8-K: Terns Pharma TERN-701 Shows Strong CML Trial Data

Terns Pharmaceuticals announced updated positive Phase 1 CARDINAL trial data for TERN-701 in previously treated chronic myeloid leukemia patients at the 67th ASH Annual Meeting.

Summary

• Updated and expanded data from the ongoing Phase 1 CARDINAL trial of TERN-701, a novel investigational allosteric BCR::ABL1 inhibitor, in patients with previously treated chronic myeloid leukemia (CML) were presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition.
• For all dose cohorts (160 mg – 500 mg, n=63), an overall (cumulative) major molecular response (MMR) rate of 74% (28/38) was observed by 24 weeks in efficacy-evaluable patients, with 64% (18/28) achieving MMR and 100% (10/10) maintaining MMR.
• In patient cohorts at doses ≥320 mg QD (n=53), the overall MMR rate was 80% (24/30) by 24 weeks, with 75% (18/24) achieving MMR and 100% (6/6) maintaining MMR.
• Deep molecular response (DMR) achievement rate by 24 weeks was 29% (10/34) for all dose cohorts and 36% (10/28) for doses ≥320 mg QD.
• The trial demonstrated an encouraging safety profile with no dose-limiting toxicities (DLTs) observed in dose escalation, and a maximum tolerated dose (MTD) was not reached.
• 87% (55/63) of patients remained on treatment as of the September 13, 2025 data cut-off.
• The company has selected 320 mg and 500 mg QD as the recommended Phase 2 doses for expansion.
• Enrollment in the CARDINAL trial has accelerated and surpassed 85 patients.

Sentiment

Score: 9

Explanation: The filing presents highly positive clinical data for TERN-701, demonstrating strong efficacy (high MMR and DMR rates) and an encouraging safety profile in a challenging patient population. Management's confidence in its 'best-in-disease' potential and accelerated trial enrollment further bolster positive sentiment, indicating significant progress towards pivotal trials.

Positives

• High overall MMR rate of 74% by 24 weeks in heavily pretreated CML patients across all dose cohorts.
• Even higher MMR rate of 80% (75% achieved) by 24 weeks in patients at doses ≥320 mg QD.
• Significant deep molecular response (DMR) achievement rates (29% overall, 36% at higher doses) by 24 weeks, indicating fast response kinetics.
• Strong efficacy observed in difficult-to-treat patient subgroups, including those with lack of efficacy to prior asciminib (60% overall MMR, 43% achieved) and ponatinib.
• Favorable safety and tolerability profile with no dose-limiting toxicities (DLTs) and no maximum tolerated dose (MTD) reached.
• Low rates of Grade 3 cytopenia, with less than 10% for both thrombocytopenia and neutropenia.
• High patient retention, with 87% (55/63) of patients remaining on treatment as of the data cut-off.
• TERN-701 exposures were approximately dose proportional across the dose range.
• The company believes TERN-701 has the potential to be a 'best-in-disease' therapy in second-line-plus (2L+) and first-line (1L) CML treatment settings.

Risks

• Actual results and the implementation of the company's plans may vary materially due to risks and uncertainties.
• Risks are associated with the initiation, cost, timing, progress, results, and utility of current and future research and development activities and preclinical studies and clinical trials.
• New risk factors may emerge over time, and the company cannot predict all of them or assess their full impact on its business.
• Forward-looking statements should not be relied upon as predictions of future events due to significant uncertainties.

Future Outlook

The company plans to advance TERN-701 through dose expansion cohorts in the CARDINAL trial in 2026, select the dose for pivotal clinical development, and seek alignment with the FDA for the design and conduct of two pivotal Phase 3 monotherapy clinical trials. These Phase 3 trials will target 2L+ CML patients and 1L CML patients, with plans to stagger their start and then conduct them in parallel, subject to regulatory feedback.

Management Comments

• "We are delighted that our investigators can share these unprecedented Phase 1 data for TERN-701 with patient groups and the broader hematology community at ASH." Amy Burroughs, CEO.
• "The safety profile and higher MMR achievement rate of 75% over 24 weeks at doses of 320mg and above supports selection of 320mg and 500mg QD as the recommended phase 2 doses (RP2Ds) for expansion." Amy Burroughs, CEO.
• "Study enrollment has accelerated and surpassed 85 patients which supports rapidly advancing TERN-701 through dose expansion cohorts, dose selection, and the initiation of pivotal studies." Amy Burroughs, CEO.
• "We are particularly encouraged to see unprecedented rates of MMR in a highly refractory population, including compelling response achievement in patients with lack of efficacy on prior asciminib, ponatinib, and/or other marketed and investigational TKIs." Emil Kuriakose, MD, CMO.
• "In the RP2D dose range, we see a 36% DMR achievement rate by 24 weeks, highlighting the fast response kinetics of TERN-701." Emil Kuriakose, MD, CMO.
• "Importantly, with a median treatment duration of six months, we continue to see a favorable safety and tolerability profile at all doses, further positioning TERN-701 as the potential best-in-disease therapy in 2L+ and 1L CML, where we intend to focus pivotal clinical development." Emil Kuriakose, MD, CMO.
• "Based on the data to date, TERN-701 represents an innovative treatment option that has the potential to achieve this important goal. I am excited to help advance this therapy for the benefit of CML patients." Elias Jabbour, MD, Lead Investigator.

Industry Context

While therapies for Chronic Myeloid Leukemia (CML) have significantly advanced since the introduction of imatinib, there remains a substantial unmet need for new drugs that can achieve early, broad, and deep molecular responses with a favorable safety and tolerability profile. This is particularly critical for long-term maintenance of response and improved quality of life for patients, especially those with heavily pretreated and refractory disease. TERN-701 aims to address this gap by offering a potentially 'best-in-disease' option in both second-line-plus (2L+) and first-line (1L) CML treatment settings.

Comparison to Industry Standards

• TERN-701 is positioned as a "potential best-in-disease therapy" in 2L+ and 1L CML treatment settings.
• Management highlights "unprecedented rates of MMR in a highly refractory population," including compelling response achievement in patients with lack of efficacy on prior asciminib, ponatinib, and/or other marketed and investigational TKIs.
• The 36% DMR achievement rate by 24 weeks in the recommended Phase 2 dose range is noted for its "fast response kinetics," suggesting a rapid onset of deep responses.
• The favorable safety and tolerability profile, maintained with longer treatment duration, is emphasized as a key differentiator compared to existing CML treatments, aiming for improved quality of life for patients.

Stakeholder Impact

• Shareholders: Highly positive impact due to strong clinical data, potential for TERN-701 to become a significant drug, and a clear path to pivotal trials, which could substantially increase company valuation.
• Patients (CML): Highly positive impact as TERN-701 shows promise as an innovative treatment option, especially for those with heavily pretreated and refractory disease, potentially offering improved efficacy, safety, and quality of life.
• Healthcare Providers: Potential new, effective, and well-tolerated treatment option for CML patients, addressing significant unmet needs in the field.

Next Steps

• Advance TERN-701 through dose expansion cohorts in the CARDINAL trial in 2026.
• Select the dose for pivotal clinical development.
• Seek alignment with the FDA for the design and conduct of two pivotal Phase 3 monotherapy clinical trials.
• Stagger the start of the two proposed pivotal clinical trials (one in 2L+ CML patients and the other in 1L CML patients) and then conduct them in parallel, subject to regulatory feedback.
• Host an investor update call and webcast on December 8, 2025, at 4:30pm ET to discuss additional TERN-701 data, patient vignettes, benchmarking comparisons, and next steps.

Key Dates

Recommendation

The clinical data for TERN-701 is exceptionally strong, demonstrating high major molecular response (MMR) and deep molecular response (DMR) rates in a heavily pretreated and refractory chronic myeloid leukemia (CML) patient population, including those who failed prior standard-of-care treatments like asciminib and ponatinib. The safety profile is also highly encouraging with no dose-limiting toxicities and high patient retention. Management's confidence in TERN-701's 'best-in-disease' potential, accelerated trial enrollment, and clear strategic path towards pivotal Phase 3 trials with FDA alignment indicate significant de-risking and a strong value proposition. This positive clinical progress significantly enhances the company's long-term prospects and market position in the CML therapeutic landscape, making it a compelling 'strong buy' for investors.

Keywords

TERN-701, Chronic Myeloid Leukemia, CML, BCR::ABL1 inhibitor, CARDINAL trial, Phase 1 clinical trial, ASH Annual Meeting, Molecular Response, Oncology, Clinical-stage oncology, Drug development, Hematology