Centessa Pharmaceuticals has decided to discontinue development of an early stage rare disease drug following a recent adverse event — marking the company's second pipeline loss this summer.
Centessa will halt development of ZF874, a pharmacological chaperone designed to rescue the folding of the Z variant of alpha-1-antitrypsin. The phase 1 study was focused on the treatment of alpha-1 antitrypsin deficiency, a rare inherited condition that raises the risk for lung and liver disease. In the trial, one patient dosed with 5mg ZF874 experienced elevated liver enzymes.
The company has "concluded that ZF874 was unlikely to achieve the desired target product profile."
This is the second recent pipeline blow for Centessa. Back in June, the company discontinued development of lixivaptan, which was being studied as treatment for a rare genetic kidney disease called Autosomal Dominant Polycystic Kidney Disease. Centessa cited numerous causes for stopping the phase 3 study — reassessment of the commercial potential of lixivaptan, incremental development challenges and associated costs, and, importantly, a recent observation of alanine aminotransferase and aspartate aminotransferase elevations — a sign of liver damage — in a trial subject.
But the company remains optimistic about the rest of its pipeline.
“We remain on track to initiate registrational studies for SerpinPC for the treatment of Hemophilia B in the second half of this year and look forward to initiating clinical trials with LB101 for solid tumors, after our planned IND filing late this year. Beyond these, we are continuing to advance our earlier stage programs and expect multiple clinical proof of concept readouts across our pipeline over the next two years. Importantly, with a world-class R&D team and cash runway that extends into 2026, we are exceptionally well positioned to deliver on these goals" said Saurabh Saha, CEO of Centessa