en.Wedoany.com Reported - Eli Lilly has entered into a global research collaboration with Ascidian Therapeutics to jointly develop RNA exon editors for inherited kidney diseases, a deal that could bring over $1.9 billion to the Boston-based biotechnology company.
The two parties have agreed to launch a global research collaboration focused on discovering and developing treatments for undisclosed monogenic kidney diseases, with the option to expand to additional targets. The core of the collaboration is Ascidian's RNA exon editor technology, which is designed to repair disease-causing genetic instructions. A single RNA exon editor can address multiple mutations spanning several exons, enabling simultaneous editing of multiple disease-causing exons. Dr. Michael Ehlers, President and CEO of Ascidian, stated that this technology does not edit single letters in the genetic code but rewrites entire chapters on a kilobase scale. Because it only replaces exons within the diseased protein, the editor's payload is small enough to be packaged into adeno-associated viruses (AAVs) or other delivery vehicles, including lipid nanoparticles.
Ehlers explained that the therapeutic agent is an AAV expressing a designed RNA exon editor. After the AAV infects target cells, its episome remains in the nucleus, expressing an engineered RNA molecule for trans-splicing. During normal transcription of DNA into RNA, non-coding introns are removed, and exons are spliced together to form messenger RNA (mRNA), which is then translated into proteins. Mutations can lead to the production of malformed proteins and cause disease. Ascidian's RNA exon editor binds to the target pre-mRNA through highly specific binding domains and replaces the disease-causing exon via a pre-mRNA trans-splicing process, allowing the cell to express wild-type mRNA and protein at the correct time and level. This approach is suitable for large genes or genes with high mutational variability. Ehlers noted that for dominant toxic gain-of-function or haploinsufficiency risks, the advantage of RNA exon editing is that it simply replaces the sequence with the wild-type version, without concerns about allele-specific knockout or other issues. The technology does not require the introduction of exogenous enzymes or proteins to perform the editing, distinguishing it from many other forms of DNA or RNA editing.
In the field of kidney disease, more than 60 genetic conditions are known or suspected to affect the kidneys, and over 3.5 million Americans suffer from serious inherited kidney diseases. Ehlers stated that the company is prioritizing diseases for which RNA exon editing is particularly well-suited to address the underlying genetic cause. Under the agreement, Ascidian has granted Lilly exclusive, target-specific rights to use its RNA exon editing technology for undisclosed kidney disease targets. Ascidian will lead discovery and specific preclinical activities, while Lilly will oversee additional preclinical work, clinical development, manufacturing, and commercialization. Lilly will pay up to $1.9 billion, including an undisclosed upfront payment, development and commercial milestone payments, and tiered royalties on global sales.
This collaboration is a continuation of Lilly's expansion in the gene medicine field in recent years. Lilly launched a $700 million gene medicine research institute in Boston in 2021 and has since acquired Prevail Therapeutics (up to $1.04 billion), a neuroscience gene therapy developer; Akouos (up to $610 million), focused on hearing loss; and Verve Therapeutics (up to $1.3 billion), a gene editing therapy developer. Lilly has also entered into RNA-related collaborations with companies such as ProQR and Orna Therapeutics.
Ascidian's most advanced pipeline candidate is ACDN-01, an RNA exon editing therapy for Stargardt disease or other ABCA4 retinopathies. The therapy contains a healthy copy of the ABCA4 RNA exon, designed to replace the mutated segment, producing healthy RNA and normal protein in the retina to help clear waste from the eye. The FDA has granted ACDN-01 Fast Track and Rare Pediatric Disease designations. The drug is being evaluated in the Phase I/II STELLAR trial (NCT06467344), studying its safety and preliminary efficacy via subretinal administration. The company has completed the adult dose-escalation portion and is expanding the study to subjects aged 12 and older. Ehlers noted that compared to other gene therapies using dual-vector technology, ACDN-01's single-vector approach is technically simpler, but ultimately clinical data will be needed for validation. Ascidian is also collaborating with Roche through a partnership launched in 2024, worth up to $1.842 billion (with an initial payment of $42 million), to develop RNA exon editing therapies for neurological targets. The company was formally launched in 2022 by venture capital firm Apple Tree Partners (ATP), which provided $50 million in Series A financing and an additional $40 million in Series A extension financing in 2023. Ascidian entered the clinic with a total of $90 million in equity financing, and its team has now grown to approximately 40 people. Ehlers stated that to support the collaboration with Lilly and technology expansion, the company may grow modestly but does not anticipate significant growth.
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