gintemetostat (KTX-1001)

P1, N=125, Recruiting, K36 Therapeutics, Inc. | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Dec 2025 --> Dec 2027

These data identify the utility of SPR in a "reverse" format, where immobilization of KTX-1001 allowed for the interrogation of binding to a protein target that may be challenging if conformation changes are induced in the coupling of that biologic target to a chip surface. Collectively, this analysis demonstrates the specific potent biochemical activity of KTX-1001 against MMSET and supports the ongoing evaluation of KTX-1001 in the clinic.

P1, N=125, Recruiting, K36 Therapeutics, Inc. | N=60 --> 125 | Trial completion date: Oct 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

The reversibility of epigenetic modifications makes them promising targets for therapeutic intervention and drugs targeting epigenetic regulators (e.g., tazemetostat, targeting the H3K27 methyltransferase EZH2) have been applied in clinical therapy for multiple cancers. The NSD family of H3K36 methyltransferase enzymes-including NSD1 (KMT3B), NSD2 (MMSET/WHSC1), and NSD3 (WHSC1L1)-are now receiving drug development attention, with the exciting advent of an NSD2 inhibitor (KTX-1001) advancing to Phase I clinical trials for relapsed or refractory multiple myeloma...Multiple studies have implicated NSD proteins in human disease, noting impacts from translocations, aberrant expression, and various dysfunctional somatic mutations. Here, we review the biological functions of NSD proteins, epigenetic cooperation related to NSD proteins, and the accumulating evidence linking these proteins to developmental disorders and tumorigenesis, while additionally considering prospects for the development of innovative epigenetic therapies.

This Phase 1 study will evaluate a potential treatment for RRMM utilizing KTX-1001, which is a novel, first-in-class, potent, oral small-molecule MMSET inhibitor. The study is open and actively enrolling patients at centers in the United States, Spain, France, and Canada.

P1, N=60, Recruiting, K36 Therapeutics, Inc.