Terns Pharma Doubles Down on CML with Promising Allosteric Inhibitor, Shifts Focus from Obesity

By Patrick Walker

SAN DIEGO, CA – November 10, 2025 – Terns Pharma, a clinical-stage biotechnology company, today announced promising Phase 1 data for TERN-701, a novel allosteric inhibitor targeting chronic myeloid leukemia (CML). Simultaneously, the company announced a strategic shift, discontinuing internal development of its metabolic disease programs to fully focus on advancing TERN-701 towards pivotal trials. This decision follows underwhelming Phase 2 data for their obesity candidate, TERN-601, and reinforces the company’s commitment to oncology.

TERN-701 represents a new approach to CML treatment, differing from the widely used tyrosine kinase inhibitors (TKIs) by targeting the ABL myristoyl pocket. This allosteric mechanism holds potential to overcome resistance and provide a more favorable safety profile for patients who have failed or become intolerant to existing therapies. Preliminary data presented today at the American Society of Hematology (ASH) annual meeting showed encouraging results in patients with previously treated CML, including those resistant to multiple TKIs and even the notoriously difficult-to-treat T315I mutation.

“The early data we are seeing with TERN-701 is quite compelling,” said one independent hematologist familiar with the data, speaking on background. “The allosteric mechanism offers a potential advantage in overcoming resistance, and the initial safety profile looks promising. It's exciting to see a new approach being developed for a disease where many patients still struggle with treatment options.”

Addressing the Evolving CML Landscape

CML treatment has been revolutionized by TKIs like imatinib, dasatinib, and nilotinib. However, resistance remains a significant challenge, often driven by mutations in the BCR-ABL1 kinase domain. The recent approval of Novartis’s asciminib, also an allosteric inhibitor, has provided a new option for patients with resistance or intolerance to earlier TKIs. However, a significant unmet need still exists, particularly for patients who have exhausted all available therapies.

“The market is becoming increasingly competitive, but there’s still room for innovation,” said a biotechnology analyst covering the oncology space, speaking anonymously. “Asciminib has established the potential of allosteric inhibition, but there’s a belief that TERN-701 could offer further improvements in efficacy, safety, or patient convenience.”

TERN-701’s mechanism of action differs from traditional TKIs by binding to a different site on the ABL1 kinase domain, restoring the protein’s natural autoinhibitory function. This approach may allow the drug to bypass resistance mutations that affect the ATP-binding site, offering a valuable option for patients with heavily pre-treated disease.

Strategic Shift: From Metabolism to Oncology

The decision to discontinue development of TERN-601, an oral GLP-1 receptor agonist for obesity, and other metabolic programs came after disappointing Phase 2 results. Data presented earlier this year showed only modest weight loss and concerning liver enzyme elevations in some participants. The company determined that the competitive landscape for obesity treatments was too crowded and that focusing on oncology offered a more promising path forward.

“We made the difficult but strategic decision to prioritize our resources and focus on TERN-701, which we believe has the potential to be a best-in-class therapy for CML,” explained a company spokesperson. “This allows us to accelerate the development of a program with significant unmet need and a clear pathway to market.”

The company is actively seeking strategic partners to advance its metabolic assets, including TERN-601, TERN-501 (thyroid hormone receptor-beta agonist), and TERN-801 (small-molecule GIPR antagonist). This approach aims to unlock value from these programs while reducing Terns’ near-term cash burn.

Financial Outlook and Next Steps

Terns Pharma reported a cash runway extending into 2028, providing financial stability to support the continued development of TERN-701. The company plans to initiate a Phase 2 trial in the coming months to further evaluate the drug’s efficacy and safety in a larger patient population.

“We are committed to bringing a novel treatment option to patients with CML,” stated the company spokesperson. “We believe TERN-701 has the potential to significantly improve outcomes and quality of life for this patient population.”

Analysts predict that the success of TERN-701 will depend on the results of the upcoming Phase 2 trial and its ability to differentiate itself from existing TKIs and asciminib. However, the company’s focused approach and promising early data position it as a key player in the evolving CML treatment landscape. The company will host a webcast following the ASH presentation to discuss the Phase 1 data in more detail and outline its plans for the future.