Tonix Announces Positive Topline Phase 1 Data for TNX-1500

Tonix Pharmaceuticals has announced positive topline data from its phase 1, single ascending dose trial of TNX-1500 in healthy participants, with results demonstrating its safety, tolerability, pharmacokinetics, and pharmacodynamics.1

According to a February 6, 2025, press release, Tonix plans to discuss these results with the US Food and Drug Administration (FDA) in an end-of-phase 1 meeting. Pending alignment with the FDA, the company plans to pursue a phase 2 study of TNX-1500 in kidney transplant recipients.1

“There remains a significant need for new agents with improved activity and safety to prevent transplant rejection and treat autoimmune diseases,” Seth Lederman, MD, chief executive officer of Tonix Pharmaceuticals, said in a press release.1 “First-generation anti-CD40L mAb therapy, particularly ruplizumab showed activity in modulating autoimmunity and rejection in allo- and xeno-transplantation but was limited by an increased risk of thrombosis. 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 studies indicate that TNX-1500 is potentially best-in-class among next-generation anti-CD40L mAbs in development.”

A humanized monoclonal antibody that interacts with the CD40-ligand (CD40L), also known as CD154, TNX-1500 is being developed for the prevention of allograft and xenograft rejection, the treatment of autoimmune diseases, and the prevention of graft-versus-host disease after hematopoietic stem cell transplantation.2

Initiated in 2023, the phase 1 trial sought to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenous TNX-1500 in 26 healthy volunteers. It was also intended to support dosing in a planned phase 2 trial in kidney transplant recipients.2

In the study, TNX-1500 solution was infused intravenously over 1 hour to achieve doses of 3 mg/kg, 10 mg/kg, and 30 mg/kg. Participants were observed in the clinic for 1 day and followed with periodic clinic visits to day 120. To evaluate the immune modulation potency of TNX-1500, participants received an antigen challenge with KLH (Immucothel®) administered subcutaneously on days 2 and 29 of the study.1

In total, 24 participants completed the study and 2 discontinued early, including 1 placebo participant who was lost to follow-up and 1 participant on TNX-1500 who withdrew consent.1

Results showed TNX-1500 was generally well-tolerated with a favorable safety and tolerability profile. Investigators noted the only treatment-emergent adverse event (TEAE) occurring in ≥ 3 participants among all TNX-1500 groups was aphthous ulcer, occurring in 1 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. No TEAEs were determined to be related to KLH administration and no TEAEs led to study discontinuation. Additionally, no serious adverse events were observed.1

TNX-1500 at 10 mg/kg and 30 mg/kg blocked both the primary and secondary anti-KLH Ab responses, as evidenced by the mean Ab level at all sampled time points 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 69% relative to the peak response to placebo.1

The mean (Standard deviation [SD]) half-life of each TNX-1500 dose was:

• 19.6 (9.29) days for 3 mg/kg
• 37.8 (5.46) days for 10 mg/kg
• 33.7 (4.83) days for 30 mg/kg

“Based on these findings, we are eager to advance this promising candidate into a Phase 2 efficacy study,” Gregory Sullivan, MD, chief medical officer of Tonix Pharmaceuticals, said in a press release.1 “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.”

References

1. Tonix Pharmaceuticals. 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. February 6, 2025. Accessed February 6, 2025. https://ir.tonixpharma.com/news-events/press-releases/detail/1548/tonix-pharmaceuticals-announces-positive-topline-results
2. Tonix Pharmaceuticals. Tonix Pharmaceuticals Initiates Phase 1 Trial of TNX-1500 (Fc-modified humanized anti-CD40L mAb) in Healthy Volunteers. August 16, 2023. Accessed February 6, 2025. https://ir.tonixpharma.com/news-events/press-releases/detail/1415/tonix-pharmaceuticals-initiates-phase-1-trial-of-tnx-1500