8-K: Terns TERN-701 CML Trial Shows Strong Efficacy

Terns Pharmaceuticals announced positive Phase 1 CARDINAL trial data for TERN-701 in relapsed/refractory CML, showing high major molecular response rates and an encouraging safety profile.

Summary

• TERN-701 is a novel investigational allosteric BCR::ABL1 inhibitor being developed for patients with relapsed/refractory chronic myeloid leukemia (CML).
• Data from the ongoing Phase 1 CARDINAL trial (dose escalation and dose expansion) was reported as of a June 30, 2025, cutoff date, with 55 patients enrolled.
• The dose escalation portion completed in January 2025 with no dose limiting toxicities (DLTs) observed up to the maximum dose of 500 mg once daily (QD).
• Dose expansion began in April 2025, randomizing patients to 320 mg or 500 mg QD cohorts, with up to 40 patients per arm.
• Of 32 efficacy-evaluable patients, an overall (cumulative) major molecular response (MMR) rate of 75% (24/32) was observed by 24 weeks.
• This included 64% (14/22) achieving MMR and 100% (10/10) maintaining MMR by 24 weeks.
• MMR rates in difficult-to-treat patient subgroups by 24 weeks were 69% (11/16) in patients with lack of efficacy to last TKI, 60% (6/10) in patients with prior asciminib, and 67% (8/12) in patients with prior asciminib/ponatinib/investigational TKI.
• No patients had lost MMR at the time of data cutoff.
• Enrolled patients had heavily pretreated, refractory disease, with a median of 3 prior TKIs and 35% having 4 or more prior TKIs; 64% discontinued their last TKI due to lack of efficacy.
• TERN-701 demonstrated an encouraging safety profile, with 87% (48/55) patients remaining on treatment as of the data cut-off.
• No DLTs were observed in dose escalation, and a maximum tolerated dose was not reached.
• The majority (74%) of treatment-emergent adverse events (TEAEs) were low grade (Grade 1 or 2) with no apparent dose relationship.
• Most common TEAEs were diarrhea (22%), headache (18%), and nausea (16%), all Grade 1 or 2.
• Grade 3 or higher TEAEs were all less than 10%, most commonly neutropenia (7%) and thrombocytopenia (4%).
• TERN-701 exposures were approximately dose proportional across the dose range.

Sentiment

Score: 9

Explanation: The clinical trial data for TERN-701 shows exceptionally strong efficacy in a difficult-to-treat patient population, coupled with an encouraging safety profile. Management's statements highlight the 'unprecedented' nature of the results and the potential for TERN-701 to be a 'best-in-disease therapy.' This positive clinical update significantly de-risks the program and suggests high future potential.

Positives

• High overall (cumulative) major molecular response (MMR) rate of 75% (24/32) by 24 weeks in efficacy-evaluable patients.
• 64% (14/22) of patients achieved MMR and 100% (10/10) maintained MMR by 24 weeks.
• Strong MMR rates in difficult-to-treat patient subgroups: 69% (11/16) in patients with lack of efficacy to last TKI, 60% (6/10) in patients with prior asciminib, and 67% (8/12) in patients with prior asciminib/ponatinib/investigational TKI.
• No patients lost MMR at the time of data cutoff.
• Encouraging safety profile with no dose-limiting toxicities (DLTs) observed and maximum tolerated dose not reached.
• Majority (74%) of treatment-emergent adverse events (TEAEs) were low grade (Grade 1 or 2).
• High patient retention: 87% (48/55) patients remained on treatment as of the data cut-off.
• TERN-701 exposures were approximately dose proportional across the dose range.

Negatives

• Patients enrolled had heavily pretreated, refractory disease, indicating a challenging patient population.
• Discontinuations due to disease progression (n=4), adverse events (n=1), and consent withdrawal/lost to follow up (n=2) were observed in 13% of patients.

Risks

• Risks associated with the initiation, cost, timing, progress, results, and utility of current and future research and development activities and preclinical studies and clinical trials.
• Actual results and implementation of plans may vary materially from forward-looking statements.
• New risk factors may emerge, and management cannot predict all risk factors or assess their full impact.
• The company undertakes no obligation to update publicly any forward-looking statements for any reason, except as required by law.

Future Outlook

Terns Pharmaceuticals believes TERN-701 has the potential to be a best-in-disease therapy with broad opportunity across all CML treatment lines. The company plans to share a more expansive and updated dataset from the CARDINAL trial at the ASH Annual Meeting in December and will discuss next steps in the development of TERN-701 during an investor call.

Management Comments

• "We are pleased that data from our CARDINAL trial have been selected for oral presentation at ASH. These data further validate the potential of TERN-701 to be a new, game-changing therapy for CML." Amy Burroughs, CEO.
• "The 24 weeks MMR achievement rate with TERN-701 is unprecedented, trending at least two times higher than the rates reported in other Phase 1 studies of CML therapies that are approved or in development." Amy Burroughs, CEO.
• "Importantly, TERN-701 also achieved consistently high overall (cumulative) MMR rates in key, difficult to treat patient subgroups while maintaining an encouraging safety profile. These emerging data strongly reinforce our conviction that TERN-701 has the potential to be a best-in-disease therapy, with broad opportunity across all CML treatment lines." Amy Burroughs, CEO.
• "We look forward to sharing additional data in December." Amy Burroughs, CEO.

Industry Context

The CML treatment landscape relies heavily on tyrosine kinase inhibitors (TKIs). TERN-701 is positioned as a novel allosteric BCR::ABL1 inhibitor, aiming to address patients with relapsed/refractory disease, particularly those who have failed previous TKI treatments, including newer agents like asciminib or ponatinib. The high MMR rates in heavily pretreated patients suggest a potential breakthrough in a challenging patient population.

Comparison to Industry Standards

• The 24-week MMR achievement rate with TERN-701 is described as "unprecedented," trending at least two times higher than rates reported in other Phase 1 studies of CML therapies that are approved or in development.
• TERN-701 showed 60% MMR in patients who had prior asciminib, and 67% in patients with prior asciminib/ponatinib/investigational TKI, indicating strong performance in highly refractory populations where existing therapies have limited efficacy.
• The safety profile, with no DLTs observed and a majority of low-grade TEAEs, appears favorable compared to the known side effect profiles of some existing TKIs, which can have significant adverse events.

Stakeholder Impact

• Shareholders: Positive impact due to strong clinical data, potentially increasing company valuation and future revenue prospects.
• Patients with CML: Potential for a new, highly effective, and well-tolerated treatment option, especially for those with relapsed/refractory disease.
• Healthcare Providers: New therapeutic option for managing challenging CML cases.

Next Steps

• Oral presentation of updated data at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition on December 8, 2025.
• Company to host an investor update call and webcast on December 8, 2025, at 4:30pm ET to discuss TERN-701 data and next steps in its development.
• Presentation materials will be made available on the Terns website after the ASH meeting.

Key Dates

Recommendation

The reported Phase 1 CARDINAL trial data for TERN-701 in relapsed/refractory CML is exceptionally positive, demonstrating "unprecedented" major molecular response rates (75% cumulative MMR by 24 weeks) in a heavily pretreated patient population, including those who failed prior advanced TKIs like asciminib. Coupled with an encouraging safety profile (no DLTs, majority low-grade TEAEs), these results suggest TERN-701 has significant potential to be a best-in-disease therapy. This strong clinical validation significantly de-risks the asset and points to substantial future commercial opportunity, making it a compelling "strong buy" for investors.

Keywords

Terns Pharmaceuticals, TERN, TERN-701, CARDINAL trial, chronic myeloid leukemia, CML, BCR::ABL1 inhibitor, Phase 1, clinical trial, oncology, major molecular response, MMR, tyrosine kinase inhibitor, TKI, asciminib, ponatinib, olverembatinib, ELVN-001, ASH Annual Meeting, hematology, drug development, clinical data, safety profile, efficacy