Dose-limiting toxicities in a phase I/II study led Theseus Pharmaceuticals Inc. to quit work with lead compound THE-630, a pan-variant KIT Inhibitor  for gastrointestinal stromal tumors (GIST), but the company plans to nominate another such candidate in the same indication during the first half of 2024. Meanwhile, the firm is prioritizing THE-349, a fourth-generation EGFR inhibitor for non-small-cell lung cancer, due for an IND application in the fourth quarter of this year.

The recent win in Japan by Otsuka Holdings Co. Ltd. subsidiary Taiho Pharmaceutical Co. Ltd. with oral heat shock protein 90 inhibitor Jeselhy (pimitespib) put gastrointestinal stromal tumors (GIST) at center stage. Jeselhy was cleared for GIST cases that have progressed after chemotherapy. A handful of companies line the runway with candidates meant to defeat the resistance that GIST often develops to approved tyrosine kinase inhibitors.

Despite big wins in precision oncology – such as last year’s accelerated FDA nod for Amgen Inc.’s Lumakras (sotorasib) in KRAS G12C-mutated locally advanced or metastatic non-small-cell lung cancer – industry has barely scratched the surface of the field’s potential. Part of the problem is on the scientific front. Only about a third of patients are currently eligible for targeted therapy, since the majority of patients “do not have a known therapeutic vulnerability for which we have a drug match,” Keith Flaherty, director of clinical research at Massachusetts General Hospital, said during a Feb. 14 session at the BIO CEO & Investor Conference. “And that’s a big problem.”