Benzinga | Jan 14, 2021 07:06AM EST

Tonix Pharmaceuticals Announces Publication of Patent Application for TNX-1500 in Development for Preventing and Treating Organ Transplant Rejection and Treating Autoimmune Conditions

Tonix Pharmaceuticals Holding Corp. (NASDAQ:TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that the World Intellectual Property Organization has published a patent application filed under the Patent Cooperation Treaty covering TNX-1500, a humanized monoclonal antibody (mAb) directed against CD40-ligand, which is also known as CD154, T-BAM, 5c8 antigen, TRAP and gp39. The patent application is titled "Anti-CD154 Antibodies and Uses Thereof" and published under International Publication No. WO 2021/001458 A1. If claims are granted, a patent issuing from a national stage of this application could potentially provide U.S. patent coverage for the TNX-1500 composition of matter through 2040 excluding possible patent term extensions or patent term adjustments.

Tonix's President and Chief Executive Officer, Seth Lederman, M.D. said, "Nearly 30 years ago my laboratory at Columbia University generated the first anti-CD40-ligand mAb (5c8), discovered and characterized human CD40-ligand and elucidated the molecular basis of T cell helper function1. Collaborating with a team at Biogen Inc., we determined the crystal structure of CD40-ligand2, developed a humanized version of our antibody (hu5c8, ruplizumab, or Antova(r)) and tested it in human trials for preventing organ transplant rejection and autoimmunity. Our studies and those of others generated a substantial body of evidence in humans and animals that indicates anti-CD40-ligand mAbs have the potential to be an important therapeutic option for preventing or treating transplant organ rejection and for treating autoimmune disorders."

Dr. Lederman continued, "Despite the recognized promise of anti-CD40-ligand mAb therapy, first generation anti-CD40-ligand mAbs were limited because their crystallizable fragment (Fc) domain interacted with a cell surface receptor called Fc?RII, which resulted in an increased risk of thrombosis. Second generation anti-CD40-ligand mAbs had dramatically reduced binding to Fc?RII, but had other issues, including decreased efficacy3-5. TNX-1500 is a third generation anti-CD40-ligand mAb that has been designed by protein engineering to decrease Fc?RII binding and the potential for thrombosis, while retaining efficacy. We believe TNX-1500 has the potential for treating and preventing organ transplant rejection and treating autoimmunity."

TNX-1500 incorporates the antigen binding fragment (Fab) region of hu5c8, which has been extensively characterized including at the atomiclevel in complex with CD40-ligand6. The newly published patent application includes claims related to proprietary anti-human CD40-ligand mAbs that were engineered to have modified effector function, including TNX-1500, which have reduced potential for Fc binding to Fc?RII. The patent application also claims uses of TNX-1500 for preventing and treating conditions, such as organ transplant rejection and autoimmune disorders.

Dr. Lederman added, "We believe the development risk of TNX-1500 is mitigated by previous clinical data and extensive preclinical science with ruplizumab. We are developing the manufacturing processes for TNX-1500 and expect Good Manufacturing Practice (GMP) TNX-1500 to be available in the third quarter of 2021. There remains a significant need for new treatments with improved activity and tolerability to prevent or treat organ transplant rejection and to treat autoimmune conditions, including systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis."

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

2 Karpusas, M et al., Structure 3:1031-1039 (1995)

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

4 NCT02273960; ClinicalTrials.gov; "Study to Evaluate Safety and Efficacy in Adult Subjects With ITP (ITP)"; results posted April 1, 2019, updated July 29, 2019 and accessed Jan 11, 2021

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

6 Karpusas M, et al. Structure. 9(4):321-9. (2001)

About CD40-Ligand

CD40-ligand is a protein expressed on the surface of activated T lymphocytes that mediates T cell helper function. CD40-ligand is also known as CD154, the T cell-B cell activating molecule (T-BAM), TRAP and gp39. CD154 is a member of the Tumor Necrosis Factor (TNF) Super Family. No mAb against CD154 has been approved for commercial use anywhere in the world. Other TNF Super Family members have been successfully targeted by antagonist mAbs. Approved mAbs against TNF? include: infliximab (Remicade(r)), adalimumab (Humira(r)), certolizumab pegol (Cimzia(r)), and golimumab (Simponi(r)) for the treatment of certain autoimmune conditions. Also, etanercept (Enbrel(r)) is a TNF? antagonist receptor fusion protein. An approved mAb against RANKL (CD254) is denosumab (Prolia(r) or Xgeva(r)) for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.

Remicade(r) and Simponi(r) are trademarks of Janssen; Humira(r) is a trademark of AbbVie Inc.; Cimzia(r) is a trademark of UCB S. A.; Enbrel(r), Prolia(r) and Xgeva(r) are trademarks of Amgen Inc.