AbbVie offers up to $335M for connection with HotSpot's preclinical small-molecule program

AbbVie has formed a connection with HotSpot Therapeutics, inking a global licensing option deal for the biotech’s preclinical small-molecule allosteric therapy and extending the opportunity for up to $295 million in biobucks.

HotSpot will use its drug discovery platform, dubbed Smart Allostery, to develop one of the first small-molecule IRF5 (interferon regulatory factor 5) inhibitors aimed at treating cancer and autoimmune diseases, according to the terms of the deal.

AbbVie will pay HotSpot $40 million upfront and provide the Boston biotech the chance to make up to $295 million in option fees and R&D milestones, with the potential to make further milestones and royalties.

If AbbVie exercises its option to license, the Big Pharma will take over all future clinical development, manufacturing and commercialization for the IRF5 program. HotSpot will have a one-time option to share in R&D costs in exchange for higher royalties.  

If successful, the IRF5 program could allow for effective drugging of what has been considered an undruggable target, Jonathon Sedgwick, Ph.D., Abbvie’s vice president and global head of discovery research, said in a Dec. 6 release.

IRF5 plays a key role in regulating certain types of immune responses, and its dysregulation has been linked to multiple autoimmune disorders that lack effective treatments. Previous small-molecule approaches to modulate IRF5 have been unsuccessful because the protein lacks a traditional active site, according to HotSpot. The biotech now believes it has discovered the first and only disclosed small-molecule IRF5 inhibitor that targets a previously unknown allosteric pocket on the protein that is critical for regulation, or what the company dubs a "natural hotspot."

Founded by former Nimbus Apollo leaders, HotSpot thinks it can thwart the selectivity problems and other issues that hamper molecules aimed at the active site. The company’s pipeline is built around these “natural hotspots,” raising a $100 million series C a year ago to bring the allosteric medicines into the clinic, though all programs currently remain in early-stage development.