HotSpot Therapeutics Achieves First-In-Human Dosing with HST-1011, An Investigational Oral Small Molecule Allosteric Inhibitor of CBL-B

Phase 1/2 study designed to evaluate the safety, tolerability, pharmacokinetics, harmacodynamics and preliminary clinical activity of HST-1011 dosed as monotherapy and in combination with Regeneron's anti-PD-1 therapy, Libtayo® (cemiplimab) in patients with advanced solid tumors

BOSTON, April 11, 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 recent initiation of dosing of HST-1011 in its Phase 1/2 clinical trial in patients with advanced solid tumors. HST-1011 is an orally bioavailable, potent, selective small molecule allosteric inhibitor of casitas B-lineage lymphoma-B (CBL-B).

"Dosing of the first patient with HST-1011 is an important milestone for HotSpot signifying our evolution into a clinical-stage company with the first-in-human dosing of a product candidate derived from our proprietary Smart Allostery™drug discovery platform," said Tim Reilly, Ph.D., Chief Development Officer of HotSpot. "Importantly, we believe that HST-1011, as a highly potent and selective inhibitor of the long sought after target CBL-B, may represent an important new immunotherapy treatment option for cancer patients."

The Phase 1/2 study of HST-1011 is an open-label clinical study designed to evaluate HST-1011 alone and subsequently in combination with Regeneron's anti-PD-1 therapy, Libtayo® (cemiplimab), in patients with advanced solid tumors that are relapsed on or are refractory to anti-PD(L)-1 or standard of care therapies. Additional information on this clinical trial can be found on www.clinicaltrials.gov (NCT05662397). The combination therapy component of the study is enabled by a clinical supply agreement with Regeneron for provision of Libtayo.

"Despite tremendous progress in the field of immuno-oncology (I-O), significant unmet need persists for patients with advanced solid tumors, as many cancers are found to be unresponsive to or lack durable responses following treatment with currently available therapies," said Jason Luke, M.D., F.A.C.P., Director of the Immunotherapy and Drug Development Center at the University of Pittsburgh Medical Center's Hillman Cancer Center and the lead Principle Investigator on HotSpot's ongoing Phase 1/2 clinical study. "We believe CBL-B's role as a master regulator of immune cell activation presents a differentiated therapeutic opportunity. We are excited to explore this novel mechanism and new I-O treatment in collaboration with HotSpot and the other investigators and sites participating in this trial."

HotSpot will be presenting the HST-1011 first-in-human Phase 1/2 clinical trial design at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2023, taking place in Orlando, Florida, during the Clinical Trials in Progress poster session. The details for the presentation are as follows:

Title: Phase 1/2 study of HST-1011, an oral CBL-B inhibitor, alone and in combination with anti-PD-1 in patients with advanced solid tumors
Session Title: Phase I and First-in-Human Clinical Trials in Progress
Session Date and Time: Tue., Apr. 18, 1:30-5:00 PM ET
Location: Poster Section 46
Poster Board Number: 14
Abstract Number: CT251

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.

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

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