PRME 8-K
Prime Medicine, Inc. (PRME)
8-K
2026-03-03
For: 2026-03-03
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April 07, 2026
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM 8-K
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CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
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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 Rule12b-2 of the Securities Exchange Act of 1934 (§250.12b-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 March 3, 2026, Prime Medicine, Inc. (the “Company”) issued a press release announcing its financial results and business highlights for the year ended December 31, 2025. A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information contained in Item 2.02 of this Current Report on Form 8-K, including Exhibit 99.1 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (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 (the “Securities Act”) or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 7.01 Regulation FD Disclosure.
On March 3, 2026, the Company posted an updated corporate presentation to its website at https://investors.primemedicine.com/news-events. A copy of the corporate presentation is furnished as Exhibit 99.2 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.
The information in this Item 7.01, including Exhibit 99.2 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of 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 or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
Exhibit Number | Description | |||||||
99.1 | ||||||||
99.2 | ||||||||
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: March 3, 2026
By: | /s/ Allan Reine | ||||
Name: | Allan Reine, M.D. | ||||
Title: | Chief Executive Officer | ||||
Exhibit 99.1
Prime Medicine Reports Full Year 2025 Financial Results and Provides Business Updates
-- On track to file IND and/or CTA for Wilson Disease and AATD programs in 1H 2026 and mid-2026, respectively; initial clinical data for both expected in 2027 --
-- Ongoing engagement with FDA for PM359 in CGD; plan to submit BLA following final alignment --
-- Prime Medicine reported cash, cash equivalents, investments, and restricted cash of $191M providing cash runway into 2027 --
Cambridge, Mass., March 3, 2026 – Prime Medicine, Inc. (Nasdaq: PRME), a biotechnology company committed to delivering a new class of differentiated one-time curative genetic therapies, today reported financial results for the full year ended December 31, 2025 and provided a business update.
“We are shaping the future of genetic medicine by advancing a platform that is rapidly emerging as the predominant gene editing technology. With Prime Editing, we have the opportunity to permanently and safely correct disease-causing mutations across a broad range of indications, supported by our comprehensive IP estate,” said Allan Reine, M.D., Chief Executive Officer of Prime Medicine. “With this foundation, our vision is bold and unwavering: to strategically deliver on the promise of Prime Editing and ensure patients have access to transformative therapies capable of delivering durable, and potentially lasting cures. This begins with PM359, our ex vivo Prime Edited autologous HSC product for CGD, for which we announced breakthrough data in 2025, which we believe supports an accelerated approval in the United States.”
Dr. Reine continued, “We are also intensely focused on R&D execution. We are progressing toward key regulatory milestones for our two liver‑focused programs – in Wilson Disease and Alpha-1 Anti-trypsin Deficiency – including planned IND and CTA submissions and the initiation of Phase 1/2 clinical trials. In parallel, we continue to generate compelling preclinical data across our portfolio, including for our program for Cystic Fibrosis; to further optimize our modular delivery and manufacturing approaches; and to explore additional collaborations that could expand the reach of our platform. These near‑ and mid‑term milestones position us to deliver important additional clinical validation of Prime Editing, as we accelerate our path toward bringing meaningful, life‑changing therapies to patients.”
Prime Medicine’s Pipeline:
Prime Medicine is advancing in vivo gene editing programs aimed at treating two of the most significant genetic liver disorders: Wilson Disease (WD) and Alpha‑1 Antitrypsin Deficiency (AATD). Prime Medicine anticipates submitting an investigational new drug (IND) and/or clinical trial application (CTA) for its anchor WD program (targeting the H1069Q mutation) in the first half of 2026, and plans to leverage the modularity of the Prime Editing platform to subsequently advance follow-on programs targeting other mutations, which collectively address a majority of WD patients. Prime Medicine expects to file an IND and/or CTA for its AATD program in mid-2026, and to report initial clinical data from both WD and AATD programs in 2027.
Following positive proof-of-concept data from the first two patients treated in its Phase 1/2 study of PM359 for the treatment of Chronic Granulomatous Disease (CGD), Prime Medicine is actively working to ensure this transformative therapy is available for patients in need.
Prime Medicine is also progressing an in vivo Cystic Fibrosis (CF) program with support from the Cystic Fibrosis Foundation, and anticipates generating preclinical proof of concept data in 2026. Additionally, its efforts to develop Prime Edited CAR-T products for hematology, immunology and oncology continue in partnership with Bristol Myers Squibb.
Recent Business Updates:
•Prime Medicine continues to engage with the U.S. Food and Drug Administration (FDA) to explore ways to make PM359 available to patients with CGD. Based on recent interactions, Prime Medicine believes clinical data generated to-date may be sufficient to support an accelerated approval of PM359. The Company is working towards final alignment with the FDA, and intends to submit a Biologics License Application (BLA).
•In December 2025, Prime Medicine announced the publication of Phase 1/2 clinical data with PM359 in the New England Journal of Medicine (NEJM). The data, which were also presented in a poster session at the 67th American Society of Hematology (ASH) Annual Meeting, showed rapid neutrophil and platelet engraftment, as well as durable restoration of NADPH oxidase activity and early clinical benefit, without any safety concerns.
Full Year 2025 Financial Results
•Research and Development (R&D) Expenses: R&D expenses were $160.6 million for the year ended December 31, 2025, as compared to $155.3 million for the year ended December 31, 2024. The increase in R&D expenses is driven primarily by license and intellectual property costs and facility related expenses, offset by Prime Medicine’s strategic focus on advancing its in vivo liver franchise, deprioritization of its CGD program, and a reduction in R&D personnel resulting from the workforce reduction.
•General and Administrative (G&A) Expenses: G&A expenses were $52.3 million for the year ended December 31, 2025, as compared to $50.2 million for the year ended December 31, 2024. The increase in G&A expenses was driven by increases in professional and consultant fees.
•Net Loss: Net loss was $201.1 million for the year ended December 31, 2025, as compared to $195.9 million for the year ended December 31, 2024.
•Cash Position: As of December 31, 2025, cash, cash equivalents, investments, and restricted cash were $191.4 million, as compared to $204.5 million as of December 31, 2024.
Financial Guidance
Based on its current operating plans, Prime Medicine expects that its cash, cash equivalents and investments as of December 31, 2025 will be sufficient to fund its operating expenses and capital expenditure requirements into 2027.
About Prime Medicine
Prime Medicine is a leading biotechnology company dedicated to creating and delivering the next generation of gene editing therapies to patients. The Company is deploying its proprietary Prime Editing platform, a versatile, precise and efficient gene editing technology, to develop a new class of differentiated one-time curative genetic therapies. Designed to make only the right edit at the right position within a gene while minimizing unwanted DNA modifications, Prime Editors have the potential to repair almost all types of genetic mutations and work in many different tissues, organs and cell types. Taken together, Prime Editing’s versatile gene editing capabilities could unlock opportunities across thousands of potential indications.
Prime Medicine is currently progressing a diversified portfolio of investigational therapeutic programs organized around its core areas of focus: hematology, immunology and oncology, liver and lung. Across each core area, Prime Medicine is focused initially on a set of high value programs, each targeting a disease with well-understood biology and a clearly defined clinical development and regulatory path, and each expected to provide the foundation for expansion into additional opportunities. Over time, the Company intends to maximize Prime Editing’s broad and versatile therapeutic potential, as well as the modularity of the Prime Editing platform, to rapidly and efficiently expand beyond the diseases in its current pipeline, potentially including additional genetic diseases, immunological diseases, cancers, infectious diseases, and targeting genetic risk factors in common diseases, which collectively impact millions of people. For more information, please visit www.primemedicine.com.
From time to time Prime Medicine may use its website, our X, formerly Twitter, account (@PrimeMedicine) or its LinkedIn profile at https://www.linkedin.com/company/prime-medicine to distribute material information. Its financial and other material information is routinely posted to and accessible on the Investors section of its website, available at www.primemedicine.com. Investors are encouraged to review the Investors section of its website because the Company may post material information on that site that is not otherwise disseminated by the Company. Information that is contained in and can be accessed through the Company’s website or its social media is not incorporated into, and does not form a part of, this press release.
© 2026 Prime Medicine, Inc. All rights reserved. PRIME MEDICINE, the Prime Medicine logos, and PASSIGE are trademarks of Prime Medicine, Inc. All other trademarks referred to herein are the property of their respective owners.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Prime Medicine’s beliefs and expectations regarding: the continued development and advancement of PM359, including the significance of data from its Phase 1/2 trial of PM359; the planned regulatory interactions with the FDA based on the data from its Phase 1/2 trial of PM359 and the outcomes of any such interactions; the continued development and advancement of its CF, AATD and WD programs, including the anticipated timing of filing an IND and/or CTA application for its WD program in the first half of 2026 and for its AATD program in mid-2026, and initial clinical data for both programs in 2027; the potential of PM359 to address the unmet medical need for patients with CGD; the potential of Prime Editing to correct the causative mutations of, and to cure, diseases, including AATD, WD, CF and CGD; the potential for its modular universal LNP platform to precisely deliver Prime Editors and enable significant efficiencies in pre-clinical development, manufacturing and clinical development; the ability to demonstrate, and the timing of, preclinical proof-of-concept in vivo for multiple programs; the further advancement of Prime Editors to maximize their versatility, precision and efficiency; the collaboration with Bristol Myers Squibb and the Cystic Fibrosis Foundation and the intended and potential benefits thereof; the initiation, timing, progress, and results of its research and development programs, preclinical studies and future clinical trials, including the release of data related thereto; the modularity of the Prime Editing platform and the benefits thereof; the potential for Prime Editors to more precisely and effectively achieve genetic modification; the potential for Prime Editors to repair genetic mutations and offer curative genetic therapies for a wide spectrum of diseases; the expansion of Prime Editing’s therapeutic potential and the creation of value through strategic business development to extend the reach and impact of Prime Editing to areas beyond Prime Medicine’s current pipeline; its expectations regarding the breadth of Prime Editing technology and the implementation of its strategic plans for its business, programs, and technology; the potential of Prime Editing to unlock opportunities across thousands of potential indications; and its expected cash runway. The words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “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 in this press release 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 press release, including, without limitation, risks associated with: uncertainties related to Prime Medicine’s product candidates entering clinical trials; the authorization, initiation, and conduct of preclinical and IND-enabling studies and other development requirements for potential product candidates, including uncertainties related to opening INDs and obtaining regulatory approvals; risks related to the development and optimization of new technologies, the results of preclinical studies, or clinical studies not being predictive of future results in connection with future studies; the scope of protection Prime Medicine is able to establish and maintain for intellectual property rights covering its Prime Editing technology; Prime Medicine’s ability to identify and enter into future license agreements and collaborations; Prime Medicine’s expectations regarding the anticipated timeline of its cash runway and future financial performance; and general economic, industry and market conditions. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Prime Medicine’s most recent Annual Report on Form 10-K, as well as any subsequent filings with the Securities and Exchange Commission. In
addition, any forward-looking statements represent Prime Medicine’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Prime Medicine explicitly disclaims any obligation to update any forward-looking statements subject to any obligations under applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.
Investor and Media Contacts
Gregory Dearborn
Prime Medicine
857-209-0696
Hannah Deresiewicz
Precision AQ
212-362-1200
| Condensed Consolidated Balance Sheet Data | ||||||||||||||
| (unaudited) | ||||||||||||||
| December 31, | ||||||||||||||
| (in thousands) | 2025 | 2024 | ||||||||||||
| Cash, cash equivalents, and investments | $ | 177,680 | $ | 190,442 | ||||||||||
| Total assets | 342,733 | 297,508 | ||||||||||||
| Total liabilities | 221,865 | 144,359 | ||||||||||||
| Total stockholders’ equity | 120,868 | 153,149 | ||||||||||||
| Condensed Consolidated Statement of Operations | ||||||||||||||
| (unaudited) | ||||||||||||||
| Year Ended December 31, | ||||||||||||||
| (in thousands, except share and per share amounts) | 2025 | 2024 | ||||||||||||
| Revenue: | ||||||||||||||
| Collaboration revenue — related party | $ | 4,586 | $ | 1,609 | ||||||||||
| Collaboration revenue | 46 | 1,374 | ||||||||||||
| Total revenue | 4,632 | 2,983 | ||||||||||||
| Operating expenses: | ||||||||||||||
| Research and development | 160,636 | 155,289 | ||||||||||||
| General and administrative | 52,346 | 50,161 | ||||||||||||
| Total operating expenses | 212,982 | 205,450 | ||||||||||||
| Loss from operations | (208,350) | (202,467) | ||||||||||||
| Other income: | ||||||||||||||
| Interest income | 4,149 | 3,522 | ||||||||||||
| Accretion (amortization) of investments | 2,479 | 3,507 | ||||||||||||
| Change in fair value of short-term investment — related party | 432 | (485) | ||||||||||||
| Other income, net | 148 | 41 | ||||||||||||
| Total other income, net | 7,208 | 6,585 | ||||||||||||
| Net loss attributable to common stockholders | $ | (201,142) | $ | (195,882) | ||||||||||
| Net loss per share attributable to common stockholders, basic and diluted | $ | (1.35) | $ | (1.65) | ||||||||||
| Weighted-average common shares outstanding, basic and diluted | 148,758,527 | 118,600,381 | ||||||||||||
1 Delivering on the promise of Prime Editing Corporate Presentation March 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 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 significance of data from our Phase 1/2 trial of PM359; the regulatory interactions with the FDA based on the data from our Phase 1/2 trial of PM359 and the outcomes of any such interactions; our ability to obtain regulatory approval for 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 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 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 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
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 strong IP position covers any permutation of Prime Editing
4 Focused execution on Wilson 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 ENSURE 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 2026 2027+ WILSON DISEASE • File PM577 IND and/or CTA in 1H • Initiate Phase 1 clinical trial • Advance follow-on Prime Editors for other common mutations • Announce PM577 initial clinical data • Capitalize on platform modularity vis-a-vis additional common mutations AATD • File PM647 IND and/or CTA mid-year • Initiate Phase 1 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 • Initiate IND-enabling studies for CF • Relaunch programs targeting neurological and other large indications
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/AAV 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 ability to make edits of any size, from small base pair swaps to large, multi-kilobase insertions or inversions
8 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
91Analysis 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 SpCas 9 Prim e E dito r 0 20 40 60 Pe rc en t I nd el s (o ff- ta rg et s ite 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
10 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
11 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 7 U.S. and 14 ex-U.S. issued patents in an extensive patent estate that protects its breakthrough Prime Editing platform, delivery technologies and therapeutics
12| Liver
13 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 PM577: Wilson Disease >20,000 7,500-15,000+ US and EU Japan IND and/or CTA 1H 2026; data 2027 Initial focus on H1069Q mutation Plan to leverage key learnings, regulatory frameworks and manufacturing synergies from PM577 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 and/or CTA mid-2026; data 2027 Opportunity (Patients) Opportunity (Patients)
14 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: 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
15 Wilson Disease
16 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 • 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
17 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
18 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 PM577 LNP = lipid nanoparticle Prime Editors delivered with Prime Medicine’s universal liver LNP administered at clinically relevant doses
19 >80% hepatocytes edited Hepatic copper concentration returns to wild-type levels at eight weeks Copper excreted normally through the feces at four weeks PM577 Efficiently Corrects the H1069Q Mutation and Completely Restores Wild- Type Copper Concentration In Vivo
20*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 Clearance Treated (H1069Q Mut)Wild Type Control Untreated (H1069Q Mut)
21IND = 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 Anticipated Enrollment Criteria Primary Safety Endpoints Primary Efficacy Endpoints Adult patients maintained on standard of care (chelators, zinc salts) Safety, tolerability Biomarkers (ceruloplasmin, serum and urinary copper) Copper PET to assess restoration of ATP7B mediated copper transport 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
22IND = 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 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 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
23 Alpha-1 Antitrypsin Deficiency (AATD)
24 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
25 • 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 1A T Co nc en 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
26M-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 20 40 60 80 100 % h ep at oc yt es p re ci se ly c or re ct ed Dose Level #1 Dose Level #2 0 25 50 75 100 % H um an A AT Is of or m * Dose Level #1 Positive Control Dose Level #2 Negative Control Prime has initiated IND-enabling activities and is on track for mid’26 IND and/or CTA application(s)
27IND = investigational new drug; CTA = clinical trial application PM647 Clinical Development: On Track for Mid’26 IND and/or CTA with Proof-of- Concept Data Anticipated in 2027 Anticipated Enrollment Criteria Primary Safety Endpoints Primary Efficacy Endpoints Group A: adult patients with pulmonary only disease Group B: adult patients with liver disease with or without pulmonary disease Safety, tolerability Group A: Measurement of serum AAT levels Group B: Measurement of Z-AAT in liver Ultimate goal of the Phase 1/2 study is to demonstrate the ability of PM647 treatment to restore wild type (M- AAT) protein levels and potentially ameliorate liver disease
28| Lung
29CFTR = 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 more than 93% of all people with CF
30 Prime Medicine has Made Significant Progress Developing Prime Editors for G542X Mutated Cystic Fibrosis Efforts towards LNP and AAV 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 G542X In vitro Prime Editor in Primary HBEs Phenotypic restoration of G542X mutated CFTR in differentiated ALI culture CFTR β-actin Patient Prime Edited C band Healthy B band Unedited
31CF = 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
32| Immunology and Oncology
33 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 • >$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
34TRAC = 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
35 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 % P rim e Ed iti ng B2M TRAC Singleplex Multiplex % P rim e Ed iti ng % S in gl ep le x Pr im e Ed iti ng TRAC B2M Target 3 Target 4 Target 5 100 80 60 40 20 0 100 80 60 40 20 0
36| Corporate
37 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)
38AATD = 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 Breakthrough data in CGD provides proof-of-concept for curative potential of Prime Editing PM577 in Wilson Disease IND and/or CTA expected in H1’26; AATD IND and/or CTA expected in mid-2026 Focused on programs in large genetic diseases, with clear path to value and multi billion-dollar opportunities 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 Pro-forma cash, cash equivalents, investments and restricted cash of $191.4M for 12/31/2025, cash runway into 2027
39| Appendix
40BP = 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 +++++
41*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: