Abstract
LILLY, ASCIDIAN LAUNCH UP-TO-$1.9B RNA EXON EDITOR COLLABORATION
Eli Lilly has agreed to partner with Ascidian Therapeutics to develop RNA exon editors intended to treat inherited kidney diseases, through a collaboration that could generate more than $1.9 billion for the Boston biotech.
The companies have agreed to launch a global research collaboration focused on discovering and developing treatments for undisclosed monogenic kidney diseases, with the option to expand into additional targets.
“RNA exon editing gives us the ability to rewrite genes at their source, without altering DNA, opening the door to diseases long out of reach. Combined with Lilly’s genetic medicine expertise, we aim to dramatically reduce the burden of genetic kidney disease,” said Michael Ehlers, MD, PhD, Ascidian’s President and CEO. 1
At the heart of the collaboration are Ascidian’s RNA exon editors, which are designed to repair genetic instructions causing disease. A single RNA exon editor can address multiple mutations spanning multiple exons, resulting in the editing of multiple disease-causing exons simultaneously, thousands of bases at a time.
Since only exons need to be replaced within the diseased protein, the exon editing payload is small enough to fit in an adeno-associated virus (AAV) or in other viral or nonviral delivery vehicles, including lipid nanoparticles (LNPs).
During the transcription of DNA into RNA, noncoding introns are usually removed, while exons that remain are spliced together to form messenger RNA (mRNA) that can be translated into protein. Mutations result in malformed proteins that cause disease.
Ascidian’s RNA exon editors are designed to bind to target pre-mRNA through what the company calls a highly specific binding domain. The editor molecules are delivered as a DNA construct and transcribed into mutation-free, exon-only RNA, designed with a highly specific binding domain.
Through a binding process called pre-mRNA trans-splicing, exon editors replace disease-causing exons, leading to what Ascidian said is expression of wild-type mRNA and protein at proper levels, in the right cells at the right time.
The exon editors are designed to address large genes or genes with high mutational variance.
Ascidian has granted Lilly exclusive, target-specific rights to Ascidian’s RNA exon editing technology for undisclosed kidney disease targets. The number of targets was also not disclosed. Ascidian has agreed to lead discovery and specified preclinical activities, with Lilly agreeing to oversee additional preclinical work, clinical development, manufacturing, and commercialization. Ascidian said it retains rights to pursue other kidney-focused targets, independently or with additional partners.
Lilly has agreed to pay Ascidian up to $1.9 billion, which consists of an undisclosed upfront payment and payments tied to achieving development and commercial milestones, as well as tiered royalties on global commercial sales.
IN TRIAL, LILLY’S VERVE-102 REDUCESPCSK9, LDL-C LEVELS UP TO 18 MONTHS
Eli Lilly researchers have published positive data from the Phase Ib Heart-2 trial (NCT06164730) showing that a single infusion of the in vivo base editing candidate VERVE-102 resulted in dose-dependent lowering of circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) protein and low-density lipoprotein cholesterol (LDL-C), with both reductions sustained over up to 18 months of follow-up in participants at high risk for cardiovascular disease.
According to the data, generated through an interim analysis of 35 participants, a single dose of VERVE-102 resulted in dose-dependent mean reductions in PCSK9 ranging from 51% to 88%, at the lowest 0.3 mg/kg dose to the highest 1.0 mg/kg dose, respectively. Corresponding mean reductions in LDL-C were 9% for the 0.3 mg/kg dose of VERVE-102, 44% for the 0.45 mg/kg dose, 45% for the 0.6 mg/kg dose, 33% for the 0.7 mg/kg dose, 51% for the 0.8 mg/kg dose, and 62% for the 1.0 mg/kg dose.
The reductions were sustained over time, with durability observed for up to 18 months following treatment, Lilly said.
VERVE-102 is designed to durably turn off the PCSK9 gene in the liver and lower blood LDL-C following a single infusion. VERVE-102 consists of an mRNA encoding an adenine base editor and a guide RNA targeting the PCSK9 gene. Both are encapsulated in an LNP and administered as a single intravenous infusion over approximately four hours.
VERVE-102 uses Verve’s GalNAc-LNP delivery technology, which is designed to allow the LNP to access liver cells using either the low-density lipoprotein receptor or the asialoglycoprotein receptor. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for VERVE-102 to reduce LDL-C in participants with hyperlipidemia and high lifetime cardiovascular risk.
Lilly inherited VERVE-102 when it acquired Verve Therapeutics last year for up to $1.3 billion.
“Twenty years ago, genetics showed us that people born with PCSK9 naturally turned off have low LDL-C for life and are remarkably protected from heart attack, yet today’s chronic therapies struggle to deliver this lifelong lowering,” said Sekar Kathiresan, MD, Lilly senior vice president and cofounder of Verve Therapeutics. “The Heart-2 results provide early clinical evidence that a single dose of VERVE-102 may mimic the LDL-C lowering effects of PCSK9 cardioprotective variants, potentially transforming cardiovascular care from chronic management to a one-time treatment.” 2
Researchers from Lilly and its clinical partners presented the data as a late-breaking oral presentation at the European Atherosclerosis Society Congress and as a study published in The New England Journal of Medicine.
As for the trial’s safety results, VERVE-102 showed itself to be well-tolerated across all dose levels with no treatment-related serious adverse events (AEs) and no dose-limiting toxicities reported. AEs related to VERVE-102 included low-grade infusion-related reactions and fatigue. All participants received the full planned dose, and no participant withdrew from the study.
The Heart-2 trial is evaluating VERVE-102 in adults with heterozygous familial hypercholesterolemia (HeFH) or premature coronary artery disease (CAD). Heart-2 is an ongoing open-label, single-ascending dose Phase Ib study designed to evaluate the safety, tolerability, and pharmacodynamic effects of VERVE-102 in adults with HeFH or premature CAD who require additional lowering of LDL-C, despite maximally tolerated oral lipid-lowering therapy.
Lilly plans to launch a Phase II clinical study of VERVE-102 by the end of this year.
LILLY TO ACQUIRE NONVIRAL DNA PLATFORM DEVELOPER ENGAGE BIO
Eli Lilly has acquired nonviral DNA delivery-focused platform developer Engage Biologics for up to $202 million cash, the companies said, in a deal intended to integrate Engage’s platform with Lilly’s genetic medicines capabilities and portfolio.
Based in the San Francisco suburb of San Carlos, CA, Engage has developed the Tethosome platform, a system for delivering nonviral DNA that is designed to overcome limitations in DNA delivery, including potency, tolerability, and redosability. Using LNP technology, Engage’s platform enables delivery of a therapeutic DNA and an mRNA encoding its Tethosome protein. The Tethosome platform is designed to be invisible to immune sensors that detect foreign DNA and that can cause lethal immune reactions, allowing for safe delivery of potent DNA, redosing when needed, and titration of expression to optimal levels.
The protein localizes DNA to the nucleus, increasing expression by over 100-fold, according to the company. Engage engineers the DNA payloads to improve tolerability while retaining key advantages of DNA-based therapies, including durability and programmability.
The company was founded in 2021 and has been supported by seed investors that include SciFounders, Pioneer Fund, Cal Innovation Fund, Y Combinator, and the Cystic Fibrosis Foundation. The company has received nondilutive funding from the Gates Foundation and the National Center for Advancing Translational Sciences, part of the National Institutes of Health.
“With a lean organization and modest seed funding, I am incredibly proud of the rapid progress Engage has made toward a new class of genetic medicines. This is a testament to what a nimble, passionate team can achieve with the tools of synthetic biology,” said Will Olsen, Engage’s Co-Founder and CEO. “We are excited to begin our next chapter with Lilly, which has demonstrated unmatched speed and a uniquely forward-thinking approach to genetic medicine. We believe that the combination of Engage’s platform with Lilly’s significant capabilities will meaningfully accelerate development of new genetic therapies.” 3
The acquisition price consists of an undisclosed upfront payment and additional payments tied to achieving specified development milestones.
ASGCT: GENE, CELL, AND RNA THERAPY SHOW POSITIVE MOMENTUM DURING Q1
At the American Society for Gene and Cell Therapy’s (ASGCT’s) recent Annual Meeting, CEO David Barrett, JD, presented highlights from the Society’s latest Landscape Report on Cell, Gene, and RNA Therapy for the first quarter of 2026.
Barrett said there are currently 42 gene therapies approved worldwide, along with 38 RNA therapies and 76 (nongenetically modified) cell therapies, of which two cell therapies were approved in Japan during Q1. Of the eight gene therapies approved over the past 12 months, half were in the United States, with three more in China.
Despite one fewer approval than in Q4 2025, regulatory momentum remained strong, the report stated: “Accelerated pathways expanded notably, with 13 additional designations granted quarter over quarter. Broad use of Fast Track, RMAT, Breakthrough, and Orphan designations continues to reflect active regulatory engagement and steady pipeline advancement.” 4
“The regulatory pace is starting to pick up, another strong indicator for the future of our field,” Barrett said, adding that in RNA therapies, similarly, “We see a steady uptick over the course of the last year.” 5
Barrett estimated that there are more than 4,200 therapies currently in development, from preclinical through preregistration. The vast majority of those (more than 4,130) are gene and genetically modified cell therapies, including about 1,300 RNA therapies.
In the field of gene-modified cell therapies, chimeric antigen receptor T cell continues to lead the pipeline for ex vivo gene therapies, with natural killer and T-cell receptors gaining traction. Genetically modified cell therapy overwhelmingly targets cancers, but Barrett noted growth in the percentage of these therapies targeting immunological diseases, including lupus, multiple sclerosis, and HIV.
Barrett also noted growth and a promising future in the clinical trials pipeline, which he said consisted of 350 Phase I, 319 Phase II, and 41 Phase III trials in gene therapy (up from 35 a year ago). A growing proportion of gene therapy trials (exceeding 60%) is for nononcology indications.
While RNA interference therapies are growing in number, the same cannot be said for mRNA-based therapies, said Barrett, citing what he called shaken confidence in the space. RNA therapies are targeting primarily nononcology indications, especially in rare diseases.
The ASGCT report is developed in conjunction with Citeline, a subsidiary of Norstella, a pharmaceutical intelligence provider covering drug development from preclinical to commercialization.
REGENXBIO REPORTS POSITIVE PHASE III DATA FOR DMD GENE THERAPY CANDIDATE RGX-202
REGENXBIO has reported positive pivotal data for its Duchenne muscular dystrophy (DMD) gene therapy candidate RGX-202 in the Phase III portion of the Phase I/II/III AFFINITY DUCHENNE® trial (NCT05693142).
The company said AFFINITY DUCHENNE met its primary endpoint as 93% of participants (28 of 30) reached at least 10% microdystrophin expression at Week 12. A 31st participant refused a muscle biopsy and, as a result, did not have a Week 12 biopsy available for evaluation. Microdystrophin expression averaged 71.1% across all participants, and 41.6% in older boys, aged ≥8 years, with 80% of participants achieving >40% microdystrophin expression, REGENXBIO said.
REGENXBIO acknowledged two reports of treatment-related serious AEs (∼6.5% of treated patients): An 8-year-old patient developed subacute myocarditis, while a 10-year-old patient showed a case of asymptomatic liver injury. Both were easily managed and resolved within weeks without sequelae, the company said.
“Today’s topline results underscore how our novel construct and differentiated therapeutic approach support a favorable safety profile and potential clinical benefit, including in older patients where progressive decline is expected. These data support the potential of RGX-202 to become a best-in-class gene therapy for Duchenne patients,” said Steve Pakola, MD, REGENXBIO’s Chief Medical Officer. 6
REGENXBIO shares nosedived 43% over two days despite the positive pivotal Phase III results, reaching 52-week lows on consecutive days. Investors and analysts concluded that the data were not encouraging enough to pose a competitive threat to Sarepta Therapeutics, the developer of the first marketed DMD gene therapy Elevidys® (delandistrogene moxeparvovec-rokl), or to Solid Biosciences, whose DMD gene therapy candidate SGT-003 is in Phase III as well as Phase I/II trials. Investors were also jolted by REGENXBIO’s disclosure that the FDA had recommended the company conduct a randomized controlled trial to assess RGX-202 in DMD during talks with agency officials. 7
REGENXBIO sought to reassure investors by noting past FDA guidance that externally controlled trials may be adequate for demonstrating substantial evidence of effectiveness, especially when the treatment effect is sufficiently large to overcome limitations of externally controlled trials. REGENXBIO also said it plans to discuss its data with FDA officials at a future meeting. The agency has offered to review the RGX-202 data and alternative proposals, according to the company.
LATUS BIO CLOSES $97M SERIES A, WITH PROCEEDS AIMED AT BUILDING SCALABLE GENE THERAPY PIPELINE
Latus Bio has closed on a $97 million Series A financing whose proceeds are intended to support its efforts to develop a pipeline of engineered, scalable gene therapies for broader patient populations.
The financing is expected to fund Latus’ operations through key milestones, including initial clinical data from the company’s two most advanced programs: LTS-201 for Huntington’s disease and LTS-101 for late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease. Proceeds are also intended to advance additional preclinical programs that apply Latus’ AAV discovery platform.
Latus focuses on scaling gene therapy to rare and nonrare diseases for patient populations numbering in millions worldwide. The company’s approach to gene therapy combines proprietary and engineered AAV capsids with optimal routes of clinical administration, with the aim of enabling highly efficient delivery at the lowest doses in the industry. That approach is designed to support scalability, enabling broader applications of gene therapy beyond traditional ultrarare disease settings.
In addition to CNS disorders, Latus is advancing capsid variants with potential applications across kidney, eye, heart, and muscle diseases through its integrated discovery engine.
“By combining proprietary and engineered AAV capsids with optimal routes for clinical delivery, we aim to achieve robust cell- and tissue-specific transduction at low doses, which we believe is critical to improving safety, efficacy, manufacturability, and costs. This approach enables a repeatable model for developing therapies across multiple underserved indications with significant unmet need,” said P. Peter Ghoroghchian, MD, PhD, Latus’ CEO. 8
LTS-201, Latus’ first large-rare CNS disease program, is an investigational AAV gene therapy designed to knock down MSH3, which drives the underlying process of somatic instability in Huntington’s disease. LTS-201 is on track for Investigational New Drug (IND) submission in the third quarter. Preclinical data have shown what Latus termed unprecedented targeting of medium spiny neurons in the deep brain, supporting the potential for durable therapeutic benefit from a single administration.
LTS-101 for CLN2 disease has received IND clearance along with Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track Designation from the FDA. Latus said it expects to launch a first-in-human investigator-initiated trial in the third quarter, with initial safety, biomarker, and clinical results expected by year’s end.
Data from the study are expected to inform follow-on programs for additional large-rare diseases and to enable expansion into broader patient populations, according to the company.
The $97 million Series A includes a $43 million extension led by 8VC, with participation from existing investors DCVC Bio, BioAdvance, Benjamin Franklin Technology Partners, Modi Ventures, Gaingels, and Hatch BioFund. Korea Development Bank and Helen’s Pink Sky Foundation participated as new investors.
VECTORBUILDER TO BUILD $50M CHICAGO CENTER FOR BIOMANUFACTURING, R&D
VectorBuilder, a provider of contract research organization and contract development and manufacturing organization services, said it plans to invest $50 million toward establishing a new Advanced Biomanufacturing and R&D Center in Chicago. The Center would mark a major expansion of the company’s regional operations and long-term commitment to supporting the development of genetic medicines.
The new Center will combine research and development with manufacturing capabilities across VectorBuilder’s gene delivery portfolio. Planned as a multiphase project, the facility is expected to begin initial operations in 2027, with further expansion to be based on customer demand and program scale.
“Despite recent volatility in the CGT [cell and gene therapy] field, we see strong long-term momentum in genetic medicine,” said Bruce Lahn, PhD, Chief Scientist of VectorBuilder. “This investment reflects our conviction that gene delivery will be a defining factor in the next phase of the industry. By expanding our capabilities, we can tap into local talent pools and strengthen our biomanufacturing and R&D capabilities in a fully integrated manner, positioning us to innovate and scale as demand accelerates.” 9
The Center is designed to support a full range of gene delivery capabilities, including plasmids, recombinant viral and nonviral vectors, and genetically engineered cells. By bringing these capabilities into a unified workflow, VectorBuilder aims to improve continuity from research-grade constructs to Good Manufacturing Practice manufacturing and reduce fragmentation across development stages.
The expansion is also expected to support increased capacity and faster turnaround times for North American customers, particularly as programs transition from early research into IND-enabling studies and clinical production.