Prime Medicine, Inc. · NASDAQ:PRME

Prime Medicine — Technical Presentation (October 2023)

15 slides from Prime Medicine's technical presentation, October 2023

  1. Slide 1: Recent Advances in Non-Viral Delivery of Prime Editors Toward the Treatment of GSD1b

    Recent Advances in Non-Viral Delivery of Prime Editors Toward the Treatment of Patients with Glycogen Storage Disease Type 1b (GSD1b) Seth C. Alexander, PhD Head of RNA Technologies Prime Medicine On behalf of the team at Prime Medicine CONFIDENTIAL 1

  2. Slide 2: Disclosures

    Disclosures Seth Alexander declares he is a current employee of Prime Medicine, Inc. and owns equity in Prime Medicine. CONFIDENTIAL 2

  3. Slide 3: Prime Editing is programmable for both Search and Replace

    Prime Editing is programmable for both Search and Replace Gene with mutation GENE GENE SEARCH SEARCH FIND FIND&&NICK NICK PRIME PRIME REPLACE REPLACE CORRECTED CORRECTED Prime editor complex Prime editor complex Nicked DNA strand Prime edited complex 3’ flap preferentially Prime editor complex Prime

  4. Slide 4: Therapeutic approach: LNP-mediated delivery of Prime Editor components to liver

    Therapeutic approach: LNP-mediated delivery of Prime Editor components to liver A universal LNP-RNA platform has potential to deliver Prime Editors to correct pathogenic mutations in the liver Prime Editor Cargo LNP Encapsulated Liver Precise Correction of Components Prime Editor Cargo Delivery Muta

  5. Slide 5: Prime's internal guide RNA capabilities provide high-quality materials supporting multiple programs

    Prime’s internal guide RNA capabilities provide high-quality materials supporting multiple programs  High purity pegRNA produced internally with consistently >80% purity pegRNA  Scalable from a few mg to multi-hundred mgs ngRNA  Robust production across gRNA sequence diversity, lengths, and chemi

  6. Slide 6: Optimization of mRNA increases Prime Editing efficiency and leads to reduction of PCSK9 protein in serum

    Optimization of mRNA increases Prime Editing efficiency and leads to reduction of PCSK9 protein in serum Optimized mRNA leads to improved Prime Editor performance PCSK9 Prime Editor LNP delivered systemically • Prime Editor mRNA • Prime editor guide RNA coding for PCSK9 premature stop codon PE mRNA

  7. Slide 7: Optimized Prime LNPs provide robust whole liver precise editing in mouse PCSK9 model

    Optimized Prime LNPs provide robust whole liver precise editing in mouse PCSK9 model PCSK9 Prime Editor LNP delivered systemically • Prime Editor mRNA PCSK9 model • Prime editor guide RNA coding for PCSK9 premature stop codon Day 0 Day 3 Lipid 1 Lipid 2 Lipid 3 Theoretical 60 maximum* 50 42.2 40.0 4

  8. Slide 8: Prime Editing to correct pathogenic mutations causing von Gierke disease or GSD1b

    Prime Editing to correct pathogenic mutations causing von Gierke disease or Glycogen Storage Disease Type 1b Initially correct the two most prevalent mutations that cause GSD1b, carried by ~ 50% of patients Fasting Glycogenolysis Glycogen Storage Disease Type 1b (GSD1b) In Hepatocytes Glycogen Break

  9. Slide 9: Identification of pegRNAs that precisely correct the p.L348fs and p.G339C mutations in vitro

    Identification of pegRNAs that precisely correct the p.L348fs and p.G339C mutations in vitro High throughput screening (HTS) identifies pegRNAs that precisely correct the p.L348fs and p.G339C mutations in hepatocytes HTS in cells harboring the Evaluation of pegRNA potency in primary p.G339C or p.L34

  10. Slide 10: LNP delivery of Prime Editor components precisely corrects the p.L348fs mutation in humanized mice

    LNP delivery of Prime Editor components to the liver precisely corrects the p.L348fs mutation in humanized mice Up to 56% whole liver precise correction in GSD1b humanized mouse LNP injection p.L348fs Humanized CC C C A T TGCC G T T T G G A Mutant Determine L348fs Heterozygous Precise Edit & Whole L

  11. Slide 11: Precise editing of the G6PT gene in liver corrects mRNA transcript and restores mRNA expression

    Precise editing of the G6PT gene in liver corrects mRNA transcript and restores mRNA expression Precise correction of the L348fs mutation corrects transcripts and reverses G6PT mRNA non- mediated decay LNP Dosing WT L348fs Het Editing/Indel (NGS) iPSC-derived Hepatocytes 7-days Liver Isolation mRNA

  12. Slide 12: G6PT transcripts and protein are restored in humanized p.L348fs mouse liver

    G6PT transcripts and protein are restored in humanized p.L348fs mouse liver following delivery of Prime Editors Precise editing of the G6PT gene restores G6PT protein expression G6PT LNP Dosing p.L348fs humanized mouse G6PC 7-days Liver Microsome Isolation Microsome G6PT Protein Measurement G6PT Exp

  13. Slide 13: Preliminary analysis showed no detectable off-target editing in patient cells

    Preliminary analysis showed no detectable off-target editing in patient cells Performed using a lead p.L348fs pegRNA and lead LNP delivery system GSD1 Program: patient cells1 Genome wide Identification of potential off-targets On-target Edit (G6PT) potential off- target editing sites Targeted Sequen

  14. Slide 14: Summary

    Summary  Prime is developing a universal LNP-RNA platform to deliver Prime Editors to treat liver and metabolic diseases  Potent Prime Editors correcting the two most prevalent GSD1b mutations were identified and engineered, resulting in high levels of allele correction [up to 56% correction of th

  15. Slide 15: Thank You!

    THANK YOU! CONFIDENTIA CONFIDENTIAL 15 L

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