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 15th European Lupus Meeting.
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.
“With strong genetic and pathway evidence elucidating IRF5’s role in a broad range of autoimmune diseases, we’re incredibly encouraged by these preclinical data for our small molecule IRF5 inhibitors, including the demonstration of dose-dependent inhibition of key pathway markers, including cytokine production and interferon and IRF5 gene signatures,” said Geraldine Harriman, PhD, Co-Founder and Chief Scientific Officer of HotSpot Therapeutics. “These preclinical data provide strong support for the potential of our IRF5 inhibitor program to offer a convenient, orally-administered treatment option for patients with SLE, as well as additional 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.
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