – Migraine Application No. Title Country / Region 18/797,812 Methods of Treating Migraine U.S.A. 18/783,734 Pharmaceutical Composition for Treating Migraine U.S.A. Tianeptine – Conditions Associated with Peroxisome Proliferator-Activated Receptor Application No. Title Country / Region PCT/US2024/021799 (S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor PCT Trademarks and Service Marks Tonix Pharmaceuticals, Inc. We seek trademark and service mark protection in the United States and outside of the United States where available and when appropriate. We are the owner of the following U.S. federally registered mark: TONIX PHARMACEUTICALS (Reg. No. 4656463, issued December 16, 2014). 56 We are the owner of the following marks for which applications for U.S. federal registration are currently pending: FYMRALIN (Serial No. 98/327953, filed December 22, 2023), 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. 98/577945, filed May 31, 2024), ANGSTRO-TECHNOLOGY (Serial No. 98/006538, filed May 22, 2023) and TNX-102 SL (Serial No. 97/185424, filed December 22, 2021). Tonix Medicines, Inc. We seek trademark and service mark protection in the United States and outside of the United States where available and when appropriate. We are the owner of the following U.S. federally registered marks: NOTIME4MIGRAINES (Reg. No. 5392512, issued January 30, 2018); SYMTOUCH (Reg. No. 5186988, issued April 18, 2017); TOSYMRA (Reg. No. 5981221, issued February 11, 2020); TOSYMRA & DROPLET Design (Reg. No. 6142333, issued August 11, 2020); ZEMBRACE (Reg. No. 5186989, issued April 18, 2017); ZEMBRACE SYMTOUCH (Reg. No.5478282, issued May 29, 2018); DROPLET Design (Reg. No. 6117797, issued August 4, 2020); TONIX ONE LOGO Design (Serial No. 99/057051, filed February 26, 2025). We are the owner of the following International Registrations under the Madrid Protocol: TOSYMRA (Reg. No. 1501060, issued October 16, 2019 – Extensions of Protection to: Canada, European Union, Japan, Republic of Korea, United Kingdom); ZEMBRACE (Reg. No. 1683288, issued August 17, 2022 – Extensions of Protection to: Canada (still pending), China, European Union, Israel, Mexico, United Kingdom); DROPLET Design (Reg. No. 1545038, issued June 29, 2020 – Extensions of Protection to: Canada, European Union, Israel, Japan, Norway, Republic of Korea, Switzerland, Turkey, United Kingdom); European Union: TONIX ONE LOGO Design (Application No. 19151272, filed March 4, 2025). Research and Development We have approximately 45 employees dedicated to research and development. Our research and development operations are located in Chatham, NJ, 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. Marketing We have nine employees supporting sales administration and marketing initiatives. We also have three sales employees who are focused on customer service requests and top-tier headache specialists. We utilize third party vendors to support trade, managed markets, marketing initiatives, and promotional compliance programs. Manufacturing We have contracted with third-party cGMP-compliant contract manufacturer organizations(“CMOs”), for the manufacture of TNX-102 SL drug substance and drug products for clinical and commercial supply. Our manufacturing operations are managed and controlled out of our Dublin, Ireland offices. All of our small molecules drug candidates are synthesized using industry standard processes, and our drug products are formulated using commercially available pharmaceutical grade excipients. We own a 45,000 square foot facility in Massachusetts, to house our new Advanced Development Center for accelerated development and manufacturing of vaccines and biologics. This facility is currently decommissioned. It was designed for the manufacture of nonclinical and clinical investigational products for our Infectious Disease portfolio. The current focus of which is TNX-801 a Smallpox and Mpox Preventing Vaccine and TNX-1800 a COVID vaccine selected by NIH/NIAID Project NextGen for Inclusion in Clinical Trials. This facility was decommissioned in 2024 but Tonix has the ability to reactivate it should we choose to do so. 57 Our two marketed products, Zembrace and Tosymra, are manufactured at cGMP compliant, FDA audited, U.S. based CMOs with expertise in pre-filled syringe and inhalation expertise. Government Regulations The 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. The 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. generally involves the following: ● 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; and ● the FDA’s review and approval of the NDA or BLA prior to any commercial marketing, sale or shipment of the drug. The 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. Nonclinical 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. 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. 58 Clinical Trials Clinical trials involve the administration of the product candidate to human subjects under the supervision of qualified medical investigators according to approved protocols that detail the objectives of the study, dosing procedures, subject selection and exclusion criteria, and the parameters to be used to monitor participant safety. Each protocol for a U.S. study is submitted to the FDA as part of the IND. Human clinical trials are typically conducted in three sequential phases, but the phases may overlap, or be combined. ● 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. ● 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. 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. 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. Clinical 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 risk. New Drug Applications Assuming 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. The 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. 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. 59 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. 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. Section 505(b) NDAs There are two types of NDAs: the Section 505(b)(1) NDA, or full NDA, and the Section 505(b)(2) NDA. 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. We submitted NDA under Section 505(b)(2) for TNX-102 SL for FM, and plan to submit an 505(b)(2)for TNX-2900 for Prader Willi Syndrome. 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). Patent Protections An 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; (2) 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) 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. 60 If 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. 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. Marketing Exclusivity Market 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. 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. Other types of exclusivities 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. 61 Section 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. Breakthrough Therapy Designation The Food and Drug Administration Safety and Innovation Act, or FDASIA, Section 902 provides for Breakthrough Therapy designation. 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; and ● 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. Fast Track Designation A Fast Track is a designation by the FDA of an investigational drug which: ● intended alone or in combination with one or more other drugs to treat a serious or life-threatening disease or condition; and ● non-clinical or clinical data demonstrate the potential to address an unmet medical need Fast 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. Material Threat Medical Countermeasures 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 SARS-CoV-2. 62 Other Regulatory Requirements Maintaining 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; and ● complying with electronic record and signature requirements. In 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. The 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. Coverage and Reimbursement Sales 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. 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. Other Healthcare Laws Because 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 programs. Failure to comply with these laws, where applicable, can result in the imposition of significant civil penalties, criminal penalties, or both. 63 The U.S. 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 Physician Payments Sunshine Act, which requires manufacturers of drugs, devices, biologics, and medical supplies to report annually to the U.S. 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. In 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. The Impact of New Legislation and Amendments to Existing Laws The 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 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. We 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. Human Capital Resources As of March 17, 2025, we had 81 full-time employees, of whom 12 hold M.D. or Ph.D. degrees. We have 45 employees dedicated to research and development. We have two employees supporting sales administration and marketing initiatives and three sales employees who are focused on customer service requests and top-tier headache specialists. 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, New Jersey, Dartmouth, Massachusetts, 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. Employee health and safety in the workplace is one of our core values. 64 Employee levels are managed to align with the pace of business and management believes it has sufficient human capital to operate its business successfully. Corporate Information 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. 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.