PM359 / Prime Medicine - LARVOL DELTA

Prime Medicine announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to PM359, an investigational autologous Prime Edited hematopoietic stem cell therapy for the treatment of p47phox-deficient chronic granulomatous disease (CGD) (GlobeNewswire) - "RMAT designation was granted based on Phase 1/2 clinical data, including data previously published in The New England Journal of Medicine."

FDA event • Genetic Disorders • Hematological Disorders

PRIME-0101: A Study of the Safety and Efficacy of Prime Editing (PM359) in Participants With p47phox Autosomal Recessive Chronic Granulomatous Disease (CGD ) (clinicaltrials.gov) - P1/2 | N=12 | Enrolling by invitation | Sponsor: Prime Medicine, Inc. | Active, not recruiting ➔ Enrolling by invitation

Enrollment open • Gene Therapies • Immunology • Primary Immunodeficiency • Transplantation

First in human prime edited autologous hematopoietic stem cell therapy for the treatment of p47phox CGD: Initial results of PRIME-0101 (ASH 2025) - "Two study participants, Participant 1 (18yo male) and Participant 2 (57yo male) underwent HSCmobilization with G-CSF and plerixafor, and the apheresis product was transferred to a centralmanufacturing facility to generate PM359. Importantly, frequency of both DHR+ neutrophils and PrimeEdited CD34+ cells exceed the 20% threshold expected to be sufficient for restoration of NADPH oxidaseanti-pathogen activity and amelioration of disease pathology. Safety was consistent with busulfanconditioning; neither participant required platelet or red blood cell transfusion support.The initial results from the Prime-0101 study provide the first-in-human demonstration of the safety andefficacy of Prime Editing and offer an autologous cell therapy for individuals with p47phox CGD."

First-in-human • P1 data • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Primary Immunodeficiency • CD34

Prime Editing for p47phox-Deficient Chronic Granulomatous Disease. (PubMed, N Engl J Med) - P1/2 | "Two participants received PM359 after myeloid conditioning with busulfan: neutrophils and platelets engrafted promptly in both patients. These results support further investigation of prime editing of CD34+ cells to treat p47-CGD. (Funded by Prime Medicine; ClinicalTrials.gov number, NCT06559176.)."

Journal • Immunology • Primary Immunodeficiency • CD34

Prime Editing: The Next Frontier in Precision Gene Therapy. (PubMed, J Gene Med) - "A significant milestone was the US Food and Drug Administration's granting of Investigational New Drug (IND) clearance for the first clinical trial of PM359, a therapeutic based on PE...Despite considerable progress, unlocking the complete therapeutic promise of PE requires overcoming significant hurdles, particularly in developing effective in vivo delivery systems for its sizable components, with ongoing research actively investigating diverse viral and nonviral approaches. The translation of this versatile platform into transformative precision gene therapies is critically dependent upon its continued responsible advancement under robust ethical and regulatory oversight."

Journal • Review • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Hematological Disorders • Immunology • Ophthalmology • Primary Immunodeficiency • Pulmonary Disease • Respiratory Diseases • Retinal Disorders • Sickle Cell Disease

A Study of the Safety and Efficacy of Prime Editing (PM359) in Participants With p47phox Autosomal Recessive Chronic Granulomatous Disease (CGD ) (clinicaltrials.gov) - P1/2 | N=12 | Active, not recruiting | Sponsor: Prime Medicine, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene Therapies • Immunology • Primary Immunodeficiency • Transplantation

Prime Medicine Reports Full Year 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "Announce initial clinical data from Cohort 1 in Phase 1/2 trial of PM359 for p47phox CGD in 2025...File IND and/or clinical trial application for PM577 in the first half of 2026."

IND • P1/2 data • Genetic Disorders • Hematological Disorders • Rare Diseases

A Study of the Safety and Efficacy of Prime Editing (PM359) in Participants With p47phox Autosomal Recessive Chronic Granulomatous Disease (CGD ) (clinicaltrials.gov) - P1/2 | N=12 | Recruiting | Sponsor: Prime Medicine, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Gene therapy • Gene Therapies • Immunology • Primary Immunodeficiency • Transplantation

A Study of the Safety and Efficacy of Prime Editing (PM359) in Participants With p47phox Autosomal Recessive Chronic Granulomatous Disease (CGD ) (clinicaltrials.gov) - P1/2 | N=12 | Not yet recruiting | Sponsor: Prime Medicine, Inc.

Gene therapy • New P1/2 trial • Gene Therapies • Immunology • Primary Immunodeficiency • Transplantation