BOSTON, Nov. 9, 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 for HST‑2011, the Company’s small molecule inhibitor of interferon regulatory factor 5 (IRF5), in a poster presentation at the American College of Rheumatology (ACR) Convergence 2026.

“IRF5 serves as a master regulator of innate and adaptive immunity, offering the potential to simultaneously address three validated pathways pathogenically implicated in systemic lupus erythematosus (SLE) and other autoimmune diseases,” said Geraldine Harriman, PhD, Co-Founder and Chief Scientific Officer of HotSpot Therapeutics. “The data being presented at ACR demonstrate the impact of IRF5 inhibition on these three key pathways: aberrant B cell activation, type I interferon signaling, and proinflammatory cytokine production, providing support for the therapeutic potential of HST‑2011. We look forward to advancing HST‑2011 toward clinical development as a potential oral treatment for people living with autoimmune diseases.”

The poster presentation describes preclinical data demonstrating the effects of HST‑2011 on three key disease-driving pathways in SLE and other autoimmune diseases: aberrant B cell activation and autoantibody production, type I interferon signaling, and proinflammatory cytokine production:

• In human cellular systems, HST‑2011 inhibited plasmablast formation and IgG production and potently inhibited type I interferon and proinflammatory cytokine production, including TNF and IL-1β.
• In human whole blood stimulated with a TLR agonist, HST‑2011 reduced plasmablast, B-cell activation and interferon gene signature scores. mRNA sequencing also demonstrated reduced expression of IFNB1, TNF and IL1B.
• Following oral dosing in cynomolgus monkeys, ex vivo whole-blood studies demonstrated that HST‑2011 drove reductions in plasmablast and interferon gene signature scores, as well as IFNB1, TNF and IL1B mRNA expression, consistent with the reductions observed in the human whole blood studies.

Collectively, these data demonstrate the ability of HST‑2011 to drive a coordinated inhibitory effect on three key disease-driving mechanisms, supporting the therapeutic potential of HST‑2011 for SLE and other autoimmune diseases.

The poster presentation is available on the “Publications” section of the HotSpot Therapeutics website.

About HST‑2011
HST‑2011 is an investigational, non-covalent, non-degrading, allosteric small molecule inhibitor of interferon regulatory factor 5 (IRF5). IRF5 is a transcription factor involved in a diverse range of biological activities in which it functions as a master regulator of innate and adaptive 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), cutaneous lupus erythematosus (CLE), Sjögren’s disease, 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 HST‑2011, a potent and selective small molecule IRF5 inhibitor that effectively drugs the target.

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
nwildenradt@hotspotthera.com

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SOURCE HotSpot Therapeutics