Biotechnology company HotSpot Therapeutics Inc announced on Thursday the presentation of preclinical data from its interferon regulatory factor 5 (IRF5) programme 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. According to HotSpot, 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 says it has discovered discovered potent and selective small molecule IRF5 inhibitors that effectively drug the target.

Preclinical data presented at EULAR 2026 includes:

* 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.