Serpin-PC in Persons with Severe Hemophilia (PwH): Updated Results from a Multicenter Multi-Part, First-in-Human Study

Abstract

Introduction SerpinPC is an investigational serine protease inhibitor (SERPIN) engineered to specifically inhibit Activated Protein C (APC). The previously presented data from the completed parts of AP-0101 showed that administration of SerpinPC reduced bleeding in persons with severe hemophilia with no observations of unexplained chronic elevation in D-dimer. We will now present all results up to the end of Part 5 by which time we anticipate the median continuous exposure will be more than 3 years. Methods AP-0101 is an ongoing first-in-human open-label multicenter study utilizing an adaptive design to investigate the safety, tolerability, pharmacokinetics and efficacy of SerpinPC in subjects with severe hemophilia A and B. Part 1a was a Single Ascending Dose Study of SerpinPC in 15 healthy male volunteers and 12 males with severe hemophilia. Part 2 enrolled 23 males with severe hemophilia (19 hemophilia A and 4 hemophilia B), who were not on replacement factor prophylaxis, to receive SerpinPC at 0.3, 0.6 or 1.2 mg/kg, administered as a subcutaneous (SC) injection once every 4 weeks over a 24-week period (6 total doses). In Part 3, subjects who completed Part 2 received a flat dose of 60 mg of SerpinPC once every 4 weeks for 48 weeks. Part 4 was a further extension in which subjects who completed Part 3 received 1.2 mg/kg of SerpinPC once every 2 weeks for 24 weeks. Part 5 was a further extension in which subjects who completed Part 4 continued to receive 1.2 mg/kg of SerpinPC once every 2 weeks for 52 weeks. Results Annualized bleed rates, safety and tolerability for Part 5 will be available and a complete summary of all results to the end of Part 5 will be presented, including available pharmacokinetic and anti-drug antibody data.