Terns Pharmaceuticals announced positive topline results from its Phase 1 clinical trial of TERN-601, a once-daily oral GLP-1 receptor agonist for the treatment of obesity. The trial demonstrated statistically significant weight loss and a favorable tolerability profile, positioning TERN-601 as a potential competitor in the oral obesity drug market. The company plans to initiate a Phase 2 clinical trial in 2025.
Phase 1 Trial Results
The Phase 1 trial was a randomized, double-blind, placebo-controlled study involving healthy adults with obesity or overweight. Participants received either TERN-601 at varying doses (240 mg, 500 mg, or 740 mg) or a placebo once daily for 28 days. The primary endpoint was to evaluate the safety and tolerability of TERN-601.
Key findings from the trial include:
- Statistically significant mean weight loss of up to 5.5% over 28 days (4.9% placebo-adjusted).
- Maximum placebo-adjusted mean weight loss of 4.9% (p<0.0001) at the highest dose of 740 mg.
- 67% of participants in the highest dose group lost 5% or more of their baseline body weight.
- TERN-601 was well-tolerated, with no treatment-related dose interruptions, reductions, or discontinuations.
"These compelling results underscore TERN-601’s potential to be a class-leading GLP-1R agonist based on its composite profile of initial indications of efficacy, tolerability and manufacturing scalability," said Amy Burroughs, chief executive officer of Terns.
Tolerability and Safety
TERN-601 demonstrated a favorable safety profile in the Phase 1 trial. The majority (>95%) of treatment-emergent adverse events were mild. Gastrointestinal events, consistent with the GLP-1R agonist class, were also mild to moderate. Importantly, there were no clinically meaningful changes in liver enzymes, vital signs, or electrocardiograms observed.
Emil Kuriakose, chief medical officer of Terns, noted, "We are delighted to demonstrate potent GLP-1R agonism with TERN-601 as its distinct drug properties allowed for sustained target coverage with once-daily dosing and the evaluation of doses up to 740 mg, while being tolerable."
Mechanism of Action and Potential Advantages
TERN-601 is an oral, small-molecule GLP-1R agonist designed for obesity treatment. Its distinct properties, including low solubility and high gut permeability, may result in prolonged absorption, sustained target coverage, and a flat pharmacokinetic curve. High drug levels in the gut wall may lead to robust GLP-1R activation in the gut, triggering satiety centers in the brain. The company believes these properties may contribute to the drug's efficacy and tolerability.
Next Steps
Terns plans to initiate a Phase 2 clinical trial in 2025 to further evaluate TERN-601. The company is also exploring potential combination therapies with other agents in its pipeline, such as TERN-501 (THR-β agonist) or a GIPR modulator from the TERN-800 series.
Market Context
The market for obesity drugs is rapidly expanding, with analysts projecting it to reach $100 billion by early next decade. While injectable GLP-1 receptor agonists from Novo Nordisk and Eli Lilly currently dominate the market, there is significant interest in developing oral alternatives. Terns is positioning TERN-601 to compete in this space, emphasizing its potential for once-daily dosing and favorable tolerability.
