Prime Medicine’s Gene-Edited Stem Cell Product PM359 Cleared for US Trial in Chronic Granulomatous Disease


The company anticipates that initial data from the study will be announced next year.

Jennifer Gori, PhD, vice president of research at Prime Medicine

Jennifer Gori, PhD

Prime Medicine’s PM359, a product consisting of autologous hematopoietic stem cells (HSCs) that have been modified outside the body using prime editing technology, has received clearance of an investigational new drug (IND) application from the FDA for a first-in-human phase 1/2 clinical trial (NCT identifier pending) for patients with chronic granulomatous disease (CGD).1

The multinational clinical trial will begin by treating adult patients with stable CGD, but pending results indicating safety and biological activity, will later expand to include patients with active infection or severe inflammation, in addition to adolescent and pediatric patients. Outcome measures for the study will cover engraftment and reconstitution of the hematopoietic system, early biological markers of restored immune function, and long-term resolution and prevention of infectious and inflammatory complications of the disease. The company anticipates that initial data from the study will be announced next year.

“We are thrilled to achieve this important milestone for our first product candidate, PM359, which represents the first-ever IND clearance for a Prime Editor product candidate and a significant advancement in the field of next-generation gene editing,” Keith Gottesdiener, MD, the president and chief executive officer of Prime Medicine, said in a statement. “Based on data from our preclinical studies, we believe PM359 has the potential to sufficiently correct a prevalent disease-causing mutation of CGD, leading to amelioration of disease for these patients. We look forward to the planned initiation of our phase 1/2 trial and further determining the potential therapeutic impact of PM359 in patients with this devastating disease.”

Chronic granulomatous disease (CGD) is a rare inherited disorder that typically results in immunodeficiency and chronic inflammatory conditions in patients as a result of their phagocytic myeloid cells having insufficient nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.2 The current standard of care is allogeneic hematopoietic stem cell transplant, but this approach has drawbacks including the need for a matched donor and a risk of complications.

PM359 is specifically intended to treat the most common autosomal recessive form of CGD, p47phox CGD, with the use of prime editing to correct for a 2 nucleotide GT deletion in exon 2 of NCF1, the disease-targeted gene in p47phox CGD. At the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California, CGTLive® spoke with Jennifer Gori, PhD, vice president of research at Prime Medicine, about preclinical research related to PM359 that she presented at the meeting.2

“I think prime editing has been a wonderful advance for the field,” Gori told CGTLive in the interview. “Other gene editing technologies, including Cas9 nuclease, may create a double-strand break, which can lead to potential off-target risks or imprecise edits. Prime editing does not create a double-strand break, and it's very precise. As a tool, it can be used to very elegantly repair any mutation in the genome. Certainly, with this program, we see very high correction—over 90% across multiple stem cell donors—and we see no off-target edits and no unintended edits at the target site. For us, this is a great demonstration of how you can use prime editing to very precisely correct a mutation with high specificity. I think prime editing will be able to be applied across multiple diseases in the future. "

Prime Medicine originally launched in July 2021 with $315 million in financing.3 The company believes that prime editing technology has the potential to address over 90% of known disease-causing mutations.

1. Prime Medicine announces FDA clearance of investigational new drug (IND) application for PM359 for the treatment of chronic granulomatous disease (CGD). News release. Prime Medicine, Inc. April 29, 2024. Accessed May 6, 2024.
2. Gori JL, Heath JM, Tedeschi JG, et al. Prime editing of human CD34+ long-term hematopoietic stem cells precisely corrects the causative mutation of p47phox chronic granulomatous disease and restores NADPH oxidase activity in myeloid progeny. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Abstract #101.
3. Prime Medicine launches with $315 million financing to deliver on the promise of prime editing. News release. Prime Medicine. July 13, 2021.
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