On June 25, 2025 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," reported the presentation of preclinical data from the Company’s interferon regulatory factor 5 (IRF5) program in an oral and poster presentation at the 25th Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS 2025) (Press release, HotSpot Therapeutics, JUN 25, 2025, View Source [SID1234654119]).
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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.