Prime Medicine, Inc. · NASDAQ:PRME
Prime Medicine — Investor Presentation (March 2025)
42 slides from Prime Medicine's investor presentation, Mar 18, 2025
Slide 1: Delivering on the promise of Prime Editing
Exhibit 99.1 Delivering on the promise of Prime Editing Corporate Presentation March 2025 1
Slide 2: Forward Looking Statements
Forward Looking Statements 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 pro
Slide 3: We are advancing Prime Editing to change the course of how diseases are treated
We are advancing Prime Editing to change the course of how diseases are treated. We aim to provide safe, effective and curative treatments, which offer lifelong benefit to patients. 3
Slide 4: Rapid Progress Since Inception: On the Cusp of Clinical Validation
Rapid Progress Since Inception: Prime Medicine is on the Cusp of Clinical Validation and Sustainable, Long-Term Value Creation Sustained Growth and Platform Discovery Platform Validation Clinical Validation Commercial Success Delivering the promise of Prime Editing Prime Editing Preclinical proof-of
Slide 5: Entering a New Era of Gene Editing: Generating Clinical Data
Prime Medicine is Entering a New Era of Gene Editing: Generating Clinical Data for Multiple Programs, Leveraging Platform Modularity 2025 2026 2027+ PM359 for p47phox CGD: PM359 for p47phox CGD: PM359 for p47phox CGD: Announce initial clinical data Advance into pivotal study Report pivotal data; pre
Slide 6: Prime Editing Can Edit, Correct, Insert and Delete DNA Sequences
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 p47 Chronic Granulomatous Disease (CGD) Prime Editing is designed with a Point Mutation Correction wide range of genome editing Wi
Slide 7: Highly Differentiated Safety Profile: No Off-Target Activity Detected
Prime Editing Has Highly Differentiated Safety Profile: No Off-Target Activity Detected in Any Lead Program No detectable off-target deletions, No detectable double No detectable No detectable chromosomal translocations or strand breakage off-target edits bystander edits rearrangements Examples from
Slide 8: 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 Off-Target Assays Prime Editors Manufacturing Clinical Delivery Nonclinical Regulatory 8
Slide 9: Our Pipeline: Aligned to Core Modular Platforms
Our Pipeline: Aligned to Core Modular Platforms, With Additional Programs Advancing as Potential Partnership Opportunities Modular Lead IND- Phase Indication Delivery Discovery Platform optimization enabling 1/2 phox p47 Chronic Granulomatous ex vivo Disease (CGD) HEMATOLOGY, X-linked CGD IMMUNOLOGY
Slide 10: Hematology, Immunology and Oncology
Hematology, Immunology and Oncology | 10 10
Slide 11: Chronic Granulomatous Disease
Chronic Granulomatous Disease phox p47 CGD and XCGD Confidential | 11 11
Slide 12: Advancing Prime Editors for CGD, A Disease of Significant Unmet Need
Advancing Prime Editors for Chronic Granulomatous Disease (CGD), A Disease of Significant Unmet Need Life threatening rare genetic disease, characterized by defective neutrophil function Disease Severity and Opportunity • Presents in childhood; life expectancy at least 40 years • Results in recurren
Slide 13: Prime Medicine's CGD Franchise Covers Vast Majority of Patient Population
Prime Medicine’s CGD Franchise Covers Vast Majority of Patient Population Leveraging modular elements from across the PM359 program, including the IND filing, CMC work and clinical trial, to accelerate advancement of XCGD program phox PM359 for p47 CGD X-linked CGD Program Current Initial data from
Slide 14: PM359: Preclinical Data Support Advancement for CGD
PM359: Preclinical Data Support Advancement for the Treatment of Chronic Granulomatous Disease Maintenance of >85% of corrected patient long-term HSCs with complete restoration of NADPH oxidase in neutrophils observed Engraftment Editing Efficiency Phenotypic Correction Prime Edited LT-HSCs showed c
Slide 15: PM359: Clinical Trial Enrolling, Initial Clinical Data in 2025
PM359: Clinical Trial Enrolling, Initial Clinical Data in 2025 PM359 is comprised of autologous HSCs modified ex vivo using Prime Editing Cohort 1: Pivotal Trial* n=2-3, age ≥ 18 Cohort 2: n=2-3, ages 12-17 Cohort 3: n=2-3, ages 6-11 Initial clinical data (2025) • Safety / engraftment • Editing rate
Slide 16: PASSIGE has Potential to Treat X-linked CGD
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 X-linked CGD patients PASSIGE reagents designed to precisely insert healthy CYBB gene sequence at prespecified site in the patient’s CY
Slide 17: Ex vivo CAR-T BMS Collaboration
Ex vivo CAR-T BMS Collaboration Confidential | 17 17
Slide 18: Strategic License and Broad Collaboration Agreement with Bristol Myers Squibb
Strategic License and Broad Collaboration Agreement with Bristol Myers Squibb (BMS) to Develop Prime Edited ex Vivo CAR-T Products First broad, multi-target collaboration advancing Prime Editing for the treatment of complex oncology and autoimmune indications • $110 million upfront • >$3.5 billion i
Slide 19: PASSIGE and Multiplex Prime Editing is the Foundation of BMS Collaboration
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 Programs Existing Limitations Prime Editing Solution ✓ >80% integration efficiency of CAR, aimed at TRAC ꭗ Low paylo
Slide 20: Simultaneously and Efficiently Multiplex Edit CAR-T Cells
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 High efficiency multiplex editing of B2M and TRAC Maintained efficiency with five multi
Slide 21: Liver
Liver | 21 21
Slide 22: Liver Franchise: Aspiring to Cure Two of the Largest Genetic Liver Diseases
Prime Medicine’s Liver Franchise: Aspiring to Cure Two of the Largest Genetic Liver Diseases, Enabled by Platform Modularity Wilson’s Disease Alpha-1 Antitrypsin Deficiency Current IND-enabling activities ongoing Final stages of lead optimization Status Rapidly IND and/or CTA on track for H1’26 IND
Slide 23: Proprietary LNP-formulated Prime Editor is a Multi-Component Drug Product
Proprietary LNP–formulated Prime Editor is a Complex Multi-Component Drug Product Designed to Support Current and Future Liver Programs Ionizable LNP Modularity: • Nucleic acid encapsulation and endosomal escape Lipid 6 out of 8 components in the LNP are the same for liver programs* Helper • Stabili
Slide 24: Modular LNP Dosed in Cynomolgus Monkey With Minimal Safety Concerns
Prime Medicine’s Modular LNP Dosed in Cynomolgus Monkey (NHP) With Minimal, If Any Safety Concerns • Well-tolerated: no acute reactions, clinical observations, or body weight changes • Transient LFT elevations • No change in platelets, coagulation or blood count • No change in blood biochemistry • M
Slide 25: Wilson's Disease
Wilson’s Disease Confidential | 25 25
Slide 26: Advancing Prime Editors for Wilson's Disease: Disease Overview
Advancing Prime Editors for Wilson’s Disease: Disease Overview Large genetically defined disease well suited for Prime Editing Disease Severity and Opportunity Healthy Blood • Common liver and systemic disease presenting in teens to 20s • Leads to liver failure, neurocognitive decline and premature
Slide 27: Prime Editor Efficiently Corrects the H1069Q Mutation
Prime Editor Efficiently Corrects the H1069Q Mutation Resulting in Liver Copper Reduction In Vivo Editing efficiency and copper reduction in fully humanized homozygous p.H1069Q ATP7B mouse model Efficient correction of the H1069Q PM577 drove 75% reduction in copper transversion mutation accumulation
Slide 28: Alpha-1 Antitrypsin Deficiency (AATD)
Alpha-1 Antitrypsin Deficiency (AATD) Confidential | 28 28
Slide 29: Advancing Prime Editors for AATD: Disease Overview
Advancing Prime Editors for AATD: Disease Overview Disease Severity and Opportunity • AATD is an inherited genetic disorder that causes low levels of A1AT protein • Low levels of A1AT protein increases the risk of lung disease (emphysema) • Patients are also at risk of liver disease (cirrhosis) caus
Slide 30: AATD Program Objective: Normalize A1AT Levels in PiZZ Patients
AATD Program Objective: Normalize A1AT Levels in PiZZ Genotype Patients to Healthy Human Levels 50 40 ` Normal human range 30 20 11uM is minimum threshold for benefit 10 0 Genotype MM MS SS MZ SZ ZZ NULLNULL Healthy Low Target patient Human Risk population** • Correcting circulating AAT protein to »
Slide 31: Prime Editor Corrects the Mutation Resulting in M-AAT Protein Restoration
Prime Editor Efficiently Corrects the Mutation Resulting in M- AAT Protein Restoration In Vivo Efficient correction Restoration M-AAT Protein AATD program in final stages of lead optimization; planning to file an IND and/or CTA in mid-2026 • Prime Editor restores AAT levels into healthy human range
Slide 32: Lung
Lung | 32 32
Slide 33: Advancing Prime Editors for Cystic Fibrosis
Advancing Prime Editors for Cystic Fibrosis (CF), a Disease for Which There is No Curative Therapy Large genetically defined disease well suited for Prime Editing Disease Severity and Opportunity Healthy • Progressive, genetic disease that affects the lungs, pancreas and other organs, leading to pre
Slide 34: Parallel Prime Editing Approaches to CF: Hotspot and PASSIGE
Parallel Prime Editing Approaches to CF: Hotspot and PASSIGE In 2024, Prime Medicine entered into agreement with CF Foundation for up to $15 million to support development of Prime Editors for CF Hotspot PASSIGE Eight hotspot Prime Editors could address the “high unmet Potential to address nearly al
Slide 35: Significant Progress Pursuing Five High Unmet Need Hotspot Mutations
Prime Medicine has Made Significant Progress Pursuing Five “High Unmet Need” Hotspot Mutations In vitro Prime Editor in Primary HBEs Phenotypic Restoration of CFTR in differentiated ALI culture 100 80 CFTR 60 40 VCL 20 G542X 0 Prime HOM Control Prime Edited Edited Efforts towards in vivo delivery to
Slide 36: Corporate
Corporate Delivering on the promise of Prime Editing
Slide 37: Beyond BMS, Business Development Will Continue to Play a Critical Role
Beyond BMS, Business Development Will Continue to Play a Critical Role in Building Prime Medicine Prime Medicine remains active in sell-side business development, with the goal of accelerating our pipeline, bolstering our financial resources Partnering Strategy Current Relationships Within Our Core
Slide 38: Extensive, Foundational Intellectual Property for Prime Editing Technologies
Prime Medicine Holds Extensive, Foundational 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 c
Slide 39: Prime Medicine is the Leader in Gene Editing
Prime Medicine is the Leader in Gene Editing Positioned to Create Sustainable Value Through Pipeline Execution and External Partnerships 4 Potential to address more than 90% of genetic diseases and opportunities in non -genetic diseases The Leader in Prime 4 Pre-clinical efficacy across variety of t
Slide 40: Appendix
Appendix Delivering on the promise of Prime Editing
Slide 41: Prime Editing is Designed with a Wide Range of Genome Editing Capabilities
Prime Editing is Designed with a Wide Range of Genome Editing Capabilities Flexibility to select right approach for each indication based on editing need Small edits Mid-sized edits Large deletions Large insertions or Prime Editing (e.g., all 12 bp swaps, 1-bp to 20- (e.g., hotspot corrections, del
Slide 42: PASSIGE Technology Enables Prime Editing to Insert Gene Sized Sequences
PASSIGE Technology Enables Prime Editing to Insert Gene Sized Sequences Precisely, Potentially Addressing Large Markets PASSIGE: Prime-Assisted Site-Specific Integrase Gene Editing: One step non-viral multi-kilobase-size gene editing approach with no double-stranded breaks Where we are working today