News Releases

• HST-1011 showed an encouraging early clinical profile demonstrating important linkages between exposure, target engagement, pharmacodynamics and initial signs of clinical activity, along with a generally manageable safety profile, in heavily pre-treated patients with advanced solid tumors
• Data represent the most comprehensive disclosure of clinical experience with a CBL-B inhibitor to date

BOSTON, Sept. 12, 2024 /PRNewswire/ -- HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting regulatory sites on proteins referred to as "natural hotspots," today announced the presentation of initial clinical data for HST-1011, an investigational oral, selective inhibitor of Casitas B-lineage lymphoma proto-oncogene (CBL-B). Data from the Phase 1 monotherapy dose escalation portion of the study are being shared in a proffered oral presentation at the European Society for Medical Oncology (ESMO) Congress 2024.

"These initial data provide the first comprehensive insight into the clinical experience with a CBL-B inhibitor, a novel immuno-oncology mechanism with the potential to meaningfully transform the treatment paradigm for patients with solid tumors," said Timothy Reilly, Ph.D., Chief Development Officer of HotSpot. "Critically, HST-1011 demonstrated important linkages between drug exposures, target engagement, and proximal and distal measures of pharmacology, and we observed initial signs of clinical benefit, in a heavily pre-treated, advanced solid tumor patient population. We believe these data provide a strong foundation for the continued evaluation of HST-1011 in dedicated patient populations and for the further assessment of HST-1011 in combination with a PD-1 inhibitor, cemiplimab."

The Phase 1/2 study of HST-1011 (NCT05662397) 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 adult patients with advanced solid tumors that are relapsed on or are refractory to anti-PD(L)-1 or standard of care therapies. The results being presented at ESMO include data from 28 patients in the monotherapy dose escalation portion of the study. The presentation describes the following data:

• Patients had a diverse range of solid tumor types and were heavily pre-treated, with a median of four prior lines of therapy, including 89% who had been treated previously with immunotherapy.
• HST-1011 was generally well tolerated across a range of twice-weekly doses, with no dose-limiting toxicities. The most frequent adverse events were gastrointestinal in nature, which were generally mitigated by the adoption of a prophylactic pre-treatment regimen.
• Encouraging linkages were observed between pharmacokinetics (PK), target engagement, pharmacodynamics (PD) and initial signals of clinical activity. Despite the heavily pre-treated, advanced cancer patient population, indications of clinical benefit, including tumor stasis or shrinkage, were observed in 10 of the 28 patients across a range of tumor types and dose levels.

These encouraging data provide support for the ongoing evaluation of HST-1011 (NCT05662397).

Presentation details are as follows:

Title: First-in-Human (FIH) Phase 1 Data of HST-1011, an Oral CBL-B Inhibitor, in Patients with Advanced Solid Tumors
Speaker: Rachel E. Sanborn, M.D., Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR
Session Name: Proffered Paper session: Investigational immunotherapy
Session Date and Time: Fri., Sep. 13, 2024, 16:00-17:30 CEST
Presentation Time: 16:50-17:00 CEST
Location: Burgos Auditorium – Hall 5, Fira Barcelona Gran Via
Presentation Number: 991O

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

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

SOURCE HotSpot Therapeutics