Profluent Announces Strategic Partnership with Lilly to Develop AI-Designed Recombinases for Genetic Medicine

• Collaboration combines Profluent's frontier AI platform with Lilly's leading capabilities in genetic medicines
• AI-designed recombinases aim to unlock kilobase-scale DNA editing capabilities across multiple diseases with severe unmet needs

EMERYVILLE, Calif.--(BUSINESS WIRE)--Profluent, the frontier AI company pioneering large-scale foundation models for protein design, today announced a multi-program strategic research collaboration with Eli Lilly and Company (“Lilly”) to develop and commercialize custom site-specific recombinases to address diseases with severe unmet needs.

The collaboration focuses on enabling large-scale, precise DNA editing capabilities that remain out of reach using conventional gene editing systems. By combining Profluent’s frontier AI models with Lilly’s clinical and developmental capabilities in genetic medicines, the companies aim to expand the scope and scalability of programmable gene editing therapeutics.

Many genetic diseases are caused by multiple different mutations across patient populations rather than a single mutation. This heterogeneity makes it difficult to develop targeted therapies that work for all patients. Large-scale DNA editing (i.e., the ability to insert long stretches of DNA, sometimes entire genes, at precise locations in the genome) could address this challenge but remains one of the most significant unsolved problems in genetic medicine.

Traditional approaches rely on finding naturally occurring enzymes that happen to work at target sites. Profluent is taking a different approach: using AI to create designer recombinases—custom enzymes programmed to target exact locations in the genome.

Under the agreement, Profluent will apply its AI models to design and optimize site-specific recombinases for multiple genomic targets. Lilly will receive an exclusive license to advance selected recombinases through in vivo research, preclinical development, clinical studies, and commercialization.

"Kilobase-scale DNA editing remains a holy grail in genetic medicine," said Ali Madani, co-founder and CEO of Profluent. "Our work with Lilly is aimed at unlocking these therapeutics previously thought impossible. We believe only AI can create the designer recombinases needed to precisely target any location in the genome. This collaboration with Lilly demonstrates that our platform is ready to build the toolkit needed to scale genetic medicines. We're seeing strong demand from the pharmaceutical industry, and this partnership validates our approach to solving previously intractable problems."

Hilary Eaton, Chief Business Officer of Profluent, added: "Standard knock-out and base editing approaches leave entire categories of disease out of reach. Kilobase-scale DNA editing is how we reach them—and Profluent's generative models, trained on the world's largest protein dataset including the most comprehensive database of naturally occurring recombinases, were built for exactly this problem. Our goal is to create a fully programmable platform applicable across rare and common diseases alike, and we believe Lilly is the ideal partner to bring these tools to the patients who need them most."

Profluent will receive an upfront payment in addition to committed research and development funding. In total, Profluent is eligible to receive up to $2.25 billion in development and commercial milestone payments plus tiered royalties on net sales. Further details of the agreement have not been disclosed.

About Profluent

Profluent is an AI-first company pushing the frontier of de novo protein design to author new biology. Grounded in nature with AI as an interpreter, Profluent’s powerful foundation model platform unlocks solutions that transform medicine, agriculture, and beyond. Founded in 2022 and headquartered in Emeryville, CA, Profluent is backed by leading investors including Altimeter Capital, Bezos Expeditions, Spark Capital, Insight Partners, Air Street Capital, AIX Ventures, and Convergent Ventures. To learn more, visit profluent.bio or follow the company on LinkedIn, X, and YouTube.