Elevated liver enzymes force Centessa to drop a 2nd asset in 2 months

Only two months after Centessa dropped its lead asset due to a patient experiencing elevated liver enzymes, the biotech has now culled an early-stage candidate over a similar adverse event.

Centessa had been studying ZF874—designed to rescue the folding of the Z variant of a liver protein called alpha-1-antitrypsin—in a phase 1 trial for alpha-1 antitrypsin deficiency (AARD), an inherited disorder that can cause lung and liver disease.

During the trial, Centessa received a recent report of an adverse event involving elevated levels of the liver enzymes aspartate transaminase and alanine transaminase. A similar adverse event had been reported from the trial in November, the company said, leading the biotech to conclude that ZF874 is “unlikely to achieve the desired target product profile.”

As a result, it has canned development of the drug, the company announced in its second-quarter earnings report Wednesday.

“While this is disappointing news for the [alpha-1-antitrypsin] patient community, we continue to believe that the pharmacological chaperone approach has the potential to address both the lung and liver manifestations of AATD,” Centessa CEO Saurabh Saha, M.D., Ph.D, said in a statement. “We are analyzing data from the phase 1 study to help inform potential future development plans for our back-up compounds.”

The latest setback comes only two months after Centessa scrapped its sole phase 3 program over a similar report of raised liver enzymes. Barely three months after dosing began on the open-label study of lixivaptan, the company announced that one patient had been hospitalized after having elevated levels of alanine aminotransferase and aspartate aminotransferase.

The recent pipeline cull leaves Centessa with just two candidates still in the clinic: the activated protein C inhibitor SerpinPC in phase 2 for hemophilia; and the anti-LIGHT antibody CBS001 in phase 1 for inflammatory and fibrotic diseases.

The company remains on track to initiate registrational studies for SerpinPC for the treatment of hemophilia B in the second half of the year, Saha said. It also expects to initiate trials with the bispecific monoclonal antibody LB101 for solid tumors.

“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,” the CEO added in his statement. “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."