HotSpot Therapeutics Presents Preclinical Data from CBL-B Program at AACR Annual Meeting 2023

Preclinical data highlighted ability of HotSpot's CBL-B inhibitors to enhance the effector function and proliferation of natural killer cells, which HotSpot believes supports the therapeutic utility of a CBL-B inhibitor

BOSTON, April 19, 2023 /PRNewswire/ -- HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies for the treatment of cancer and autoimmune diseases, today announced the presentation of additional preclinical data on the Company's casitas B-lineage lymphoma-B (CBL-B) program in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2023.

"We believe the targeting of CBL-B, a master regulator of immune cell activation, represents a promising therapeutic approach given preclinical data that indicated CBL-B's ability to lower the threshold for both T cell and natural killer (NK) cell activation, which has the potential to drive benefit for patients with tumors that respond poorly or do not respond to standard-of-care immunotherapies," said Geraldine Harriman, Ph.D., Co-Founder and Chief Scientific Officer of HotSpot. "These data lend strong support to the ability of CBL-B inhibition to affect change to the tumor microenvironment through the enhancement of NK cell proliferation and activity. We look forward to continuing to advance HST-1011, our lead CBL-B inhibitor clinical candidate, through our ongoing Phase 1 clinical study in patients."

The presentation describes preclinical data for a HotSpot compound that is designed as a novel, allosteric, small molecule inhibitor of CBL-B E3 ubiquitin ligase activity:

• In in vitro studies, HotSpot's CBL-B inhibitor demonstrated an ability to increase the single-cell polyfunctionality of NK cells and to enhance the activation of NK cells, NK cell proliferation, and NK cell-mediated cytotoxic activity against K562 cells. Additionally, HotSpot's CBL-B inhibitor enhanced NK cell function in tumor models in vivo. Collectively, we believe these data demonstrated that inhibition of CBL-B can enhance the effector function of NK cells and, in turn, promote NK cell-mediated killing of cancer cells.

About HST-1011

HST-1011 is an investigational orally bioavailable, selective, small molecule allosteric inhibitor of CBL-B, an E3 ubiquitin protein ligase critically involved in immune cell response. Because CBL-B functions as a master regulator of effector cell (T cell and natural killer cell) immunity, its inactivation removes its endogenous negative regulatory functions to substantially enhance anti-tumor immunity. Preclinical data has demonstrated HST-1011's ability to bind to and inhibit a natural hotspot on CBL-B, yielding the activation and propagation of a targeted anti-tumor immune response. Enabled by HotSpot's proprietary Smart Allostery™ platform, HST-1011 is designed with tight binding, low nanomolar potency, a slow dissociation rate from the target to enable sustained pharmacology, and greater selectivity for CBL-B relative to C-CBL.

About HotSpot Therapeutics, Inc.

HotSpot Therapeutics, Inc. 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 cancer and autoimmune diseases. To learn more, visit www.hotspotthera.com.

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Natalie Wildenradt
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SOURCE HotSpot Therapeutics