Prime Medicine, Inc. · NASDAQ:PRME
Prime Medicine — Investor Presentation (May 2025)
36 slides from Prime Medicine's investor presentation, May 19, 2025
Slide 1: Delivering on the promise of Prime Editing
Exhibit 99.3 Delivering on the promise of Prime Editing Corporate Presentation May 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 Clinical Validation and Platform Validation Commercial Success Platform Discovery Focused Execution Delivering the promise of Prime Editing Prime Editin
Slide 5: Entering a New Era of Gene Editing: Generating Clinical Data for Multiple Programs
Prime Medicine is Entering a New Era of Gene Editing: Generating Clinical Data for Multiple Programs, Leveraging Platform Modularity 2025 2026 2027+ PM577 for Wilson’s Disease: PM577 for Wilson’s Disease: PM577 for Wilson’s Disease: Prepare for 2026 clinical entry, advance File IND and/or CTA in 1H
Slide 6: 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 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: Prime Editing Has Highly Differentiated Safety Profile
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: Initial Clinical Data Shows PM359 Safely and Effectively Corrects p47phox CGD Mutation
Breakthrough Initial Clinical Data Shows PM359 Safely and phox Effectively Corrects Disease-Causing Mutation in p47 CGD Treatment with PM359 led to rapid engraftment and restoration of DHR positivity, well above minimum threshold for clinical benefit in single adult patient • Successful manufacturin
Slide 9: 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 9
Slide 10: Pipeline Focused on Value Creating Opportunities
Pipeline Focused on Value Creating Opportunities Modular Lead IND- Phase Indication Delivery Discovery Platform optimization enabling 1/2 Wilson’s Disease LNP LIVER Alpha-1 Antitrypsin Deficiency LNP (AATD) 1 Cystic Fibrosis LUNG LNP/AAV (including PASSIGE ) 2 IMMUNOLOGY & Ex vivo CAR-T ex vivo ONCO
Slide 11: Liver
Liver | 11 11
Slide 12: Prime Medicine's Liver Franchise: Wilson's Disease and AATD
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 13: Proprietary LNP-formulated Prime Editor 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 14: Modular LNP Dosed as Single Administration in Cynomolgus Monkey
Prime Medicine’s Modular LNP Dosed as a Single Administration 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 chang
Slide 15: Wilson's Disease
Wilson’s Disease Confidential | 15 15
Slide 16: 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 17: Prime Editor Efficiently Corrects H1069Q Mutation Resulting in Liver Copper Reduction
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 18: Alpha-1 Antitrypsin Deficiency (AATD)
Alpha-1 Antitrypsin Deficiency (AATD) Confidential | 18 18
Slide 19: 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 20: 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 21: Prime Editor Efficiently Corrects 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 rang
Slide 22: Lung
Lung | 22 22
Slide 23: 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 24: 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 25: Significant Progress Pursuing Five High Unmet Need Hotspot Mutations
Prime Medicine has Made Significant Progress Pursuing Five “High Unmet Need” Hotspot Mutations Phenotypic Restoration of CFTR in In vitro Prime Editor in Primary HBEs differentiated ALI culture CFTR VCL G542X Prime HOM Edited Efforts towards in vivo delivery to humanized mice and large animals using
Slide 26: Immunology and Oncology
Immunology and Oncology | 26 26
Slide 27: Strategic License and 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 28: 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 29: 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 30: Corporate
Corporate Delivering on the promise of Prime Editing
Slide 31: 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 32: 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 33: Leader in Gene Editing Positioned to Create Sustainable Value
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 34: Appendix
Appendix Delivering on the promise of Prime Editing
Slide 35: Prime Editing 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 36: 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