Initiation of Phase 1/2 study anticipated in the first quarter of 2023

BOSTON, MA, USA I January 3, 2023 I 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 clearance by the U.S. Food and Drug Administration (FDA) of the Investigational New Drug (IND) application for HST-1011, the Company’s investigational small molecule allosteric inhibitor of casitas B-lineage lymphoma-B (CBL-B). This represents the first IND filing for HotSpot. The Company expects to initiate the Phase 1/2 study of HST-1011 in the first quarter of 2023, with an initial focus on the evaluation of HST-1011 as monotherapy in patients with advanced solid tumors who are relapsed or refractory to anti-PD(L)1 therapy.

“Clearance of our first IND is an important step forward for our Smart Allostery™ platform and our mission to produce a pipeline of differentiated product candidates for clinically meaningful, yet historically difficult-to-drug, targets,” said Tim Reilly, Ph.D., Chief Development Officer of HotSpot Therapeutics. “Despite tremendous advances in the field of immuno-oncology (I-O), a significant unmet need persists for patients with tumors that either do not respond to or relapse following treatment with existing immunotherapies. With robust preclinical data supporting the potential of CBL-B inhibition to create an immunostimulatory tumor microenvironment and in turn, address the underlying factors that serve as a basis for poor response, we believe the therapeutic advancement of CBL-B inhibition represents a significant turning point for I-O.”

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

SOURCE: HotSpot Therapeutics