HotSpot Therapeutics Presents Preclinical Data from Small Molecule CBM Signalosome Inhibitor Program at ESMO Gastrointestinal Cancers Congress 2025

BOSTON, July 4, 2025 /PRNewswire/ -- HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting Smart Allostery platform-identified regulatory sites on proteins referred to as "natural hotspots," today announced the presentation of preclinical data from the Company's CARD11-BCL10-MALT1 (CBM) signalosome program at the European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress 2025.

The CBM signalosome is a molecular hub that serves as a key regulator of multiple oncogenic pathways, including NFkB, JNK, mTORC1 and MYC. As such, the CBM signalosome serves as a critical regulator of tumor development and survival, particularly in KRAS-driven colorectal cancer (CRC), as well as other KRAS-driven cancers, including pancreatic and lung cancer. Leveraging the Company's proprietary Smart Allostery™ platform, HotSpot has discovered small molecule CBM signalosome inhibitors that bind and inactivate the complex, with preclinical data demonstrating dose-dependent tumor inhibition and regression in multiple KRAS-driven tumor models.

"While KRAS activation is a prominent genetic feature of CRC, KRAS inhibitors do not yield deep or durable responses for the vast majority of CRC patients. For the first time, we have shown that KRASG^12X CRC depends on the CBM signalosome for survival, supporting the significant potential of a CBM signalosome inhibitor to transform the treatment landscape of KRASG^12C CRC, as well as additional KRAS-associated solid tumors," said Geraldine Harriman, Ph.D., Chief Scientific Officer of HotSpot Therapeutics. "Leveraging our Smart Allostery™ platform, we have developed potent inhibitors of the CBM signalosome complex, with robust in vitro and in vivo data demonstrating apoptosis and tumor growth inhibition and regression in KRASG^12C CRC, providing support for the profound clinical potential of a CBM signalosome inhibitor."

The poster presentations describe the following data:

• HotSpot's CBM signalosome inhibitors demonstrated selectively induced potent apoptosis in KRAS^G12 CRC cell lines, outperforming KRAS, BCL2 and Bcl-xL inhibitors.
• In combination with a KRAS inhibitor, HotSpot's CBM signalosome inhibitor achieved complete suppression of downstream signaling in KRASG^12X cell lines.
• HotSpot's CBM signalosome inhibitor demonstrated dose-dependent tumor inhibition or regression both alone and in combination with a KRAS inhibitor in multiple in vivo models.

About HotSpot Therapeutics, Inc.
HotSpot Therapeutics, Inc. is a clinical-stage biotechnology company that is pioneering a new class of allosteric drugs that target certain naturally occurring pockets on proteins called "natural hotspots." These pockets are decisive in controlling a protein's cellular function and have significant potential for new drug discovery by enabling the systematic design of potent and selective small molecules with novel pharmacology. The Company's proprietary Smart Allostery™ platform combines computational approaches and AI-driven data mining of large and diverse data sets to uncover hotspots with tailored pharmacology toolkits and bespoke chemistry to drive the rapid discovery of novel hotspot-targeted small molecules. Leveraging this approach, HotSpot is building a broad pipeline of novel allosteric therapies for the treatment of autoimmune diseases and cancer. To learn more, visit www.hotspotthera.com.

HotSpot Investor & Media Contact:
Natalie Wildenradt
nwildenradt@hotspotthera.com

SOURCE HotSpot Therapeutics