Prime Medicine, Inc. · NASDAQ:PRME
Prime Medicine — American Society of Gene & Cell Therapy (ASGCT) 2025
17 slides from Prime Medicine's conference presentation, May 16, 2025
Slide 1: Developing Hotspot Prime Editors to enable therapeutic correction of multiple CFTR mutations in Cystic Fibrosis
Delivering on the promise of Prime Editing Abstract 287 Developing Hotspot Prime Editors to enable therapeutic correction of multiple CFTR mutations in Cystic Fibrosis Vivian W. Choi, PhD Vice President, Head of LLME, Prime Medicine American Society of Gene & Cell Therapy May 16th, 2025 On behalf of
Slide 2: Disclosures
Disclosures Vivian Choi declares she is currently an employee of Prime Medicine, Inc. and owns equity in Prime Medicine Confidential | 2
Slide 3: Prime Editing is programmable for both search and replace
Prime Editing is programmable for both search and replace The PE technology utilizes a Prime Editor protein and a Prime Editing guide RNA (pegRNA) to directly write new genetic information into a targeted DNA site without requiring a DSB Gene with mutation GENE SEARCH FIND & NICK PRIME REPLACE CORRE
Slide 4: Prime Editing is the Only Gene Editing Technology That Can Edit, Correct, Insert and Delete DNA
We believe Prime Editing is the Only Gene Editing Technology That Can Edit, Correct, Insert and Delete DNA Sequences in Any Target Tissue Deletion / Insertion Correction Chronic Granulomatous Disease (CGD) Prime Editing is designed with a Prime Editor Point Mutation Correction wide range of genome e
Slide 5: Prime Editing Platform Modularity Accelerates and De-Risks Ongoing Efforts
Prime Editing Platform Modularity Accelerates and De-Risks Ongoing Efforts, Enables Rapid Generation of New Product Candidates Prime Editors Off-Target Manufacturing Clinical Assays Delivery Nonclinical Regulatory Confidential | 5
Slide 6: Challenges and opportunities for developing treatment for Cystic Fibrosis
Challenges and opportunities for developing treatment for Cystic Fibrosis 2 Barriers to reach the cell types to correct the cause of the disease 4 Each delivery vehicle encounters different challenges to reach target cell type with safety profile to enable clinical efficacy 1 3 > 360 disease Limited
Slide 7: Initial approach: correct prevalent mutational hotspots by Prime Editors
Initial approach: correct prevalent mutational hotspots by Prime Editors Correct the causative mutation back to normal wild type sequence in lung epithelial progenitors 7 hotspot correcting Prime Editors could address Precise Correction of >93% of the patient population* CFTR p.G542X mutation in lun
Slide 8: Parallel Prime Editing Approaches to CF: Hotspot & PASSIGE
Parallel Prime Editing Approaches to CF: Hotspot & PASSIGE In 2024, Prime Medicine entered into agreement with CF Foundation to support development of Prime Editors for Cystic Fibrosis CF = Cystic fibrosis; attP = complimentary recognition sequence for attb; SA = spliace acceptor; 3’UTR = 3’ untrans
Slide 9: Highly active CFTR Prime Editors for correcting multiple Cystic Fibrosis mutational hotspots
Highly active CFTR Prime Editors for correcting multiple Cystic Fibrosis mutational hotspots* Exemplary Prime Editors shown here for CFTR G542X correction Modular delivery system In vitro Prime Editor In vitro Prime Editor in Primary Highly potent Prime Editor in Primary Restoration of CFTR protein
Slide 10: Restoration of CFTR function in human bronchial epithelial cells and patient-derived intestinal organoids
Restoration of CFTR function in human bronchial epithelial cells and patient-derived intestinal organoids with unoptimized G542X Prime Editor One-time, non-viral delivery to patient CFTRG542X/G542X cells restores CFTR function Delivery of Prime Editors to p.G542X HBEs restores CFTR function Delivery
Slide 11: Prime's approach is to deliver Prime Editors to critical epithelial cells in patient lung
Prime’s approach is to deliver Prime Editors to critical epithelial cells in patient lung for efficacy and durability Prime Editors correct the CFTR gene to normal resulting in physiological control of CFTR Prime Editors Basal Cells Club Cell, Goblet cell & other - containing human lung progenitor c
Slide 12: Viral (AAV) & non-viral (LNP) delivery systems are effective at delivering Prime Editors in vivo
Viral (AAV) & non-viral (LNP) delivery systems are effective at delivering Prime Editors in vivo Prime Medicine Lung Delivery Platform Non-Viral Delivery Viral Delivery Liver LNP AAV Eye • LNPs tolerated in clinical • Safe and tolerated in In-vivo editing using an optimized LNP- trials for mRNA ther
Slide 13: In vivo LNP screen identified Prime-designed LNPs that effectively deliver Prime Editors to lung epithelium
In vivo LNP screen identified Prime-designed LNPs that effectively deliver Prime Editors to lung epithelium Established an in-vivo LNP HT screening platform LNP-RNA prime editors demonstrated Delivery tropism to ciliated and club cells using tailored for Prime Editing efficient G542X editing in pati
Slide 14: Initial PoC in humanized CFTR p.G542X mice with an unoptimized CFTR Prime Editor delivered by dual AAV
Initial PoC in humanized CFTR p.G542X mice with an unoptimized CFTR Prime Editor delivered by dual AAV using lung trophic capsid Lead optimization of p.G542X Prime Editors is currently ongoing Several AAV capsids efficiently transduce mouse Single dose, bronchoscopic delivery of Dual-AAV Prime Edito
Slide 15: Summary
Summary Prime Editing is a potentially best-in-class gene editing technology Hotspot Prime Editing to correct multiple mutations could address many patients with cystic fibrosis: 7 Hotspot Prime Editors could address >93% of patients with cystic fibrosis Prime’s LNP-RNA capabilities have provided
Slide 16: Thank you!
Thank you! In collaboration with Cystic Fibrosis Foundation Confidential | 16
Slide 17: Thank you!
Thank you! Delivering on the promise of Prime Editing primemedicine.com Confidential | 17
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