Emeryville, California-based Profluent and Indianapolis-based Eli Lilly and Company (NYSE: LLY) have announced a multi-program strategic research collaboration to design and commercialize custom site-specific recombinases for diseases with high unmet need. The collaboration applies Profluent’s AI foundation model platform to generate novel recombinase enzymes programmed to recognize precise genomic loci, with Lilly responsible for advancing selected candidates through in vivo research, preclinical development, clinical studies, and commercialization under an exclusive license. Specific disease indications and genomic targets have not been disclosed.
Profluent will receive an upfront payment alongside committed research and development funding, with amounts undisclosed. The company is eligible for up to USD 2.25 billion in development and commercial milestone payments, plus tiered royalties on net sales. No per-program milestone breakdown, royalty rate ranges, or geographic carve-outs were disclosed; the exclusive license to Lilly is implied to be global based on the language of the announcement.
Profluent’s platform uses large-scale generative AI models trained on what the company describes as the world’s largest curated recombinase dataset, alongside broad protein universe data, to design enzymes that can recognize user-specified DNA sequences. Unlike nuclease-based editing approaches such as CRISPR-Cas9, site-specific recombinases catalyze DNA recombination without inducing double-strand breaks, enabling insertion, deletion, or inversion of large DNA segments at targeted genomic locations. The ability to insert kilobase-scale payloads at precise sites addresses a longstanding limitation of first-generation editing tools, which have faced constraints around payload size and off-target activity driven by break-and-repair mechanisms.
Under the collaboration’s work-share structure, Profluent will apply its AI models to design and optimize recombinases across multiple genomic targets. Lilly will select candidates and lead all downstream development and commercialization activity. No co-promotion, co-development option, or profit-sharing alternative to the royalty structure was described.