Prime Medicine, Inc. · NASDAQ:PRME
Prime Medicine — American Society of Gene & Cell Therapy (ASGCT) 2025
21 slides from Prime Medicine's conference presentation, May 14, 2025
Slide 1: Delivering on the promise of Prime Editing
Delivering on the promise of Prime Editing Abstract 102 LNP-formulated Prime Editor enables in vivo therapeutic precise editing of the ATP7B p.H1069Q and p.R778L mutations causing Wilson disease Vivian W. Choi, PhD Vice President, Head of LLME, Prime Medicine American Society of Gene & Cell Therapy
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
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: Prime Medicine's approach to developing Prime Editors for liver and metabolic diseases
Prime Medicine’s approach to developing Prime Editors to treat liver and metabolic diseases Prime Editors are specific to human patient DNA sequence and designed for the correction of human mutations Establish potency and activity of lead Prime Editor drug candidates Prime Medicine’s Establish g
Slide 7: Prime Medicine has developed a universal LNP for liver and metabolic programs
Prime Medicine has developed a universal LNP for our liver and metabolic programs Universal LNP contains a Universal LNP leads to minimal off-target novel GalNAc ligand tissue biodistribution and no detectable editing mRNA biodistribution in rat Tissue editing in humanized mice Ionizable lipid ASGPR
Slide 8: LNP-Formulated Prime Editors to correct common pathogenic mutations causing Wilson Disease
LNP-Formulated Prime Editors to correct common pathogenic mutations causing Wilson Disease (WD) Blood Common liver and systemic disease presenting in Disease teens to 20’s (prevalence approx. 1:30,000) Healthy severity Leads to liver failure, neurocognitive decline and Copper ceruloplasmin prema
Slide 9: Therapeutic approach: LNP-mediated delivery of Prime Editor components to liver
Therapeutic approach: LNP-mediated delivery of Prime Editor components to liver One-time delivery of LNP Prime Editor cargo with potential to correct pathogenic mutations in the liver Prime Editor LNP-encapsulated Liver Precise Correction of Wilson disease Cargo Components Prime Editor Cargo Deliver
Slide 10: Identification of lead Prime Editors for correction of ATP7B p.H1069Q mutation
Identification of lead Prime Editors for correction of ATP7B p.H1069Q mutation High throughput screening Validation of Prime Editors in primary in hepatocyte cell line mouse hepatocytes from humanized mouse model Delivery of RNA Prime Editing components LNP delivery of RNA Prime Editing components H
Slide 11: Prime editing restores ceruloplasmin abundance in patient-derived H1069Q iHeps in vitro
Prime editing restores ceruloplasmin abundance in patient-derived H1069Q iHeps in vitro Ceruloplasmin reduction in WD hepatocytes Restoration of ceruloplasmin levels in vitro RNA Prime Editing Blood (urinary excretion) components Copper ceruloplasmin CTR1 ATP7B ATP7B Patient-derived Bile H1069Q iHep
Slide 12: Prime Editor optimizations enable durable DNA and mRNA correction in humanized WD mouse model
Prime Editor optimizations enable durable DNA and mRNA correction in a fully humanized ATP7B p.H1069Q WD mouse model H1069Q correction Durability of H1069Q Genome and transcript in WD mouse model correction over time correction of H1069Q Prime Editors demonstrate efficient and durable in vivo correc
Slide 13: Further Prime Editor optimizations substantially improve potency in humanized mice
Further Prime Editor optimizations substantially improve potency in humanized mice Improved Prime Editors enable therapeutic Optimized Prime Editor editing at low dose in WD mouse model dose response Dose reduction Dose level: 1X Dose level: 1/3X Improved Prime Editors demonstrate efficient in vivo
Slide 14: Copper homeostasis is restored in humanized WD mouse model following H1069Q correction
Copper homeostasis is restored in humanized WD mouse model following H1069Q correction by Prime Editing Liver copper Urinary copper Fecal copper Prime Edited Correction of H1069Q in WD mouse model reduces liver copper by >75% and restores copper excretion from urine to feces Confidential | 14
Slide 15: Therapeutic approach: LNP-mediated delivery of Prime Editor components to liver
Therapeutic approach: LNP-mediated delivery of Prime Editor components to liver One-time delivery of LNP Prime Editor cargo with potential to correct pathogenic mutations in the liver Prime Editor LNP-encapsulated Liver Precise Correction of Wilson disease Cargo Components Prime Editor Cargo Deliver
Slide 16: Multiple Prime Editors demonstrate efficient ATP7B p.R778L correction in vitro and in vivo
Multiple Prime Editors demonstrate efficient ATP7B p.R778L correction in vitro and in vivo Correction of R778L in vitro in Correction of R778L in vivo with LNP immortalized hepatocyte-like cells delivery to humanized mouse model Lipofection of RNA LNP delivery of Prime Editing RNA Prime Editing comp
Slide 17: Proof of concept for Wilson Disease H1069 using Universal LNP-formulated NHP surrogate Prime Editors
Proof of concept for Wilson Disease H1069 using Prime Medicine’s Universal LNP-formulated NHP surrogate Prime Editors following single administration Prime Editing of ATP7B H1069 in Precise in vivo NHP editing at ATP7B* NHP using unoptimized surrogate with no detectable unintended edits PE RNA encap
Slide 18: Universal LNP exhibits an excellent safety profile in cynomolgus monkey after single administration
Prime Medicine’s Universal LNP exhibits an excellent safety profile in cynomolgus monkey (NHP) after single administration Well-tolerated with no acute reactions, clinical observations, or body weight changes Animals healthy at 54 weeks No observed change in platelets, coagulation time or bloo
Slide 19: Preliminary analysis: no detectable off-target editing in patient cells treated with Wilson Disease
Preliminary analysis: no detectable off-target editing in patient cells treated with Wilson Disease “IND ready” set of comprehensive off-target assays patient cells1 Genome wide identification using in silico and biochemical methods % editing over mock On-target Potential off-target edit (ATP7B) edi
Slide 20: Summary
Summary LNP-formulated Prime Editor enables in vivo therapeutic precise editing of the ATP7B p.H1069Q and p.R778L mutations causing Wilson disease Modular LNP platform Prime Medicine has developed a universal liver targeted LNP-PE platform with the potential to deliver Prime Editors to precisely c
Slide 21: Thank you!
Delivering on the promise of Prime Editing Thank you! primemedicine.com Confidential | 21
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