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 KRASG12X CRC depends on the CBM signalosome for survival, supporting the significant potential of a CBM signalosome inhibitor to transform the treatment landscape of KRASG12C 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 KRASG12C 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 KRASG12 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 KRASG12X 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
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SOURCE HotSpot Therapeutics
