Summary of Terns Pharmaceuticals Conference Call Company Overview - **Company**: Terns Pharmaceuticals - **Product**: Tern 701, an investigational next-generation oral allosteric BCR-ABL inhibitor for chronic myeloid leukemia (CML) treatment [2][41] Industry Context - **Disease**: Chronic Myeloid Leukemia (CML) - **Current Treatments**: First-generation and second-generation active-site tyrosine kinase inhibitors (TKIs) like Imatinib and Asciminib - **Market Need**: Significant unmet need for improved efficacy, safety, and tolerability in CML treatments, with approximately 40% of patients switching therapies within five years due to inadequate response or side effects [4][5] Key Points from the Call Efficacy and Safety Data - **Tern 701 Efficacy**: - Achieved a 75% major molecular response (MMR) and 36% deep molecular response (DMR) at 24 weeks in the recommended phase two dose range of 320 mg and above [8][31] - In a refractory patient population, 64% MMR was achieved by 24 weeks across all doses, with 75% MMR in patients at higher doses [10][22] - DMR rates are approximately two times higher than those seen with Asciminib [22][34] - **Safety Profile**: - Most treatment-emergent adverse events (AEs) were low-grade, with all grade three AEs being less than 10% [8][41] - No signs of pancreatic toxicity or significant blood pressure changes were observed, differentiating Tern 701 from Asciminib [18][41] Competitive Landscape - **Asciminib**: - First allosteric BCR-ABL inhibitor approved for CML, achieving a 22% market share in the U.S. within three quarters of launch and peak sales estimates revised to over $4 billion [5][6] - Tern 701 is positioned to potentially outperform Asciminib based on early clinical data [6][34] Clinical Trial Insights - **Cardinal Study**: - A two-part multicenter global study enrolling patients with chronic phase CML who have failed prior TKIs [12] - Enrollment has accelerated, with over 85 patients currently participating [3][41] Future Development Plans - **Next Steps**: - Plans to select a single dose for pivotal studies based on ongoing data collection and regulatory feedback [38][41] - Anticipated catalysts include expanded long-term data from the Cardinal study and potential regulatory meetings in 2026 [42][41] Market Opportunity - **Patient Population**: - Approximately 17,000 new CML patients annually in G7 nations, with a significant portion expected to switch to allosteric therapies due to better efficacy and tolerability [39][40] - **Treatment Goals**: - Focus on achieving rapid and deep molecular responses to improve long-term outcomes and quality of life for CML patients [39][52] Conclusion - Tern 701 shows promising efficacy and safety data, positioning it as a potential best-in-disease therapy for CML, with ongoing trials and future studies aimed at confirming its clinical benefits and market potential [41][42]

Core Insights - Terns Pharmaceuticals announced the topline results from its Phase 2 trial of TERN-601, a novel oral GLP-1 receptor agonist for obesity, which showed a maximum placebo-adjusted weight loss of 4.6% but did not meet the high threshold for safety, tolerability, and efficacy required for further development [1][2][3] - The company will not advance TERN-601 or invest in other metabolic assets, instead focusing on TERN-701, a potential best-in-class allosteric BCR-ABL inhibitor for chronic myeloid leukemia, with new clinical data expected this quarter [1][2] Phase 2 Trial Results - The Phase 2 trial demonstrated statistically significant weight loss at doses greater than 500 mg, with the following placebo-adjusted weight loss results: - 250 mg: -1.8% - 500 mg slow titration: -3.6% - 500 mg: -4.6% - 750 mg: -3.0% - p-values for these results were significant, particularly for the 500 mg dose [3][4] - The trial included 134 participants, with 11.9% discontinuing treatment and 8.2% modifying doses due to adverse events, primarily gastrointestinal [4][9] Safety and Tolerability - The most common adverse events were gastrointestinal, with nausea reported in 56% of participants and vomiting in 26.9% [4][9] - No severe gastrointestinal adverse events were reported, and liver function tests remained stable during the treatment period, although three participants experienced grade 3 liver enzyme elevations post-treatment, with two deemed drug-related [9][10] Participant Demographics - The trial participants were predominantly female (78-79%), with a mean age range of 47-53 years, and mean weight and BMI ranges of 99-102 kg and 36-37 kg/m², respectively [5][10] Company Focus - Following the trial results, the company reiterated its commitment to advancing the TERN-701 program for chronic myeloid leukemia, with new data from the Phase 1 CARDINAL trial expected to be announced this quarter [2][8]

Core Insights - Terns Pharmaceuticals is presenting preclinical data on TERN-701, a next-generation allosteric BCR-ABL inhibitor, at the European Hematology Association Congress, highlighting its improved potency against various resistance mutations in chronic myeloid leukemia (CML) [1][2][3] Group 1: TERN-701 Overview - TERN-701 targets the ABL myristoyl pocket and shows potency against over 20 clinically relevant resistance mutations in BCR-ABL [2] - The drug is expected to provide meaningful clinical benefits over existing therapies, particularly in patients with difficult-to-treat resistance mutations [2][3] Group 2: Clinical Trial Details - The CARDINAL Phase 1 clinical trial is assessing the safety, tolerability, and efficacy of TERN-701 in previously treated CML patients, with the dose escalation portion completed in January 2025 [5][6] - No dose-limiting toxicities were observed up to the maximum dose of 500 mg QD, and the trial has moved into the dose expansion phase [5][6] Group 3: Presentation Details - The oral presentation titled "Characterization & Efficacy of TERN-701 in Pre-Clinical Models of Chronic Myeloid Leukemia" is scheduled for June 13, 2025, at EHA25 [4] Group 4: Safety and Efficacy Data - Interim data from the trial indicated compelling molecular responses in heavily pre-treated CML patients, with an encouraging safety profile and no adverse event-related treatment discontinuations [6] - Additional safety and efficacy data, including 6-month major molecular response rates, are expected in Q4 2025 [1][5]