Item 1A. Risk Factors 59
Item 1B. Unresolved Staff Comments 84
Item 1C. Cybersecurity Disclosures 85
Item 2. Properties 85
Item 3. Legal Proceedings 86
Item 4. Mine Safety Disclosures 86
PART II
Item 6. Reserved 87
Item 7A. Quantitative and Qualitative Disclosures about Market Risk 93
Item 8. Financial Statements and Supplementary Data F-1 – F-29
Item 9A. Controls and Procedures 99
Item 9B. Other Information 100
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 100
PART III
Item 10. Directors, Executive Officers and Corporate Governance 101
Item 11. Executive Compensation 108
Item 14. Principal Accounting Fees and Services 119
PART IV
Item 15. Exhibits, Financial Statement Schedules 120
2
PART
I
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. All statements contained in this Annual Report other than statements of historical fact, including, but not limited to,
statements regarding the launch and commercialization of TONMYA and our migraine products, our future results of operations and
financial position, business strategy, market size, potential growth opportunities, clinical and nonclinical development activities,
efficacy and safety profile of our marketed products and product candidates, potential therapeutic benefits and economic value of
TONMYATM, our migraine products and our product candidates, our ability to market and sell our products while maintaining full
compliance with applicable federal and state laws, rules and regulations, the timing and results of nonclinical studies and clinical
trials, the potential impact of global business or macroeconomic conditions, including as a result of inflation, changing interest
rates, cybersecurity incidents, significant political, trade or regulatory developments and global regional conflicts on our
operations, and the receipt and timing of potential regulatory designations, approvals and commercialization of product candidates.
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.
3
Business
Overview
We (“Tonix” or the “Company”) are a fully-integrated
biopharmaceutical company commercializing and developing innovative therapies for central nervous system (“CNS”) disorders,
immunology, infectious diseases, and rare diseases. Our portfolio consists of commercial, development and discovery-stage programs. In
August 2025, we received approval from the U.S. Food and Drug Administration (“FDA”) for TONMYA for the treatment of fibromyalgia
in adults. TONMYA is our first internally developed product to receive FDA approval. We hold worldwide commercialization rights to TONMYA, a centrally acting, non-opioid analgesic designed for bedtime administration and long-term use.
We launched TONMYATM (cyclobenzaprine HCl sublingual tablets) for
the treatment of fibromyalgia in adults on November 17, 2025. TONMYA is the first new medicine for fibromyalgia in more than 15 years.
In addition to TONMYA, we market two FDA-approved prescription products for the treatment of acute migraine: Zembrace® SymTouch®
(sumatriptan injection) and Tosymra® (sumatriptan nasal spray). Our commercial platform includes sales, marketing, market access,
distribution, and patient support capabilities. We have generated a diversified pipeline of development candidates through internal discovery,
in-licensing, acquisitions, and collaborations with, commercial, academic and non-profit institutions. With commercial operations established
and a broad development portfolio, our strategy is to grow TONMYA into a leading therapy for fibromyalgia, advance pipeline programs,
and pursue strategic business development opportunities.
Our development pipeline includes multiple programs in clinical and preclinical development.
The proprietary cyclobenzaprine HCl sublingual tablet formulation contained
in TONMYA is referred to as “TNX-102 SL” outside of the fibromyalgia indication. We are exploring the utility of TNX-102
SL (cyclobenzaprine HCl sublingual tablets) in Phase 2 clinical trials for major depressive disorder (“MDD”) and acute stress
disorder (“ASD”) and acute stress reaction (“ASR”). TNX-102 SL is being developed to treat ASR and ASD under an
Investigator-Initiated investigational new drug application (“IND”) at the University of North Carolina (“UNC”)
in the ongoing OASIS study for which UNC received funding from the U.S. Department of Defense (“DoD”). A Phase 2 study of
TNX-102 SL for MDD is expected to commence mid-2026 under a Tonix IND that has been cleared by the FDA.
Our clinical stage programs
also include:
Our pre-clinical programs
include:
With
commercial operations established and a broad development portfolio advancing, our strategy is to grow TONMYA into a
leading therapy for fibromyalgia, advance pipeline programs, and pursue strategic business
development opportunities.
Our commercial portfolio
of FDA-approved medicines includes:
TONMYA
(cyclobenzaprine HCl sublingual tablets) – Fibromyalgia
TONMYA,
a proprietary sublingual formulation of cyclobenzaprine designed for bedtime dosing and long-term use, is approved in the United
States for the treatment of fibromyalgia in adults and was launched in November 2025. TONMYA was approved under the 505(b)(2)
pathway based on three Phase 3 studies, including two studies that demonstrated statistically significant improvement in pain
compared with placebo. Clinical studies showed rapid onset of benefit, sustained efficacy, and a safety profile consistent with
known cyclobenzaprine effects, with the most common adverse events being transient local oral reactions.
4
TONMYA
is designed to target the non-restorative sleep that we believe is central to fibromyalgia pathophysiology. TONMYA’s sublingual
formulation is designed for transmucosal delivery to bypass first-pass hepatic metabolism, which reduces formation of norcyclobenzaprine,
the persistent active metabolite that we believe interferes with the duration of any treatment effects from oral, swallowed cyclobenzaprine.
The sublingual, transmucosal formulation results in a distinct pharmacokinetic profile compared to oral cyclobenzaprine, with
greater relative bioavailability of the parent drug and reduced active metabolite exposure during sleep.
We commercialize TONMYA through
our sales organization, which includes an internal sales force, and a contracted salesforce, non-personal promotion, digital engagement,
market access programs, patient support services, and distribution through national wholesalers and specialty distributors. We are focused
on obtaining payer coverage, building physician awareness, and driving adoption primarily in practices that have a history of diagnosing
and treating fibromyalgia, which includes rheumatology, primary care, pain management and neurology practices.
We have contracted for two commercial supply sources of TONMYA, one of
which is Almac Pharma Services, a member of the privately owned Almac Group.
We are pursuing lifecycle management strategies for TONMYA, including potential
label expansion, real-world evidence generation, and geographic expansion.
Zembrace®
SymTouch® (sumatriptan injection) and Tosymra® (sumatriptan nasal spray) - Migraine Franchise
Zembrace
SymTouch (sumatriptan injection) 3 mg is a low-dose autoinjector designed for ease of use and rapid onset of action. Zembrace
is the only branded sumatriptan autoinjector actively promoted in the United States and has patent protection into 2036. Tosymra
(sumatriptan nasal spray) 10 mg is a rapid-acting intranasal formulation using Intravail® permeation enhancer technology
with patent protection into 2031. Effective January 1, 2026, Tosymra has preferred exclusive placement on a payer formulary representing
approximately 16 million covered lives.
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.
Development
Pipeline
Central
Nervous System
In September 2025, we
announced the successful completion of a Type B Pre-IND meeting with the FDA regarding the development of TNX-102 SL for the treatment
of MDD. We received positive feedback from the FDA and plan to pursue a supplemental new drug application (“sNDA”) to expand
the therapeutic indication of TNX-102 SL to include MDD, based on exploratory findings suggesting that improving sleep quality may positively
impact depressive symptoms.
In November 2025, we announced
the FDA cleared the IND application to support clinical development of TNX-102 SL 5.6 mg for the treatment of MDD in adults. The unique
pharmacological profile of TNX-102 SL is designed to target the disturbed sleep which is often associated with depression. Prior studies
of TNX-102 SL in fibromyalgia and post-traumatic stress disorder (“PTSD”) showed promising signals for improvement of depressive
symptoms on the Beck Depression Inventory-II and the Montgomery-Åsberg Depression Rating Scale (“MADRS”), respectively.
The IND clearance enables Tonix to proceed with a potentially pivotal Phase
2 HORIZON study, a 6-week, randomized, double-blind, placebo-controlled study of TNX-102 SL as a first-line monotherapy in adults with
MDD. About 360 patients will be enrolled at approximately 30 U.S. sites. Eligible participants are 18 years or older and currently experiencing
a moderate to severe major depressive episode. The study will compare TNX-102 SL 5.6 mg, taken sublingually at bedtime, to placebo, with
the primary endpoint being the MADRS total score change from baseline at Week 6. Secondary endpoints include global impression scores,
anxiety ratings, and measures of sleep disturbance. We plan to initiate enrollment of the study in mid-year 2026.
5
TNX-102 SL also is being
developed as a treatment for ASR and ASD under an investigator-initiated IND with the University of North Carolina 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, Long COVID or AUD, and are continuously evaluating further indications for which TNX-102 SL could potentially
provide benefit.
We are also developing 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. 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, and the funding period is now completed. Because of the challenges of recruiting eligible patients
into a Phase 2 study, we terminated that study and intend to meet with the FDA in 2026 to inform the clinical design of our next Phase
2 study.
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, bone health in pediatric autism, and arginine-vasopressin deficiency.
Finally,
in December 2025, we in-licensed TNX-4900, formerly known as PW507, from Rutgers University. TNX-4900 is a highly selective
S1R antagonist with demonstrated analgesic activity in multiple models of neuropathic pain. TNX-4900 is in the pre-IND stages
of development.
Immunology
and Infectious Disease
Our lead candidate in the infectious disease pipeline is TNX-4800. Tonix
in-licensed worldwide rights to TNX-4800 (formerly known as mAb 2217LS), in September 2025. TNX-4800 is a long-acting fully human monoclonal
antibody that targets the outer surface protein A (OspA) of Borrelia burgdorferi, the causative agent of Lyme disease in humans.
TNX-4800 is being developed for annual seasonal use and was invented and developed by researchers at UMass Chan Medical School, which
has licensed the technology to Tonix. There are currently no FDA-approved vaccines or prophylactics to protect against Lyme disease.
TNX-4800 has an engineered extended half-life and targets the outer-surface
protein A (OspA) on Lyme-causing Borrelia bacteria. By binding OspA when TNX-4800 containing blood is ingested by the tick, TNX-4800
kills and blocks the maturation of Borrelia burgdorferi in the mid-gut of infected deer ticks. Published work in non-human primates
showed that TNX-4800 was 95% effective in preventing infection after 6 days of exposure to ticks infected with Borrelia burgdorferi.
TNX-4800 was derived from mAb 2217 by amino acid substitutions in its crystallizable fragment (Fc) domain which served to prolong the
serum half-life. A single administration in the Spring is designed to provide onset of immunity within two days and maintain protective
antibody titers for the entire tick season, providing pre-exposure prophylaxis against Lyme disease without relying on the recipient’s
immune system to generate antibodies. By delivering a well-characterized antibody directly, TNX-4800 has been shown to block transmission
of the major Borrelia genospecies from ticks to animals. TNX-4800 also sidesteps the elaborate immunization schedules required
for OspA vaccines in development and an FDA-approved vaccine that was withdrawn from the market. Tonix intends to advance TNX-4800 through
additional clinical trials with the goal of submitting a Biologics Licensing Application (BLA) to the FDA.
We
intend to meet with the FDA in 2026 to explore Phase 2/3 development options for TNX-4800, including a Phase 2 field study and a
Phase 2 human challenge study. The proposed field study would test TNX-4800 for prevention of Lyme in volunteers at risk for Lyme in
regions of the U.S. where Lyme is endemic. The proposed challenge study – also called a controlled human infection model
(“CHIM”) study – would test the ability of TNX-4800 to protect against Borrelia infection by exposing
treated or control volunteers to Borrelia-infected ticks that mimic natural infection. Pending clearances from FDA, we plan
to initiate the Phase 2 field study in 2027 and the Phase 2 human challenge study in 2028. Production of investigational product
under GMP is underway to enable initiation of the field early in 2027, pending FDA clearance. In animals, TNX-4800 provides
protection in approximately two days against the bacteria that causes Lyme disease after a single administration. The passive
immunity conferred by TNX-4800 is very different from the active immunity conferred by vaccines in development to protect against
Lyme disease in that TNX-4800 kills and blocks the metamorphic-like transformation of Borrelia in the tick’s
midgut, preventing transmission of the bacteria, whereas vaccines illicit an immune response in the body of a vaccinated person. Prophylaxis with TNX-4800 may also mitigate some of the limitations of vaccine products designed to actively immunize
against Lyme, including suboptimal immune responses due to age, immunocompetence, and other reasons.
6
Within immunology, we are developing TNX-1500, an Fc-modified humanized
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 were reported in the first quarter of 2025. Pharmacokinetic
results showed mean half-life (t1/2) 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. In November 2025, we announced an investigator-initiated
study with MGH, a founding member of Mass General Brigham (“MGB”), to conduct a Phase 2 clinical trial evaluating TNX-1500
in kidney transplant recipients. The investigator-initiated study will be led by Ayman Al Jurdi, M.D., at MGH and is designed to assess
the safety, tolerability and activity of Fc-modified anti-CD40L mAb TNX-1500 in preventing kidney transplant rejection while significantly
minimizing the dose of conventional immunosuppressive drugs, which are associated with infection, cancer, cardiovascular side effects
and various metabolic derangements. The study is expected to be initiated mid-year 2026 pending FDA clearance of the IND.
Our
immunology pipeline also includes TNX-1700, a recombinant Trefoil Factor Family 2 fused to human serum albumin (“hTFF2-HSA”)
that was licensed from Columbia University in 2019. TNX-1700 is an immunotherapy being developed to treat gastric and colorectal cancers,
in combination with PD-1 blockers, and is at the preclinical stage of development. Results of preclinical testing demonstrated that a
mouse version of TNX-1700 was able to evoke an increase in anti-tumor immunity in combination with anti-PD-1 in several mouse models
of gastric cancer by reducing immunosuppressive neutrophils and activating anti-tumoral CD8+ T cell responses. TNX-1700 as both monotherapy
and in combination with anti-PD-1 was also able to dramatically reduce metastasis and increase survival in these models. TNX-1700 also
exhibits efficacy in various mouse models of colorectal cancer in combination with anti-PD-1. An INTERACT (INitial Targeted Engagement
for Regulatory Advice on CBER/CDER ProducTs) meeting was held with the FDA in 2025 and received constructive early guidance on program
development.
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. Preclinical data/studies demonstrate
that TNX-801, regardless of route of administration (i.e. intradermal, subcutaneous or intramuscular), provided 100% protection against
vaccinia virus and monkeypox virus challenge in terms of both mortality and clinical disease (lesions) in a highly sensitive rabbitpox
model.
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. Our GMP-capable advanced
manufacturing facility in Dartmouth, Massachusetts was purpose-built to manufacture TNX-801. The GMP suites are currently decommissioned
and may be reactivated on the earlier of 2027 or in the case of a national or international emergency.
We are developing a potential broad-spectrum antiviral CD45-targeted therapeutic
(TNX-4200). The DoD announced in December 2022 a plan to move beyond a “one bug, one drug” approach and is seeking
broad-spectrum drugs as it may be hard to predict which or how many viruses may be deployed on the battlefield.
In
July 2024, we were 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. The program focuses on optimization and development of TNX-4200 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. We believe that partial inhibition of CD45
will provide optimal antiviral protection while requiring lower plasma drug concentrations, a lower dose, and a better safety
profile.
We will utilize our state-of-the-art
research laboratory capabilities, including a Biosafety Level 3 (BSL-3) lab and Animal Biosafety Level 3 (ABSL-3) facility, in Frederick,
Maryland (“RDC”), as well as experienced in-house personnel, to develop vaccines and antiviral therapies for mpox, smallpox
and other infectious diseases. We intend to collaborate with academic partners to test the efficacy of CD45 inhibitor compounds against
multiple viral select agents using BSL-4 facilities.
7
Rare
Disease Pipeline
Our rare disease portfolio consists of TNX-2900 (intranasal potentiated oxytocin) for Prader-Willi syndrome (“PWS”),
a rare genetic disorder and the leading cause of life-threatening childhood obesity, affecting about 1 in 10,000 to 1 in 30,000
births. Infants often present with poor muscle tone and feeding difficulties, while children and adolescents develop hyperphagia,
behavioral challenges, and severe obesity and metabolic disease. Current interventions are difficult to sustain and often inadequate.
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 in March 2024, which would make us eligible for a transferable Priority
Review Voucher upon approval.
We
plan to progress our TNX-2900 program for the treatment of PWS into a Phase 2, randomized, double-blind, placebo-controlled,
parallel-design study to evaluate the safety, tolerability, and efficacy of TNX-2900 in male and female participants with PWS,
ages 8 to 17.5 years. Eligible participants will be randomized to receive 12-weeks of treatment with TNX-2900 at one of three
dose levels, or placebo, in a 1:1:1:1 ratio. The primary efficacy endpoint will be the change from baseline in the validated Hyperphagia
Questionnaire for Clinical Trials (HQ-CT), a widely used measure of hyperphagia severity in PWS. Secondary objectives will include
assessments of behavior, caregiver burden, and quality of life measures, as well as safety and tolerability outcomes. We intend
to initiate enrollment in this study in the first quarter of 2027.
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, and may be reactivated on the earlier of 2027 or in the
case of a national or international emergency.
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:
8
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 case 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
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.
9
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.
Based
on market research which 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, including opioids, 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.
Major
Depressive Disorder
MDD is a prevalent and serious psychiatric illness that affects adults of all ages, races, and backgrounds.
It is characterized by persistent feelings of sadness or loss of interest, along with symptoms such as sleep and appetite disturbances,
fatigue, difficulty concentrating, and thoughts of worthlessness or suicide. These symptoms must last at least two weeks and significantly
impair daily functioning. In the United States, more than 21 million adults experience a major depressive episode each year. While
several antidepressant medications are available, many individuals do not achieve adequate relief or discontinue treatment due
to side effects like weight gain, sleep disruption, and sexual dysfunction. MDD is associated with increased risk of suicide and
substantial impairment in quality of life, underscoring the urgent need for new, first-line therapies that are both effective
and well-tolerated.
Acute
Stress Disorder and Acute Stress Reaction
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. ASR is a transient, often severe, emotional and physical response
occurring minutes to days after a traumatic event, such as assault, disaster, or accident. Symptoms include anxiety, flashbacks, numbness,
and insomnia, typically resolving within a few days or up to one month. 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.
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.
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 trigger an immune reaction that leads to rejection. Overcoming this difficulty is paramount to a patient’s
survival as organ donations are in limited supply.
10
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 3rd leading cause of cancer death in women, and 2nd in men.
Infectious
Diseases
Lyme
Disease
Lyme
disease is caused by the bacterium Borrelia burgdorferi. Lyme disease remains the most common vector-borne infection in the United
States and its incidence is climbing each year. It occurs most commonly in the Northeast, mid-Atlantic, and upper-Midwest regions. Lyme
disease bacteria are transmitted through the bite of infected Ixodes ticks. Typical symptoms include fever, headache, fatigue, and a
characteristic skin rash called erythema migrans. If left untreated, infection can spread to joints, the heart, and the nervous system.
Laboratory testing is helpful if used correctly and performed with FDA-cleared tests.
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. Although PHEIC designation
has been lifted by WHO, mpox continues to spread in Africa and mutations of the virus are considered by public health experts
to be an ongoing threat to be monitored for new epidemic spread.
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.
11
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. PWS results from the absence of expression of a group of genes, specifically related to the
MAGE (melanoma antigen) gene family on the Prader–Willi critical region (15q11–q13) on the paternally acquired
chromosome. The hallmarks of PWS are lack of suckling in newborns and, in children and adolescents, severe hyperphagia – an
overriding physiological drive to eat, leading to severe obesity and other complications associated with significant mortality. A
systematic review of the morbidity and mortality as a consequence of hyperphagia in PWS found that the average age of death in PWS
was 22.1 years. Given the serious or life-threatening manifestations of these conditions, there is a critical need for effective
treatments to decrease morbidity and mortality, improve quality of life, and increase life expectancy in people with PWS. Oxytocin
has potent effects in correcting behavioral characteristics of the MAGEL2 knock-out mouse model for PWS and autism. Six clinical
trials have investigated intranasal oxytocin as a treatment in pediatric patients with PWS. Four clinical studies showed evidence
for improvement in PWS-related behaviors/symptoms. Three of these clinical studies reported evidence for improvement in hyperphagia
and one showed an improvement in sucking in infants.
Tonix’s
Marketed Products
TONMYA
– Treatment of Fibromyalgia
In
August 2025, we received approval from the FDA for TONMYA (cyclobenzaprine HCl sublingual tablets) for the treatment
of fibromyalgia. TONMYA in adults, Tonix’s first internally developed product, was commercially launched by the Company in the United
States on November 17, 2025. TONMYA is the first new treatment for fibromyalgia in more than 15 years and is a centrally acting,
differentiated non-opioid analgesic designed for bedtime administration and long-term use, addressing core symptoms of fibromyalgia
including pain, disturbed sleep and fatigue. The approval and launch of TONMYA marked a major milestone in our evolution
as an organization with growing revenues and an expanding customer footprint. We hold worldwide commercialization rights to TONMYA.
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.
Together,
these products form the foundation of our commercial platform, including sales, marketing, market access, distribution,
and patient support capabilities.
Product
Candidates in Development
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 Major Depressive Disorder Phase 2 expected to commence mid-2026
TNX-102 SL Acute Stress Reaction/Acute Stress Disorder Phase 2 enrolling*
TNX-1500 Kidney Transplant Rejection Phase 2 study planned for mid 2026*
TNX-1300 Cocaine Intoxication Mid-Phase 2
TNX-2900 Prader-Willi Syndrome Phase 2 expected to commence first quarter 2027
TNX-801 Smallpox and Mpox vaccine Preclinical, pre-IND
TNX-4200 Treatment or Prevention of Viral Disease Preclinical, pre-IND
TNX-4900 Neuropathic pain Preclinical, pre-IND
TNX-1700 Gastric and colorectal Cancer Preclinical, pre-IND
*Investigator
Initiated Studies
12
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. TNX-102 SL is approved under the brand name TONMYA, for the treatment of
fibromyalgia in the U.S. We have active IND’s for TNX-102 SL as a treatment for MDD, ASD/ASR, PTSD, or multi-site pain
associated with Long COVID, AAD and AUD however, we are not currently studying TNX-102 SL in PTSD, AAD, Long Covid or AUD. We own all rights to TNX-102 SL in all geographies, and we bear no obligations to third
parties for any future development or commercialization. Excipients used in TNX-102 SL are approved for pharmaceutical use. Some of
the excipients were specially selected to promote a local oral environment that facilitates 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.
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 active 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.
13
Global
NDA Requirements
We
are planning to develop TNX-102 SL for the treatment of FM in the UK, Europe and Japan. We plan to discuss the
development of TNX-102 SL for the treatment of FM with the UK’s Medicines and Healthcare products Regulatory Agency (MHRA),
the European Medicines Agency (EMA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Cyclobenzaprine, the active ingredient of TNX-102 SL, has not been approved in the
UK, most countries in Europe, or in Japan. In February 2022, we held an End of Phase 2 Consultation with the Japanese PMDA, to
discuss the potential Japan development plan. PMDA has provided guidance on the overall nonclinical package to support a Japan NDA
filing for TNX-102 SL for the treatment of FM. We plan to have another Consultation with PMDA to provide program updates and discuss
the Japan development plan.
We
have also successfully completed a Phase 1 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.
A
Phase 1 PK 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, AUC0-T and AUC0-∞ 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, AUC0-T and AUC0-∞,
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.
TNX-102
SL (cyclobenzaprine HCl sublingual tablets) – Major Depressive Disorder (MDD) Program
We
are developing TNX-102 SL as a treatment for MDD. In September 2025, Tonix announced the successful completion of a Type B Pre-IND
meeting with the FDA regarding the development of TNX-102 SL for the treatment of MDD. The Company received positive feedback
from the FDA and plans to pursue a supplemental new drug application (sNDA) to expand the therapeutic indication of TNX-102 SL
to include MDD, based on exploratory findings suggesting that improving sleep quality may positively impact depressive symptoms.
In
November 2025, the FDA cleared the IND application to support clinical development of TNX-102 SL 5.6 mg for the treatment of MDD
in adults. The unique pharmacological profile of TNX-102 SL is designed to target the disruptive sleep which is often associated
with depression. Prior studies of TNX-102 SL in fibromyalgia and post-traumatic stress disorder (PTSD) showed promising signals
for improvement of depressive symptoms on the Beck Depression Inventory-II and the MADRS,
respectively.
The IND clearance enables Tonix to proceed with a potentially pivotal Phase
2 HORIZON study, a 6-week, randomized, double-blind, placebo-controlled study of TNX-102 SL as a first-line monotherapy in adults with
MDD. About 360 patients will be enrolled at approximately 30 U.S. sites. Eligible participants are 18 years or older and currently experiencing
a moderate to severe major depressive episode. The study will compare TNX-102 SL 5.6 mg, taken sublingually at bedtime to placebo, with
the primary endpoint being the MADRS total score change from baseline at Week 6. Secondary endpoints include global impression scores,
anxiety ratings, and measures of sleep disturbance. Tonix plans to initiate enrollment of the study in mid-year 2026.
TNX-102
SL – Acute Stress Disorder Program
TNX-102 SL is being developed as a bedtime treatment for ASR/ASD in collaboration
with the University of North Carolina under an investigator-initiated IND.
Phase
2 OASIS Study
This