NEW YORK – Prime Medicine, a biotech company aiming to cure diseases with a form of gene editing known as prime editing, on Monday unveiled its pipeline of therapeutic development candidates in three core areas: hematology, immunology, and oncology; liver; and lung.
The company launched in 2021 with $315 million in financing and ambitions to use its next-generation gene-editing technology "like a DNA word processor to 'search and replace' disease-causing genetic sequences at their precise location in the genome, without resulting in double-strand DNA breaks that cause unwanted cellular changes."
In March, the company reported a net loss of $198.1 million in 2023, compared to a net loss of $121.8 million in 2022. The company attributed the increase in net loss to a one-time charge related to a settlement with Myeloid Therapeutics, a company Prime Medicine was collaborating with under a 2022 deal, but then, both firms filed arbitration claims related to the deal. As of Dec. 31, 2023, Prime Medicine said it had $135.2 million in cash, cash equivalents, investments, and restricted cash, compared to $307.4 million at the same time in 2022.
Now, undergoing a pipeline prioritization, Cambridge, Massachusetts-based Prime Medicine has narrowed its focus to development candidates that target a disease with well-understood biology and have a defined clinical development and regulatory path. Each candidate is expected to provide a foundation to expand into additional opportunities and efficiently generate follow-on candidates, the company added in a statement.
This pipeline prioritization will streamline the company's operating expenses and capital expenditures, and, combined with $110 million in upfront consideration as part of a new collaboration and licensing deal with Bristol Myers Squibb, Prime Medicine said it has enough cash to fund operations into the first half of 2026.
"In order to maximize prime editing's reach, we believe now is the time to strategically focus our efforts on a set of high value programs," Prime Medicine President and CEO Keith Gottesdiener said in a statement. "Importantly, each prioritized program is intended to serve as a beachhead, allowing us to advance our technological leadership across a number of target tissues and cell types, while providing insights into research and development, regulatory strategy, [chemistry, manufacturing, and controls], and delivery that will potentially allow us to progress our follow-on programs more rapidly and efficiently."
Prime Medicine, for example, is developing two programs to treat chronic granulomatous disease (CGD), a rare and inherited hematologic disorder that can be caused by mutations in multiple genes.
One of the candidates, PM359, uses prime editing to modify patients' own hematopoietic stem cells (HSC) ex vivo to correct a high percentage of cells containing the p47phox variant in the NCF1 gene. The company has launched a Phase I/II trial to test PM359 and expects to be able to share initial clinical data from the study next year. This is the first time the US Food and Drug Administration has cleared an investigational new drug (IND) application for a prime-edited treatment.
The other candidate Prime Medicine is developing is aimed at treating X-linked CGD, in which autologous HSCs are modified ex vivo using the company's Prime Assisted Site-Specific Integrate Gene Editing (PASSIGE) technology to address more than 90 percent of known mutations in the CYBB gene that cause the disease. Prime Medicine said it expects to leverage elements from PM359, including data filed in the IND application and information on chemistry, manufacturing, and controls, to quickly advance the X-linked CGD program.
Separately, Prime Medicine by the end of 2024 plans to initiate IND-enabling activities for a prime editor that it is developing as a treatment for Wilson's disease that targets prevalent mutations in the ATP7B gene. The company expects to file an IND or a clinical trial application in the first half of 2026 for this program. The therapeutic candidate uses a lipid nanoparticle delivery system that Prime Medicine intends to use across all its liver disease programs.
Prime Medicine is also advancing two prime editing approaches for a potential cystic fibrosis cure, using PASSIGE and hotspot editing, in which the company aims to address multiple mutations at mutational hotspots with a small number of prime editors. The Cystic Fibrosis Foundation is funding this work.
Outside of these immediate focus areas, Prime Medicine said it is seeking partners to advance other programs, such as those in neurology, cell therapy, ocular diseases, and hearing loss, though it may choose to advance these programs internally in the future.
Under the research collaboration and license agreement with BMS, which Prime Medicine announced in parallel with its pipeline prioritization, the partners will develop and commercialize prime-edited ex vivo T-cell therapies. BMS will pay Prime Medicine $55 million upfront and make a $55 million equity investment into the company, as well. Prime Medicine is also eligible for more than $3.5 billion in milestone payments, including up to $1.4 billion in payments tied to development milestones and more than $2.1 billion tied to commercialization milestones, as well as royalties on net sales.
As part of the deal, Prime Medicine will design prime editor and PASSIGE reagents for a number of targets in immunological diseases and cancer. BMS will be responsible for development, manufacturing, and potential commercialization activities, while Prime Medicine will also support gene-editing strategies and reagent development.