Tonix Pharmaceuticals Announces Positive Topline Results from Phase 1 Trial for TNX-1500, a Next Generation anti-CD40L mAb Candidate for Prevention of Kidney Transplant Rejection and Treatment of Autoimmune Diseases
Tonix Pharmaceuticals (TNXP) announced positive topline results from its Phase 1 trial of TNX-1500, a next-generation anti-CD40L monoclonal antibody for kidney transplant rejection prevention and autoimmune disease treatment. The trial demonstrated that TNX-1500 effectively blocked primary and secondary antibody responses at 10 mg/kg and 30 mg/kg doses, with a mean half-life of 34-38 days supporting monthly dosing.
The drug showed a favorable safety profile and was generally well-tolerated. The only notable treatment-emergent adverse event was mild aphthous ulcer in three participants. Importantly, no thromboembolic events were reported. The study involved 26 participants across three dosing cohorts (3 mg/kg, 10 mg/kg, and 30 mg/kg), with 24 completing the trial.
Following these results, Tonix plans to discuss with the FDA in an End-of-Phase 1 meeting before proceeding with Phase 2 trials in kidney transplant recipients.
Tonix Pharmaceuticals (TNXP) ha annunciato risultati positivi nella fase finale del suo studio di Fase 1 su TNX-1500, un anticorpo monoclonale anti-CD40L di nuova generazione per la prevenzione del rigetto nei trapianti di rene e il trattamento delle malattie autoimmuni. Lo studio ha dimostrato che TNX-1500 ha bloccato efficacemente le risposte anticorpali primarie e secondarie a dosi di 10 mg/kg e 30 mg/kg, con una emivita media di 34-38 giorni che supporta la somministrazione mensile.
Il farmaco ha mostrato un profilo di sicurezza favorevole ed è stato generalmente ben tollerato. L'unico evento avverso significativo emerso dal trattamento è stata una leggera ulcera aftosa in tre partecipanti. Importante, non sono stati riportati eventi tromboembolici. Lo studio ha coinvolto 26 partecipanti suddivisi in tre coorti di dosaggio (3 mg/kg, 10 mg/kg e 30 mg/kg), con 24 partecipanti che hanno completato la sperimentazione.
Dopo questi risultati, Tonix prevede di discutere con la FDA in un incontro di fine Fase 1 prima di procedere con gli studi di Fase 2 nei riceventi di trapianto di rene.
Tonix Pharmaceuticals (TNXP) anunció resultados positivos de su ensayo clínico de Fase 1 para TNX-1500, un anticuerpo monoclonal anti-CD40L de nueva generación para la prevención del rechazo en trasplantes de riñón y el tratamiento de enfermedades autoinmunes. El ensayo demostró que TNX-1500 bloqueó efectivamente las respuestas humorales primarias y secundarias a dosis de 10 mg/kg y 30 mg/kg, con una vida media de 34-38 días que respalda una dosificación mensual.
El medicamento mostró un perfil de seguridad favorable y fue generalmente bien tolerado. El único evento adverso notable emergente del tratamiento fue una leve úlcera aftosa en tres participantes. Es importante destacar que no se reportaron eventos tromboembólicos. El estudio involucró a 26 participantes en tres cohortes de dosificación (3 mg/kg, 10 mg/kg y 30 mg/kg), con 24 participantes que completaron el ensayo.
Tras estos resultados, Tonix planea discutir con la FDA en una reunión de Fin de Fase 1 antes de proceder con los ensayos de Fase 2 en receptores de trasplante de riñón.
톤익스 제약 (TNXP)은 TNX-1500, 신장 이식 거부 반응 방지 및 자가면역 질환 치료를 위한 차세대 항-CD40L 단일클론 항체의 1상 시험에서 긍정적인 최종 결과를 발표했습니다. 이 시험에서는 TNX-1500이 10 mg/kg 및 30 mg/kg 용량에서 1차 및 2차 항체 반응을 효과적으로 차단했으며, 평균 반감기가 34-38일로 월간 투여를 뒷받침했습니다.
이 약물은 유리한 안전성을 보였으며 일반적으로 잘 내약되었습니다. 주목할 만한 치료 유발 부작용은 세 명의 참가자에서 경미한 아프타 구내염이었습니다. 중요하게도, 혈전색전증 사건은 보고되지 않았습니다. 이 연구는 3 mg/kg, 10 mg/kg 및 30 mg/kg의 세 가지 투여 집단에서 26명의 참가자가 참여했고, 24명이 시험을 완료했습니다.
이러한 결과에 따라 톤익스는 2상 시험을 신장 이식 수혜자를 대상으로 진행하기 전에 FDA와의 1상 종료 회의에서 논의할 계획입니다.
Tonix Pharmaceuticals (TNXP) a annoncé des résultats préliminaires positifs de son essai de Phase 1 sur TNX-1500, un anticorps monoclonal anti-CD40L de nouvelle génération pour la prévention du rejet de greffe de rein et le traitement des maladies auto-immunes. L'essai a démontré que TNX-1500 bloquait efficacement les réponses des anticorps primaires et secondaires à des doses de 10 mg/kg et 30 mg/kg, avec une demi-vie moyenne de 34-38 jours soutenant une posologie mensuelle.
Le médicament a montré un profil de sécurité favorable et a généralement été bien toléré. Le seul effet indésirable notoire lié au traitement a été une légère ulcère aphteux chez trois participants. Il est important de noter qu'aucun événement thromboembolique n'a été signalé. L'étude a impliqué 26 participants répartis en trois cohortes de dosage (3 mg/kg, 10 mg/kg et 30 mg/kg), dont 24 ont complété l'essai.
Suite à ces résultats, Tonix prévoit de discuter avec la FDA lors d'une réunion de fin de Phase 1 avant de passer aux essais de Phase 2 chez les receveurs de greffe de rein.
Tonix Pharmaceuticals (TNXP) hat positive vorläufige Ergebnisse aus seiner Phase-1-Studie zu TNX-1500, einem nächsten Generation Anti-CD40L-monoklonalen Antikörper zur Verhinderung von Nierentransplantationsabstoßung und zur Behandlung von Autoimmunerkrankungen, bekannt gegeben. Die Studie zeigte, dass TNX-1500 bei Dosen von 10 mg/kg und 30 mg/kg effektiv die primären und sekundären Antikörperreaktionen blockierte, mit einer mittleren Halbwertszeit von 34-38 Tagen, die eine monatliche Dosis unterstützt.
Das Medikament wies ein günstiges Sicherheitsprofil auf und wurde allgemein gut vertragen. Das einzige bemerkenswerte nebenwirkungsbedingte Ereignis war eine leichte aphthöse Ulze bei drei Teilnehmern. Wichtig ist, dass keine thromboembolischen Ereignisse gemeldet wurden. An der Studie nahmen 26 Teilnehmer in drei Dosierungsgruppen (3 mg/kg, 10 mg/kg und 30 mg/kg) teil, von denen 24 die Studie abschlossen.
Nach diesen Ergebnissen plant Tonix, in einem Abschlussgespräch zur Phase 1 mit der FDA zu diskutieren, bevor die Phase 2-Studien bei Nierenempfängern fortgesetzt werden.
- Successful Phase 1 trial results showing efficacy in blocking antibody responses
- Long half-life of 34-38 days enabling monthly dosing schedule
- Favorable safety profile with no serious adverse events
- Clear path forward to Phase 2 trials
- Mild adverse events (aphthous ulcers) reported in three participants
- Two participants discontinued the trial (one withdrew consent, one lost to follow-up)
Insights
The Phase 1 results for TNX-1500 represent a significant advancement in transplant medicine and autoimmune disease treatment. The data reveals three important achievements that position this drug favorably for Phase 2 development:
- Superior Safety Profile: The absence of thromboembolic events is particularly noteworthy, as this was the key limitation of first-generation anti-CD40L antibodies like ruplizumab. The only notable adverse event was mild aphthous ulcers in 3 participants, representing a remarkably clean safety profile for an immunomodulator.
- Optimal Pharmacokinetics: The demonstrated 34-38 day half-life at effective doses (10mg/kg and 30mg/kg) supports monthly dosing, offering a significant advantage over current anti-rejection medications that often require daily administration. This could substantially improve patient compliance and quality of life.
- Robust Efficacy Signals: Complete blockade of both primary and secondary antibody responses at the higher doses indicates potent immunosuppression, suggesting potential superiority over current standard-of-care treatments.
The market implications are substantial. The global transplant rejection drugs market exceeds
The risk-reward profile appears particularly attractive given the unmet need for safer, more effective transplant rejection treatments. Current standard therapies like tacrolimus and cyclosporine carry significant toxicity risks, including nephrotoxicity and increased cancer risk. TNX-1500's clean safety profile and monthly dosing could position it as a preferred option for both physicians and patients.
Results from the Phase 1 single ascending dose study support proceeding to develop a Phase 2 trial for the prevention of kidney transplant rejection
TNX-1500 blocked the primary and secondary antibody responses to a test antigen at the 10 mg/kg and 30 mg/kg i.v. doses
TNX-1500 showed mean half-life of 34-38 days for the 10 mg/kg and 30 mg/kg doses supporting monthly dosing for future efficacy trials
TNX-1500 was generally well-tolerated with a favorable safety profile
Anti-CD40L has multiple potential indications in addition to solid organ and bone marrow transplantation including autoimmune diseases: potential pipeline in a product
CHATHAM, N.J., Feb. 06, 2025 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, today announced positive topline results from its Phase 1, single ascending dose trial of TNX-1500 (Fc-modified humanized anti-CD40L monoclonal antibody, or mAb)* in healthy participants. The objectives of the Phase 1 trial were to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenous TNX-1500, as well as to support dosing in a planned Phase 2 trial in kidney transplant recipients.
“There remains a significant need for new agents with improved activity and safety to prevent transplant rejection and treat autoimmune diseases,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “First generation anti-CD40L mAb therapy, particularly ruplizumab (a.k.a., humanized 5c8 or BG9588) showed activity in modulating autoimmunity and rejection in allo- and xeno-transplantation but was limited by an increased risk of thrombosis.1-3 Tonix created TNX-1500, a next generation anti-CD40L mAb, by reengineering the Fc region of ruplizumab, to preserve activity with improved safety. The results of the Phase 1 study indicate that TNX-1500 has met these design objectives. We believe the results of this study and our prior animal studies4,5 indicate that TNX-1500 is potentially best-in-class among next-generation anti-CD40L mAbs in development.”
Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals said, “Topline results from the TNX-1500 Phase 1 study showed TNX-1500 at the 10 mg/kg and 30 mg/kg doses blocked both the primary and secondary antibody responses to a test antigen. The pharmacokinetic data support monthly dosing at doses of 10 mg/kg or above. Based on these findings, we are eager to advance this promising candidate into a Phase 2 efficacy study. We believe TNX-1500 has the potential to prevent organ transplant rejection and improve graft survival with reduced long-term toxicity burden relative to current immunosuppressive regimens.”
Methods and Topline Results
- Dosing: TNX-1500 solution was infused i.v. over a period of one hour to achieve doses of 3 mg/kg, 10 mg/kg, and 30 mg/kg. Participants were observed in the clinic for one day and followed with periodic clinic visits to Day 120.
- Keyhole Limpet Hemocyanin (KLH) Challenge: To evaluate the immune modulation potency of TNX-1500, participants received an antigen challenge with KLH (Immucothel®) administered subcutaneously (SC) on Day 2 and Day 29 of the study.
- Disposition: A total of 26 participants were enrolled in three Cohorts (3 mg/kg, 10 mg/kg, and 30 mg/kg). A total of 24 participants completed the study and two discontinued early (one placebo participant was lost to follow-up and one on TNX-1500 withdrew consent).
- Tolerability: TNX-1500 was generally well-tolerated with a favorable safety and tolerability profile. The only treatment-emergent adverse event (TEAE) occurring in ≥ 3 participants among all TNX-1500 groups was aphthous ulcer, occurring in one participant each in the 3 mg/kg, 10 mg/kg, and 30 mg/kg groups; all were rated as mild, possibly related, and resolved in 2-10 days. There were no TEAEs assessed as related to KLH administration. No TEAEs led to study discontinuation and there were no serious adverse events. There were no thromboembolic events, which were prespecified as TEAEs of special interest.
- Pharmacodynamics: TNX-1500 at 10 mg/kg and 30 mg/kg blocked both the primary and secondary anti-KLH Ab responses, evidenced by the mean Ab level at all sampled timepoints (through Day 120) being below the lower limit of quantitation (400 µg/L). TNX-1500 at 3 mg/kg blocked the primary response to KLH Day 2 challenge and reduced the peak secondary response to KLH Day 29 challenge by approximately two thirds (
69% ) relative to the peak response to placebo. - Pharmacokinetics: The mean (SD) half-life of TNX-1500 was: 3 mg/kg, 19.6 (9.29) days; 10 mg/kg, 37.8 (5.46) days; and 30 mg/kg, 33.7 (4.83) days.
Tonix plans to discuss these results with the U.S. Food and Drug Administration (FDA) in an End-of-Phase 1 meeting. Pending alignment with the FDA, a Phase 2 study of TNX-1500 in kidney transplant recipients will be pursued.
About TNX-1500
TNX-1500 (Fc-modified humanized anti-CD40L mAb) is a humanized monoclonal antibody that binds and functionally inhibits the CD40-ligand (CD40L), also known as CD154. TNX-1500 is being developed for the prevention of allograft and xenograft rejection, for the prevention of graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation (HCT) and for the treatment of autoimmune diseases. Two published articles in the American Journal of Transplantation demonstrate TNX-1500 prevents rejection, prolongs survival and preserves graft function as a single agent or in combination with other drugs in non-human primate renal and heart allografts. 4,5
*TNX-1500 is an investigational new biologic and is not approved for any indication
Citations
- Lederman S, et al, J Exp Med. 1992;175(4):1091-101. doi: 10.1084/jem.175.4.1091. PMID: 1348081; PMCID: PMC2119166.
- Boumpas DT, et. al. Arthritis Rheum. 2003;48(3):719-27. doi: 10.1002/art.10856. PMID: 12632425.
- Pierson RN 3rd, et al. Transplantation. 1999;68(11):1800-5. doi: 10.1097/00007890-199912150-00026. PMID: 10609959.
- Lassiter G, et al. Am J Transplant. 2023;23(8):1171-1181. doi: 10.1016/j.ajt.2023.03.022.
- Miura S, et al. Am J Transplant. 2023;23(8):1182-1193. doi: 10.1016/j.ajt.2023.03.025.
Tonix Pharmaceuticals Holding Corp.*
Tonix is a fully-integrated biopharmaceutical company focused on transforming therapies for pain management and vaccines for public health challenges. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to advance TNX-102 SL, a product candidate for the management of fibromyalgia, for which an NDA was submitted based on two statistically significant Phase 3 studies for the management of fibromyalgia and for which a PDUFA (Prescription Drug User Fee act) goal date of August 15, 2025 has been assigned for a decision on marketing authorization. The FDA has also granted Fast Track designation to TNX-102 SL for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction and acute stress disorder under a Physician-Initiated IND at the University of North Carolina in the OASIS study funded by the U.S. Department of Defense (DoD). Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase), a biologic in Phase 2 development designed to treat cocaine intoxication that has FDA Breakthrough Therapy designation, and its development is supported by a grant from the U.S. National Institute on Drug Abuse. Tonix’s immunology development portfolio consists of biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is an 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 also has product candidates in development in infectious disease, including a vaccine for mpox, TNX-801. Tonix recently announced a contract with the U.S. DoD’s Defense Threat Reduction Agency (DTRA) for up to
* 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.
Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. All other marks are property of their respective owners.
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 obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; 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, 2023, as filed with the Securities and Exchange Commission (the “SEC”) on April 1, 2024, 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.
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FAQ
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