Title : SYN023 mAb cocktail for rabies prophylaxis

Abstract:

SYN023 is a mixture of two anti-rabies humanized monoclonal IgG1κ antibodies which bind to distinct and non-overlapping antigenic sites on the rabies virus glycoprotein.  A Phase 2b and a Phase 3 randomized double-blinded trials were conducted to demonstrate the safety and efficacy of SYN023 in 1448 Category III rabies patients.  The analysis of the safety profile of SYN023 based on the integrated data from all 6 clinical trials demonstrated that SYN023 was generally well tolerated when administered alone or with rabies vaccine in subjects with rabies exposure as well as healthy subjects and has a favorable safety profile.  The safety profile was similar to that of the currently approved HRIG in the US. Overall, the incidence of serious TEAEs throughout the studies was low (<5.0%) and similar between the SYN023 and HRIG groups.  No TEAE led to study withdrawal in subjects treated with SYN023. The most common solicited TEAEs with SYN023 and HRIG were injection site swelling, injection site pain, headache, and injection site erythema. A higher incidence of these TEAEs was noted in subjects treated with HRIG than in subjects treated with SYN023.  Across 6 clinical trials, RVNA appeared to be adequate at the 0.3 mg/kg dose level to rapidly establish RVNA of ≥0.5 IU/mL in the rabies-exposed person. The primary endpoint for the ISE was the GMC of the RVNA on Study Day 8 in the FAS (SYN023, N=978; HRIG, N=469). The GMC ratio of RVNA (SYN023 vs HRIG) on Study Day 8 was 13.977 (97.5% CI: 11.887, infinity; P<0.0001); SYN023 was considered superior to HRIG with respect to GMC of RVNA on Study Day 8, as the lower bound of the 97.5% CI was above the prespecified margin 1.2.  The immune response (RVNA ≥0.5 IU/mL) rate ratio (SYN023 vs HRIG) was 0.99 (95% CI: 0.96, 1.01; P<0.0001); SYN023 was considered noninferior to HRIG with respect to immune response rates on Study Day 99, as the lower bound of the 95% CI was above the prespecified margin 0.9.  There were no deaths, serious adverse events, or AEs leading to study discontinuation up to 365 days after dosing. 

Biography:

Dr. Eric Tsao has served as the Chief Executive Officer of Synermore Biologics since the founding of the company in 2013.  He has over 25 years of direct experience with more than 20 products in clinical development, four US and EU approved products on the market, and eight biotech manufacturing facilities. His areas of expertise include biological product development, process design, facility engineering, and operations.  Under his leadership, SYN023, an innovative anti-rabies monoclonal antibody cocktail, has been expertly developed and commercialized for rabies post-exposure prophylaxis.  Since 2008, Dr. Tsao has worked with Morningside Group on biotech investments.  He was instrumental in enhancing portfolio companies’ CMC capabilities. Dr. Tsao was the Vice President of Technical Operations at Aeras, a Gates Foundation sponsored vaccine development organization.  At MedImmune, Dr. Tsao rose to the position of Vice President of Process and Manufacturing Sciences responsible for process development as well as manufacturing of monoclonal antibodies and recombinant vaccines.  The development and manufacturing efforts led to the successful licensing of Synagis, FluMist, and Cervarix.  He was a process development scientist at Johnson & Johnson, where he focused on the development of cell culture processes and start-up of the commercial manufacturing facility for erythropoietin.  Dr. Tsao received his Ph.D. in Chemical Engineering from the University of Michigan.