TNXP US Equity☆

UNITED

STATES

SECURITIES

AND EXCHANGE COMMISSION

WASHINGTON,

D.C. 20549

FORM

10-K

(Mark

One)

☒

ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For

the Fiscal Year Ended December 31, 2023

☐

TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

Commission

File Number 001-36019

TONIX

PHARMACEUTICALS HOLDING CORP.

(Exact

name of registrant as specified in its charter)

26 Main Street, Suite 101 Chatham, New Jersey 07928

(Address of principal executive office) (Zip Code)

(862) 799-8599 (Registrant’s telephone number, including area code)

Securities

registered pursuant to Section 12(b) of the Act:

Title of each class Trading Symbol Name of each exchange on which registered

Common Stock, $0.001 par value TNXP The NASDAQ Stock Market LLC

Securities

registered pursuant to Section 12(g) of the Act: None

Indicate

by check mark if the registrant is a well-known seasoned issuer, as defined by Rule 405 of the Securities Act. Yes ☐ No

☒

Indicate

by check mark if the registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. Yes ☐ No ☒

Indicate

by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange

Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports),

and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐

Indicate

by check mark whether the registrant has submitted electronically, if any, every Interactive Data File required to be submitted

pursuant to Rule 405 of Regulation S-T (§ 229.405 of this chapter) during the preceding 12 months (or for such shorter period

that the registrant was required to submit such files). Yes ☒ No ☐

Indicate

by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting

company, or an emerging growth company. See definitions of “large accelerated filer,” “accelerated filer,”

“smaller reporting company,” and an “emerging growth company” in Rule 12b-2 of the Exchange Act

Large accelerated filer ☐ Accelerated filer ☐

Non-accelerated filer ☒ Smaller reporting company ☒

Emerging growth company ☐

If

an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for

complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Indicate

by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness

of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered

public accounting firm that prepared or issued its audit report. ☐

If

securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the

registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐

Indicate

by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation

received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b).

☐

Indicate

by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒

The

aggregate market value of the voting common equity held by non-affiliates as of June 30, 2023, based on the closing sales price

of the common stock as quoted on The NASDAQ Global Market was $16,996,283. For purposes of this computation, all officers and

directors are deemed to be affiliates. Such determination should not be deemed an admission that such directors, officers, or

5 percent beneficial owners are, in fact, affiliates of the registrant.

As

of April 1, 2024, there were 84,490,862shares of registrant’s common stock outstanding.

DOCUMENTS

INCORPORATED BY REFERENCE

None.

TABLE

OF CONTENTS

PAGE

PART I

Item 1. Business 3

Item 1A. Risk Factors 47

Item 1B. Unresolved Staff Comments 72

Item 1C. Cybersecurity Disclosures 72

Item 2. Properties 73

Item 3. Legal Proceedings 73

Item 4. Mine Safety Disclosures 74

PART II

Item 6. Reserved 74

Item 7A. Quantitative and Qualitative Disclosures about Market Risk 86

Item 8. Financial Statements and Supplementary Data F-1 – F-30

Item 9A. Controls and Procedures 87

Item 9B. Other Information 87

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 88

PART III

Item 10. Directors, Executive Officers and Corporate Governance 88

Item 11. Executive Compensation 93

Item 14. Principal Accounting Fees and Services 101

PART IV

Item 15. Exhibits, Financial Statement Schedules 102

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. 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:

Business

Overview

We are a fully-integrated

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

Our near-term priority is

to submit a New Drug Application (“NDA”) to the U.S. Food and Drug Administration (“FDA”) for TonmyaTM* (also

known as TNX-102 SL, cyclobenzaprine HCl sublingual tablet) for the management of fibromyalgia (“FM”). FM is a chronic pain

disorder characterized by chronic widespread pain, non-restorative sleep, fatigue and impaired cognition. Tonmya is a non-opioid analgesic

designed for long-term bedtime use and has completed two positive Phase 3 studies. Tonix announced the positive results of the second

Phase 3 study in December of 2023. Tonmya treatment resulted in highly statistically significant improvement in the primary endpoint of

pain reduction (p=0.00005) and statistical significance in all six of the key secondary endpoints. Tonmya was well tolerated. Systemic

adverse events were similar between Tonmya and placebo. No serious adverse events were reported. The FDA conditionally accepted Tonmya

as the trade name for TNX-102 SL for the management of fibromyalgia in January 2024. We have scheduled a type B pre-NDA meeting with the

FDA in the first half of 2024, plan to submit an NDA for the approval of Tonmya in the second half of 2024 and expect an FDA decision

on the NDA in the second half of 2025. We are preparing for a commercial launch of Tonmya conditional on FDA approval.

3

Tonmya is a proprietary sublingual

tablet formulation of cyclobenzaprine (“CBP”) designed for bedtime administration. In December 2020, we reported positive

results from the Phase 3 RELIEF study of Tonmya 5.6 mg for the management of FM. In July 2021, we had disappointing results from a second

Phase 3 study, RALLY. In December 2023, we reported positive results from the third Phase 3 RESILIENT study, which met its pre-specified

endpoint by significantly reducing daily pain compared to placebo in patients with fibromyalgia.

In preparation for the launch

of Tonmya, we have built a team of professionals to market and distribute our products. Our commercial portfolio consists of two FDA-approved

prescription products for the treatment of migraine which were acquired from Upsher-Smith Laboratories (“Upsher Smith”) in June 2023:

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. Our commercial team is engaged in marketing and distributing

our products, and also engaged in planning the launch of Tonmya.

In addition to Tonmya and

our marketed products, we have a pipeline of products in development that include therapeutics and vaccines which are based on small molecules

and biologics. Our pipeline has been generated from internal discovery, as well as licenses, acquisitions and collaborations with academic

institutions and non-profit organizations.

Our portfolio is focused on

central nervous system (“CNS”), disorders, but also consists of rare disease, immunology, and infectious disease product candidates. The

CNS portfolio includes small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Our immunology portfolio

includes TNX-1500*, a biologic to address organ transplant rejection and autoimmune diseases. Finally, our infectious disease portfolio

includes a vaccine in development to prevent smallpox and mpox (formerly known as monkeypox), TNX-801*. TNX-801 also serves as the live

virus vaccine platform or recombinant pox vaccine (“RPV”) platform for vaccines to protect against other infectious diseases,

including TNX-1800* and TNX-1850* for COVID-19.

In addition to fibromyalgia,

TNX-102 SL* is being developed as a potential treatment for a type of Long COVID, the symptoms of which overlap with fibromyalgia, that

we term fibromyalgia-type Long COVID. TNX-102 SL has completed a Phase 2 proof-of-concept study. Long COVID is also known as PASC, (“post-acute

sequelae of SARS-CoV-2 infection”) is a chronic post-acute COVID-19 condition. We initiated enrollment in the Phase 2 PREVAIL study, in

August 2022, and topline results were reported in September 2023. The study did not meet the primary endpoint of change in mean pain from

baseline but did show activity in improving fatigue, a hallmark symptom of Long COVID.

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. The

Phase 2 OASIS study at UNC is supported by the U.S. Department of Defense (“DoD”). We expect enrollment in the OASIS

study to begin in the second quarter of 2024. The UNC-led OASIS study will build upon the existing AURORA initiative, a major

national research initiative to improve the understanding, prevention, and recovery of individuals who have experienced a traumatic

event.

In addition, TNX-102 SL has

active INDs for PTSD, agitation in Alzheimer’s disease (“AAD”), and alcohol use disorder (“AUD”). 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.

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. We expect to initiate enrollment in a potentially pivotal Phase 2 study of TNX-1300 in emergency rooms in the second

quarter of 2024.

Our rare disease

portfolio includes 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 genes.

4

We are developing a different intranasal

oxytocin product, TNX-1900* (intranasal potentiated oxytocin with magnesium) for several CNS disorders through investigator-initiated

studies. TNX-1900 is in development through investigator-initiated studies for the treatment of binge eating disorder (“BED”),

adolescent obesity, social anxiety disorder (“SAD”), and bone health in pediatric autism. We received IND clearance from the

FDA in the fourth quarter of 2021 to study TNX-1900 in chronic migraine and we initiated the Phase 2 PREVENTION study for the prevention

of migraine headaches in chronic migraineurs in the first quarter of 2023. Topline results from the study, reported in December 2023,

showed that TNX-1900 did not meet the primary endpoint as measured by a reduction from 28-day run-in baseline in the mean number of migraine

headache days during the last 28 days of the treatment phase. PREVENTION was a small proof-of-concept study with 88 patients enrolled

across three arms (TNX-1900 30 IU QD, TNX-1900 30 IU BID, and placebo), and was not powered to result in a statistically significant outcome.

In the trial, TNX-1900 was generally well-tolerated with no treatment-emergent serious or severe adverse events. We have discontinued

development of TNX-1900 in chronic migraine.

Our lead candidate in the immunology pipeline

is 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. TNX-1500 is being developed as a prophylaxis against organ transplant rejection as well as to treat autoimmune

conditions. The IND was cleared and a Phase 1 study of TNX-1500 in healthy volunteers was initiated in the second quarter of 2023 and

completed the clinical phase in the first quarter of 2024. TNX-1500 is being studied in combination with other immunosuppressive agents

in allogeneic and xenogeneic organ transplants in non-human primates at Massachusetts General Hospital, a teaching hospital of Harvard

Medical School (“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.

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.

Our immunology pipeline also includes

TNX-1700*, a recombinant Trefoil Factor Family 2 (“rTFF2”) fusion protein that was licensed from Columbia University in 2019.

TNX-1700 consists of TFF2 fused to human serum albumin (HAS) 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.

Our infectious disease

portfolio includes vaccines based on our live virus vaccine or 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

attenuated vaccine based on synthesized horsepox, is in the pre-IND stage of development to protect against smallpox and mpox. 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 men who

have sex with men. Non-human primates 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 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 attenuated than older

vaccinia-based smallpox vaccines in both human primary cell lines and immunocompromised mice. That work has been posted on

BioRxiv, which is not peer-reviewed. 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.

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 the third quarter of 2023, TNX-1800 was selected by the U.S. National Institute of Allergy and

Infectious Diseases (“NIAID”), a part of the NIH, to be included in their Project NextGen initiative,

an initiative to advance a pipeline of new, innovative vaccines and therapeutics for COVID-19. 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.

5

Tonix has three pre-clinical research

and development programs developing broad spectrum antivirals. 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. TNX-3900* are broad-spectrum small molecule oral antivirals which inhibit essential cathepsins required by viruses

such as coronaviruses and filoviruses to infect cells. TNX-4200* are orally available CD45 antagonists in preclinical development. We

believe that partial inhibition of CD45 will provide optimal antiviral protection while requiring lower plasma drug concentrations and

a lower dose, and therefore will have a higher safety window. Tonix plans to leverage previous research on phosphatase inhibitors, specifically

compounds that target CD45, to optimize lead compounds for therapeutic intervention of biothreat agents. TNX-4000* are viral glycan-targeted

engineered biologics. These antivirals are currently in preclinical development.

Relating to our development programs,

we own and operate the Research and Development Center (“RDC”) in Frederick, Maryland consisting of one building totaling

approximately 48,000 square feet. The RDC conducts research on central nervous system, immunology, and infectious disease candidates.

The RDC facility is mostly biosafety level 2 (BSL-2), with some components designated BSL-3. We also own and operate 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 and clinical scale manufacturing of live-virus vaccines and biologics to support

clinical trials. We have engaged CBRE, an international real estate brokerage firm, to find a strategic partner for, or buyer of, ADC.

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

We

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

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

Our

Strategy

Our

strategy is to use our integrated development engine 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:

6

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)

FM

is a chronic syndrome characterized by widespread pain accompanied by fatigue, non-restorative sleep, cognitive dysfunction or

“brain fog” and mood issues. The peak incidence of FM occurs between 20-50 years of age, and the majority of diagnosed

patients are female. FM may have a substantial negative impact on social and occupational function, including disrupted relationships

with family and friends, social isolation, reduced activities of daily living and leisure activities, avoidance of physical activity,

and loss of career or inability to advance in career or education. According to the American Chronic Pain Association, an estimated

six to twelve million adults in the U.S. have FM.

According

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

fail therapy due to either insufficient efficacy, poor tolerability, or both. Prescription pain and sleep medications are frequently

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

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

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

and toxicity, including overdose.

Fibromyalgia-type

Long COVID

Long COVID, or PASC, is a

condition that some survivors of COVID-19 infection experience in varying degrees of severity. It is a chronic disabling condition that

is expected to result in a significant global health and economic burden. We are focusing the development of TNX-102 SL specifically on

fibromyalgia-type Long COVID, the symptoms of which include intense fatigue, sleep problems, multi-site pain, and cognitive issues (“brain

fog”). The proposed indication is for the management of multi-site pain associated with PASC.

Post

infection, many patients experience one or many of the symptoms of Long COVID: some patients have initial symptoms that become prolonged;

others manifest entirely new syndromes that impact more than one system or organ. According to a 2021 publication in the Journal of

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

moderate to severe symptom eight months later. Research shows that Long COVID occurs in approximately 19% of recovered COVID-19 patients.

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

Migraine

Headaches

Migraine

is a primary headache disorder characterized by recurrent headaches that are moderate to severe. Typically, episodes affect one

side of the head, are pulsating in nature, and last from a few hours to three days. Associated symptoms may include nausea, vomiting,

and sensitivity to light, sound, or smell. The pain is generally made worse by physical activity, although regular exercise may

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

that the headache will soon occur. Occasionally, aura can occur with little or no headache following it. Approximately one billion

individuals worldwide suffer from migraine (~14% of the population). Migraine is the second leading cause of years lived with

disability.

7

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.

Rare

Disease

Prader-Willi

Syndrome (PWS)

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.

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 33.3%. According to 2017-2019 data, approximately

0.8 percent of men and women will be diagnosed with stomach cancer during their lifetime. In 2019, there were an estimated 123,920

people living with stomach cancer in the U.S.

Colorectal

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

of food-waste. Most colorectal cancers start as a growth or polyp on the inner lining of the colon or rectum. Some types of polyps

can change into cancer over time (usually many years), but not all polyps become cancer. Adenomatous polyps are the ones that

turn malignant with time. Similar to gastric cancer, the malignancy begins in the mucosal layer and spreads outwards.

8

The

5-year relative survival rate is 65.1%, per the National Cancer Institute. According to 2017-2019 data, approximately 4.1 percent

of men and women will be diagnosed with colorectal cancer during their lifetime. In 2019, there were an estimated 1,369,005 people

living with colorectal cancer in the United States.

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 2 cases spread rapidly in the U.S. and other countries. More than 30,000

cases in the U.S. have been reported according to the U.S. Centers for Disease Control and Prevention. An outbreak of Clade 1 mpox in

the Democratic Republic of the Congo is raising concerns by the U.S. Bipartisan Commission on Biodefense.

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.

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. At least three major variants have swept

across the world in successive waves and overwhelmed healthcare systems during these waves. With new variants of the virus emerging,

therapeutic research is addressing the challenge of keeping up with this rapidly mutating virus. The early vaccines have been

effective in limiting the severity of disease in vaccinated individuals. Vaccines that elicit strong T cell responses are believed

to have the potential to provide long-term or durable protection.

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. These products collectively generated combined gross retail product

sales of approximately $28.5 million for the twelve months ended December 31, 2023.

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.

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-type Long COVID Phase 2 study completed

TNX-102 SL Acute Stress Reaction Phase 2 ready* – investigator-initiated IND

TNX-1300 Cocaine Intoxication Mid-Phase 2, targeted 2Q 2024 start

TNX-2900 Prader-Willi Syndrome Phase 2 ready, IND cleared

TNX-1500 Kidney Transplant Rejection Phase 1 study ongoing

TNX-801 Smallpox and Mpox vaccine Preclinical, pre-IND

TNX-1800 COVID-19 vaccine Preclinical, pre-IND

*Investigator

Initiated Studies

9

TNX-102

SL

Overview

TNX-102 SL is a proprietary

sublingual tablet formulation of CBP that efficiently delivers CBP across the oral mucosal membrane into

the systemic circulation. We have active IND’s for TNX-102 SL as a bedtime treatment for fibromyalgia, PTSD, fibromyalgia-type 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 mucosal absorption of CBP.

The

current TNX-102 SL sublingual tablets each contain 2.8 mg of CBP. TNX-102 SL 5.6 mg (two 2.8 mg tablets) at

bedtime has completed two positive Phase 3 studies for the management of fibromyalgia. 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 the active ingredient of two products that are approved in the U.S. for the treatment of muscle spasm: Flexeril® (5 mg

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

Flexeril brand of CBP IR tablet has been discontinued since May 2013. There are numerous generic versions of CBP IR tablets on

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

therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions. CBP IR tablets are recommended for

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

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

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 largely bypasses the “first pass”

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

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

serious and unexpected adverse reactions reported in these studies. Some subjects experienced transient numbness of the tongue after

TNX-102 SL administration.

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 reference listed drug (RLD). In general, the

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

chemical entities, or NCEs, that have never been approved in the U.S. We believe that TNX-102 SL has the potential to provide clinical

benefit to fibromyalgia, fibromyalgia-type Long COVID, and PTSD patients and possibly other CNS (central nervous system) indications that

are underserved by currently marketed products or have no approved treatment.

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.

Tonmya

(TNX-102 SL) – FM program

We

are developing Tonmya as a bedtime treatment for FM under an active IND application. The potential approval of Tonmya for FM is

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

Clinical

Development Plan

Completed

Positive Phase 3 RESILIENT Study (F307)

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 Tonmya 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 Tonmya 2.8 mg (1 tablet) or placebo. Thereafter,

all participants increase their dose to Tonmya 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 Tonmya 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. Tonmya was well tolerated and consistent with prior trials, with no new safety

signals observed. Among participants randomized to the Tonmya and placebo arms, 81.0% and 79.2%, respectively, completed the 14-week dosing

period. As expected based on prior Tonmya studies, administration site reactions were the most commonly reported adverse events and were

higher in the Tonmya 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 Tonmya 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 Tonmya arm. Of the two in the Tonmya 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.

10

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 Tonmya 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 Tonmya 2.8 mg (1 tablet) or placebo. After the first two weeks, all patients had the dose increased to Tonmya

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,

Tonmya did not achieve statistical significance over placebo on the primary endpoint of reduction in daily pain, and relative to the previous

positive Phase 3 Study (RELIEF), RALLY had an unexpected increase in study participant adverse event-related discontinuations in both

drug and placebo groups.

Completed

Positive Phase 3 RELIEF Study (F304)

In

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

of Tonmya 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 Tonmya 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 Tonmya 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). Consistent with the proposed mechanism that Tonmya

acts in fibromyalgia through improving sleep quality, Tonmya 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, Tonmya 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 ratings and

PROMIS Sleep Disturbance instrument were 0.31 and 0.32, respectively.

In the RELIEF study, Tonmya

was similarly well tolerated as in the Phase 2 BESTFIT and Phase 3 AFFIRM studies, which both studied Tonmya 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 Tonmya

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 Tonmya 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 almost all occurrences. The only systemic treatment-emergent adverse

events that occurred at a rate of 5.0% or greater in either arm was somnolence/sedation at 5.6% in the Tonmya 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 Tonmya 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 Tonmya arm. Of the two

in the Tonmya arm, one was a motor vehicle accident with multiple bone fractures, and the other was a case of pneumonia secondary to an

infection.

11

Completed

Phase 3 AFFIRM Study (F301)