HotSpot Therapeutics Presents Preclinical Data from Small Molecule IRF5 Program at FOCIS 2025

BOSTON, June 25, 2025 /PRNewswire/ -- HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting Smart Allostery platform-identified regulatory sites on proteins referred to as "natural hotspots," today announced the presentation of preclinical data from the Company's interferon regulatory factor 5 (IRF5) program in an oral and poster presentation at the 25^th Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS 2025).

IRF5 is a transcription factor involved in a diverse range of biological activities in which it functions as a master regulator of innate immunity. Genome-wide association studies have established compelling evidence as to the involvement of IRF5 in multiple inflammatory and immune system disorders, including systemic lupus erythematosus, Sjögren's, rheumatoid arthritis, systemic sclerosis, and myositis. Historical efforts to modulate IRF5 using traditional small molecule approaches have been unsuccessful because IRF5 lacks a traditional active site. Leveraging the Company's proprietary Smart Allostery^™ platform, HotSpot has discovered potent and selective small molecule IRF5 inhibitors that effectively drug the target.

"Our Smart Allostery platform has yielded highly potent and selective small molecule inhibitors of IRF5, with preclinical in vivo data demonstrating dose-dependent reductions in key biological markers of IRF5 inhibition, as well as efficacy in arthritis disease models," said Geraldine Harriman, Ph.D., Chief Scientific Officer of HotSpot Therapeutics. "With robust genetic and biologic validation implicating IRF5's role in a range of autoimmune diseases, we look forward to continuing to advance this program with the goal of offering novel, oral treatment options for patients."

The presentation described preclinical data for HotSpot's Smart Allostery platform-enabled IRF5 program:

• HotSpot's Smart Allostery platform enabled the discovery of potent and selective small molecule inhibitors of IRF5.
• HotSpot's IRF5 inhibitors demonstrated complete, dose-dependent inhibition of IRF5 phosphorylation and nuclear translocation.
• HotSpot IRF5 inhibitors demonstrated a reduction in interferon response genes, antigen-specific antibodies, and joint swelling in two in vivo mouse models of arthritis.

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

HotSpot Investor & Media Contact:
Natalie Wildenradt
[email protected]

SOURCE HotSpot Therapeutics