Terns Pharmaceuticals (TERN) investor relations material

Study background and rationale

• TURN701 (TERN-701) is a next-generation oral allosteric BCR-ABL inhibitor for CML, aiming to improve efficacy, safety, and convenience over current therapies, including asciminib.

• CML remains a chronic disease with unmet needs, as 40% of patients on active site TKIs switch therapy within five years due to insufficient response or side effects.

• Allosteric TKIs like asciminib have improved efficacy and safety but still have limitations, such as fasting requirements and specific adverse events.

• TURN701 is designed for once-daily dosing without food restrictions and potentially superior efficacy and safety.

Study design and objectives

• The CARDINAL Phase I study enrolled CML patients with prior TKI failure or intolerance, including those previously treated with asciminib.

• Dose escalation evaluated 160–500 mg daily, with higher doses (320 mg and 500 mg) selected for randomized expansion; over 50 patients have been enrolled.

• The study aims to establish safety, tolerability, pharmacokinetics, and efficacy benchmarks for TURN701.

• Primary endpoints include safety/tolerability and efficacy, with upcoming data to provide 6-month molecular response rates and subset analyses in refractory populations.

• The goal is to position TURN701 as a best-in-class allosteric TKI for CML.

Preclinical and early clinical findings

• TURN701 demonstrates high target selectivity and greater potency than asciminib against multiple BCR-ABL variants in preclinical studies.

• Clinical PK data show TURN701 achieves 2–7 times higher target coverage than asciminib 80 mg at all doses.

• Early clinical data include rescue of response in patients who failed asciminib and rapid deep molecular response in asciminib-naïve patients.

• No dose-limiting toxicities observed up to 500 mg, suggesting a wide therapeutic index and favorable safety profile.

• Early safety data suggest lower rates of pancreatic toxicity and hypertension compared to asciminib.