Centessa IPO Presentation Deck slide image

Centessa IPO Presentation Deck

ZF874: Status and Competition STATUS & UPCOMING MILESTONES Phase 1 study ongoing • Single ascending dose study in 7 cohorts of healthy volunteers (Part A) • 28 days of BID dosing in subjects with at least one Z allele (PiXZ) subjects (Part B) • Seven cohorts of healthy volunteers successfully dosed up to 50mg/kg fasted • All doses well-tolerated, except for a transient apparent Cmax effect at 50mg/kg in the fasted state, similar to what was observed in the dog at doses above 100mg/kg • 50mg/kg was well-tolerated when given as 25mg/kg bid (12-hour interval) • PK is consistent with expectations, with excellent oral availability and a ~4- hour half-life • Food effect decreases rate of absorption, but not AUC • Exposure in humans is 7-times greater than in mice, so a dose ~7mg/kg/day Mid-to-late 2021 Mid-to-late 2021 in humans is expected to have a similar effect to the dose of 50mg/kg/day in the PIZ mouse on plasma levels of Z-A1AT and liver burden Up to 14 subjects with at least one Z allele (PiXZ) are being recruited for Part B (2 placebos) Data from 28-day repeat dosing study in PiXZ subjects (Phase 1, Part B) US IND Filing COMPETITIVE LANDSCAPE VX-864, Z-A1AT folding corrector: Phase 2 (Vertex Pharmaceuticals) ~ exp readout Q2 2021 ~ ARO-AAT, RNAi therapy for knockdown of Z-A1AT: Phase 2 (Arrowhead/Takeda) Belcesiran, RNAi therapy for knockdown of Z-A1AT: Early clinical trials (Dicerna) ALN-AATO2, RNAi therapy for knockdown of Z-A1AT: Early clinical trials (Alnylam) ZFactor CENTESSA 24
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