Centessa halted ZF874 following the report of an adverse event that involved elevated liver enzymes in a Phase I study. This is the second development program the company has stopped in as many months.
Boston-based Centessa Pharmaceuticals announced Wednesday that it is discontinuing the development of ZF874 for Alpha-1 Antitrypsin Deficiency (AATD), an inherited disorder that can lead to lung and liver disease development, two months after halting another asset, lixivaptan.
As could be expected, the news was not met with happiness from investors, who began to dump the company stock. Shares of Centessa fell more than 5% in afternoon trading to close at $4.75.
The company halted development of ZF874 following the report of an adverse event that involved elevated liver enzymes in a patient dosed with 5 mg of the experimental treatment during a Phase I study. This was the second such event. Last year, in the first cohort of the Phase I study, a patient experienced elevated enzymes following a higher dose of 15 mg.
ZF874 is a pharmacological chaperone designed to rescue the folding of the Z variant of alpha-1-antitrypsin. Not only did the two patients experience the adverse events, but, based on data observed in the study, Centessa has concluded that ZF874 was unlikely to achieve the desired target product profile.
Saurabh Saha, chief executive officer of Centessa, said the decision to discontinue the study is disappointing news for the A1AT patient community. Saha said the company will continue to analyze data from the Phase I study in order to inform future developmental programs for other compounds in its pipeline. Saha added that Centessa continues to believe the “pharmacological chaperone approach has the potential to address both the lung and liver manifestations of AATD.”
In June, the company, which launched last year following the merger of 10 private biotech companies, scrapped the development of lixivaptan due to similar safety concerns. The company noted alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations in one subject who participated in the open-label ALERT study.
At the time, Centessa said its decision to halt development was based on a “thorough reassessment of the commercial potential of lixivaptan,” which was being studied in Phase III for APKD, a genetic, progressive disorder characterized by the growth of numerous cysts in the kidneys. Typically, symptoms for APKD include kidney cysts, pain in the back, the sides and headaches. Other symptoms include liver and pancreatic cysts, urinary tract infections, abnormal heart valves, high blood pressure, kidney stones and brain aneurysms.
With the halt of development for lixivaptan and ZF874, Centessa is left with two clinical assets in its pipeline. SerpinPC, an activated protein C inhibitor, is in mid-stage development for hemophilia A and B. The company’s other clinical-stage candidate is CBS001, an anti-LIGHT monoclonal antibody in development for inflammatory and fibrotic diseases. CBS001 is currently in Phase I.
Centessa has other preclinical programs, including the anti-BDCA1 monoclonal antibody CBS004 for autoimmune diseases and checkpoint inhibitors LB101 and LB201, which are expected to be assessed against undisclosed solid tumors.
“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,” Saha continued in his statement. “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.”
Centessa reported cash and cash equivalents of $484.2 million as of June 30.
