Terns Pharmaceuticals (TERN) investor relations material

Industry landscape and unmet needs

• Chronic myeloid leukemia (CML) has evolved into a chronic disease with multiple approved therapies, but significant unmet needs remain, especially in safety and efficacy for long-term treatment.

• Allosteric inhibitors like asciminib are gaining traction due to improved safety profiles and comparable efficacy to second-generation TKIs, with asciminib now holding about 25% frontline market share.

• Only 15%-20% of patients achieve treatment-free remission, highlighting the need for therapies that drive deeper, faster responses.

• Resistance mutations are not the primary driver of therapy failure in CML; target coverage and tolerability are more critical factors.

• Physicians increasingly prioritize safety and tolerability, as these factors directly impact long-term efficacy and patient outcomes.

Clinical development and data highlights

• Phase I CARDINAL data for TERN-701 showed promising efficacy: 75% achieved MMR, 36% achieved DMR, and 62% achieved MR2 in expansion cohorts.

• As of December, 85 patients were enrolled, with ongoing expansion at 320 mg and 500 mg doses; dose selection will be based on exposure-safety and exposure-efficacy analyses.

• Plans are in place to meet with the FDA mid-year to discuss pivotal trial designs for both second-line and frontline settings.

• A mutation cohort using the 500 mg dose is underway, initially as a signal-seeking effort, with potential for label expansion based on results.

• Safety profile is favorable, with hematologic adverse events being most common but less frequent than with other therapies; no dose relationship observed for adverse events.

Differentiation and competitive positioning

• TERN-701 demonstrates higher target coverage and potency, including activity against mutations resistant to asciminib, such as F317L.

• No food effect observed with TERN-701, simplifying dosing compared to asciminib.

• Confidence intervals for efficacy at 320 mg and above do not overlap with those of asciminib, suggesting superior performance.

• TERN-701 is positioned for use in both first and second-line settings, aiming to compete with generics and asciminib.

• Combination with active site inhibitors is not a current priority due to strong monotherapy responses and concerns about added toxicity.