Tonix Pharmaceuticals Announces Licensing TNX-4900, a Selective Sigma-1 Receptor Antagonist for Chronic Neuropathic Pain from Rutgers University

Rhea-AI Summary

Tonix Pharmaceuticals (Nasdaq: TNXP) announced exclusive worldwide licensing of TNX-4900, a selective small-molecule Sigma-1 receptor antagonist for chronic neuropathic pain, on December 16, 2025. TNX-4900 binds human S1R with Ki = 7.5 nM, shows >100-fold selectivity over Sigma-2, and demonstrates high blood-brain barrier penetration and oral bioavailability of ~28%. In animal models of diabetic and chemotherapy-induced neuropathic pain, TNX-4900 produced significant, durable analgesia after acute and chronic dosing without tolerance or motor impairment. Tonix plans expanded PK, formulation, and safety studies to support IND-enabling development.

Positive

• Exclusive worldwide license secured for TNX-4900
• High potency: S1R binding Ki = 7.5 nM
• >100-fold selectivity versus Sigma-2 receptor
• BBB penetration and oral bioavailability ≈ 28%
• Preclinical efficacy in diabetic and chemotherapy neuropathic pain models
• No evidence of tolerance or motor impairment in animal studies

Negative

• TNX-4900 remains preclinical with no human clinical data
• Oral bioavailability is moderate at ~28%

News Market Reaction

-1.38%

2 alerts

-1.38% News Effect

-$3M Valuation Impact

$232M Market Cap

0.0x Rel. Volume

On the day this news was published, TNXP declined 1.38%, reflecting a mild negative market reaction. Our momentum scanner triggered 2 alerts that day, indicating moderate trading interest and price volatility. This price movement removed approximately $3M from the company's valuation, bringing the market cap to $232M at that time.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

Sigma-1 receptor affinity: Ki = 7.5 nM Sigma-1 vs Sigma-2 selectivity: >100-fold selectivity Oral bioavailability: 28% +4 more

7 metrics

Sigma-1 receptor affinity Ki = 7.5 nM Binding of TNX-4900 to human Sigma-1 receptor

Sigma-1 vs Sigma-2 selectivity >100-fold selectivity Selectivity of TNX-4900 over Sigma-2 receptor

Oral bioavailability 28% Oral bioavailability of TNX-4900 in animal studies

DTRA contract value $34 million Contract for TNX-4200 over five years

DTRA contract term five years Duration of U.S. DoD DTRA contract for TNX-4200

Fibromyalgia drug gap more than 15 years First new FDA-approved fibromyalgia prescription medicine timeframe

Pain models multiple animal models Diabetic and chemotherapy-induced neuropathic pain models for TNX-4900

Market Reality Check

Price: $17.24 Vol: Volume 354,244 is below t...

low vol

$17.24 Last Close

Volume Volume 354,244 is below the 20-day average of 788,122 (about 45% of typical activity). low

Technical Shares at $18.86 are trading below the 200-day MA of $26.82 and sit 85.49% under the 52-week high and 178.99% above the 52-week low.

Peers on Argus

Key biotech peers like NMRA (-5.31%), CADL (-10.12%), and OMER (-9.8%) are down,...

Key biotech peers like NMRA (-5.31%), CADL (-10.12%), and OMER (-9.8%) are down, indicating broader biotech pressure, but the momentum scanner does not flag a coordinated sector move tied to this headline.

Historical Context

5 past events · Latest: Dec 09 (Neutral)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Dec 09	Management addition	Neutral	-1.5%	Appointment of experienced General Counsel to lead legal and compliance functions.
Nov 24	IND clearance	Positive	-11.3%	FDA IND clearance for potentially pivotal Phase 2 HORIZON study in MDD.
Nov 17	Product launch	Positive	+5.7%	U.S. commercial availability of TONMYA as first-in-class fibromyalgia treatment.
Nov 10	Earnings update	Positive	+4.1%	Q3 2025 results with Tonmya approval, launch plans, and cash runway into Q1 2027.
Nov 06	Conference participation	Neutral	-3.9%	Announcement of presentation at Stifel Healthcare Conference highlighting pipeline.

Pattern Detected

Recent positive clinical and commercial milestones often saw aligned price gains, but the MDD IND clearance drew a notable negative reaction.

Recent Company History

Over the past months, Tonix advanced from FDA approval of TONMYA for fibromyalgia to its U.S. commercial availability on Nov 17, 2025, while reporting Q3 2025 results with cash runway into Q1 2027. The company also secured FDA IND clearance for a Phase 2 MDD study and expanded its leadership with a new General Counsel. Against this backdrop of CNS and pain-focused growth, today’s licensing of TNX-4900 adds another non-opioid neuropathic pain asset to the portfolio.

Regulatory & Risk Context

Active S-3 Shelf

Shelf Active

Active S-3 Shelf Registration 2025-09-04

The company has an active S-3/A shelf registration filed on 2025-09-04, with at least one recent usage via a 424B5 prospectus supplement on 2025-11-21, indicating the ability to issue additional securities, subject to effectiveness and market conditions.

Market Pulse Summary

This announcement adds TNX-4900, a selective Sigma‑1 receptor antagonist with nanomolar affinity and...

Analysis

This announcement adds TNX-4900, a selective Sigma‑1 receptor antagonist with nanomolar affinity and >100‑fold selectivity, to Tonix’s non‑opioid pain pipeline. The compound’s animal data and pharmacokinetic profile support planned IND‑enabling studies in chronic neuropathic pain. In the context of recent milestones—such as TONMYA’s approval and launch and the MDD Phase 2 IND—investors may watch for clear clinical timelines, partnering or funding updates, and how management prioritizes this asset within the broader CNS and pain strategy.

Key Terms

sigma-1 receptor, sigma-2 receptor, blood-brain barrier, adme, +4 more

8 terms

sigma-1 receptor medical

"a highly selective small-molecule Sigma-1 receptor (S1R) antagonist with demonstrated..."

A sigma-1 receptor is a protein found on the surface and inside certain cells that helps regulate how cells respond to stress and signals, acting like a cellular switchboard or traffic controller. It matters to investors because drugs that interact with this receptor are being explored for treating conditions such as neurological, psychiatric, pain and heart disorders; success or failure in development and trials can strongly affect a company’s value and future revenue prospects.

sigma-2 receptor medical

"demonstrates > 100-fold selectivity over the Sigma-2 receptor, and exhibits high..."

A sigma-2 receptor is a protein on or inside cells that binds certain small molecules and influences cell functions such as growth, death, and signaling; researchers study it as a biological target for drugs and imaging agents. For investors, it matters because therapies or diagnostics that hit this receptor can become new treatments or tools for diseases like cancer and brain disorders, affecting a company’s development prospects, regulatory path, and market value much like a promising new engine can change a carmaker’s product line.

blood-brain barrier medical

"and exhibits high blood-brain barrier penetration and favorable adsorption..."

A protective barrier of tightly packed cells and supporting tissue that controls what substances in the blood can enter the brain, acting like a security checkpoint that keeps out most pathogens and many drugs while allowing essential nutrients through. For investors, the barrier matters because whether a therapy can cross or safely bypass it often determines clinical success, regulatory approval and commercial potential for treatments of brain disorders.

adme medical

"favorable adsorption, distribution, metabolism and elimination (ADME) properties..."

ADME stands for Absorption, Distribution, Metabolism and Excretion — the four processes that determine how a drug enters the body, moves to target tissues, is chemically changed, and is removed. For investors, ADME profiles signal whether a drug is likely to be effective, safe and practical to dose; weak ADME can sink a program just like delivery problems can ruin a product launch, while strong ADME improves chances of regulatory approval and commercial success.

oral bioavailability medical

"including oral bioavailability of approximately 28%."

Oral bioavailability is the share of a pill or liquid medicine that survives the digestive system and reaches the bloodstream to have an effect. It matters to investors because low bioavailability can mean higher doses, more side effects, tougher manufacturing, and greater clinical or regulatory risk, all of which affect a drug’s cost, pricing and commercial prospects—like ordering a package and finding only part of it arrives.

investigational new drug regulatory

"support IND-enabling studies"

An investigational new drug is a medication that is still being tested in clinical trials to determine if it is safe and effective for treating a specific condition. For investors, it represents a potential breakthrough that could lead to a new treatment and significant financial gains if successful, but also carries risks since it has not yet been approved for widespread use.

monoclonal antibody medical

"a Phase 2- ready Fc-modified humanized monoclonal antibody targeting CD40-ligand..."

A monoclonal antibody is a laboratory-made protein designed to recognize and attach to a specific target in the body, such as a disease-causing substance or cell. It functions like a highly precise lock-and-key tool, helping to treat or detect illnesses. For investors, companies developing monoclonal antibodies can represent promising opportunities in the healthcare sector, especially as these treatments often address unmet medical needs.

prader-willi syndrome medical

"TNX-2900, intranasal oxytocin potentiated with magnesium, in development for Prader-Willi syndrome..."

A rare genetic disorder caused by missing or altered instructions on a specific chromosome that leads to constant hunger, low muscle tone, learning challenges, and hormonal problems; think of it as a faulty instruction manual that affects growth, appetite control, and development. Investors care because the condition creates a defined patient population, special regulatory incentives, and long-term medical needs that shape demand for therapies, diagnostics, and care services, influencing market size and risk for drug developers.

AI-generated analysis. Not financial advice.

Non-opioid analgesic shows efficacy in several animal pain models, including diabetic and chemotherapy-induced neuropathic pain

Compelling safety and pharmacokinetic profiles in animals support IND-enabling studies

CHATHAM, N.J., Dec. 16, 2025 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (“Tonix” or the “Company”), a fully-integrated commercial biotechnology company, today announced licensing exclusive worldwide rights to TNX-4900 (formerly known as PW507), a highly selective small-molecule Sigma-1 receptor (S1R) antagonist with demonstrated analgesic activity in multiple models of neuropathic pain.

“Sigma-1 receptor antagonism has generated considerable scientific interest as a promising class of non-opioid, non-addictive analgesics,” said Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals. “With our extensive experience studying and developing an FDA approved non-opioid analgesic we are well-positioned to oversee this new development program. We believe TNX-4900 has the potential to be best-in-class.”

Dr. Youyi Peng, co-inventor of TNX-4900, formerly a Senior Bioinformatics Specialist at the Rutgers Cancer Institute of New Jersey and now a consultant to Tonix, added, “We used computer-aided and AI-driven approaches to design this new class of selective Sigma-1 receptor antagonists. TNX-4900 showed robust analgesic efficacy in multiple pain models and an encouraging safety profile, supporting its potential as a new non-opioid approach to treating neuropathic pain.”

TNX-4900 was created from a structure-based drug design program led by Dr. Youyi Peng and Dr. William Welsh at Rutgers University that produced a series of potent and selective triazole-based S1R antagonists. The compound binds the human Sigma-1 receptor with nanomolar affinity (K_i = 7.5 nM), demonstrates > 100-fold selectivity over the Sigma-2 receptor, and exhibits high blood-brain barrier penetration and favorable adsorption, distribution, metabolism and elimination (ADME) properties, including oral bioavailability of approximately 28%.

“Our foundational research into TNX-4900 represents an important step toward developing non-opioid solutions for chronic pain. We are pleased to see this innovation progress toward potential clinical application, which could address a critical need for safer pain management options,” said Dr. William Welsh, Distinguished Professor in the Department of Pharmacology at Rutgers Robert Wood Johnson Medical School (RWJMS).

In preclinical models of diabetic and chemotherapy-induced neuropathic pain, TNX-4900 produced significant and durable reductions in pain behaviors after both acute and chronic dosing without evidence of tolerance or motor impairment. Tonix plans to advance TNX-4900 through expanded pharmacokinetic, formulation, and safety studies to support IND-enabling development.

Tonix Pharmaceuticals Holding Corp.
Tonix Pharmaceuticals is a fully-integrated biotechnology company with marketed products and a pipeline of development candidates. Tonix markets FDA-approved TONMYA^TM, a first-in-class, non-opioid analgesic medicine for the treatment of fibromyalgia, a chronic pain condition that affects millions of adults. TONMYA is the first new prescription medicine approved by the FDA for fibromyalgia in more than 15 years. TONMYA was investigated as TNX-102 SL. Tonix also markets two treatments for acute migraine in adults: Zembrace^® SymTouch^® (sumatriptan injection) and Tosymra^® (sumatriptan nasal spray). Tonix’s development portfolio* is focused on central nervous system (CNS) disorders, immunology, immuno-oncology, rare disease and infectious disease. TNX-102 SL is being developed to treat acute stress reaction and acute stress disorder under an Investigator-Initiated IND at the University of North Carolina in the OASIS study funded by the U.S. Department of Defense (DoD). TNX-102 SL is also in development for major depressive disorder. Tonix’s immunology development portfolio consists of biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a Phase 2- ready Fc-modified humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. Tonix’s rare disease portfolio includes TNX-2900, intranasal oxytocin potentiated with magnesium, in development for Prader-Willi syndrome and expected to start a potential pivotal Phase 2 study in 2026. Tonix’s infectious disease portfolio includes TNX-801, a vaccine in development for mpox and smallpox, as well as TNX-4800, a Phase 2- ready long-acting humanized monoclonal antibody for the seasonal prevention of Lyme disease. Finally, TNX-4200 for which Tonix has a contract with the U.S. DoD’s Defense Threat Reduction Agency (DTRA) for up to $34 million over five years, is a small molecule broad-spectrum antiviral agent targeting CD45 for the prevention or treatment of high lethality infections to improve the medical readiness of military personnel in biological threat environments. Tonix owns and operates a state-of-the-art infectious disease research facility in Frederick, Md.

*Tonix’s product development candidates are investigational new drugs or biologics; their efficacy and safety have not been established and have not been approved for any indication under development.

This press release and further information about Tonix can be found at www.tonixpharma.com.

Forward Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to successfully launch and commercialize Tonmya and any of our approved products; risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2024, as filed with the Securities and Exchange Commission (the “SEC”) on March 18, 2025, and periodic reports filed with the SEC on or after the date thereof. All of Tonix's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Investor Contacts
Jessica Morris 
Tonix Pharmaceuticals 
investor.relations@tonixpharma.com 
(862) 799-8599 

Brian Korb 
astr partners 
(917) 653-5122 
brian.korb@astrpartners.com 

Media Contacts
Mary Ann Ondish
MaryAnn.Ondish@tonixpharma.com
(862) 799-8599

Ray Jordan 
Putnam Insights 
ray@putnaminsights.com 

INDICATION
TONMYA is indicated for the treatment of fibromyalgia in adults.

CONTRAINDICATIONS
TONMYA is contraindicated:

In patients with hypersensitivity to cyclobenzaprine or any inactive ingredient in TONMYA. Hypersensitivity reactions may manifest as an anaphylactic reaction, urticaria, facial and/or tongue swelling, or pruritus. Discontinue TONMYA if a hypersensitivity reaction is suspected.

With concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days after discontinuation of an MAO inhibitor. Hyperpyretic crisis seizures and deaths have occurred in patients who received cyclobenzaprine (or structurally similar tricyclic antidepressants) concomitantly with MAO inhibitors drugs.

During the acute recovery phase of myocardial infarction, and in patients with arrhythmias, heart block or conduction disturbances, or congestive heart failure.

In patients with hyperthyroidism.

WARNINGS AND PRECAUTIONS
Embryofetal toxicity: Based on animal data, TONMYA may cause neural tube defects when used two weeks prior to conception and during the first trimester of pregnancy. Advise females of reproductive potential of the potential risk and to use effective contraception during treatment and for two weeks after the final dose. Perform a pregnancy test prior to initiation of treatment with TONMYA to exclude use of TONMYA during the first trimester of pregnancy.

Serotonin syndrome: Concomitant use of TONMYA with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors increases the risk of serotonin syndrome, a potentially life-threatening condition. Serotonin syndrome symptoms may include mental status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms. Treatment with TONMYA and any concomitant serotonergic agent should be discontinued immediately if serotonin syndrome symptoms occur and supportive symptomatic treatment should be initiated. If concomitant treatment with TONMYA and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dosage increases.

Tricyclic antidepressant-like adverse reactions: Cyclobenzaprine is structurally related to TCAs. TCAs have been reported to produce arrhythmias, sinus tachycardia, prolongation of the conduction time leading to myocardial infarction and stroke. If clinically significant central nervous system (CNS) symptoms develop, consider discontinuation of TONMYA. Caution should be used when TCAs are given to patients with a history of seizure disorder, because TCAs may lower the seizure threshold. Patients with a history of seizures should be monitored during TCA use to identify recurrence of seizures or an increase in the frequency of seizures.

Atropine-like effects: Use with caution in patients with a history of urinary retention, angle-closure glaucoma, increased intraocular pressure, and in patients taking anticholinergic drugs.

CNS depression and risk of operating a motor vehicle or hazardous machinery: TONMYA monotherapy may cause CNS depression. Concomitant use of TONMYA with alcohol, barbiturates, or other CNS depressants may increase the risk of CNS depression. Advise patients not to operate a motor vehicle or dangerous machinery until they are reasonably certain that TONMYA therapy will not adversely affect their ability to engage in such activities.

Oral mucosal adverse reactions: In clinical studies with TONMYA, oral mucosal adverse reactions occurred more frequently in patients treated with TONMYA compared to placebo. Advise patients to moisten the mouth with sips of water before administration of TONMYA to reduce the risk of oral sensory changes (hypoesthesia). Consider discontinuation of TONMYA if severe reactions occur.

ADVERSE REACTIONS
The most common adverse reactions (incidence ≥2% and at a higher incidence in TONMYA-treated patients compared to placebo-treated patients) were oral hypoesthesia, oral discomfort, abnormal product taste, somnolence, oral paresthesia, oral pain, fatigue, dry mouth, and aphthous ulcer.

DRUG INTERACTIONS
MAO inhibitors: Life-threatening interactions may occur.

Other serotonergic drugs: Serotonin syndrome has been reported.

CNS depressants: CNS depressant effects of alcohol, barbiturates, and other CNS depressants may be enhanced.

Tramadol: Seizure risk may be enhanced.

Guanethidine or other similar acting drugs: The antihypertensive action of these drugs may be blocked.

USE IN SPECIFIC POPULATIONS
Pregnancy: Based on animal data, TONMYA may cause fetal harm when administered to a pregnant woman. The limited amount of available observational data on oral cyclobenzaprine use in pregnancy is of insufficient quality to inform a TONMYA-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Advise pregnant women about the potential risk to the fetus with maternal exposure to TONMYA and to avoid use of TONMYA two weeks prior to conception and through the first trimester of pregnancy. Report pregnancies to the Tonix Medicines, Inc., adverse-event reporting line at 1-888-869-7633 (1-888-TNXPMED).

Lactation: A small number of published cases report the transfer of cyclobenzaprine into human milk in low amounts, but these data cannot be confirmed. There are no data on the effects of cyclobenzaprine on a breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TONMYA and any potential adverse effects on the breastfed child from TONMYA or from the underlying maternal condition.

Pediatric use: The safety and effectiveness of TONMYA have not been established.

Geriatric patients: Of the total number of TONMYA-treated patients in the clinical trials in adult patients with fibromyalgia, none were 65 years of age and older. Clinical trials of TONMYA did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

Hepatic impairment: The recommended dosage of TONMYA in patients with mild hepatic impairment (HI) (Child Pugh A) is 2.8 mg once daily at bedtime, lower than the recommended dosage in patients with normal hepatic function. The use of TONMYA is not recommended in patients with moderate HI (Child Pugh B) or severe HI (Child Pugh C). Cyclobenzaprine exposure (AUC) was increased in patients with mild HI and moderate HI compared to subjects with normal hepatic function, which may increase the risk of TONMYA-associated adverse reactions.

Please see additional safety information in the full Prescribing Information.

To report suspected adverse reactions, contact Tonix Medicines, Inc. at 1-888-869-7633, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

FAQ

What did Tonix (TNXP) announce on December 16, 2025 about TNX-4900?

Tonix announced exclusive worldwide licensing of TNX-4900, a selective Sigma-1 receptor antagonist for neuropathic pain.

How potent and selective is TNX-4900 reported by Tonix (TNXP)?

TNX-4900 binds human S1R with Ki = 7.5 nM and shows >100-fold selectivity over Sigma-2.

What preclinical pain models showed efficacy for TNX-4900 (TNXP)?

TNX-4900 produced significant, durable analgesia in diabetic and chemotherapy-induced neuropathic pain models.

What pharmacokinetic properties of TNX-4900 did Tonix disclose?

Tonix reported high blood-brain barrier penetration and oral bioavailability of approximately 28%.

Will Tonix (TNXP) pursue clinical development for TNX-4900 and what steps are planned?

Tonix plans expanded pharmacokinetic, formulation, and safety studies to support IND-enabling development.

Does TNX-4900 show safety concerns in animal studies per Tonix (TNXP)?

In reported animal studies, TNX-4900 showed analgesia without evidence of tolerance or motor impairment.