Terns Pharmaceuticals Announces Data from Ongoing Phase 1 Pharmacokinetic Study of Allosteric BCR-ABL Inhibitor TERN-701 in Adult Healthy Volunteers and Highlights Potential for Competitive Differentiation - Seite 2

The Phase 1 single-ascending dose (SAD) trial is ongoing in the United States and has enrolled 32 healthy volunteers in four dose escalation cohorts of eight participants each to evaluate PK, food effect and safety and tolerability at single doses ranging from 20 mg to 160 mg. No clinically meaningful changes or trends were observed in clinical laboratory data, vital signs or electrocardiogram (ECG) parameters at any dose level. Across the dose range administered to date, TERN-701 PK was linear with a median half-life ranging from 8 to 12 hours. At the 80 mg and 160 mg doses, TERN-701 exposures over 24 hours met or exceeded the predicted efficacious concentrations based on preclinical data¹, consistent with observed clinical activity and safety at these doses in the ongoing Phase 1 study in China conducted by our partner, Hansoh Pharmaceuticals. Overall, the PK profile of TERN-701 in Western participants was generally consistent with that observed in the Phase 1 clinical study in Chinese CML patients.

Results of the food effect evaluation at 80 mg of TERN-701 showed no clinically significant differences in plasma exposures (area under curve, AUC) when dosed with a high-fat meal, relative to the fasted state. These results support potential dosing of TERN-701 with or without food, an initial differentiation for TERN-701 as a potentially best-in-class allosteric BCR-ABL inhibitor.

The Phase 1 healthy volunteer study remains ongoing and will proceed to enroll 320 mg and 400 mg dose cohorts. Terns plans to present these healthy volunteer data at an upcoming scientific conference.

Phase 1 CARDINAL Trial Design
The CARDINAL trial is a global, multicenter, open-label, two-part Phase 1 clinical trial to evaluate the safety, PK, and efficacy of TERN-701 in participants with previously treated CML. Part 1 is the dose escalation portion of the trial that will evaluate once-daily TERN-701 monotherapy in approximately 24-36 adults living with CML to be enrolled in up to five dose cohorts. Participants will have chronic phase CML with confirmed BCR-ABL and a history of treatment failure or suboptimal response to at least one second generation TKI (nilotinib, dasatinib or bosutinib). Participants who are intolerant to prior TKI treatment (including asciminib) are also allowed. The primary endpoints for Part 1 are the incidence of dose limiting toxicities (DLTs) during the first treatment cycle, and additional measures of safety and tolerability. Secondary endpoints include TERN-701 PK and efficacy assessments, such as hematologic and molecular responses as measured by the change from baseline in BCR-ABL transcript levels. The starting dose is 160 mg QD with dose escalations as high as 500 mg QD and the option to explore a lower dose of 80 mg QD.