Benzinga | Jan 5, 2021 07:16AM EST

Tonix Pharmaceuticals And Massachusetts General Hospital Enter Into Research Collaboration On Tonix's Third Generation Anti-CD40-Ligand Monoclonal Antibody, TNX-1500, For Treatment And Prevention Of Kidney Transplant Rejection

Expands Ongoing Research Collaboration Between Tonix and MGH Studying TNX-1500 in Heart Transplantation



TNX-1500 May Hold Potential in Treating Autoimmune Diseases Including Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis

CHATHAM, N.J., Jan. 05, 2021 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (NASDAQ:TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced the signing of a second research collaboration agreement with Massachusetts General Hospital (MGH), a teaching hospital of Harvard Medical School, to develop TNX-1500, a humanized monoclonal antibody (mAb) that targets the CD40-ligand (also known as CD154, T-BAM or 5c8 antigen1) for the prevention and treatment of organ transplant rejection. Transplant organ rejection occurs when the immune system of the organ recipient attacks the new organ as if it was an infection or tumor. The new collaboration will focus on kidney transplantation, while an earlier collaboration with MGH is focused on heart transplantation.

Transplantation experts led by Tatsuo Kawai, M.D., Ph.D., Surgical Director of the Living Donor Transplantation and Dialysis Access Program at MGH and Professor of Surgery at Harvard Medical School (HMS) will study TNX-1500 in kidney transplantation in a variety of models including non-human primates. The goal of the collaboration is to advance TNX-1500 as a potential first-in-class therapeutic to prevent and treat kidney transplant rejection.

Dr. Kawai said, "Anti-CD40-ligand therapy has a unique activity in controlling the immune response to organ transplants.2 There remains a significant need for new treatments to reduce the toxicity of current treatments by more selectively suppressing immune responses or inducing specific tolerance to the transplanted organ. Anti-CD40-ligand has shown promise not only to effectively suppress rejection but also to facilitate 'transplant tolerance' in multiple preclinical transplant models.6"

The study of TNX-1500 in heart transplantation at MGH began last year under the direction of Richard N. Pierson III, M.D., scientific director of the Center for Transplantation Sciences in the Department of Surgery at MGH and Professor of Surgery HMS.

Key Advances in Anti-CD40-Ligand Antibody Engineering Led to TNX-1500

Tonix's President and Chief Executive Officer, Seth Lederman, M.D. said, "A substantial body of evidence in humans and animals indicates that mAbs targeting CD40-ligand have the potential to be an important therapeutic option for preventing or treating transplant organ rejection and as a treatment for autoimmune disorders. Despite the recognized promise of anti-CD40-ligand therapy, first generation anti-CD40- ligand mAbs were limited because their constant fragment (Fc) domain interacted with a receptor called Fc?RII, which raised concerns over an increased risk of thrombosis. Second generation anti-CD40- ligand mAbs had dramatically reduced binding to Fc?RII, but had other issues, including decreased efficacy5-7. TNX-1500 is a third generation anti-CD40- ligand mAb that has been designed by protein engineering to target CD40-ligand therapeutically, while potentially decreasing Fc?RII binding and the potential for thrombosis."

1 Lederman, S. & al. J. Exp. Med. 175:1091-1101 (1992)

2 Kawai T, et al. Am J Transplant. 4(9):1391 (2004)

3 ONeill NA, et al. Transplantation. 101(9): 2038 (2017)

4 Zhang T, et al. Immunotherapy. 7(8):899 (2015)

5 Waters J, Biocentury; October 26, (2018)

6 NCT02273960; ClinicalTrials.gov; "Study to Evaluate Safety and Efficacy in Adult Subjects With ITP (ITP)"; results posted April 1, 2019, accessed July 29, 2019)

7 Ferrant JL et al., International Immunol. (11):1583 (2004)