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1 Delivering on the promise of Prime Editing November 12, 2025 Restoring Copper Homeostasis: Prime Medicine’s Path to Developing Transformative Therapies for Wilson Disease
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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 operations, which are based on currently available information. All statements other than statements of historical facts contained in this presentation, including statements regarding our strategy, projects and plans are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “hope,” “intend,” “may,” “might,” “objective,” “opportunity,” “plan,” “predict,” “positioned,” “possible,” “potential,” “project,” “seek,” “should,” “strategy,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. These forward-looking statements include, but are not limited to, express or implied statements about Prime’s beliefs and expectations regarding: the potential of Prime Editing to correct the causative mutations of diseases, including CGD, Wilson Disease, CF, and AATD; the continued development and advancement of its AATD and Wilson Disease programs, including the timing of the filing of IND and/or CTA applications in mid-2026 and 1H 2026, respectively, and the timing of initial data for both programs in 2027; the initiation, timing, progress and results of our research and development programs, preclinical studies and future clinical trials, including the release of data related thereto; the safety profile of Prime Editing, our modular LNP, and our programs; our ability to launch therapeutics; the timing of, and our ability to achieve, clinical validation and sustained, long-term value creation; the modularity of the Prime Editing platform and the benefits thereof; the collaboration with Bristol Myers Squibb and the intended and potential benefits thereof, including the receipt of potential milestone and royalty payments from commercial product sales, if any; the 2025 agreement with the Cystic Fibrosis Foundation ("CF Foundation"), its expanded funding pursuant thereto, and the intended and potential benefits thereof, including the receipt of payments based on scientific milestones; our expectations regarding the breadth of Prime Editing, including the potential of Prime Editing to address more than 90% of genetic diseases and to address non-genetic diseases; the continued development and optimization of various non-viral and viral delivery systems, including our universal liver-targeted LNP delivery approach; the scope of protection we are able to establish and maintain for intellectual property rights covering our Prime Editing technology; the implementation of our strategic plans for our business, programs and technology, including our ability to maintain collaborations or strategic relationships and identify and enter into future license agreements and collaborations; regulatory developments in the United States and foreign countries; developments related to our competitors and our industry; our ability to attract and retain key scientific and management personnel; our estimates of our expenses, capital requirements, and needs for additional financing; and our expectations regarding the anticipated timeline of our cash runway and future financial performance. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make due to a number of risks and uncertainties. These and other risks, uncertainties and important factors are described in the section entitled "Risk Factors" in our most recent Annual Report on Form 10-K, as well as any subsequent filings with the Securities and Exchange Commission. Any forward-looking statements represent our views only as of the date of this presentation and we undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, the occurrence of certain events or otherwise subject to any obligations under applicable law. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, we have not independently verified, and make no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of our internal estimates or research and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research. Forward Looking Statements
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3 SETTING THE STAGE ‒ Welcome and Introduction ‒ Why Prime Editing for Wilson Disease WILSON DISEASE OVERVIEW ‒ Global Market Opportunity ‒ Wilson Disease Treatment Landscape and the Opportunity for Prime Editing PM577 FOR WILSON DISEASE ‒ Emerging Preclinical Data from AASLD ‒ Initial Clinical Plans ‒ Upcoming Milestones Q&A Today’s Agenda SPEAKERS Allan Reine, M.D. Chief Executive Officer Mohammed Asmal, M.D., Ph.D. Chief Medical Officer Michael Schilsky, M.D. Professor of Medicine, Yale University
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4 Key Takeaways from Today’s Event 2 Prime Editing has the potential to provide a durable cure , by precisely and permanently correcting the causative mutation and restoring wild -type enzyme function, normalizing copper metabolism and halting disease progression. 3 Prime Medicine intends to leverage platform modularity to accelerate the development of multiple Prime Editors for Wilson Disease, a multi -billion -dollar global opportunity and other liver diseases Wilson Disease is an area of tremendous unmet need: no curative therapies available; physicians and patients dissatisfied with current standards of care.1
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5 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.
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6 We Believe Prime Editing is the Only Technology That Can Edit, Correct, Insert and Delete DNA Sequences in Any Target Tissue REPLACEMENT Prime Editor Deletion / Insertion Correction p47 Chronic Granulomatous Disease (CGD) Point Mutation Correction Wilson Disease , Alpha -1 Antitrypsin Deficiency (AATD) Targeted Full Gene Insertion (PASSIGE ) CAR-T, Cystic Fibrosis Repeat Excision Repeat expansion diseases Hotspot Correction Cystic Fibrosis, Retinitis Pigmentosa (RHO adRP) Prime Editing is designed with a wide range of genome editing capabilities and the ability to make edits of any size , from small base pair swaps to large, multi -kilobase inversions or insertions. This provides tremendous flexibility to select the right approach for each indication and editing need.
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7 Modular Platform Indication Delivery Discovery Lead optimization IND- enabling Phase 1/2 LIVER Wilson Disease LNP Alpha -1 Antitrypsin Deficiency (AATD) LNP LUNG Cystic Fibrosis 1 (including PASSIGE ) LNP/AAV IMMUNOLOGY & ONCOLOGY Ex vivo CAR-T2 (with PASSIGE ) ex vivo We Are Focused on Value Creating Opportunities: Substantial Need, Clear Biology, Potential for Meaningful Commercial Impact 1 In January 2024 and July 2025, Prime entered into agreements with the CF Foundation for up to $15 million and $24 million, respectively, to support development of Prime Editors for Cystic Fibrosis. 2 In September 2024, Prime entered into a strategic research collaboration and license agreement with Bristol Myers Squibb to develop and commercialize multiple ex vivo T cell products in immunology and oncology. LNP = lipid nanoparticle; AAV = adeno-associated virus; CGD = chronic granulomatous disease Prime Medicine is identifying opportunities to advance its other programs, including CGD, neurological diseases, cell therapy, ocular diseases and hearing loss, in partnership or through internal efforts in the future.
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8 Our Initial Efforts Are Focused on Two of the Largest Genetic Liver Diseases WD = Wilson Disease; AATD = Alpha-1 Antitrypsin Deficiency; IND = investigational new drug; CTA = clinical trial application; *Little Rock is a rare mutation in the SERPINA1 gene which leads to destabilization of the A1AT protein; **Based on the estimates of 10-15% of patients diagnosed Wilson Disease Alpha -1 Antitrypsin Deficiency IND-enabling studies ongoing IND-enabling studies ongoing IND and/or CTA on track for 1H 2026 Clinical data in 2027 IND and/or CTA on track for mid-2026 Clinical data in 2027 H1069Q (anchor program), R778L (fast follow-on) E342K (Pi*Z Mutation), D341H (Little Rock*) CURRENT STATUS UPCOMING MILESTONES TARGETED MUTATION
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9 We are Advancing a Franchise of Programs for Genetic Liver Diseases, Which Share Our Proprietary, Universal LNP Vast majority of components can be used across liver programs, allowing potential benefit of shared toxicology, manufacturing and regulatory experience Accelerates, derisks and reduces costs of follow -on efforts
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10 Prime Medicine’s Wilson Disease Programs Have Potential to Address Multi-Billion Dollar Market H1069Q R778L Other Common Mutations All Other Mutations Prime Addressable Patients Up to 7k Six most common mutations account for up to 26,000 patients in addressable markets (US, Europe, Japan) with unique geographic mutational distribution; incidence rate of approximately 300 new patients per year Consistency in disease presentation and management across mutations and key markets enables Prime Medicine to establish an anchor with PM577 (H1069Q) to provide leverage and read -through to other mutations Prime Addressable Patients Up to 9k Prime Addressable Patients Up to 10k
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11 We Plan to Leverage Platform Modularity to Rapidly Advance Prime Editors for a Majority of Wilson Disease Patients Goal to incorporate into existing regulatory filings Large commercial opportunity in Japan Attractive business case to develop follow -on programs Fast path to DC (potentially off in vitro data) R778L Other Mutations H1069Q (PM577) ANCHOR MUTATION: Large commercial opportunity in U.S. and Europe 1H 2026 IND/CTA Lead in observational study will expedite patient recruitment >90% editing efficiency , minimal preclinical work to formalize DC Follow -on programs to leverage same liver - targeted LNP; swap out guide sequence Goal to incorporate into existing regulatory filings; engage PMDA IND = investigational new drug; CTA = clinical trial application; LNP = lipid nanoparticle; DC = development candidate; PMDA = Japan’s Pharmaceuticals and Medical Devices Agency
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12 Confidential | 12 A Clinician’s Perspective on Wilson Disease Michael Schilsky, M.D. Professor of Medicine, Yale University
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Wilson Disease: A Large, Genetically Defined Disease With No Curative Options Autosomal -recessive disorder due to mutations in the ATP7B gene, which encodes a copper -transporting ATPase Mutations in ATP7B impair copper excretion into bile and its incorporation into ceruloplasmin, leading to pathologic copper accumulation in the liver and other organs, including in the CNS In WD patients, restoring normal copper homeostasis occurs only by targeting the liver for correction of the underlying genetic defect 13
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Phenotype at Presentation of Wilson Disease From Ott et al Designing clinical trials in Wilson disease. Hepatology 2021 Michael L Schilsky MD FAASLD 14
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Treatment Goal Depends on Phase of Disease From Schilsky et al AASLD Guidance on Wilson Disease in Hepatology 2022 Michael L Schilsky MD FAASLD Time PREVENTION Hepatic TREATMENT Inflammation Asymptomatic elevation of serum aminotransferases Nonspecific symptoms of liver disease RESCUE End-stage Liver Failure Cirrhosis Neuropsychiatric symptoms Complications of portal hypertension • Ascites • Variceal bleeding • Hepatic encephalopathy • HCC or cholangiocarcinoma 35% with acute liver failure Death 15
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Penicillamine (Chelator) Trientine (Chelator) Zinc Liver Transplant Initial therapy Penicillamine intolerant patients Maintenance therapy Available only to severe patients with significant liver damage with or without neurologic involvement Chelates copper , causing increased urinary excretion Chelates copper , causing increased urinary excretion, blocks copper absorption Induces metallothionein and blocks absorption of copper in intestine Eliminates disease by removing inherited metabolic defect causing WD Limitation: Neurological worsening, cutaneous eruptions, lymphadenopathy, neutropenia, thrombocytopenia, proteinuria Limitation: Gastrointestinal intolerance, not all patients respond Limitation: Lifelong immunosuppression Current Standard-of-Care: High Rates of Non-Adherence, Side Effects Require multiple daily doses with large pill burden under fasting conditions; therapies bring adverse side effects that can f orce discontinuation or exacerbate other disease symptoms Patients are advised to restrict dietary copper, found in soy, legumes, nuts, chocolate, shellfish, mushrooms, etc. 16
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17 Confidential | 17 Prime Medicine’s Approach to Wilson Disease
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18 Prime Editing Has the Potential to Change the Treatment Paradigm in Wilson Disease TODAY Chronic treatment burden: standard - of-care agents and low copper diets are burdensome and often hard to tolerate; long -term compliance is challenging. Liver transplantation is the only option for patients who progress to liver failure OUR VISION One time therapy that precisely and permanently restores wild -type ATP7B function, normalizing copper metabolism, halting disease progression and providing a durable cure
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19 Preclinical Data Strongly Support Potential for PM577 as Transformative Therapy DELIVERY Optimized Prime Editors achieve high levels of hepatocyte editing SAFETY Favorable safety profile in mice and NHPs, with no evidence of off -target editing or meaningful LFT elevations at clinically relevant doses EFFICACY Efficient correction of the H1069Q and R778L mutations in fully humanized mouse models Evidence of restored copper homeostasis in vivo as measured by phenotypic markers and copper PET
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20 Efficient correction of the H1069Q and R778L mutations in fully humanized mouse models Prime Editors Efficiently and Precisely Corrected the Two Most Prevalent Disease-Causing Mutations in Wilson Disease Prime Editors delivered with Prime Medicine’s universal liver LNP administered at clinically relevant doses No detectable off -target editing identified in patient -derived cells LNP = lipid nanoparticle
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21 >80% hepatocytes edited Hepatic copper concentration* returns to wild-type levels at eight weeks Copper** excreted normally through the feces at four weeks *Wet tissue weight **Radiolabeled copper Prime Editors Efficiently Correct the H1069Q Mutation and Completely Restore Wild-Type Copper Concentration In Vivo Using optimized Prime Editor in partially humanized homozygous p.H1069Q ATP7B mouse model
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22 Treated (H1069Q Mut) Wild Type Control *Copper challenge and PET imaging performed 4 weeks post PE treatment Prime Edited Mice Challenged with Radiolabeled Copper Demonstrated Normal Copper Clearance 24h Post Injection Untreated (H1069Q Mut)
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23 IND = investigational new drug; CTA = clinical trial application PM577 Clinical Development: On Track for H1’26 IND and/or CTA with Proof-of-Concept Data Anticipated in 2027 Ultimate goal of the Phase 1/2 study is to demonstrate the ability of PM577 treatment to maintain copper balance post - discontinuation of standard -of- care therapies ANTICIPATED ENROLLMENT CRITERIA: • Adult patients who are maintained on standard of care (chelators, zinc salts) PRIMARY SAFETY ENDPOINTS: • Safety, tolerability PRIMARY EFFICACY ENDPOINTS: • Biomarkers including ceruloplasmin, serum copper, urinary copper • Copper PET imaging to assess restoration of ATP7B -mediated copper transport
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24 AATD = Alpha-1 Antitrypsin Deficiency; CF = cystic fibrosis; IND = investigational new drug; CTA = clinical trial application; C GD = chronic granulomatous disease Prime Medicine is Entering a New Era of Gene Editing: Generating Clinical Data for Multiple Programs, Leveraging Platform Modularity Secure multiple additional strategic partnerships to accelerate our pipeline and bolster our financial resources 2025 2026 2027+ Advance additional high -value programs: • Share in vivo proof -of-concept data in CF and initiate IND -enabling studies • Expand pipeline within priority focus areas and beyond Advance additional high -value programs: • File IND and/or CTA for CF and initiate Phase 1 clinical trials • Relaunch programs targeting neurological and other large indications PM577 for Wilson Disease: Prepare for 2026 clinical entry, advance additional mutations pre -clinically PM577 for Wilson Disease: File IND and/or CTA in 1H 2026; initiate Phase 1/2 clinical trial PM577 for Wilson Disease: Announce initial clinical data in 2027 Leverage business development to accelerate pipeline, extend reach PM647 for AATD: File IND and/or CTA mid-2026; initiate Phase 1/2 clinical trial PM647 for AATD: Prepare for 2026 clinical entry PM647 for AATD: Announce initial clinical data in 2027 Announced initial positive clinical data on PM359 in CGD, reinforcing our confidence in the promise of Prime Editing
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25 | 25 Q&A
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26 Prime Medicine is the Leader in Gene Editing Positioned to Create Sustainable Value Through Pipeline Execution and External Partnerships The Leader in Prime Editing Potential to address approximate ly 90% of genetic diseases and opportunities in non -genetic diseases Breakthrough initial clinical data in CGD demonstrates clinical proof of concept for Prime Editing Comprehensive intellectual property position Platform Modularity Oriented for Growth Fully integrated modular platform - pre-clinical, clinical, manufacturing, regulatory Proprietary modular delivery systems within target tissues Advancing Prime Editing regulatory paradigms - streamlined development Pipeline Positioned for Value Creation PM577 in Wilson Disease IND and/or CTA expected in H1’26 ; AATD IND and/or CTA expected in mid -2026 Strategically focused on programs in large genetic diseases, with clear path to value inflection and multi billion - dollar opportunities Partnerships and BD Potential BMS partnership to develop Prime Edited ex vivo CAR-T products Cystic Fibrosis Foundation relationship and funding to advance Prime Editors for Cystic Fibrosis Additional business development to accelerate and expand pipeline Pro-forma cash, cash equivalents, investments and restricted cash of $227.0M for 9/30/2025, cash runway into 2027 AATD = Alpha-1 Antitrypsin Deficiency; IND = investigational new drug; CTA = clinical trial application; CGD = chronic granulomatous disease
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27 | 27 Thank You!