HotSpot Therapeutics Presents Preclinical Data from Small Molecule IRF5 Inhibitor Program at EULAR 2026

BOSTON, June 4, 2026 /PRNewswire/ -- HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, allosteric small molecules that target natural regulatory pockets, today announced the presentation of preclinical data from the Company's interferon regulatory factor 5 (IRF5) program in a poster presentation at the European Congress of Rheumatology (EULAR) 2026.

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 (SLE), 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.

"IRF5 serves as a critical node in immune system regulation, and its inhibition has been shown uniquely to simultaneously impact three key inflammatory pathways, including aberrant B cell activation, type 1 interferon production, and pro-inflammatory cytokine secretion," said Geraldine Harriman, PhD, Co-Founder and Chief Scientific Officer of HotSpot Therapeutics. "At HotSpot, we have successfully applied our Smart Allostery platform to develop potent and selective IRF5 inhibitors, and we are encouraged to share these pre-clinical data that support the profound impact of IRF5 inhibition on these three immune pathways. We look forward to continuing to advance this program with the goal of bringing forward a novel, orally-administered treatment option for patients with a broad range of autoimmune diseases."

The poster presentation describes preclinical data from HotSpot's small molecule IRF5 inhibitor program:

• HotSpot's small molecule IRF5 inhibitors achieved potent, dose-dependent suppression of cytokine production in multiple human immune cell types. Additionally, in B cells, IRF5 inhibition prevented plasmablast differentiation, a key pathogenic driver in SLE.
• In SLE PBMCs, IRF5 inhibition demonstrated dose-dependent cytokine suppression with enhanced potency as compared to key benchmarks.
• In an in vivo mouse model, HotSpot's IRF5 inhibitors demonstrated dose-dependent inhibition of cytokines and mRNA response, as well as dose-dependent down-regulation of interferon and IRF5-driven gene signatures, confirming pathway-level modulation in this model.
• In a cynomolgus monkey model, HotSpot's IRF5 inhibitors demonstrated complete inhibition of the IRF5 pathway for 24 hours, as measured by plasma cytokine and mRNA levels, including at the lowest dose levels evaluated.

About HotSpot Therapeutics, Inc.
HotSpot Therapeutics, Inc. is a 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, as well as 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. To learn more, visit www.hotspotthera.com.

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

SOURCE HotSpot Therapeutics