Roche has axed one of the obesity assets from its $2.7 billion Carmot Therapeutics buyout, sending the molecule to the scrap heap months after hyping its potential to drive weight loss past the GLP-1 plateau. The drugmaker disclosed the action alongside news of a cull of early-phase solid tumor programs.
The dropped obesity candidate, CT-173, is a long-acting PYY analog. Roche was planning (PDF) to start a phase 1 trial of the molecule this year. However, the Swiss drugmaker has decided to stop development before entering the clinic. Roche disclosed (PDF) the decision as part of its financial results for the second quarter. Teresa Graham, CEO Roche Pharmaceuticals, discussed the decision on the company's conference call with the media.
"This is a very early stage program ... and ultimately, when we bounced it up against our bar assessment, the criteria for developability and competitiveness just weren't there, and so we made the decision to terminate it," Graham said. "Overall with our obesity portfolio, I think we still feel very confident that we have a potentially best in disease and highly competitive portfolio of products."
The discontinuation marks a rapid reversal in Roche’s take on the molecule. Roche picked CT-173 out for special attention at an investor event in September. Manu Chakravarthy, M.D., Ph.D., global head of cardiovascular, renal and metabolism product development at Roche, used the event to discuss preclinical data he called “very exciting.”
Roche found combining CT-173 with its GLP-1/GIP asset CT-388 drove a “very deep and fairly sustained reduction in body weight, way above and beyond either agent alone,” Chakravarthy said. Beyond that, Chakravarthy said the data pointed to a potential answer to “the big question” in obesity: Can you reset body weight at a lower level than the plateau reached by GLP-1 drugs and other incretins?
“On the plateau, when you treat these animals that are overweight or actually obese in this case, you actually drive even further weight loss,” Chakravarthy said. “So this is very exciting for us, because this is actually telling us potentially that there’s an opportunity to maybe reset the body weight set point.”
Roche revealed it has dropped CT-173 as part of a quarterly update that also saw it toss out four phase 1 candidates. CEO Thomas Schinecker discussed Roche's approach to prioritization on the media call, explaining that the company has increased the value per pipeline program and freed up money for new assets and high-value activities such as obesity and Alzheimer's disease studies.
The discarded phase 1 programs include three solid tumor assets. Eciskafusp alfa is a fusion protein that consists of an anti-PD-1 antibody linked to an engineered, variant form of IL-2, the cytokine at the heart of multiple big, failed immuno-oncology bets.
The Swiss drugmaker started a phase 1 trial of the candidate in 2020 but stopped enrollment well short of its original target last year. Roche recently withdrew a phase 1 bladder cancer trial before enrolling any patients. In 2022, Roche paid $250 million for a Good Therapeutics PD-1-regulated IL-2 program that it said “nicely complements” its existing work on the targets.
Roche also jettisoned RG6614, a USP1 inhibitor it picked up in a deal with KSQ Therapeutics in 2023. The regulation of DNA damage response pathways by USP1 spurred hope that inhibitors of the enzyme could work as single agents and in combination with PARP inhibitors. However, responses were very rare in phase 1. Roche recently stopped enrollment in the trial and brought the completion date forward.
Bayer’s Vividion Therapeutics disclosed Roche’s other solid tumor discontinuation last month. The drug candidate, which inhibits DNA repair enzyme WRN, has slotted back into Vividion’s pipeline, and a phase 1 trial is continuing.
Finally, Roche culled the phase 1 eye disease candidate RG7921. Little is known publicly about the asset. Roche initially took (PDF) the molecule into the clinic as a treatment for neovascular age-related macular degeneration. The company began listing (PDF) retinal vein occlusion as the lead indication in 2023.