Prime Medicine, Inc. · NASDAQ:PRME
Prime Medicine — Investor Presentation (September 2024)
42 slides from Prime Medicine's investor presentation, Sep 30, 2024
Slide 1: Delivering on the promise of Prime Editing
1 Delivering on the promise of Prime Editing September 2024 Corporate Presentation
Slide 2: Forward-looking statements
2 This presentation contains forward-looking statements of Prime Medicine, Inc. ("Prime", "we" or "our") within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. These forward-looking statements contain information about our current and future prospects and our operati
Slide 3: Corporate Update: Delivering on the promise of Prime Editing
Corporate Update Delivering on the promise of Prime Editing
Slide 4: Developing One-Time, Curative Genetic Therapies: Strategic priorities
4 Prime Medicine is Developing One-Time, Curative Genetic Therapies Share first ever clinical data for a Prime Editor (PM359 in CGD) in 2025 Advance lead liver program (Wilson’s Disease) to IND in H1 2026 Progress other high value programs across focused target tissues Continue to build and execute
Slide 5: Entering a Phase of Focused Execution
5 Prime Medicine is Entering a Phase of Focused Execution Advance Prime Editing, Build Pipeline (2020 – 2024) Focus Pipeline, De-Risk Platform (2024 - 2026) Expand, Capture Value Potential (2026+) ✓ Prime Medicine began operations in 2020 ✓ First Prime Editor IND accepted for PM359 in p47phox CGD ✓
Slide 6: Our Pipeline: Focused on Significant Opportunities with High Value Potential
6CGD = chronic granulomatous disease; XCGD = x-linked CGD; LNP = lipid nanoparticle Our Pipeline: Focused on Significant Opportunities with High Value Potential Prime Medicine’s focused pipeline emphasizes significant opportunities with clear path to value inflection Selection of Prioritized Investm
Slide 7: Our Pipeline: Aligned to Core Modular Platforms
7 Modular Platform Indication Delivery Discovery Lead optimization IND- enabling Phase 1/2 HEMATOLOGY, IMMUNOLOGY & ONCOLOGY p47phox Chronic Granulomatous Disease (CGD) ex vivo X-linked CGD (with PASSIGE ) ex vivo Ex vivo CAR-T1 (with PASSIGE ) ex vivo LIVER Wilson’s Disease LNP Undisclosed Program
Slide 8: Strategic License and Broad Collaboration Agreement with Bristol Myers Squibb
8 • $110 million upfront • >$3.5 billion in potential milestones, including: ‒ $185 million in preclinical milestones ‒ $1.2 billion in development milestones ‒ More than $2.1 billion in commercial milestones ‒ Royalties on net sales • Multiple targets in immunological diseases and cancer, beyond ra
Slide 9: PASSIGE and Multiplex Prime Editing is the Foundation of BMS Collaboration
9TRAC = T-cell receptor alpha constant; Data presented at ASH, December 2022, ASGCT, May 2023 and ASH, December 2023 CAR-T: PASSIGE and Multiplex Prime Editing is the Foundation of Prime Medicine’s Collaboration with BMS Platform modularity has potential to accelerate development of additional CAR-T
Slide 10: Multiplex Editing of CAR-T Cells
10 Data presented at ASGCT 26th Annual Meeting, May 2023. Beyond Precisely Inserting a Chimeric Antigen Receptor, We Can Simultaneously and Efficiently Multiplex Edit CAR-T Cells Prime Editors can be multiplexed to introduce multiple genomic modifications in CAR-T cells • Knockout with Prime Editing
Slide 11: Platform Overview
Platform Overview Delivering on the promise of Prime Editing
Slide 12: Prime Medicine brings together the right people and the right technology
12 Delivering on the promise of Prime Editing Prime Medicine brings together the right people and the right technology at the right time Now is our moment: we are building on decades of progress to deliver the promise of one-time, curative genetic therapies to address the widest spectrum of diseases
Slide 13: Prime Editing Can Edit, Correct, Insert and Delete DNA Sequences
13 REPLACEMENT Prime Editor Deletion / Insertion Correction p47 Chronic Granulomatous Disease (CGD) Point Mutation Correction Wilson’s Disease Targeted Gene Insertion (PASSIGE ) XCGD, CAR-T, Cystic Fibrosis Repeat Excision Friedreich’s Ataxia Hotspot Correction Cystic Fibrosis, Retinitis Pigmentosa
Slide 14: Prime Editing is Designed with a Wide Range of Genome Editing Capabilities
14BP = base pair; KB = kilobase Prime Editing is Designed with a Wide Range of Genome Editing Capabilities Prime Editing Approach Small edits (e.g., all 12 bp swaps, 1-bp to 20-bp ins or del, combinations thereof) Mid-sized edits (e.g., hotspot corrections, del up to 1-kb, ins up to 250 bp) Large de
Slide 15: PASSIGE Technology Enables Insertion of Gene Sized Sequences
15 PASSIGE Technology Enables Prime Editing to Insert Gene Sized Sequences Precisely, Potentially Addressing Large Markets Correct inversion mutations (e.g., Hemophilia A) In vivo protein factory (e.g., GLA enzyme for Fabry’s disease) Targeted whole gene replacement for rare liver diseases (e.g., Ph
Slide 16: Platform Modularity Accelerates and De-Risks Ongoing Efforts
16 Prime Editing Platform Modularity Accelerates and De-Risks Ongoing Efforts, Enables Rapid Generation of New Product Candidates Core components can be readily leveraged to accelerate pipeline growth, efficiency and execution Prime Editors Manufacturing Delivery Clinical Regulatory Off-Target Assay
Slide 17: Prime Editing Can Be Delivered with High Efficiency
17 Proof-of-concept in initial indications may accelerate development of subsequent programs within each area of focus 1 Ex Vivo (Human CD34+ Cells) >90% editing of CD34+ cells ex vivo via electroporation In Vivo – AAV (Mouse Brain and Eye) 3 >80% precise editing in mouse CNS >70% precise editing in
Slide 18: Highly Differentiated Safety Profile: No Off-Target Activity Detected
18 No detectable double strand breakage No detectable off-target deletions, chromosomal translocations or rearrangements No detectable off-target edits No detectable bystander edits 1Analysis of edited CD34+ cells from CGD program: Targeted in vitro Analysis of 550 potential off-target sites of off-
Slide 19: Direct Comparisons of Prime Editors to CRISPR Showed Fewer Off-Target Edits
19 Direct Comparisons of Prime Editors to CRISPR Showed Substantially Fewer Off-Target Edits Detected with Prime Editing Examples from evaluation of potential off-target sites in Prime Edited or CRISPR-edited cells by deep sequencing 12 Spacers S pC as 9 P ri m e E dito r 0 20 40 60 P e rc e n t In
Slide 20: Hematology and Immunology
20| Hematology and Immunology
Slide 21: Advancing Prime Editors for Chronic Granulomatous Disease
21HSCT = hematopoietic stem cell transplant; GvHD = graft vs. host disease Advancing Prime Editors for Chronic Granulomatous Disease (CGD), A Disease of Significant Unmet Need Rare genetic disease, characterized by defective neutrophil function • Serious life-threatening disease presents in childhoo
Slide 22: CGD Franchise Covers Vast Majority of Patient Population
22 Current Status Initial data from Phase 1/2 clinical trial expected in 2025 Preclinical development ongoing Rapidly Advancing IND cleared in April 2024, within 30 days of submission Leveraging modular elements of PM359 program to inform and accelerate advancement Targeted Mutations delGT mutation
Slide 23: PM359: Preclinical Data Support Advancement for CGD
23 • Full immune system reconstitution by Prime Edited LT-HSCs • Edited LT-HSC derived neutrophils had normal enzymatic activity (NADPH oxidase) HSC = hematopoietic stem cell; LT-HSC = long term HSC; DHR = dihydrorhodamine; * normalized to healthy donor control. 1Minimal threshold for patient benefi
Slide 24: PM359: Poised to Deliver Initial Clinical Data in 2025
24 DP = drug product; GMP = good manufacturing practice; QC = quality control; IND = investigational new drug PM359: Prime Medicine Poised to Deliver Initial Clinical Data in 2025 PM359 is comprised of autologous HSCs modified ex vivo using Prime Editing Key eligibility criteria • delGT mutation in
Slide 25: PASSIGE has Potential to Treat X-linked CGD
25 PASSIGE has Potential to Treat X-linked CGD (XCGD) ’All in one’ delivery of PASSIGE reagents for CYBB gene replacement in CD34+ cells has potential to treat >90% of XCGD patients PASSIGE demonstrated high multiplex editing efficiency Potential synergies to accelerate leveraging p47phox CGD progra
Slide 26: Liver Disease
26| Liver Disease
Slide 27: Advancing Prime Editors for Multiple Mutations Within Wilson's Disease
27 • Disease severity and opportunity • Common liver and systemic disease presenting in teens to 20’s • Leads to liver failure, neurocognitive decline and premature death • Greater than 20,000 patients in US and Europe, 30-50% harboring H1069Q mutation • R778L is the predominant mutation in Asian po
Slide 28: Wilson's Disease Program Utilizing Universal LNP Continues to Make Progress
28 Prime Medicine to present initial in vivo data at ESGCT and AASLD in Q4 2024 Wilson’s Disease Program Utilizing Universal LNP Continues to Make Progress; IND Anticipated in H1 2026 First effort targeting H1069Q mutation; follow-on targeting R778 mutation In vitro Prime Editor in Primary Hepatocyt
Slide 29: Proprietary LNP-formulated Prime Editor Drug Product
29 Proprietary LNP–formulated Prime Editor is a Complex Multi-Component Drug Product Designed to Support Current and Future Liver Programs Cholesterol Ionizable Lipids PEG Lipids Helper Lipids Targeting Ligand Prime Editor mRNA Two Guide RNAs • Nucleic acid encapsulation and endosomal escape • Stabi
Slide 30: Lung Disease
30| Lung Disease
Slide 31: Agreement with CF Foundation for Up to $15 Million
31 CF impacts close to 40,000 people in the United States. There is no cure and existing treatments are ineffective for, or not tolerated by, approximately 15% of patients. Prime Medicine believes Prime Editing-based approaches could eventually benefit more than 93% of all people with CF. • Hotspot
Slide 32: Hotspot Editing Corrected High Unmet Need CF Mutations
32 With Hotspot Editing, Prime Editors Corrected “High Unmet Need” CF Mutations, Including the Prevalent G542X (null) Mutation Eight hotspot Prime Editors could address the “high unmet need” mutations; These same eight hotspot Prime Editors could address >93% of all CF patients G542X F508del 0 20 40
Slide 33: Corporate
Corporate Delivering on the promise of Prime Editing
Slide 34: Business Development Will Continue to Play a Critical Role
34 Prime Medicine plans to remain active in sell-side business development, with the goal of accelerating our pipeline, bolstering our financial resources Beyond BMS, Business Development Will Continue to Play a Critical Role in Building Prime Medicine Within Our Core Outside Our Core Access Enablin
Slide 35: Extensive Intellectual Property for Prime Editing Technologies
35 Prime Medicine Holds Extensive Intellectual Property for Prime Editing Technologies • Multiple configurations of RNA-templated gene editing - Prime Editor protein configurations: fusion, separate and split configurations - pegRNA configurations: fusion, split, separate and engineered configuratio
Slide 36: Our Pipeline: Aligned to Core Modular Platforms
36 Modular Platform Indication Delivery Discovery Lead optimization IND- enabling Phase 1/2 HEMATOLOGY, IMMUNOLOGY & ONCOLOGY p47phox Chronic Granulomatous Disease (CGD) ex vivo X-linked CGD (with PASSIGE ) ex vivo Ex vivo CAR-T1 (with PASSIGE ) ex vivo LIVER Wilson’s Disease LNP Undisclosed Program
Slide 37: Appendix
37 primemedicine.com Delivering on the promise of Prime Editing Appendix
Slide 38: Management, Board of Directors and Scientific Advisory Board
38 Keith Gottesdiener, M.D. President and CEO Allan Reine, M.D. Chief Financial Officer Jeremy Duffield, M.D., Ph.D. Chief Scientific Officer Ann L. Lee, Ph.D. Chief Technical Officer Andrew Anzalone, M.D., Ph.D. Co-Founder and Head of Prime Editing Platform Meredith Goldwasser, Sc.D. SVP, Head of S
Slide 39: Non-Viral PASSIGE Delivery Supports Integration of CD19 CAR
39 ✓Loss of endogenous TCR with attB insertion in TRAC exon 1 ✓Use of endogenous TRAC promoter allows for tuned regulation of CAR expression1 ✓Promoter-less cargo will not express if integrated elsewhere in genome ✓Pilot studies – no integration elsewhere in genome ✓Up to 8.9kB insertion with high e
Slide 40: Multiplexed CD19 CAR-T Cells are Functional In Vitro and In Vivo
40CAR = chimeric antigen receptor; PASSIGE = prime assisted site-specific integrase gene editing; CD19 = cluster of differentiation 19; Control T has GFP inserted in T cells instead of CD19 CAR; TRAC = T cell receptor alpha constant; in vitro data: statistical significance determine by one-way analy
Slide 41: Hotspot Editing Corrected High Unmet Need CF Mutations
41 Eight hotspot Prime Editors could address the “high unmet need” mutations; These same eight hotspot Prime Editors could address >93% of all CF patients G542X F508del 0 20 40 60 80 % p re c is e c o rr e c ti o n With Hotspot Editing, Prime Editors Corrected “High Unmet Need” CF Mutations, Includi
Slide 42: Hotspot Editing Corrected High Unmet Need CF Mutations
42 Eight hotspot Prime Editors could address the “high unmet need” mutations; These same eight hotspot Prime Editors could address >93% of all CF patients G542X F508del 0 20 40 60 80 % p re c is e c o rr e c ti o n With Hotspot Editing, Prime Editors Corrected “High Unmet Need” CF Mutations, Includi
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