Prime Medicine will partner with Bristol Myers Squibb (BMS) to develop and commercialize an unspecified number of reagents for ex vivo T-cell therapies through a collaboration that could generate more than $3.5 billion for the developer of prime editing treatments—which simultaneously announced plans to slash its therapeutic areas of focus from 18 to three genetic diseases.
Prime has granted to BMS an exclusive worldwide license to its Prime Editing technology, through which Prime agreed to design Prime Editing reagents through its Prime Assisted Site-Specific Integrase Gene Editing (PASSIGE™) platform. The reagents will be used by BMS to develop, manufacture, and commercialize “multiple” ex vivo T-cell therapeutic products directed to undisclosed specific targets in immunology and oncology, to be selected by the pharma giant, the companies said.
Prime also agreed to support BMS in gene editing strategy and reagent development.
“Through this effort, we will apply our Prime Editing technology beyond the rare genetic diseases in our internal pipeline, potentially unlocking opportunities in areas of high unmet needs in immunological diseases and cancer,” said Keith Gottesdiener, MD, Prime Medicine’s president and CEO. “We are particularly excited that efforts under this collaboration will leverage our PASSIGE technology, that we believe will advance our one-step, non-viral, multi-kilobase-size gene editing approach into the clinic.”
Investors appeared to share Gottesdiener’s enthusiasm, signaling approval of the collaboration with a stock buying surge that sent Prime’s price soaring 45% from $3.46 at the closing bell Friday to $5.02 at 10:19 a.m. ET today, before settling for an 11% gain at $3.85 as of 2:25 p.m. ET.
“There is tremendous opportunity for PASSIGE and Prime Editing to revolutionize the field of cell therapy, and we look forward to expanding our reach over time through both internal and partnered efforts,” Gottesdiener added.
PASSIGE combines Prime Editing with an integrase or other site-specific recombinase to introduce large gene-sized cargo into the genome for stable cargo expression. PASSIGE is delivered through an entirely non-viral manufacturing process without introducing double-stranded DNA breaks or off-target edits—features which according to Prime may enable more precise and effective genetic modification.
$110M Upfront after “going concern” warning
In return for the license, BMS has agreed to pay Prime Medicine $110 million upfront—half of it in cash, and the other half as an equity investment from BMS, which agreed to purchase 11,006,163 shares of Prime.
The upfront total is expected to extend Prime’s cash runway toward fund operations into the first half of 2026—coupled with company plans to “streamline its operating expenses and capital expenditures,” which Prime did not detail in its statement today announcing the narrower pipeline.
Just last month, Prime warned in its most recent Form 10-Q quarterly filing that “substantial doubt exists about the company’s ability to continue as a going concern for 12 months,” since certain elements of management’s plans to address its financial crunch “are outside of the company’s control, including the ability to raise capital through an equity or other financing.”
The upfront total amounts to 62% of the $176.4 million in cash, cash equivalents, investments, and restricted cash that Prime reported as of June 30, 2024, up 30% from $135.2 million as of December 31, 2023.
BMS also agreed to pay Prime up to $1.4 billion in development milestones including up to $185 million in preclinical milestones, more than $2.1 billion in commercialization milestones, as well as royalties on net sales.
“Integrating Prime Medicine’s technologies with our internal capabilities has the potential to open new avenues for innovation and we look forward to collaborating with them as we continue to bring the promise of cell therapy to immunology and oncology,” added Teri Foy, PhD, senior vice president of the Cancer Immunology and Cell Therapy Therapeutic Research Center at BMS.
Immunocology and oncology are disease areas that Prime will combine into a single area of focus combined with hematology—one of three areas of focus identified by the company following a narrowing of its pipeline from as many as 18 genetic diseases.
Furthest along in development within Prime’s pipeline are two programs for the treatment of chronic granulomatous disease (CGD), which according to the company have the combined potential of addressing the vast majority of people living with CGD.
One program is PM359, an ex vivo autologous hematopoietic stem cell (HSC) product for the treatment of CGD patients with a mutation in p47phox. Prime has launched a Phase I/II trial (NCT06559176) assessing the safety, biological activity, and preliminary efficacy of PM359 in adults and children after the FDA cleared Prime’s investigational new drug (IND) application for PM359 in April, less than one month after the IND filing was submitted to the agency.
Pivotal study plans
Prime said it expects to release initial clinical data from the trial in 2025. Once it establishes proof-of-concept, Prime said today, it plans to advance “rapidly” into a pivotal study of PM359, which has received the FDA’s rare pediatric drug and orphan drug designations.
The other CGD program is an ex vivo HSC product for the treatment of X-linked CGD., disclosed by the company today. The program, which applies PASSIGE, is expected to address over 90% of known mutations in the CYBB gene with a single approach. Mutations in the CYBB gene occur in approximately two thirds of patients with CGD.
Prime said it aims to accelerate advancement of its X-CGD program by leveraging work it has carried out for the PM359 program, including the IND filing, chemistry, manufacturing and controls (CMC) work and clinical trial.
Prime’s two other therapeutic areas are liver and lung diseases. In liver disease, Prime is focused on advancing its Wilson’s Disease program, which targets prevalent mutations in the ATP7B gene through a lipid nanoparticle (LNP) Prime Editor. Prime expects to present new preclinical data and initiate IND-enabling activities for the Wilson’s disease program in the fourth quarter, to be followed by an IND and/or clinical trial application (CTA) that the company said it intends to file in the first half of 2026.
The Wilson’s disease program will use Prime’s universal LNP, a multi-component and modular delivery system that the company expects will be used across all liver disease programs—something that Prime said will allow faster and more cost-efficient expansion into follow-on rare and non-rare liver indications.
In lung disease, Prime is advancing two LNP / adeno-associated virus (AAV) Prime Editor programs aimed at treating cystic fibrosis (CF), with funding from the Cystic Fibrosis Foundation. One program uses Prime’s hotspot editing approach to address multiple mutations at mutational hotspots with a small number of Prime Editors. The other program uses PASSIGE to address nearly all people with CF with a single superexon insertion strategy.
The Cystic Fibrosis Foundation has given Prime access to infrastructural support and foundational guidance, including established assays, animal models reagents and patient samples, which the company believes may accelerate advancement of the company’s Prime Editors for CF.
Speaking in January at the 42nd Annual J.P. Morgan Healthcare Conference, Gottesdiener laid out Prime’s then-strategy of organizing its pipeline around four therapeutic area specialties or “pillars.” In addition to a combined hematology and immunology pillar and a liver disease pillar, Prime previously planned for pillars within ocular disorders and neurological and muscular diseases.
“Awful lot of programs”
“Frankly, many investors have come to us and said, ‘That’s an awful lot of programs. Can you help us to understand what’s most important in your pipeline?’” Gottesdiener revealed during his J.P. Morgan presentation.
In a statement today, Prime said it was working to identify partnership opportunities to advance its other programs, citing specifically its neurological diseases, cell therapy, ocular diseases and hearing loss programs. But the company also did not rule out opting to advance any of those programs internally.
“Prime Medicine expects that business development will continue to play a critical role in accelerating and funding its pipeline, allowing the company to maximize the potential and reach of Prime Editing, including in areas outside its core focus,” Prime stated.
Prime editing was first described in a 2019 paper published in Nature by Andrew Anzalone, MD, PhD, and colleagues in the Broad Institute lab of genome editing pioneer David Liu, PhD, whose lab a few years earlier developed another genome editing approach without double-stranded breaks in DNA called base editing. Anzalone discussed the technology and the company on GEN’s “Close to the Edge” video interview series. (Anzalone is Prime’s lead developer of prime editing, and the company’s scientific co-founder.)
Prime editing can introduce targeted insertions, deletions, and all 12 possible base-to-base substitutions. Liu told GEN at the time that of the roughly 75,000 cataloged pathogenic mutations in human genetic diseases, prime editing had the versatility and potential to correct the majority (89%) of them.
Liu co-founded Prime Medicine in 2020 to commercialize prime editing based on Anzalone’s groundbreaking work when he was a postdoctoral fellow, by developing treatments based on applying the technology’s “search and replace” approach to genome editing. The company went public in 2022.
