Company: PRME
Filing Date: 2025-02-28
Form Type: 10-K
Source: 0001628280-25-008884
Chunk: 35

Company: Prime Medicine, Inc.
Filing Date: 2025-02-28
Form: 10-K
Item: Item 1
Chunk 35
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 figure below). No off-target edits or unintended edits at the target site were detected in the in vivo humanized mouse or NHP studies.

Next Steps

We have initiated IND enabling studies to develop PM577 for the treatment of WD and are on track to submit an IND and/or Clinical Trial Application, or CTA, in the first half of 2026. 

13

Non-Viral Delivery In Vivo with Lipid Nanoparticles

LNPs are multicomponent systems that encapsulate the Prime Editor cargo to prevent its degradation by the ubiquitous endonucleases present in biological fluids, thereby enabling the transient delivery and expression of the Prime Editor in cells. We are investing strategically to build our LNP formulations for delivery as a platform technology to enable target tissue delivery. Specifically, we are establishing end-to-end capabilities including design and synthesis of proprietary lipids, high-throughput LNP screening in vivo using complementary and orthogonal approaches such as DNA bar coding and next generation sequencing, LNP formulation process development, manufacturing of preclinical and clinical formulations, and in vivo evaluation of LNP delivered Prime Editors. We are integrating automation, analytical quality control, characterization data, in vitro and in vivo preclinical data, along with data knowledge management tools such as machine learning to develop correlative analyses that we believe can expedite LNP discovery and inform drug product formulation development and drug product specification setting. We believe that building an iterative and integrated system will increase efficiencies in identifying potent and safe LNPs capable of delivering Prime Editors to extra-hepatic tissues.

We have developed a Universal LNP delivery system (see schematic in figure below) that is targeted to the liver, and specifically targets the LNP to the hepatocytes. This approach, we believe, improves biodistribution to the target cell type. We expect that the LNP system will be modular in that simply swapping out the pegRNA (and ngRNA where required) will result in a new product, with the potential to accelerate the development of additional liver programs thereafter.

Our Lung Program

Cystic Fibrosis

The Disease

CF is a progressive lung disease characterized by production of thick mucus lung secretions which lead to blockage of airways, inflammation, and lung infection, progressing ultimately to lung failure. It also affects the pancreas gland and biliary system of the liver in a similar way, leading to exocrine pancreatic failure and mild to moderate cholestatic liver disease in some patients. Overall CF prevalence in the United States and Europe is approximately 70,000 to 90,000 people