Prime Medicine, Inc. · NASDAQ:PRME
Prime Medicine — American Association for the Study of Liver Diseases (AASLD) 2024
17 slides from Prime Medicine's conference presentation, Nov 18, 2024
Slide 1: Delivering on the promise of Prime Editing
Delivering on the promise of Prime Editing Advances in Prime Editing enable in vivo therapeutic correction of the ATP7B p.H1069Q and p.R778L mutations causing Wilson’s Disease Jeremy S. Duffield MD PhD FRCP Chief Scientific Officer, Prime Medicine American Association for the Study of Liver Diseases
Slide 2: Disclosures
Disclosures Jeremy Duffield declares he 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 can edit, correct, insert and delete DNA sequences in any target tissue
We believe Prime Editing is the only gene editing technology that can edit, correct, insert and delete DNA sequences in any target tissue Corrects mutations across many tissues, organs and cell types, in dividing and non-dividing human cells Deletion / Insertion Correction Chronic Granulomatous Dise
Slide 5: Prime Editing platform modularity accelerates and de-risks ongoing efforts
Prime Editing platform modularity accelerates and de-risks ongoing efforts, enabling rapid generation of new product candidates Core components can be readily leveraged to accelerate pipeline growth, efficiency and execution Prime Editors Off-Target Manufacturing Clinical Assays Delivery Nonclinical
Slide 6: Approach to developing Prime Editors to treat 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 Editing & functions Safety, Editing & efficacy in hepatocytes in Safety in rats pharmacology, in hum
Slide 7: Universal LNP for liver and metabolic programs
Prime Medicine has developed a universal LNP for our liver and metabolic programs Prime Medicine’s Universal LNP contains a Multiple different drug product candidates novel GalNAc targeting ligand (DP) A from one LNP compositionB 25 LNP D LNP509 LNP D LNP615 Shared LNP/PE components LNP DP Avg. (nm)
Slide 8: 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 Precise Correction of Mutation in Hepatocytes Prime Editor Cargo LNP-encapsulated Liver Delivery p.H1069Q Components
Slide 9: LNP-Formulated Prime Editors to correct mutations causing Wilson's Disease
LNP-Formulated Prime Editors to correct common pathogenic mutations causing Wilson’s Disease (WD) Healthy Blood Wilson’s Disease Disease severity Copper ceruloplasmin ▪ Common liver and systemic disease presenting in teens to 20’s (prevalence approx. 1:30,000) ▪ Leads to liver failure, neurocognitiv
Slide 10: Identification of lead Prime Editors for correction of ATP7B H1069Q and R778L
Identification of lead Prime Editors for correction of ATP7B H1069Q and R778L High throughput screening Validation in primary in hepatocyte cell line humanized mouse hepatocytes Delivery of RNA Prime Editing components LNP delivery of RNA Prime Editing components HOM humanized ATP7B H1069Q Precise c
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 Reduction in ceruloplasmin in WD hepatocytes Restoration of ceruloplasmin levels in vitro RNA Prime Editing Blood (urinary excretion) components Copper ceruloplasmin CTR1 X ATP7B ATP7B X Patient-derived Bile H106
Slide 12: Efficient DNA and mRNA correction and reduced liver copper in humanized mouse model
Prime Editors demonstrate efficient DNA and mRNA correction and reduce liver copper in humanized Wilson’s Disease mouse model Fully humanized homozygous p.H1069Q ATP7B mouse model Correction of H1069Q High efficiency of genome and >75% reduction in liver Cu2+ transversion mutation transcript correct
Slide 13: Proof of concept in NHP using Universal LNP
Proof of concept for Wilson’s Disease H1069 surrogate Prime Editor in NHP using Prime Medicine’s Universal LNP Initial in vivo WD NHP studies show up to 51% ATP7B p.H1069 precise hepatocyte editing (interim data) ATP7B* in vivo Prime Editing in NHP IV injection of PE Precise Editing at H1069 with no
Slide 14: Universal LNP safety profile in cynomolgus monkey
Prime Medicine’s Universal LNP exhibits an excellent safety profile in cynomolgus monkey (NHP) ➢ 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 blood count ➢ No observed change
Slide 15: No detectable off-target editing in patient cells
Preliminary analysis: no detectable off-target editing in patient cells treated with Wilson’s 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) e
Slide 16: Summary
Summary Advances in Prime Editing enable in vivo therapeutic correction of the ATP7B p.H1069Q and p.R778L mutations causing Wilson’s disease Modular LNP platform ➢ Prime Medicine has developed a universal liver targeted LNP-PE platform with the potential to deliver Prime Editors to precisely correct
Slide 17: Thank you!
Delivering on the promise of Prime Editing Thank you! primemedicine.com Confidential | 17
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