Two patients experienced grade 3 liver enzyme elevations that were deemed related to Terns’ investigational obesity pill TERN-601.
Terns Pharmaceuticals’ oral GLP-1 drug TERN-601 delivered underwhelming weight-loss results and showed concerning safety signals in a mid-stage trial, prompting the California biotech to end its work on the asset.
Writing to investors on Tuesday, analysts at BMO Capital Markets called TERN-601’s performance “uncompetitive” in obesity, noting its efficacy “that appears less competitive versus other oral agents in development,” compounded by “a clear safety signal with three instances of liver enzyme elevation.” Terns was trading at $7.25 in pre-market trading Wednesday, down 10% from its Tuesday closing price of $8.12.
Data toplined on Tuesday did show placebo-adjusted weight loss in patients treated with at least 500 mg of TERN-601. In those who were titrated slowly, for instance, body weight dropped 3.6% at 12 weeks, with effect peaking at 4.6% weight loss in patients given a 500-mg dose with normal titration. A 750-mg dose also elicited significant weight reduction but was weaker in magnitude than both 500-mg regimens.
As for safety, Terns reported that nearly 12% of participants dropped out of the study due to side effects, while 8.9% required dose modifications. Most of the adverse events were gastrointestinal, though none were classified as severe. Common toxicities included nausea, vomiting and constipation.
Over the course of the study, three patients experienced grade 3 elevations in liver enzymes, two of whom had profiles that were consistent with liver injury related to TERN-601. None of the dropouts or dose disruptions were linked to abnormal liver tests.
For William Blair, the liver signals were somewhat expected. “We are not surprised by the liver toxicity signal,” the firm wrote to investors on Tuesday, “especially since TERN-601 shares the same pharmacophore as Pfizer’s danuglipron and lotiglipron,” both of which have been discontinued due to safety reasons. Such a safety profile will “likely eliminate partnership potential for TERN-601” as Terns seeks to pivot away from obesity.
The failure throws a wrench in the company’s plans in that regard. In August, Terns announced that it was looking to offload its metabolic disease pipeline, led by TERN-601, as it moves away from the obesity space. Aside from TERN-601, the biotech is looking to partner out the GIPR modulator TERN-800 and the THR-beta agonist TERN-501, both being tested for obesity.
With TERN-601 out of the picture, Terns now plans to go all-in on TERN-701, its investigational BCR-ABL blocker for chronic myeloid leukemia (CML), the biotech said on Tuesday. The company expects to read out clinical data “this quarter.”
BMO appears to be optimistic about this shift, noting that the upcoming data could present “an opportunity for Terns to meaningfully differentiate” in the CML space. Such differentiation, the analysts continued, is “rooted in a more convenient dosing schedule (no food effect), and potential improvements in safety and efficacy.”
