TNX-1500, a third generation anti-CD40L mAb, was Fc-modified to preserve the activity and bioavailability of first generation mAbs while addressing their thrombosis risk
Sanofi projects its Fc-modified humanized anti-CD40L mAb frexalimab will exceed €5B per year in peak sales1 based on Phase 2 multiple sclerosis data recently published in the
Topline results of TNX-1500 Phase 1 trial expected in the third quarter of 2024; clinical stage completed last month
TNX-1500 has multiple potential indications including solid organ and bone marrow transplantation and the treatment of autoimmune diseases: potential ‘pipeline in a product’
“For more than 30 years, anti-CD40L therapy has shown promise in transplantation and the treatment of autoimmunity, but first-generation humanized mAbs were associated with an increased risk of thrombosis and second-generation agents had poor PK properties or reduced activity,” said
“Anti-CD40L therapy has multiple possible indications in addition to solid organ and bone marrow transplantation, including autoimmune diseases,”
About the Translation of Human Pharmacokinetic Parameters from Animal Data
Results of a single dose PK study in animals were analyzed to predict human PK parameters. The PK study was conducted in six healthy cynomolgus monkeys at 30, 100 and 300 mg/kg and revealed linear PK across those doses, consistent with an antibody with no target mediated drug disposition.6,7 The half-life in cynomolgus monkeys is approximately 14 days. Human half-life prediction for TNX-1500 was based on allometric scaling for mAbs with linear PK.6 Clearance in cynomolgus animals was 6.24 ml/day (26.6% C.V.) and the predicted clearance in humans was 141 mL/day (C.V. 22.9%).6,7 The predicted human half-life for TNX 1500 is 23.8 days (range of 18.3 to 27.6 days) which supports monthly dosing. 6,7
About TNX-1500
TNX-1500 (Fc-modified humanized anti-CD40L mAb) is a humanized monoclonal antibody that binds and blocks 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. A first-in-human Phase 1 trial of TNX-1500 has completed the clinical phase. Topline results are expected in the third quarter of 2024. The primary objective of the Phase 1 trial is to assess the safety, tolerability, PK, and pharmacodynamics of intravenous (i.v.) TNX-1500. Eligible participants enrolled in the Phase 1 trial were distributed across three dosing cohorts (3 mg/kg, 10 mg/kg, and 30 mg/kg, respectively) and evaluated regularly over a 120-day period after dosing. The Phase 1 trial is intended to support dosing in a planned Phase 2 trial in kidney transplant recipients. Two published articles in the
About anti-CD40L Therapeutics in Development
No anti-CD40L mAb has been approved in any jurisdiction. In addition to TNX-1500, frexalimab and tegoprubart, tn03 fusion protein dazodalibep is being developed by Amgen (formerly Horizon Therapeutics Public Limited Company) for the treatment of Sjögren's Syndrome.9,10 Dapirolizumab pegol, an anti-CD40L pegylated Fab, is being developed by UCB for the treatment of systemic lupus erythematosus.11
*TNX-1500 is an investigational new biologic and is not approved for any indication
- Dunn, A. Endpoints.
December 7, 2023 . “Sanofi CEOPaul Hudson pitches 12 blockbusters in a bid to convince investors on boosting R&D spend”. https://endpts.com/sanofi-rd-day-ceo-paul-hudson-touts-12-blockbusters-ups-rd-spend/ - Vermersch P., et al. N Engl J Med. 2024. 390(7):589-600 https://doi.org/10.1056/nejmoa2309439
- Lassiter G., et al. Am J Transplantation. 2023. https://doi.org/10.1016/j.ajt.2023.03.022
- Miura S., et al. Am J Transplantation. 2023. https://doi.org/10.1016/j.ajt.2023.03.025
- Anand, R.P., et al Nature. 622, 393–401 (2023). https://doi.org/10.1038/s41586-023-06594-4
- Deng R., et al. Mabs. 2011. https://doi.org/10.4161/mabs.3.1.13799
Tonix Pharmaceuticals – Data on File- Eledon press release.
November 2, 2023 . https://ir.eledon.com/news-releases/news-release-details/eledon-reports-updated-data-ongoing-phase-1b-trial-evaluating (accessedFebruary 2024 ) BioSpace .September 12, 2022 . https://www.biospace.com/article/releases/horizon-therapeutics-plc-announces-phase-2-trial-evaluating-dazodalibep-for-the-treatment-of-sjoegren-s-syndrome-meets-primary-endpoint (accessedFebruary 2024 )BioSpace .January 18, 2023 . https://www.biospace.com/article/horizon-bags-second-phase-ii-win-in-sjoegren-s-syndrome (accessedFebruary 2024 )- https://www.ucb.com/our-science/pipeline (accessed
August 2023 )
Tonix is a biopharmaceutical company focused on developing, licensing and commercializing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to submit a New Drug Application (NDA) to the FDA in the second half of 2024 for Tonmya1, a product candidate for which two positive Phase 3 studies have been completed for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction as well as fibromyalgia-type Long COVID. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase) a biologic designed to treat cocaine intoxication with Breakthrough Therapy designation. Tonix’s immunology development portfolio consists of biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a 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 the areas of rare disease and infectious disease. Tonix Medicines, our commercial subsidiary, markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults.
*Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication.
1Tonmya™ is conditionally accepted by the
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
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