Summary of Prime Medicine Conference Call Company Overview - **Company**: Prime Medicine (NasdaqGM:PRME) - **Event**: Citi's Life Sciences Conference - **Date**: March 11, 2026 Key Highlights and Core Points Clinical Programs - Prime Medicine is on the verge of entering the clinic with its first two in vivo programs targeting Wilson's disease and alpha-1 antitrypsin deficiency (AATD), with clinical data expected in 2027 [4][6] - The company has existing clinical data from an ex vivo program in chronic granulomatous disease [4][6] Regulatory Strategy - The company plans to submit a Biologics License Application (BLA) for its chronic granulomatous disease program, with a focus on enrolling one more pediatric patient [10][11] - The estimated cost for the BLA submission has significantly decreased from $50 million-$100 million to a much smaller fraction due to FDA flexibility in requirements [13] Unmet Medical Needs - There is a significant unmet need in Wilson's disease, with 20-30% of patients still progressing despite adherence to standard care [18][19] - Prime Medicine's approach aims to provide a more effective treatment option compared to existing therapies, which do not cure the disease [23][24] Competitive Landscape - In the AATD space, Prime Medicine's gene editing technology is positioned as the only modality that can restore the wild-type protein by fixing the mutation at the DNA level [52][53] - The company acknowledges competition but emphasizes the unique benefits of its Prime Editing approach over other gene therapies [51][52] Patient Population and Market Potential - The initial target mutation for Wilson's disease (H1069Q) affects approximately 30%-50% of the Caucasian population, with plans to address additional mutations globally [45][46] - The company aims to treat a significant portion of the global patient population, with a focus on early intervention to prevent disease onset [46][47] Safety and Delivery - Prime Medicine's lipid nanoparticle (LNP) delivery system has shown a wider therapeutic index in preclinical studies, indicating a favorable safety profile [58][59] - The technology is designed to minimize off-target effects, which is a common concern in CRISPR therapies [59] Additional Important Insights - The company is optimistic about the potential for its therapies to significantly improve patient outcomes, although it remains cautious about using the term "cure" due to the complexity of the diseases involved [42][43] - The regulatory pathway is still evolving, and Prime Medicine aims to be a trailblazer in the gene editing space, potentially leading to expedited approvals based on strong clinical data [44] This summary encapsulates the critical points discussed during the conference call, highlighting Prime Medicine's strategic direction, clinical programs, and the broader implications for the gene editing landscape.

Financial Performance - Prime Medicine Inc. reported a net loss of $201.1 million for the year 2025, with R&D expenses at $160.6 million, indicating a stable investment in research despite financial losses [1] - The company ended the year with $191.4 million in cash, cash equivalents, and investments, providing a financial runway into 2027 [1] Strategic Focus - The company is shifting its focus toward its in vivo liver franchise, specifically targeting Wilson Disease and Alpha-1 Antitrypsin Deficiency [2] - Prime Medicine plans to submit an IND or CTA for the Wilson Disease program in the first half of 2026, followed by a mid-2026 submission for the Alpha-1 Antitrypsin Deficiency program [2] Clinical Developments - Prime Medicine is actively engaging with the FDA to pursue an accelerated approval pathway for its CGD candidate, PM359, which has shown positive Phase 1/2 data [3] - The company intends to submit a BLA for PM359 once final alignment with the FDA is achieved, potentially making it the first Prime Edited therapy available to patients [3] Partnerships and Support - The company is progressing its Cystic Fibrosis program with support from the Cystic Fibrosis Foundation and continues its CAR-T partnership with Bristol Myers Squibb [2]

Company Overview - The company is experiencing a significant year with excitement surrounding the progress made in the previous year [1] - The company is preparing to launch its first two in vivo liver-directed programs, targeting Wilson disease and alpha-1 antitrypsin deficiency [1] - Regulatory submissions (IND/CTAs) for Wilson disease are expected in the first half of the year, while submissions for alpha-1 antitrypsin deficiency are anticipated in the middle of the year [1]

Summary of Prime Medicine FY Conference Call Company Overview - **Company**: Prime Medicine (NasdaqGM:PRME) - **Key Focus**: Gene editing therapies, particularly for rare diseases such as Wilson disease, alpha-1 antitrypsin deficiency (AATD), and cystic fibrosis [2][34] Core Points and Arguments Progress and Pipeline - **Clinical Programs**: - Two in vivo liver-directed programs targeting Wilson disease and alpha-1 antitrypsin deficiency are set to enter the clinic in 2026 [2][3] - Cystic fibrosis program is progressing with funding from the Cystic Fibrosis Foundation, aiming for preclinical proof of concept data this year [3] - A Biologics License Application (BLA) for the Chronic Granulomatous Disease (CGD) program is planned [3][10] Wilson Disease - **Unmet Need**: High unmet need due to impaired copper metabolism leading to severe liver and neuropsychiatric issues. Current treatments are burdensome and often lead to non-compliance [13][15] - **Therapeutic Approach**: Prime Editing aims to provide a transformative therapy that could prevent symptoms and improve patient outcomes [15][21] - **Regulatory Path**: The company is considering accelerated approval based on strong clinical data and novel endpoints such as copper PET imaging [23][24] Alpha-1 Antitrypsin Deficiency (AATD) - **Market Landscape**: The space is competitive, but no new therapies have been approved recently. Current standard of care is questioned for its efficacy [28] - **Prime Editing Advantage**: The technology aims to restore normal protein levels, potentially positioning it as a best-in-class therapy [28] Cystic Fibrosis - **Target Population**: 10%-15% of cystic fibrosis patients cannot use standard therapies. Prime Editing aims to address this gap by restoring normal CFTR protein levels [34] - **Delivery Mechanism**: The therapy will utilize endogenous control to ensure appropriate protein expression [34] Financial and Operational Insights - **Cash Runway**: The company has sufficient cash to fund operations into 2027, with additional funding opportunities from milestones and potential approvals [46][47] - **Partnerships**: Collaboration with BMS for CAR T therapies is strategic, allowing Prime Medicine to leverage BMS's expertise in oncology [38][41] Additional Important Content - **Regulatory Considerations**: The company is actively engaging with the FDA to clarify the path for CGD and other programs, with a focus on minimizing costs and maximizing the potential for approval [5][9][10] - **Patient-Centric Approach**: Emphasis on understanding patient needs and experiences to guide therapy development and regulatory discussions [13][15] - **Intellectual Property**: Strong patent estate is seen as a competitive advantage in the gene editing space, particularly against other companies like Beam [28][29] This summary encapsulates the key points discussed during the Prime Medicine FY Conference Call, highlighting the company's strategic direction, pipeline developments, and market positioning.

Core Viewpoint - Prime Medicine, Inc. reported a quarterly loss of $0.22 per share, which was better than the Zacks Consensus Estimate of a loss of $0.25, indicating an earnings surprise of +13.39% [1] Financial Performance - The company posted revenues of $0.84 million for the quarter ended December 2025, missing the Zacks Consensus Estimate by 63.64%, and a decline from year-ago revenues of $2.18 million [2] - Over the last four quarters, Prime Medicine has surpassed consensus EPS estimates only once [2] Stock Performance - Prime Medicine shares have increased by approximately 34.3% since the beginning of the year, significantly outperforming the S&P 500's gain of 0.5% [3] Future Outlook - The company's earnings outlook will be crucial for investors, including current consensus earnings expectations for upcoming quarters and any recent changes to these expectations [4] - The current consensus EPS estimate for the coming quarter is -$0.25 on revenues of $1.77 million, and for the current fiscal year, it is -$0.96 on revenues of $5.31 million [7] Industry Context - The Medical - Biomedical and Genetics industry, to which Prime Medicine belongs, is currently ranked in the bottom 45% of over 250 Zacks industries, which may negatively impact stock performance [8]

Financial Performance - The net loss for the years ended December 31, 2025, and 2024, was $201.1 million and $195.9 million, respectively, with an accumulated deficit of $888.4 million as of December 31, 2025[223]. - As of December 31, 2025, the company had cash, cash equivalents, and investments totaling $177.7 million, excluding restricted cash, which is projected to fund operations into 2027[232]. - The company expects to incur significant expenses and increasing operating losses for the foreseeable future due to ongoing research and development activities[223]. - The company has not generated any revenue from product sales and does not anticipate doing so for many years, if ever[237]. - The company has incurred significant costs associated with operating as a public company, which will continue to increase as it seeks to commercialize product candidates[231]. - The company may need to relinquish rights to its technologies or product candidates if it raises additional capital through equity or collaboration agreements[233]. - The company has incurred losses since inception and may never achieve profitability, with net operating loss carryforwards potentially limited due to ownership changes[239]. Capital and Funding - The company plans to finance its operations through public and private equity offerings, debt financings, and collaborations, but there is no assurance of raising additional capital on acceptable terms[233]. - The company faces substantial doubt regarding its ability to continue as a going concern due to insufficient cash to fund operations beyond one year from the filing date[226]. Research and Development - The company has prioritized research programs in hematology, immunology, and oncology, which may lead to delays in pursuing other potentially viable product candidates[228]. - The company is focused on developing therapies utilizing gene editing technology, which has not been extensively clinically validated[249]. - The company is early in its development efforts and expects it will take many years before any product candidate is commercialized, if at all[263]. - The company has commenced a Phase 1/2 clinical trial for PM359 in 2024, but this program was deprioritized in May 2025[264]. - The company has not achieved preclinical proof of concept for many of its programs, and its proposed in-vivo delivery methods have never been evaluated in human clinical trials[264]. Regulatory and Compliance Challenges - The regulatory landscape for gene editing technologies is evolving, with uncertainties regarding the approval process for product candidates[254]. - The FDA and EMA may revise requirements for gene therapy products based on adverse developments in the industry, which could harm the company's business[257]. - The regulatory approval process for novel product candidates can be more expensive and time-consuming compared to established products, potentially delaying commercialization[258]. - The company must ensure compliance with regulatory requirements in its clinical trials, and failure to do so could result in fines and delays in product approval[341]. Market and Competitive Landscape - Adverse macroeconomic conditions, including high inflation and geopolitical developments, could materially affect the company's business operations and financial condition[240]. - A prolonged economic downturn could weaken demand for the company's product candidates and hinder its ability to raise capital on acceptable terms[244]. - The company faces significant competition in the rapidly changing gene editing field, with major pharmaceutical and biotechnology companies potentially achieving regulatory approval before it does[294]. - The potential market for the company's product candidates may be smaller than anticipated, affecting revenue projections and overall business viability[304]. Intellectual Property Risks - The company relies heavily on patent protection for its Prime Editing technology and product candidates, facing challenges in obtaining and maintaining such protections[358]. - The company may not be able to obtain sufficient patent protection for its product candidates, which could allow competitors to develop similar products and adversely affect its commercialization efforts[357]. - The company is co-owner of certain patent rights with Broad Institute and other institutions, which may limit its ability to enforce these rights independently[368]. - The company may face claims of infringement from licensors, which could adversely affect its competitive position and financial condition[374]. - The evolving intellectual property landscape in gene editing may lead to uncertainties and potential litigation that could impact the company's product development efforts[395]. Clinical Trial Challenges - Patient enrollment in clinical trials may be challenging due to the limited number of patients with targeted diseases, which could delay regulatory approvals[272]. - Enrollment delays in clinical trials may result in increased development costs, adversely affecting the company's financial condition and prospects[275]. - Clinical trials are costly and time-consuming, with potential delays impacting the development and commercialization of product candidates[322][326]. - The company may need to conduct additional clinical trials if initial results are not satisfactory, leading to increased costs and potential delays[325][326]. Collaboration and Partnerships - The company has entered into a collaboration and license agreement with Beam, granting certain exclusive rights in Prime Editing technology, while retaining the majority of rights for other applications[276]. - The company may face challenges in maintaining control over collaborations, which could affect the development and commercialization of its product candidates[332][333]. - Collaborations with third parties for research and development may not yield successful outcomes, impacting the company's ability to capitalize on market potential[331][334]. Manufacturing and Supply Chain Risks - The company has limited internal manufacturing capabilities and relies on third-party manufacturers, which increases the risk of supply shortages or delays in product development[345]. - Manufacturing complexities associated with gene editing therapies may lead to delays in development programs and regulatory approvals[315]. - The company expects to continue relying on third parties for the storage and distribution of drug supplies, which could delay clinical development if those distributors fail to perform[344]. Ethical and Public Perception Issues - Public perception and ethical concerns regarding gene editing may influence participation in clinical trials and acceptance of new therapies[252]. - Adverse public perception of gene editing technologies could negatively impact regulatory approval and demand for the company's products[301]. - The company is developing product candidates in areas of unmet medical need, which may attract social media campaigns that could harm its reputation[327][328].

Financial Performance - Prime Medicine reported total revenue of $4.632 million for the year ended December 31, 2025, compared to $2.983 million in 2024, representing a 55.2% increase[21]. - The net loss for 2025 was $201.1 million, compared to a net loss of $195.9 million in 2024, reflecting a 2.3% increase in losses[11]. - As of December 31, 2025, Prime Medicine had cash, cash equivalents, investments, and restricted cash totaling $191.4 million, down from $204.5 million in 2024[11]. Research and Development - Research and development (R&D) expenses increased to $160.6 million in 2025 from $155.3 million in 2024, driven primarily by license and intellectual property costs[11]. - The company anticipates generating preclinical proof of concept data for its Cystic Fibrosis program in 2026, supported by the Cystic Fibrosis Foundation[5]. Administrative Expenses - General and administrative (G&A) expenses rose to $52.3 million in 2025, up from $50.2 million in 2024, attributed to higher professional and consultant fees[11]. Regulatory and Clinical Developments - Prime Medicine plans to submit an investigational new drug (IND) application for its Wilson Disease program in the first half of 2026 and for its Alpha-1 Antitrypsin Deficiency program in mid-2026[3]. - Initial clinical data for both the Wilson Disease and Alpha-1 Antitrypsin Deficiency programs is expected in 2027[3]. - The company is actively engaging with the FDA regarding PM359 for Chronic Granulomatous Disease (CGD) and plans to submit a Biologics License Application (BLA) following final alignment[11]. - Prime Medicine's Phase 1/2 study of PM359 showed rapid neutrophil and platelet engraftment, with durable restoration of NADPH oxidase activity and early clinical benefits[11].

Core Insights - Prime Medicine is advancing its gene editing technology, Prime Editing, to develop one-time curative genetic therapies, with a focus on addressing significant genetic disorders such as Wilson Disease and Alpha-1 Antitrypsin Deficiency [2][3] Financial Overview - For the year ended December 31, 2025, Prime Medicine reported a net loss of $201.1 million, compared to a net loss of $195.9 million in 2024 [14] - Research and development (R&D) expenses increased to $160.6 million in 2025 from $155.3 million in 2024, primarily due to license and intellectual property costs [14] - As of December 31, 2025, the company had cash, cash equivalents, investments, and restricted cash totaling $191 million, providing a cash runway into 2027 [1][9] Pipeline and Regulatory Milestones - Prime Medicine plans to file an Investigational New Drug (IND) application for its Wilson Disease program in the first half of 2026 and for its Alpha-1 Antitrypsin Deficiency program in mid-2026, with initial clinical data expected in 2027 [1][3] - The company is actively engaging with the FDA regarding PM359 for Chronic Granulomatous Disease (CGD) and intends to submit a Biologics License Application (BLA) following final alignment [1][6] Research and Development Focus - The company is focused on advancing its in vivo gene editing programs, particularly for Wilson Disease and Alpha-1 Antitrypsin Deficiency, while also progressing a Cystic Fibrosis program with support from the Cystic Fibrosis Foundation [5][11] - Prime Medicine has reported breakthrough data for PM359, which supports the potential for accelerated approval in the U.S. [2][4] Collaboration and Strategic Vision - Prime Medicine aims to expand its Prime Editing platform through collaborations, including ongoing partnerships with Bristol Myers Squibb for CAR-T products [5][11] - The company envisions delivering transformative therapies that provide durable and potentially lasting cures, leveraging its comprehensive intellectual property estate [2]

2 Delivering on the promise of Prime Editing Corporate Presentation March 2026 1 Forward Looking Statements This presentation contains forward-looking statements of Prime Medicine, Inc. ("Prime", "we" or "our") within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. These forward-looking statements contain information about our current and future prospects and our operations, which are based on currently available information. All statements other than statements of historica ...

Core Insights - Jacob Funds released its fourth-quarter 2025 investor letter, noting a slight correction in equity markets in November despite robust economic growth throughout the year [1] - Divergent data on consumer spending and the labor market has raised doubts about future economic projections, a trend that has become common in recent years [1] - The Fund's strategy indicates that moderation in AI tech companies may benefit small companies, potentially leading to expansion in valuation multiples and favorable performance compared to peers [1] Company Focus: Prime Medicine, Inc. - Prime Medicine, Inc. (NASDAQ:PRME) is highlighted as a biotechnology company specializing in gene editing technology, with a market capitalization of $597.49 million [2] - As of February 17, 2026, Prime Medicine's stock closed at $3.31 per share, with a one-month return of -17.46% and a 12-month increase of 0.76% [2] - Jacob Funds added Prime Medicine to its portfolio, expressing confidence in its gene editing technology and the potential for significant upside if the technology proves viable [3] - The company acknowledges challenges in the gene therapy field, including safety, durability, and cost, but remains optimistic about the potential for effective cures for chronic and deadly diseases [3] - Promising efficacy and safety signals were observed in Prime Medicine's first clinical trial, indicating early positive developments in its gene editing capabilities [3]