Prime Medicine Shows PM359 Can Correct CGD Mutation Efficiently and Durably

Prime Medicine, Inc., a biotechnology company, has released promising preclinical data on its Prime Editing program, PM359, which targets a common mutation causing chronic granulomatous disease (CGD). The findings were presented at the American Society of Cell & Gene Therapy's 27th Annual Meeting in Baltimore. The U.S. Food and Drug Administration (FDA) has recently cleared Prime Medicine's investigational new drug (IND) application for PM359, paving the way for Phase 1/2 clinical trials.

PM359 aims to correct a prevalent mutation in the NCF1 gene, which encodes the p47phox protein, a subunit of the NADPH oxidase complex. This complex is crucial for the immune system's ability to fight infections. CGD is an inherited disorder resulting in severe, recurrent infections due to defects in this enzyme complex. The disease affects between one in 100,000 and one in 200,000 births in the U.S., with most diagnoses occurring within the first three years of life. The second most common form of CGD arises from mutations in both copies of the NCF1 gene, accounting for about 25% of cases.

The preclinical studies utilized human blood stem cells from CGD patients, specifically CD34+ hematopoietic stem cells (HSCs). The Prime Editing technology successfully corrected the CGD-causing mutation in over 75% of these cells. Post-engraftment in rodent models, the corrected cells produced neutrophils with restored immune function and no off-target genetic edits were observed. Furthermore, the Prime Edited cells exhibited reduced interferon-regulated gene expression, similar to healthy donor cells, indicating a return to a healthy state.

Additional findings demonstrated that NADPH oxidase activity was restored in the bone marrow neutrophils of mice engrafted with Prime Edited CGD patient cells. The process development also showed the ability to scale up production of these edited cells to a clinical scale, maintaining high purity, viability, potency, and editing efficiency. Long-term engraftment of these healthy donor drug products (HDDP) was achieved, with sustained human multilineage blood production and biodistribution.

Jennifer Gori, Ph.D., Vice President, Head of Hematology and Immunology at Prime Medicine, highlighted the significance of these findings, noting the successful clinical-scale production of Prime Edited blood stem cells as a key milestone supporting the advancement into clinical trials. Jeremy Duffield, M.D., Ph.D., Chief Scientific Officer of Prime Medicine, emphasized the importance of these results in their IND application to the FDA and expressed optimism about moving forward with the Phase 1/2 clinical trial. Initial human data from these trials is expected in 2025.

Chronic granulomatous disease (CGD) is a rare genetic disorder characterized by the immune system's inability to effectively combat infections, leading to severe and often life-threatening conditions. Patients with CGD suffer from recurrent infections and inflammatory complications, which, if left untreated, result in significant morbidity and mortality.

Prime Medicine is pioneering a new class of gene editing therapies using its proprietary Prime Editing platform. This technology allows precise, efficient genetic corrections with minimal unintended modifications, making it a promising tool for treating a variety of genetic disorders. The company's pipeline includes therapies targeting hematology and immunology, liver, lung, ocular, and neuromuscular diseases, with an initial focus on conditions with high unmet medical needs.

The company aims to leverage the versatile capabilities of Prime Editing to develop curative therapies for a broad spectrum of genetic diseases, potentially extending to immunological diseases, cancers, infectious diseases, and common diseases influenced by genetic risk factors.