AbbVie and HotSpot Therapeutics, Inc., a biotechnology company developing small molecule allosteric therapies for the treatment of cancer and autoimmune diseases, entered an exclusive worldwide collaboration and option to license agreement for HotSpot’s discovery-stage IRF5 program for the treatment of autoimmune diseases.
 
IRF5 is a transcription factor that acts as a key regulator of certain types of immune responses, and its dysregulation is strongly implicated in several poorly treated autoimmune disorders. Efforts to modulate IRF5 using conventional small molecule approaches have been unsuccessful because IRF5 lacks a traditional active site. Leveraging the Smart Allostery platform, HotSpot discovered what it believes to be the first and only disclosed small molecule IRF5 inhibitor that targets a previously unknown allosteric pocket on the protein that is critical for its endogenous regulation – a “natural hotspot”.
 
HotSpot will receive $40 million upfront and may be eligible to receive as much as $295 million in option fees and R&D milestones, with potential for further commercial milestones as well as royalties on sales. Should AbbVie exercise its option to license, AbbVie will conduct all future clinical development, manufacturing and commercialization activities for the IRF5 inhibitor program. In addition, HotSpot would have a one-time option to share in global R&D costs in exchange for increased royalty payments. 
 
“This collaboration with HotSpot has the potential to deliver an entirely new target class of modulators to patients with serious autoimmune diseases, such as systemic lupus erythematosus, and will help to further strengthen our robust immunology pipeline,” said Jonathon Sedgwick, Ph.D., vice president and global head of discovery research, AbbVie. “HotSpot’s drug discovery platform has been able to identify molecules that bind to IRF5 in a predictable, reproducible manner potentially enabling effective drugging of what has been considered an undruggable target.”
 
“Today’s agreement with AbbVie underscores our significant progress in rapidly building a substantial pipeline of novel allosteric small molecule therapeutic candidates for the treatment of autoimmune diseases and cancer,” said Jonathan Montagu, Co-Founder and Chief Executive Officer of HotSpot Therapeutics. “We look forward to collaborating with AbbVie, an industry leader in developing and commercializing important immunology therapeutics.”