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1 Delivering on the promise of Prime Editing November 2025 Corporate Presentation
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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’s Disease, CF, and AATD; the continued development and advancement of its AATD and Wilson’s 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 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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4 Platform Validation Clinical Validation and Focused Execution Platform Discovery Sustained Growth and Commercial Success We Believe Prime Medicine has Demonstrated Clinical Proof of Concept and is Poised for Long-Term Value Creation 2020 - 2023 2024 - 2026 Breakthrough clinical data from first -in-human study of Prime Editor. Focused investment on high value programs in large indications. Seek strategic collaborations to expand and accelerate .2019 Prime Editing discovered in Dr. David Liu’s lab as next-generation gene editing technology. 2027 - FUTURE Progress multiple clinical programs. Leverage platform modularity to accelerate pipeline expansion . Accelerate growth and bolster our financial resources with strategic collaborations. Preclinical proof -of- concept achieved in multiple diseases . Proprietary delivery capabilities established . Advancing the promise of Prime Editing
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5 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’s Disease: Prepare for 2026 clinical entry, advance additional mutations pre -clinically PM577 for Wilson’s Disease: File IND and/or CTA in 1H 2026; initiate Phase 1 clinical trial PM577 for Wilson’s 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 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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6 We Believe Prime Editing is the Only Gene Editing 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’s Disease , 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. AATD = Alpha-1 Antitrypsin Deficiency
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7 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-target editing. 2Data from in vivo analysis from mouse bone marrow harvested 16 weeks after engraftment was complete. 3Cas9 nuclease-edited cells, generated by transfecting HEK293T with sgRNA targeting NCF1 and SpCas9 mRNA. CGD = chronic granulomatous disease; HSC = hematopoietic stem cell; IND = investigational new drug; CTA = clinical trial application Prime Editing Has Highly Differentiated Safety Profile: No Off-Target Activity Detected in Any Lead Program Examples from CGD program used to support IND/CTA filings No off -target editing detected in healthy human donor CD34+ cells 1 Genomic location No large deletions or translocations observed in bone marrow engrafted Prime -Edited LT-HSCs 2 vs. Cas -9 nuclease edited cells On-target (NCF1) Translocation Positive Control 3TranslocationDeletion No Off -Target Edits detected with Prime Editing vs. Cas9 12 Spacers SpCas9 Prime Editor 0 20 40 60 Percent Indels (off-target sites) Indel Comparison of Prime Editors and Cas9
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8 ✓ Successful manufacturing from single mobilizations ✓ Tolerable myeloablative conditioning at fully therapeutic exposures with expected adverse events (transitory mucositis, pancytopenia) ✓ No serious adverse events attributed to PM359 ✓ Rapid neutrophil and platelet engraftment confirmed within 2-3 weeks post transplant, markedly faster than current autologous genetic therapy benchmarks ✓ Rapid recovery of NADPH oxidase activity as measured by DHR: ~3 -4x therapeutic threshold by day 30 ✓ Patient #2 demonstrated improvement in inflammatory markers: Fecal calprotectin (a measure of intestinal inflammation) returning to normal levels at day 45 from 15x the upper limit of normal prior to myeloablative conditioning *Source: CASGEVY label, median time to engraftment for neutrophils and platelets observed at days 27 and 35, respectively ** Patient 2 day 60 data not yet available Note: patient #1 was an 18 year old male, patient #2 was a 57 year old male DHR = dihydrorhodamine, an assay to measure NADPH oxidase activity Treatment with PM359 Led to Rapid Engraftment and Restoration of DHR Positivity, Along With Improvement in Inflammatory Markers Plan to continue regulatory interactions based on the current data set **
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9 Prime Editing Platform Modularity Potentially De-Risks Ongoing Efforts and Accelerates Program Advancement Prime Editors Manufacturing Delivery Off-Target Assays Nonclinical Regulatory Clinical
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10 Modular Platform Indication Delivery Discovery Lead optimization IND- enabling Phase 1/2 LIVER Wilson’s 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 Pipeline Focused on Value Creating Opportunities 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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11 | 11 Liver
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12 Prime Medicine’s Liver Franchise: Aspiring to Cure Two of the Largest Genetic Liver Diseases, Enabled by Platform Modularity Current Status IND-enabling activities ongoing IND-enabling activities ongoing Rapidly Advancing IND and/or CTA on track for H1’26 IND and/or CTA anticipated in mid -2026 Targeted Mutations H1069Q, R778L E342K (Pi*Z Mutation), D341H (Little Rock*) Opportunity >20,000 WD patients in US and EU 7,500 – 15,000+ WD patients in Japan 200,000 AATD patients in the US and EU (20,000 to 30,000 patients diagnosed**) Modularity • Both programs use Prime Medicine's universal, proprietary liver LNP • Planning to leverage key learnings, regulatory frameworks and manufacturing synergies from Wilson's Disease program to potentially accelerate efforts and reduce costs in AATD and any follow -on liver programs Delivery • Achieved >70% hepatocyte editing using Prime Editors delivered with universal liver LNPs in humanized mice • Achieved >50% hepatocyte editing with surrogate, unoptimized Prime Editors delivered with universal liver LNP in NHPs*** • LNP was well tolerated in NHPs at clinically relevant doses and improved tolerability vs benchmark LNP PM577: Wilson’s Disease PM647: Alpha -1 Antitrypsin Deficiency WD = Wilson’s Disease; AATD = Alpha-1 Antitrypsin Deficiency; IND = investigational new drug; CTA = clinical trial application; LNP= lipid nanoparticle; NHP = non-human primate. *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; ***Preclinical studies using unoptimized surrogate Prime Editors for genetic diseases in NHP models
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13 LNP = lipid nanoparticle; PEG = Polyethylene glycol; GalNAc = N-acetylgalactosamine; PE = Prime Editor; pegRNA = Prime Editing guide RNA; ngRNA = nicking guide RNA *May require slight modifications to mRNA depending on disease context Proprietary LNP–formulated Prime Editor is a Complex Multi-Component Drug Product Designed to Support Current and Future Liver Programs • Control particle size and stability • Stealth coating reduces serum interactions and increases half -lifePEG Lipids • Stabilize and improve LNP pharmacokinetics • Facilitate membrane fusion and endosomal escape Helper Lipid • Improve intracellular delivery • Increase LNP stabilityCholesterol • Proprietary GalNAc formulation to improve biodistribution of LNPs to hepatocytes Targeting Ligand LNP Modularity: 6 out of 8 components in the LNP are the same for liver programs* Ionizable Lipid • Nucleic acid encapsulation and endosomal escape • pegRNA is disease and mutation specificpegRNA ngRNA • ngRNA is disease and mutation specific; usage is dependent on the Prime Editing strategy applied • Prime editor enzymePE mRNA*
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14 Confidential | 14 Wilson’s Disease
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15 Wilson’s Disease Advancing Prime Editors for Wilson’s Disease: Disease Overview Large genetically defined disease well suited for Prime Editing ceruloplasmin Blood Bile (fecal excretion) ATP7B ATP7B Copper CTR1 ceruloplasmin Blood (urinary excretion) Bile ATP7BATP7B Copper CTR1 X X Healthy • Common liver and systemic disease presenting in teens to 20s • Leads to liver failure, neurocognitive decline and premature death • Greater than 20,000 patients in US and Europe, 30 -50% harboring H1069Q mutation • 7,500 – 15,000+ patients in Japan, R778L is the predominant mutation in the Asian population Disease Severity and Opportunity • Many patients die without liver transplant • No approved disease modifying therapies • Current standard of care aims to prevent copper accumulation; options include chelating agents and low copper diet Unmet Need • Autosomal recessive due to loss of function mutations in ATP7B • Affects copper homeostasis, leading to toxic accumulation of copper in liver and brain Human Biology
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16 Prime Editors delivered with Prime Medicine’s universal liver LNP administered at clinically relevant doses Prime Editors Efficiently Corrected the Two Most Prevalent Disease-Causing Mutations in Wilson’s Disease Editing efficiency in fully humanized homozygous p.H1069Q and R778L ATP7B mouse models Efficient correction of the H1069Q and R778L mutations
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17 IND = investigational new drug; CTA = clinical trial application * % Normalized to saline treated Prime has initiated IND -enabling activities planning for a H1’26 IND and/or CTA application(s) Efficient Correction of the H1069Q Mutation Reduced Liver Copper and Restored Copper Homeostasis In Vivo Using unoptimized Prime Editor in fully humanized homozygous p.H1069Q ATP7B mouse model ~75% reduction in liver copper ~80% decrease in urinary copper ~100% increase in fecal copper
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18 Confidential | 18 Alpha-1 Antitrypsin Deficiency (AATD)
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19 Advancing Prime Editors for AATD: Disease Overview AATD = Alpha-1 Antitrypsin Deficiency; A1AT = alpha-1 antitrypsin • AATD is an inherited genetic disorder that causes low levels of AAT protein • Low levels of AAT protein increases the risk of lung disease (emphysema) • Patients are also at risk of liver disease (cirrhosis) caused by mutant protein aggregation • Approximately 200,000 patients in the US and EU, ~10 -15% of which are diagnosed today Disease Severity and Opportunity • Many patients progress to liver failure or severe lung disease, requiring transplant • Current standard of care includes chronic AAT augmentation therapy for lung disease; no approved curative therapies • No approved treatments for liver disease Unmet Need • Autosomal codominant disorder due to mutations in SERPINA1 gene • Lung: lack of functional AAT leads to unrestricted neutrophil elastase activity, among other pathological changes (loss of function) • Liver: defective AAT protein misfolding and accumulation (gain of function) • 20-30% correction in hepatocytes could be curative Human Biology We believe Prime Editing is uniquely well-suited to correct mutant AAT protein to wild -type without the risk of bystander edits
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20 • Correcting circulating AAT protein to 20uM or more restored to healthy levels and predicted to prevent disease progression • 11uM is the current minimum level accepted by Regulators for replacement therapies • Decreased Z -AAT in the liver will potentially ameliorate the liver manifestations of AATD • Prime Editing corrected the mutation while leaving it under endogenous control *Taken from Vidal R, Blanco I, Casas F, et al. Arch Bronconeumol. 2006;42(12):645-59 and Ferrarotti I, Thun GA, Zorzetto M, et al. Thorax 2012; 67: 669–674; ** ZZ genotype contain Pi*Z mutation; Z-AAT = mutant A1AT protein. There are many genotypes (alleles) of the AATD gene. The M genotype is the most common and encodes for the normal (wild-type), fully functional AATD protein (M-AAT), and most people have the MM genotype (i.e., two, fully functional copies of the normal gene and normal AATD levels). The Z genotype (PI*Z mutation) encodes for a dysfunctional protein (Z -AAT) and patients with the ZZ genotype also have low levels of AATD, and develop the disease of AATD deficiency, with lung and liver manifestations. MZ heterozygotes serum A1AT levels are usually lower but sufficient, so they only carry some risk in the setting of other contributory factors. The S genotype is less common, and encodes for a protein that is not fully functional; combinations of the S genotype (e.g., MS) are not usually associated with increased risk, others (e.g., SS) can carry low risk, while SZ have serum A1AT levels usually below the protective threshold value, putting people at increased risk of developing emphysema and chronic bronchitis. AATD Program Objective: Normalize AAT Levels in PiZZ Genotype Patients to Healthy Human Levels 50 40 30 20 10 0 Target patient population** Normal human range 11uM is minimum threshold for benefit Genotype MM MS SS MZ SZ ZZ NULLNULL Serum A1AT Concentration (μM) Healthy Human Low Risk `
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21 M-AAT = healthy A1AT protein; Z-AAT = mutant A1AT protein; IND = investigational new drug; CTA = clinical trial application *Performed by LC-MS; **Analysis at day 7 positive control = healthy human serum Prime has initiated IND -enabling activities planning for Mid’26 IND and/or CTA application(s) PM647 Efficiently Corrected the Mutation Resulting in M-AAT Protein Restoration In Vivo at Clinically Relevant Doses Efficient correction Restoration M -AAT Protein** • PM647 restored AAT levels into healthy human range in fully humanized mouse model • Potential to correct mutated protein back to wild type (M -AAT) without bystander or off -target edits 0 20 40 60 80 100 % hepatocytes precisely corrected Dose Level #1 0.5mpk 1.0mpk Dose Level #2 0 25 50 75 100 % Human AAT Isoform* % Corrected AAT % Mutant AAT Dose Level #1 Positive Control Dose Level #2 Negative Control 0 10 20 30 40 50 60 70 Serum M-AAT Protein* (µM) Healthy Human Range Negative Control Dose Level #1 Positive Control 0.5mpk 1.0mpk Dose Level #2
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22 | 22 Lung
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23 We believe Prime Editing -based approaches could eventually benefit more than 93% of all people with CF CFTR = cystic fibrosis transmembrane conductance regulator 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 • Progressive, genetic disease that affects the lungs, pancreas and other organs, leading to premature death • Impacts close to 40,000 people in the United States, ~1,000 new cases diagnosed each year Disease Severity and Opportunity • Existing treatment options include airway clearance, inhaled medicines, pancreatic enzyme supplements, fitness plans and CFTR modulators for patients with specific mutations • No cure and existing treatments are ineffective for, or not tolerated by, approximately 15% of patients Unmet Need • Autosomal recessive disorder caused by mutations in the CFTR gene, which cause CFTR protein to become dysfunctional • Dysfunctional CFTR reduces chloride and bicarbonate transport to epithelial lumen Human Biology Cystic Fibrosis Healthy
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24 CF = cystic fibrosis; attP = complimentary recognition sequence for attB; SA = splice acceptor; 3’ UTR = 3’ untranslated region; *Exons in gray introns in black 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 need” mutations; these same Prime Editors could address >93% of all CF patients Potential to address nearly all CF patients with a single super exon insertion strategy Super exon SA 3’ UTR attB attP DNA donor + Bxb1 CFTR gene showing exons & introns* Restoring CFTR function in Prime Edited cells under endogenous control
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25 Efforts towards in vivo delivery to humanized mice and large animals ongoing • We believe primary human lung progenitor data is most predictive of in vivo efficacy • Comprehensive suite of assays in development to enable selection of development candidate and advance to IND enabling studies • Humanized mouse colonies, ferret and NHP colony established for in vivo optimization • Prime’s targeted modular lung LNP as well as alternative delivery system are being applied to accelerate CF hotspot editing in vivo LNP = lipid nanoparticle; NHP = non-human primate; CFTR = cystic fibrosis transmembrane conductance regulator; HBEs = human bronchial epithelial cells; ALI = air-liquid interface Prime Medicine has Made Significant Progress Developing Prime Editors for G542X Mutated Cystic Fibrosis In July 2025, Prime Medicine expanded its agreement with the CF Foundation for additional funding of up to $24 million to support development of Prime Editors for CF G542X In vitro Prime Editor in Primary HBEs Phenotypic restoration of G542X mutated CFTR in differentiated ALI culture CFTR -actin Patient Prime Edited C band Healthy B band Unedited
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26 | 26 Immunology and Oncology
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27 • $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 the genetic diseases in Prime Medicine’s internal pipeline 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 Prime Medicine retains rights to advance certain target reagents designed under this collaboration for applications beyond ex vivo T cell products, including in vivo T cell and other cell therapy applications Leadership in Prime Editing; PASSIGE technology may enable one -step, non - viral, multi -kilobase -size editing approach with no double -stranded breaks Global leader in cell therapy for hematology, immunology and oncology
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28 TRAC = 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 Programs Existing Limitations Prime Editing Solution Multiplex Engineering ꭗ Low payload integration efficiency ꭗ Constrained to limited number of knock -outs and limited single base pair changes ✓ >80% integration efficiency of CAR, aimed at TRAC locus to maintain endogenous control ✓ Capable of multiple edits done safely , each with a full suite of functional modifications Safety ꭗ Random or semi -random integration ꭗ High rate of translocations / chromosomal abnormalities ✓ Precise on -target transgene integration ✓ Based on our extensive off -target evaluations in other settings, there is the potential for no detectable off -target edits, translocations, or unintended structural abnormalities in Prime - Edited CAR -T’s Manufacturing / Cost of Goods ꭗ Dependence on viral components ꭗ Complicated by multi -step engineering ✓ Entirely non -viral manufacturing process ✓ Single -step editing and integration
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29 Maintained efficiency with five multiplex edits B2M = b2 macroglobulin; TRAC = T-cell receptor alpha constant 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 B2M TRAC 0 20 40 60 80 100% Prime Editing Multiplex Singleplex % Prime Editing B2M TRAC Singleplex Multiplex % Prime Editing % Singleplex Prime Editing TRAC B2M Target 3 Target 4 Target 5 100 80 60 40 20 0 100 80 60 40 20 0
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30 | 30 Corporate
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31 Prime Medicine remains 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 Enabling Innovation Within the Core Develop Prime Edited CAR -T products leveraging PASSIGE and platform Funding to accelerate the development of Prime Editors for Cystic Fibrosis BMS CF Foundation Current Relationships Partnering Strategy Enabled by scientific leadership in gene editing and program advancement
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32 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 configurations - Dual flap and dual guide RNA editing systems • Broad diversity of RNA -templated gene editing systems - Large variety of nucleic acid programmable DNA binding proteins - Extensive range of RNA -dependent DNA polymerases (reverse transcriptases ) • PASSIGE : System using Prime Editing and recombinase to insert gene -sized DNA at chosen target location in genome - PASSIGE systems include various gene editing configurations and recombinases • Additional gene editing technology including DNA -dependent DNA polymerase editing • Program -specific patent filings for pipeline programs Prime Medicine holds 6 U.S. and 12 ex -U.S. issued patents - Prime Medicine also holds 2 U.S. and 4 ex -U.S. allowed patent applications - Numerous Prime -owned and in -licensed patent applications with broad coverage filed worldwide - Pursuing aggressive filing strategy to cover technological advances Seminal Prime Editing Publication Dual Flap Prime Editing PASSIGE System Engineered pegRNAs pegRNA Enhancements PE4, PE5, PEmax Novel PE Proteins Improved recombinases Novel RT Proteins pegRNA = Prime Editing guide RNA
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33 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’s 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
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34 | 34 Appendix
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35 BP = base pair; KB = kilobase Prime Editing is Designed with a Wide Range of Genome Editing Capabilities Flexibility to select right approach for each indication based on editing need 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 deletions (e.g., multi -kb repeat excision, exon del) Large insertions or inversions (e.g., targeted multi -kb gene integration) Short Flap Prime Editing Dual Flap Prime Editing Long Flap Prime Editing PASSIGE +++ ++ +++ ++ ++ +++ +++ +/++/+++ = how fit Prime Medicine believes the technology is for making the edit, based on Prime Medicine’s internal assessment = capable of the edit +++++
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36 *Not part of Prime Medicine’s current pipeline 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 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., Phenylketonuria, Tyrosinemia) Targeted whole gene replacement for bone marrow diseases (e.g., Hereditary anemias, such as Fanconi Anemia) Cystic Fibrosis Areas of opportunity:* Non-viral, multiplex -edited CAR -T therapies BMS collaboration (e.g., oncology and autoimmune diseases) Recombinase enzyme Where we are working today: X-Linked Chronic Granulomatous Disease (XCGD)