BioCryst reports initial clinical data on BCX10013

BioCryst Pharmaceuticals announced that initial data from ongoing phase 1 single ascending dose and multiple ascending dose trials in healthy volunteers show rapid, sustained and greater than97 percent suppression of the alternative pathway of the complement system 24 hours following a single 110 mg dose. BCX10013 has been safe and generally well-tolerated at all doses studied to date. These data support the development of BCX10013 as a potential best-in-class, once-daily, oral Factor D inhibitor for multiple complement-mediated diseases. BioCryst has initiated plans to advance BCX10013 into patient studies in mid-2023, including in patients with paroxysmal nocturnal hemoglobinuria, to evaluate once-daily dosing. The company expects to confirm the optimal dosing for pivotal trials by the end of the year, move directly into a pivotal trial in patients with immunoglobulin A nephropathy, and rapidly expand into pivotal trials in additional indications. In the SAD assessment to date, cohorts of healthy volunteers received a single dose of 1 mg, 3 mg, 10 mg, 40 mg, 80 mg or 110 mg of oral BCX10013 or placebo. In the MAD assessment to date, cohorts of healthy volunteers received 20 mg, 40 mg or 80 mg of oral BCX10013 or placebo administered once daily for seven days or 14 days. Following single BCX10013 dose administration, the onset of AP inhibition occurred within one hour and increased in a dose-dependent manner. At 110 mg, the highest dose studied to date, AP activity was suppressed by a mean of 97.8 percent at 24 hours post-dose. Suppression of AP activity by BCX10013 was assessed using the AP Wieslab assay, which measures functional activity of the complement system. In the MAD studies with once-daily dosing, exposure to BCX10013 was approximately dose proportional over the studied dose range and steady-state was achieved in 7 to 14 days with modest accumulation. In addition to BCX10013, which targets Factor D in the alternative pathway of complement, BioCryst is pursuing oral medicines directed at other targets across the classical, lectin and terminal pathways of the complement system, including C2, a critical upstream serine protease enzyme for activation of the classical and lectin pathways. The company has developed potent, selective molecules targeting C2, which are currently in lead optimization.