Tonix Pharmaceuticals Holding Corp. announced the results of modeling key human pharmacokinetic (PK) properties for TNX-1500 (Fc-modified humanized anti-CD40L monoclonal antibody, or mAb) from animal studies. TNX-1500 is in development for the prevention of rejection in solid organ and bone marrow transplantation and for the treatment of autoimmune disorders.

Dr. Lederman continued, ?Recently, positive clinical data have been reported by Sanofi, with its Fc-modified humanized anti-CD40L mAb frexalimab in treating relapsing multiple sclerosis with monthly i.v. or biweekly s.c. dosing regimens. Based on its results in multiple sclerosis, Sanofi projects that frexalimab will exceed ?5B per year in peak sales. TNX-1500 was designed to reduce binding to the Fc-receptor for IgG type 2a, or Fc?R2a, which has been shown to play a role in the thrombosis associated with first-generation anti-CD40L mAbs, similar to frexalimab.

In addition, Eledon Pharmaceuticals is in Phase 2 development for the prevention of rejection of kidney transplants with tegoprubart, a non-covalent dimer antibody with no heavy-light or heavy-heavy interchain disulfide bridges for the prevention of rejection of kidney transplants. 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.

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. 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%).

The predicted human half-life for TNX 1500 is 23.8 days (range of 18.3 to 27.6 days) which supports monthly dosing.