Prime Medicine estimates ~$61.2M cash and investments
PM577a and PM647 initial clinical data are anticipated in 2027, while a PM359 BLA submission is planned for the first half of 2027 after final FDA alignment.
Sentiment and the balance of points
Rhea-AI Sentiment reads the wording of the document, how positive or negative its language is on a 1 to 5 scale. The balance of points shown with the takes weighs what the document actually discloses, so the two can disagree, for example when a trial that missed its main goal is described in upbeat language.
Form Type
8-K
Rhea-AI Filing Summary
Prime Medicine, Inc. reported preliminary, unaudited estimates of approximately $61.2 million in cash, cash equivalents and short-term investments as of September 30, 2026, excluding approximately $13.7 million of restricted cash. Its quarter-end close was incomplete; management said the estimates could change, potentially materially. Complete results will be included in the Form 10-Q for the quarter ended September 30, 2026.
Prime Medicine’s PM359 chronic granulomatous disease update reported neutrophil and platelet engraftment within 2-3 weeks, NADPH oxidase activity at approximately 3-4x the therapeutic threshold by day 30 and sustained through six months, and no serious adverse events attributed to PM359. The PM577a Wilson disease trial is underway, with initial data anticipated in 2027; PM647’s IND is cleared, its Phase 1/2 trial is planned, and initial data are anticipated in 2027. A PM359 BLA submission is planned for the first half of 2027 following final FDA alignment. The Bristol Myers Squibb collaboration terms include $110 million upfront, including a $55 million equity investment, and more than $3.5 billion in potential milestones, plus royalties on net sales.
8-K Event Classification
3 items: 2.02, 8.01, 9.01
3 items
Item 2.02
Results of Operations and Financial Condition
Financial
Disclosure of earnings results, typically an earnings press release or preliminary financials.
Item 8.01
Other Events
Other
Voluntary disclosure of events the company deems important to shareholders but not covered by other items.
Item 9.01
Financial Statements and Exhibits
Exhibits
Financial statements, pro forma financial information, or exhibit attachments filed with this report.
Key Figures
Cash, cash equivalents and short-term investments: Approximately $61.2 million
Restricted cash: Approximately $13.7 million
Neutrophil and platelet engraftment: Within 2-3 weeks
+5 more
8 metrics
Cash, cash equivalents and short-term investments
Approximately $61.2 million
Preliminary, unaudited estimate as of September 30, 2026
Restricted cash
Approximately $13.7 million
As of September 30, 2026; excluded from the cash, cash equivalents and short-term investments estimate
Neutrophil and platelet engraftment
Within 2-3 weeks
PM359 chronic granulomatous disease update
NADPH oxidase activity
Approximately 3-4x the therapeutic threshold
By day 30; sustained through six months post-infusion in the PM359 update
Bristol Myers Squibb collaboration upfront
$110 million
Collaboration terms
Equity investment
$55 million
Included in the Bristol Myers Squibb collaboration upfront
Potential milestones
More than $3.5 billion
Bristol Myers Squibb collaboration
Commercial milestones
More than $2.1 billion
Bristol Myers Squibb collaboration
Key Terms
Prime Editing, BLA, IND, LNP, +1 more
5 terms
Prime Editing technical
"the potential of Prime Editing to correct the causative mutations"
Prime editing is a gene‑editing method that can precisely rewrite small stretches of DNA inside living cells without cutting both strands, functioning like a targeted “find-and-replace” for genetic code rather than tearing out a paragraph. It matters to investors because it expands the range of treatable genetic conditions and may reduce side effects and development risk, influencing biotech valuations, clinical prospects, intellectual property stakes and regulatory outlooks.
BLA regulatory
"Submit BLA for PM359 in CGD"
IND regulatory
"PM647 IND cleared"
LNP technical
"LNP = lipid nanoparticle"
LNP stands for lipid nanoparticle, a tiny fatty-particle carrier used to deliver medicines like RNA therapies into cells. Think of it as a microscopic delivery van that protects fragile drug cargo on the way to its destination; for investors, LNP technology matters because it affects a therapy’s effectiveness, safety, manufacturing complexity and intellectual property value, all of which influence a drug candidate’s commercial prospects and regulatory risk.
PASSIGE technical
"Prime-Assisted Site-Specific Integrase Gene Editing"
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
How much cash did PRME estimate as of September 30, 2026?
Prime Medicine estimated approximately $61.2 million in cash, cash equivalents and short-term investments as of September 30, 2026, excluding approximately $13.7 million of restricted cash. The estimates were preliminary and unaudited while its quarter-end close remained incomplete.
What are the potential milestones in PRME’s Bristol Myers Squibb collaboration?
The collaboration lists more than $3.5 billion in potential milestones: $185 million in preclinical milestones, $1.2 billion in development milestones and more than $2.1 billion in commercial milestones. It also includes royalties on net sales.
When does PRME plan to submit a BLA for PM359?
Prime Medicine plans to submit a BLA for PM359 in chronic granulomatous disease in the first half of 2027, following final FDA alignment.
AI-generated analysis. How Rhea-AI works. Not financial advice.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
___________________________________
FORM 8-K
___________________________________
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (date of earliest event reported)
___________________________________
(Exact name of registrant as specified in its charter)
___________________________________
(State or other jurisdiction of incorporation) | (Commission File Number) | (I.R.S. Employer Identification No.) | ||||||
(Address of principal executive offices and zip code) | ||||||||
( | ||||||||
(Registrant's telephone number, including area code) | ||||||||
___________________________________
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) | |||||
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) | |||||
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) | |||||
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) | |||||
Securities registered pursuant to Section 12(b) of the Act: | ||||||||||||||
Title of each class | Trading Symbol | Name of each exchange on which registered | ||||||||||||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 2.02 Results of Operations and Financial Condition
On November 10, 2026, Prime Medicine, Inc. (the “Company”) announced that the preliminary unaudited estimates of its cash, cash equivalents, and short-term investments were approximately $61.2 million as of September 30, 2026, excluding its restricted cash of approximately $13.7 million. The Company has not yet completed its quarter-end financial close process for the quarter ended September 30, 2026. The foregoing information is based on preliminary unaudited information and management estimates as of and for the quarter ended September 30, 2026, is not a comprehensive statement of the Company’s financial results, and is subject to completion of the Company’s financial closing procedures. There can be no assurance that the Company’s actual financial results as of September 30, 2026 will not differ from these estimates, including as a result of the completion of the Company’s final adjustments, and other developments arising between the date of this filing and the time that the Company’s financial results for such period are finalized, and any such changes could be material.
These preliminary unaudited estimates have been prepared by, and are the responsibility of, the Company’s management. PricewaterhouseCoopers LLP has not audited, reviewed, examined, compiled, nor applied agreed-upon procedures with respect to the preliminary financial data. Accordingly, PricewaterhouseCoopers LLP does not express an opinion or any other form of assurance with respect thereto. These estimates should not be viewed as a substitute for interim financial statements prepared in accordance with accounting principles generally accepted in the United States and they are not necessarily indicative of the results to be achieved in any future period. Complete results as of September 30, 2026 will be included in the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2026. The Company assumes no duty to update these preliminary estimates, except as required by law.
The information contained in Item 2.02 of this Current Report on Form 8-K is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 8.01 Other Events
On November 10, 2026, the Company posted an updated corporate presentation to its website at https://investors.primemedicine.com/news-events. A copy of the updated corporate presentation is attached hereto as Exhibit 99.1 to this Current Report on Form 8-K, which is incorporated herein by reference. Reference to the Company’s website is for inactive textual reference only and the content of the website should not be deemed incorporated by reference into this Current Report on Form 8-K.
Cautionary Note Regarding Forward Looking Statements
This Current Report on Form 8-K contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the Company’s preliminary unaudited estimates of its cash, cash equivalents, and short-term investments as of September 30, 2026. The words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target” and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements contained in this Current Report on Form 8-K are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this Current Report on Form 8-K. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in the Company’s most recent Annual Report on Form 10-K for the year ended December 31, 2025, Quarterly Report on Form 10-Q for the quarter ended June 30, 2026, and any of its subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent the Company’s views only as of today and should not be relied upon as representing its views as of any subsequent date. The Company explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements, except as required by law.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
Exhibit Number | Description | |||||||
99.1 | Corporate Presentation, dated November 2026 | |||||||
104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |||||||
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
Date: November 10, 2026
By: | /s/ Allan Reine | ||||
Name: | Allan Reine, M.D. | ||||
Title: | Chief Executive Officer | ||||
1 Delivering on the promise of Prime Editing Corporate Presentation November 2026
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 Wilson disease ("WD"), Alpha-1 Antitrypsin Deficiency (“AATD”), chronic granulomatous disease ("CGD"), and Cystic Fibrosis; the continued development and advancement of PM577a and PM647, including the ongoing Phase 1/2 trial of PM577a, planned Phase 1/2 trial of PM647, and the timing of initial data for both in 2027; the ongoing regulatory engagement with the FDA on PM359 and the outcomes of such engagement, including the planned submission of a BLA filing in the first half of 2027 and our ability to obtain regulatory approval for, and commercially launch, PM359 in CGD; 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 significance of data from our Phase 1/2 trial of PM359; the safety profile of Prime Editing, our modular LNP, and our programs; the timing of, and our ability to achieve, clinical validation and sustained, long-term value creation; the modularity of the Prime Editing platform and our LNP and the benefits thereof; the 2025 agreement with the Cystic Fibrosis Foundation, its expanded funding pursuant thereto, and the intended and potential 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; our expectations regarding the breadth of Prime Editing, including the potential of Prime Editing to address approximately 90% of genetic diseases and to address non-genetic diseases; the continued development and optimization of various 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 estimates of our expenses, capital requirements, and needs for additional financing; our ability to continue as a going concern; 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 SEC. 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 (express 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
3 Prime Editing: Emerging as the Predominant Gene Editing Technology Gene editing permanently corrects genetic alterations Prime Editing is the most versatile gene editing technology Clinical data with Prime Editors support curative potential Prime Editing does not cause double-strand breaks or bystander edits New regulatory models pave way for platform- based approvals Prime Medicine’s IP position covers any permutation of Prime Editing
4 Focused execution on Wilson disease and Alpha-1 Antitrypsin Deficiency Initial efforts underway to expand liver franchise Prime Medicine is Strategically Delivering on the Promise of Prime Editing DISCIPLINED CLINICAL DEVELOPMENT, MAXIMIZE PLATFORM IMPACT AND E NSURE ACCESS TO BREAKTHROUGH THERAPIES Pursue complementary partnerships to expand reach Make PM359 available for patients with CGD
5 Secure multiple additional strategic partnerships to accelerate our pipeline and bolster our financial resources Near-Term, Focused Execution Positions Prime Medicine to Capitalize on the Full Potential of Prime Editing Achieved and Anticipated Milestones 2026 2027 WILSON DISEASE ✓PM577a CTA and IND cleared ✓Initiate clinical trial • Advance follow-on Prime Editors for other common mutations • Announce PM577a initial clinical data • Capitalize on platform modularity vis-a-vis additional common mutations (e.g., R778L in Asia among other pathogenic variants) AATD ✓PM647 IND cleared • Initiate clinical trial • Announce PM647 initial clinical data OTHER • Progress towards a BLA filing for CGD • Share in vivo proof-of-concept data in CF • Expand pipeline within priority focus areas and beyond • Submit BLA for PM359 in CGD
6 Therapeutic Area Indication Delivery Discovery Lead Optimization IND- enabling Phase 1/2 Pivotal / Registration LIVER Wilson Disease LNP Alpha-1 Antitrypsin Deficiency (AATD) LNP LUNG Cystic Fibrosis1 (including PASSIGE ) LNP IMMUNOLOGY & ONCOLOGY p47phox Chronic Granulomatous Disease ex vivo Plan to submit BLA following final FDA alignment Ex vivo CAR-T2 (with PASSIGE ) ex vivo Multi-target collaboration advancing Prime Editors for the treatment of complex oncology and autoimmune indications 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’s Pipeline: Focused on Value Creating Opportunities Prime Medicine is identifying opportunities to expand the reach of Prime Editing either via organic growth around its liver franchise and / or business development
7 We Plan to Leverage the Versatility of Prime Editing to Address a Range of Diseases Across Target Tissues REPLACEMENT Deletion / Insertion Correction p47 Chronic Granulomatous Disease (CGD) Point Mutation Correction Wilson Disease, Alpha-1 Antitrypsin Deficiency Targeted Full Gene Insertion (PASSIGE ) CAR-T, Cystic Fibrosis Repeat Excision Repeat expansion diseases Hotspot Correction Cystic Fibrosis, Retinitis Pigmentosa (RHO adRP) Prime Editor Prime Editing is designed with a wide range of genome editing capabilities and the potential to make edits of any size, from small base pair swaps to large, multi-kilobase insertions or inversions
8 Manufacturing Processes and Assays Regulatory Frameworks Clinical Development Consolidated safety and platform clinical trials Computational Design and Screening of Core Components PE proteins, RNAs, lipids Off-Target Analysis to Advance Highest Precision Guide RNAs Non-Clinical Development In-vitro, in-vivo Modular Prime Editing Platform Flywheel Effect: Industrialized Engine is Reused Across Programs LEARN OPTIMIZE REUSE SCALE
9 Prime Medicine Holds Extensive, Foundational Intellectual Property for Prime Editing Technologies CRISPR-Cas Enzyme Any programmable nuclease to specifically identify and cut DNA sequences Guide RNA Engineered RNAs that locate the exact editing site and provide the template for transcription Reverse Transcriptase Converts RNA into complementary DNA Any combination or permutation of a CRISPR-Cas enzyme, template Guide RNA with a Reverse Transcriptase is Prime Editing and is covered by our extensive patent estate Prime Medicine holds 10 U.S. and 21 ex-U.S. issued patents in an extensive patent estate that protects its breakthrough Prime Editing platform, delivery technologies and therapeutics
10| Liver
11 PM647: AATD Prime Medicine’s Initial Liver Franchise: Aspiring to Cure Two of the Largest Genetic Liver Diseases, Enabled by Platform Modularity WD = Wilson Disease; AATD = Alpha-1 Antitrypsin Deficiency; IND = investigational new drug; CTA = clinical trial application *Prime Medicine estimate PM577: Wilson Disease >20,000 7,500-15,000+ US and EU Japan Clinical trial initiated; data anticipated 2027 Initial focus on H1069Q mutation Plan to leverage key learnings, regulatory frameworks and manufacturing synergies from PM577a to accelerate efforts and reduce costs for other Wilson Disease mutations, AATD and future follow -on liver programs 200,000 US and EU 20,000-30,000 Diagnosed* IND cleared; data anticipated 2027 Opportunity (Patients: All Mutations) Opportunity (Patients)
12 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-life PEG 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: Majority of components in the LNP are the same across 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
13 Wilson Disease
14 Wilson Disease Advancing Prime Editors for Wilson 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 ATP7B ATP7B 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 • No approved disease modifying therapies • Current standard of care aims to prevent copper accumulation; options include chelating agents and low copper diet • Liver transplantation is last resort option in most severe patients 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
15 Prime Medicine’s Wilson Disease Programs Have Potential to Address Large Commercial Opportunity 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 PM577a (H1069Q) to provide leverage and read- through to other mutations Prime Addressable Patients Up to 9k Prime Addressable Patients Up to 10k
16 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 No detectable off-target editing identified in patient-derived cells for PM577a LNP = lipid nanoparticle Prime Editors delivered with Prime Medicine’s universal liver LNP administered at clinically relevant doses
17*ATP7B protein expression and liver copper measurements taken at 4 weeks PM577a Efficiently Corrected the H1069Q Mutation and Restored Wild-Type Copper Concentration at Multiple Doses in Preclinical Studies ~45% editing restored copper levels to near wild-type levels Liver copper restored to wild-type levels* Increase in wild-type ATP7B protein expression* Precise correction of ATP7B p.H1069Q in mice
18 Untreated (Wild Type) Treated (H1069Q Mut) Untreated (H1069Q Mut) Copper challenge and PET imaging performed 4 weeks post PE treatment, PET imaging performed 24hrs post copper challenge Prime Edited Mice Challenged with Radiolabeled Copper Demonstrated Normal Copper Metabolism At Multiple Doses 0.4 mg/kg 0.8 mg/kg
19 Trial Overview Design Phase 1/2, open-label Population Adults and adolescents with Wilson Disease and at least one ATP7B p.H1069Q allele Treatment Single IV infusion of PM577a Primary Endpoints Safety and tolerability Key Secondary Endpoints Ability to discontinue SOC, NCC-Sp, ceruloplasmin, 24-hour urinary copper and radiolabeled CuPET Dose Escalation Dose Cohort 1 Dose Cohort 2 Dose Cohort 3 Dose Cohort 4+ (if required) Part 1 (Extension) Adults stable on SOC Identify Optimal Biologic Dose Part 2 Adolescents stable on SOC OBD = Optimal Biological Dose; NCC = Non-Ceruloplasmin-bound Copper; PD = Pharmacodynamics; LNP = Lipid Nanoparticle; SOC = Standard of Care; LTFU = Long-Term Follow-Up; RP3D = recommended phase 3 dose PM577a Clinical Trial Overview Clinical trial initiated, anticipate initial clinical data in 2027 H1069Q adult patients stable on SOC Dose Expansion
20IND = investigational new drug; CTA = clinical trial application; LNP = lipid nanoparticle; DC = development candidate; PMDA = Japan’s Pharmaceuticals and Medical Devices Agency 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 target and in vitro data) R778L Other Mutations H1069Q (PM577a) ANCHOR MUTATION: Large commercial opportunity in U.S. and Europe Clinical trial initiated Lead in observational study to potentially expedite patient recruitment >90% editing efficiency, minimal preclinical work to formalize DCFollow-on programs to leverage same liver- targeted LNP; swap out guide sequence Goal to incorporate into existing regulatory filings; engage PMDA
21 Alpha-1 Antitrypsin Deficiency (AATD)
22 Advancing Prime Editors for AATD: Disease Overview AATD = Alpha-1 Antitrypsin Deficiency; A1AT = alpha-1 antitrypsin *Prime Medicine estimate • 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) Human Biology We believe Prime Editing is uniquely well-suited to correct mutant AAT protein to wild-type without the risk of bystander edits
23 • Restore SERPINA1 gene to wild type, without bystander or other unwanted edits • Increase M-AAT levels minimally above protective threshold (~11 µM), ideally into healthy human range (>20 µM) • Maintain wild-type protein under endogenous control to protect patients during acute episodes (M -AAT levels rise 2-4x) • Decreasing Z-AAT in the liver may potentially ameliorate the liver manifestations of AATD *Taken from Vidal R, Blanco I, Casas F, et al. Arch Bronconeumol. 2006;42(12):645-59; ** MZ, SZ and ZZ genotype contain Pi*Z mutation; Z-AAT = mutant A1AT protein. AATD Program Objective: Normalize AAT Levels in PiZZ Genotype Patients to Healthy Human Levels 0 10 20 30 40 50 MM MS SS MZ SZ ZZ NULLNULL Se ru m A 1 A T C o n ce n tr at io n (µ M ) 11uM is minimum threshold for benefit Target patient population** Genotype Healthy Human Low Risk Program Goals Normal Human Range
24M-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 PM647 Efficiently Corrected the Mutation In Vivo Resulting in M-AAT Protein Restoration at Clinically Relevant Doses Efficient correction Restoration M-AAT Protein** 0 25 50 75 100 % H u m a n A A T I s o fo rm * % Corrected AAT % Mutant AAT Dose Level #1 Positive Control Dose Level #2 Negative Control
25 Trial Overview Design Phase 1/2, open-label Population Adults with PiZZ AATD: lung-only (Group A) or lung + liver / liver-only disease (Group B) Treatment One-time IV infusion of PM647a Primary Endpoints Safety, tolerability Key Secondary Endpoints Serum AAT thresholds and isoforms; pulmonary and liver measures Dose Escalation Dose Cohort 1 Dose Cohort 2 Dose Cohort 3 Cohort 4+ (if required) Identify Optimal Biologic Dose AATD = Alpha-1 Antitrypsin Deficiency; BAL = Bronchoalveolar Lavage; DLT = Dose-Limiting Toxicity; FIH = First-in-Human; MTD = Maximum Tolerated Dose; OBD = Optimal Biological Dose; RP3D = Recommended Phase 3 Dose; SRC = Safety Review Committee PM647 Clinical Trial Overview IND cleared for Phase 1/2 trial, anticipate initial clinical data in 2027 Group A: adults with lung-only AATD (Pi*ZZ) Dose Finding & Expansion Group A (Extension) Lung-only AATD Group B Lung + liver or liver-only AATD
26| Lung
27CFTR = cystic fibrosis transmembrane conductance regulator Advancing Prime Editors for Cystic Fibrosis (CF), a Disease for Which There is No Curative Therapy Prime Medicine’s efforts in Cystic Fibrosis funded through multiple grants from the Cystic Fibrosis Foundation • 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 We believe Prime Editing-based approaches could eventually benefit the vast majority of people with cystic fibrosis.
28 G542X In vitro Prime Editor in Primary HBEs Phenotypic restoration of G542X mutated CFTR in differentiated ALI culture Prime Medicine has Made Significant Progress Developing Prime Editors for G542X Mutated Cystic Fibrosis CFTR -actin Patient Prime Edited C band Healthy B band Unedited Efforts towards LNP in vivo delivery to humanized mice and large animals ongoing
29CF = 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 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
30| Immunology and Oncology
31 Chronic Granulomatous Disease (CGD)
32 Advancing Prime Editor for CGD: Disease Overview Rare genetic disease, characterized by defective neutrophil function • Serious life-threatening disease presents in childhood; life expectancy approximately 40 years • Results in recurrent, life-threatening infections which are difficult to eradicate, leads to frequent hospitalizations • Potentially deadly infections from normal exposures (e.g., gardening, swimming) Disease Severity and Opportunity • Current treatment options include • Lifelong anti-microbial therapy (frequently leading to antimicrobial resistance) • Allogenetic HSCT is the only curative option made complicated by GvHD, graft failure and limited availability (e.g., matched donor) Unmet Need • p47phox is a cytosolic regulatory subunit of the NADPH oxidase complex • Majority of p47phox CGD patients share single causative dinucleotide deletion (∆GT) • Defective NADPH oxidase renders neutrophils, monocytes and macrophages ineffective Human Biology p47phox CGD Healthy Membrane gp91phox (NOX2) p22phox p67phox p40phox p47phox NADPH NADP+ H+ 2e-+ + Cytosol Extracellular Space Membrane Rac gp91phox (NOX2) p22phox p67phox p40phox p47phox NADPH Cytosol Extracellular Space Rac
33 Prime Medicine plans to submit a BLA following final regulatory alignment 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 benchmarks Rapid recovery of NADPH oxidase activity: ~3-4x therapeutic threshold by day 30, sustained out to six months post infusion Both patients remain free of new CGD-related complications or significant intercurrent illness post-infusion; patient 2 demonstrated improvement in inflammatory markers of CAC *Source: CASGEVY label, median time to engraftment for neutrophils and platelets observed at days 27 and 35, respectively 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 Breakthrough Clinical Data with PM359 in CGD Provide Proof-of-Concept for Prime Editing as the Foundation for a New Class of Curative Therapies Observed rapid engraftment, restored DHR positivity and improvement in inflammatory markers, with acceptable safety
341Analysis 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 Medicine Has Not Observed Any Detectable Off-Target Editing, Large Deletions, or Translocations in Any Lead Program Prime Medicine uses CRISPR-Cas9 editors as a positive control in off-target analyses No detectable double strand breakage No detectable deletions, chromosomal translocations or rearrangements No detectable off-target edits No detectable bystander edits Examples from CGD program used to support IND/CTA filings No off-target editing detected in healthy human donor CD34+ cells1 Genomic location On-target (NCF1) Translocation Positive Control3 TranslocationDeletion 12 Spacers S pC as 9 P ri m e E dito r 0 20 40 60 P e rc e n t In d e ls ( o ff -t a rg e t s it e s ) Indel Comparison of Prime Editors and Cas9 No large deletions or translocations observed in Prime-Edited LT-HSCs2 vs. Cas-9 nuclease edited cells No off-target edits detected with Prime Editing vs. Cas9
35 Ex-Vivo CAR-T
36TRAC = 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
37 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 Editors for the treatment of complex oncology and autoimmune indications • $110 million upfront (including $55M equity investment) • >$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 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 Prime Medicine retains the ability to advance reagents designed under this collaboration in certain ex vivo (non-BMS targets) and all in vivo T cell and other cell therapy applications
38 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 Maintained efficiency with five multiplex editsHigh efficiency multiplex editing of B2M and TRAC B2M TRAC 0 20 40 60 80 100 % P ri m e E d it in g Multiplex Singleplex % P ri m e E d it in g B2M TR C Singl lex Multiplex % P ri m e Ed it in g % S in gl ep le x P ri m e Ed it in g TRAC B2M Target 3 Target 4 Target 5 0 0 0 0 20 0 100 80 60 40 20 0
39| Corporate
40 Our Strategy to Maximize the Broad Therapeutic Potential of Prime Editing Within Our Core Outside Our Core Enabling Innovation By pairing our internal resources with strategic partners and best-in-class enabling technologies, we aim to accelerate platform development and extend the reach of Prime Editing Funding accelerates the development of Prime Editors for Cystic Fibrosis Developing Prime Edited CAR-T products leveraging PASSIGE and platform Partner at the right time to fund, advance and commercialize our wholly owned pipeline programs (e.g., liver, lung) Form strategic partnerships to access expertise and expand into therapeutic areas beyond our near-term internal focus (e.g., cell therapy, CNS) Access best-in-class enabling technologies to unlock the full potential of Prime Editing (e.g., delivery technologies)
41CGD = Chronic granulomatous disease; AATD = Alpha-1 Antitrypsin Deficiency; IND = investigational new drug; CTA = clinical trial application Prime Medicine is Leading the Next Generation of Gene Editing Preeminent Editing Technology Permanently corrects genetic alterations, without causing double-strand breaks or bystander edits Potential to address approximately 90% of genetic diseases and opportunities in non -genetic diseases Prime Medicine’s comprehensive IP portfolio covers any permutation of Prime Editing Platform Modularity Oriented for Growth Fully integrated modular platform powers every program and drives leverage Proprietary modular delivery systems accelerate follow-on programs within target tissues New regulatory models pave way for platform-based approvals Pipeline Positioned for Value Creation Wilson disease clinical trial underway; AATD IND cleared; initial clinical data from both anticipated in 2027 Focused on programs in large genetic diseases, with clear path to value and multi billion -dollar opportunities CGD progressing towards BLA submission planned for the first half of 2027 Significant 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 Cash, cash equivalents, investments and restricted cash of $108.8M for 6/30/2026, cash runway into 2027
42| Appendix
43BP = 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 +++++
44*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: