Tern's oral GLP-1 achieves 5% weight loss in one month at highest dose

Terns Pharmaceuticals appears to be on the right path after shifting its focus from liver disease research to weight loss treatment. The company recently released Phase 1 data for TERN-601, a GLP-1 agonist, showing promising results in reducing body weight among participants. The 28-day study involved 36 healthy adults who were either obese or overweight. These participants were divided into groups receiving different doses of TERN-601—740 mg, 500 mg, or 240 mg—or a placebo.

The highest dose, 740 mg, resulted in a placebo-adjusted mean weight loss of 4.9%, with 67% of those participants losing 5% or more of their baseline body weight. In contrast, the 500 mg and 240 mg doses led to weight losses of 3.8% and 1.9%, respectively. The study showed that TERN-601 was generally well tolerated across all doses. Over 95% of the adverse effects were mild, and no severe treatment-related interruptions, reductions, or discontinuations were reported. Six out of nine participants on the highest dose experienced moderate adverse effects, but none were severe.

The company noted that all gastrointestinal events were mild to moderate and consistent with what is expected from the GLP-1 receptor agonist class. Importantly, no significant changes were observed in liver enzymes, vital signs, or electrocardiograms, underscoring the drug's safety profile.

This data has been well-received by analysts at Mizhuo, who expressed satisfaction with the results, citing no significant concerns. The positive reaction was also reflected in Terns Pharmaceuticals' stock price, which saw a 15% increase in pre-market trading.

Despite being a latecomer in the obesity treatment market, which is currently led by Novo Nordisk's WeGovy and Eli Lilly's Zepbound, Terns Pharmaceuticals' oral drug shows potential. Novo Nordisk’s drug is known for an average weight loss of almost 15% over 68 weeks, but Terns’ short-term data is comparable to Viking Therapeutics. Viking demonstrated that 57% of patients who received 40 mg doses of its dual GLP-1 and GIP receptor agonist achieved a 5% or more reduction in body weight.

Terns Pharmaceuticals believes that TERN-601 has unique attributes that could make it a competitive oral GLP-1 receptor agonist. The drug’s low solubility and high gut permeability may allow it to be absorbed more effectively into the gut wall, thereby activating the brain’s hunger control mechanisms. Additionally, TERN-601 has a low free fraction in circulation and a flat pharmacokinetic curve, which might make it tolerable even at higher doses.

The company aims to advance TERN-601 into a Phase 2 trial next year. They also plan to explore its potential as both a standalone treatment for obesity and in combination with other candidates in their pipeline. These include the thyroid hormone receptor-beta agonist TERN-501 and a GIPR modulator from the TERN-800 program.

Earlier this year, Terns Pharmaceuticals decided to halt work on their Phase 2-stage TERN-501 for metabolic dysfunction-associated steatohepatitis (MASH) due to limited interest from potential partners. This pivot allowed the company to concentrate on TERN-601 for obesity and TERN-701 for chronic myeloid leukemia.

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