Lilly Bets Over $3 Billion on Hearing Loss Therapies with Seamless Therapeutics Collaboration

On January 28, Seamless Therapeutics entered into a global strategic research collaboration and license agreement with Eli Lilly. Under the terms of the agreement, Seamless will leverage its proprietary recombinase platform to design and program site-specific recombinases targeting hearing loss indications, aiming to correct mutations in certain genes of interest associated with hearing loss. Eli Lilly willSecured an exclusive license for programmable recombinases to advance preclinical and clinical drug development and commercialization.

Under the terms of the agreement, Seamless will receive a guaranteed upfront payment and committed R&D funding. Overall, SeamlessEligible to receive over $1.12 billion in funding,Including potential development and commercial milestone payments, excluding tiered royalties on successfully marketed drugs.

Recombinases are a class of enzymes that have been widely used in scientific research for decades to precisely modify the genomes of model organisms. However, due to their limited programmability for new target sites, they were previously unsuitable for therapeutic applications. The breakthrough of Seamless’s proprietary platform lies in its innovative recombinase reprogramming technology, which enables the creation of site-specific recombinases that can precisely target any given genomic sequence. This allows for large-scale cleavage, exchange, inversion, or insertion of any DNA fragment, independent of the cell’s natural DNA repair pathways.

For Eli Lilly, this collaboration will diversify its portfolio in the field of hearing loss, establishing a multi-technology asset ecosystem encompassing DNA, RNA, and recombinase platforms.

Seamless was officially launched in 2023 with initial funding of €12.5 million (approximately $14.8 million), co-led by Forbion and Wellington Partners. The German Federal Ministry of Education and Research (BMBF) provided non-dilutive funding through its GO-Bio program to support innovative life sciences startups. In the same year, this seed financing was gradually increased to $25 million and then to $40 million.

The company was founded by two pioneers in recombinase-mediated cassette exchange: Professor Frank Buchholz, Dean of Research at the Medical Faculty and Head of Medical Systems Biology at the Center for Regenerative Therapies Dresden (CRTD) at Technische Universität Dresden, and Dr. Felix Lansing, Co-founder and Chief Scientific Officer of Seamless.

Professor Frank Buchholz and his team developed a method utilizing directed evolution of reprogrammed recombinases—this approach involves random mutagenesis of recombinases, followed by screening and iterative cycles, until the desired recombinase properties are retained; simultaneously, the genomic binding sites are modified at the DNA level to match the desired targets.

In the early days of its founding, Dr. Felix Lansing stated in an interview with Endpoints News: “With advances in technology and our understanding of it, we can now produce a new enzyme in just a few months. We have been committed to accelerating the production process for novel recombinases, as this will truly unlock their applications from a broader perspective, and we also aim to explore additional use cases.”

Early in vivo preclinical evidence indicates that Seamless’s programmable recombinase can precisely edit a 138-kilobase fragment via inversion. Editing through this mechanism is independent of the cell’s DNA repair pathways. This platform offers the opportunity to address multiple pathogenic mutations with a single therapeutic modality and extends gene editing to non-dividing cell types.

In 2024, Seamless secured new financing, expanding its seed round to $25 million and then $40 million, appointed professional executives to its senior leadership team, and established a subsidiary in Lexington, Massachusetts, to explore the translation of its differentiated recombinase technology from early discovery into the clinic. The newly appointed President and CEO, Dr. Albert Seymour, and Independent Chairman of the Board, Adam Rosenber, both have proven track records of long-term leadership at successful, pioneering biotechnology companies focused on gene editing and novel technologies.

Regarding this transaction, Albert Seymour, President of Seamless, stated in an interview with GENengnews: “We will employ a range of different models and bioinformatics tools to scan all nucleotides within the regions of interest. We will identify areas that resemble the wild-type binding sites for these enzymes, or we are optimistic about our ability to evolve them toward these specific sites.”Seamless has effectively shortened the academic process of enzyme discovery, which previously took two years, to a timeline closer to industrial standards, requiring approximately six months.”

Seamless leveraged its platform to reprogram two recombinase families: Cre (causes recombination) and large serine recombinases (LSRs). “Starting from a region of the genome, we select nucleotide sequences and then specifically evolve enzymes that are active at these specific sites. We conduct the evolution in bacteria because they replicate very rapidly, allowing the team to complete many cycles of validation quickly. We then extract these enzymes and test them in mammalian cell lines,” he mentioned.Engagement with Eli Lilly commenced in 2024, when the Eli Lilly team proactively contacted Seamless to seek further information on its recombinase technology, aiming to facilitate its application to genes of interest to Eli Lilly.

For Seamless, Eli Lilly brings expertise and practical experience in biopharmaceuticals, Investigational New Drug (IND) applications, and pipeline development. Meanwhile, through this collaboration, Eli Lilly will expand its footprint in the gene therapy sector and continue to bet on hearing loss—a blue-ocean market with no approved drugs to date.

In 2022, Eli Lilly launched the $700 million Institute for Genetic Medicine in Boston, marking a key strategic move to advance gene research and therapies involving gene editing, RNA, and other nucleic acids. This “Seaport Innovation Center” officially opened in August 2024 as its first biotech hosting portal laboratory (Gateway Labs) on the East Coast.

Andrew C. Adams, then Vice President of Genetic Medicine at Eli Lilly and Co- Director of the Institute, stated that genetic medicines currently account for more than 20% of its research portfolio in diabetes, immunology, and central nervous system disorders, and that Eli Lilly plans to further increase this proportion through the Institute.

Hearing impairment is the most prevalent sensory deficit disorder worldwide. According to the World Report on Hearing published by the WHO, over 430 million people globally suffer from hearing loss. Genetic mutations are a major cause of deafness, accounting for approximately 60% of cases. Hereditary deafness is primarily caused by single-gene mutations, and therapeutic strategies mainly focus on gene replacement, gene editing, and gene suppression.

In addition to the recombinase involved in this collaboration, Eli Lilly is also expanding its footprint in the hearing loss sector through AAV (adeno-associated virus) gene therapy and RNA editing, with total transaction values exceeding $3 billion.

In 2022, Eli Lilly acquired Akouos at a $610 million premium to develop AAV gene therapies for inner ear disorders and hearing loss. Through this acquisition, Eli Lilly obtainedThe World’s First Gene Therapy for Hereditary DeafnessAK-OTOF-101 is a dual-vector AAVAnc80 gene therapy that leverages the AAVAnc80 capsid, which exhibits high transduction efficiency in cochlear inner hair cells (IHCs). It separately packages nearly 6 kb of human cDNA and delivers it to IHCs to enable durable expression of the replacement gene, thereby restoring inner ear cell function and treating sensorineural hearing loss caused by otoferlin (OTOF) mutations.

AK-OTOF-101 has received FDA Orphan Drug and Rare Pediatric Disease designations, with its Phase 1/2 clinical trials expected to conclude in 2028. Preliminary clinical results indicate that the first participant (an individual with a history of severe hearing loss spanning over 10 years) regained hearing within 30 days after receiving AK-OTOF. In terms of competitors, Regeneron’s DB-OTO and Sensorion Therapeutics’ OTOF-GT (SENS-501) are both investigational dual-AAV gene therapies.

In May 2025, Eli Lilly partnered with Rznomics, a South Korean RNA therapeutics biotech company, in a deal valued at over $1.3 billion to develop and commercialize novel RNA editing therapies for sensorineural hearing loss using its proprietary trans-splicing ribozyme platform.

Notably, beyond the hearing impairment sector, Eli LillyExpand gene therapy collaborations to multiple disease areas, including ophthalmology, the central nervous system, and cardiovascular diseases.Especially AAV gene therapy.

In 2021, Eli Lilly acquired Prevail Therapeutics, a developer of gene therapies for neurological disorders, for $1.04 billion, to advance gene therapies based on engineered AAV9 vectors for indications including Parkinson’s disease with GBA1 mutations (PD-GBA), neuronopathic Gaucher disease (nGD), and frontotemporal dementia with GRN mutations (FTD-GRN).

In April 2025, Eli Lilly and Sangamo Therapeutics entered into a gene therapy licensing agreement featuring an $18 million upfront payment and potential milestone payments totaling $1.4 billion. The collaboration will leverage Sangamo’s neurotropic adeno-associated virus (AAV) capsids to develop gene therapies targeting central nervous system disorders.

In June 2025, Eli Lilly acquired Verve Therapeutics for $1.3 billion to leverage base editing technology in the development of gene therapies for cardiovascular diseases. Its core technologies include a GalNAc-LNP delivery system and adenine base editors (ABEs). The lead candidate, VERVE-102, targets the PCSK9 gene to achieve permanent reduction of LDL-C and is currently in Phase Ib clinical trials.

In October 2025, Eli Lilly acquired Adverum Biotechnologies for $262 million, obtaining its core asset Ixo-vec, an AAV.7m8 vector-based gene therapy in Phase III clinical trials for the treatment of wet age-related macular degeneration (wAMD).

On November 10, 2025, Eli Lilly and MeiraGTx entered into a strategic collaboration valued at $475 million, granting Eli Lilly global rights to MeiraGTx’s AAV-AIPL1 gene therapy for the treatment of Leber congenital amaurosis type 4 (LCA4), an inherited retinal disease.