HotSpot Therapeutics Presents Phase 1 Data on Novel CBL-B Inhibitor HST-1011 at ESMO 2024

HotSpot Therapeutics, Inc., known for pioneering the development of oral, small molecule allosteric therapies that target critical regulatory sites on proteins called "natural hotspots," has unveiled promising initial clinical data for HST-1011. This investigational drug is a selective inhibitor of the Casitas B-lineage lymphoma proto-oncogene (CBL-B). The findings come from the Phase 1 monotherapy dose escalation segment of a clinical study and were presented at the European Society for Medical Oncology (ESMO) Congress 2024.

According to Timothy Reilly, Ph.D., Chief Development Officer of HotSpot, these early results provide the first extensive look into the clinical potential of a CBL-B inhibitor. This novel immuno-oncology mechanism could potentially revolutionize the treatment landscape for patients with solid tumors. HST-1011 demonstrated essential connections between drug exposure levels, target engagement, and pharmacological measures, showing initial signs of clinical benefit in patients with advanced, heavily pre-treated solid tumors. These findings set a solid groundwork for further evaluation of HST-1011 in specific patient groups and in combination with the PD-1 inhibitor, cemiplimab.

The Phase 1/2 clinical study (NCT05662397) aims to evaluate HST-1011 both as a standalone treatment and in combination with Regeneron's anti-PD-1 therapy, Libtayo® (cemiplimab). The study involves adult patients with advanced solid tumors that have either relapsed or are resistant to anti-PD(L)-1 or standard care therapies. The initial results presented at ESMO included data from 28 patients who were part of the monotherapy dose escalation portion of the study.

The data revealed that the patients had a diverse range of solid tumors and had undergone multiple prior treatments, with a median of four previous therapy lines. Notably, 89% of the patients had previously received immunotherapy. HST-1011 was found to be generally well tolerated across various twice-weekly doses, with no dose-limiting toxicities observed. The most frequent adverse events were gastrointestinal issues, which were largely mitigated through a pre-emptive treatment regimen.

The study observed encouraging relationships between pharmacokinetics (PK), target engagement, pharmacodynamics (PD), and initial signs of clinical activity. Despite dealing with a heavily pre-treated cancer patient population, the study noted indications of clinical benefit, such as tumor stasis or reduction, in 10 of the 28 patients across various tumor types and dose levels.

These promising initial results support the continued evaluation of HST-1011. The details of the presentation 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: Friday, September 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

HotSpot Therapeutics, Inc. is a clinical-stage biotechnology company pioneering a new class of allosteric drugs targeting naturally occurring regulatory pockets on proteins referred to as "natural hotspots." These hotspots play a critical role in controlling a protein's cellular function and offer substantial potential for new drug discovery. The company's proprietary Smart Allostery™ platform leverages computational approaches and AI-driven data mining to uncover these hotspots, facilitating the rapid discovery of novel allosteric therapies for cancer and autoimmune diseases. Through this innovative approach, HotSpot is developing a broad pipeline of new treatments, aiming to make significant strides in the field of targeted therapeutics.

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