Eli Lilly has entered into a multi-program research collaboration with California-based Profluent to develop genetic medicines using artificial intelligence-designed enzymes. The agreement focuses on creating site-specific recombinases capable of making precise changes to DNA, with the aim of addressing diseases that are difficult to treat using existing gene-editing technologies and currently available approaches in the field.
Profluent, headquartered in Emeryville, describes itself as a company focused on developing large-scale artificial intelligence models for protein design. The company has stated that it has demonstrated the ability of large language models to generate functional proteins and has assembled a dataset of more than 115 billion unique proteins. This resource is described by the company as one of the largest collections of protein data currently available and compiled to date.
Under the terms of the agreement, Profluent will use its AI-based technology to design custom enzymes targeting specific genomic locations across multiple programs and disease areas. Eli Lilly will receive exclusive rights to further develop selected recombinases and advance them through preclinical development and potential commercialization. The collaboration is aimed at creating therapies for conditions with significant unmet medical needs, particularly those that cannot be effectively treated with current gene-editing approaches or existing tools and technologies.
Financially, the deal includes an upfront payment to Profluent, along with research funding to support ongoing work under the collaboration. The company could also receive up to $2.25 billion in development and commercial milestone payments tied to progress. In addition, Profluent is eligible for tiered royalties on any resulting products that reach the market. Specific details regarding the upfront payment were not disclosed by the companies involved in the agreement.
The partnership focuses on advancing genetic medicines, which are treatments designed to modify genes or their activity within the body to address disease. Existing gene-editing technologies are often limited to making small changes in DNA sequences. This limitation can present challenges when treating inherited diseases caused by diverse genetic mutations across different patients and populations in practice.
According to Profluent, its AI-driven approach may enable larger and more precise modifications, potentially allowing for the replacement of faulty genes rather than incremental corrections to small sections of DNA.
“Kilobase-scale DNA editing remains a holy grail in genetic medicine,” said Profluent CEO Ali Madani in an April 28 release. He added that the collaboration with Lilly is intended to unlock therapeutic possibilities that have previously been considered unattainable, and stated that AI is required to design recombinases capable of targeting any genomic location with precision and specificity in applications.
This agreement marks Eli Lilly’s second collaboration this year focused on recombinase technology. In January, the company announced a partnership with Seamless Therapeutics to develop treatments for hearing loss using a recombinase platform and related tools.
The Profluent deal also follows a series of recent transactions by Lilly, including acquisitions of Verve Therapeutics, Ventyx, Kelonia Therapeutics, and Ajax Therapeutics, each involving upfront payments ranging from $1 billion to over $3 billion in separate deals and transactions.
Profluent has entered a landmark multi-program collaboration with Eli Lilly and Company, with the total deal value reaching up to $2.25 billion. The agreement positions Profluent at the forefront of AI-driven biotechnology, focusing on designing next-generation genetic medicines.
The partnership represents one of the largest recent investments in AI-driven genetic medicine, reflecting a broader shift toward computational biology as a core pillar of drug discovery. By combining advanced machine learning with molecular biology, the collaboration aims to dramatically shorten development timelines while increasing precision in targeting genetic diseases.
Unlike conventional biotech partnerships, this agreement is structured around multiple therapeutic programs, allowing both companies to explore a wide range of disease areas simultaneously rather than relying on a single lead asset.
Technology Behind AI-Designed Enzymes
At the heart of the collaboration is a next-generation approach to enzyme engineering. Instead of modifying naturally occurring proteins, scientists are now able to design entirely new enzymes from scratch using AI models trained on vast biological datasets.
Strategic Importance of Profluent in Biotech
For Profluent, this deal is a major validation of its technology and positions the company as a leader in AI-driven protein design. The collaboration also aligns with broader industry trends where pharmaceutical companies are investing heavily in artificial intelligence to accelerate drug discovery.
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