Theseus Pharmaceuticals, Inc. announced key anticipated milestones for 2023 and introduced its third development program, a pan-variant tyrosine kinase inhibitor (TKI) targeting BCR-ABL for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Pipeline update: THE-630 is a pan-variant inhibitor of the receptor tyrosine kinase KIT, designed for patients with gastrointestinal stromal tumors (GIST) which have developed resistance to earlier lines of therapy. Enrollment is ongoing for the Phase 1 portion of the Phase 1/2 dosescalation and expansion clinical trial evaluauating THE-630 in patients with advanced GIST, with all seven U.S. sites open and accruing.

Theseus is treating patients in cohort 5 of dose escalation as of the end of 2022. Theseus plans to present preliminary safety, pharmacokinetic, and initial clinical activity data, as well as an analysis of circulating tumor DNA (ctDNA), at a scientific conference in the second quarter of 2023, with follow-up data on additional cohorts expected in the fourth quarter of 2023. Patients enrolled in the trial have had a median of four prior therapies.

ctDNA samples are being collected before, during, and after treatment and are being analyzed by next-generation sequencing (NGS) to characterize mutational heterogeneity and the effects of THE-630 on mutant allele fraction over time. Theseus aims to develop THE-630 as a best-in-class molecule for patients with KIT-driven GIST. Preclinical data demonstrate the potential of THE-630 as a pan-variant inhibitor of all major classes of activating and resistance mutations in KIT, which could overcome a critical limitation of approved therapies.

Based on clinical data from the ongoing Phase 1/2 study, Theseus plans to pursue parallel registration trials in second- and fifth-line patients with advanced GIST.