Granulomatous Disease, Chronic

-- Maturing into clinical-stage company; on-track to file IND application or CTA for PM359 in 1H 2024, with initial data expected in 2025 -- -- Progressing broader portfolio across core areas of focus; expect to initiate IND-enabling activities in first liver and ocular disease programs in 2024 -- -- Advancing hotspot and PASSIGE™ Prime Editors for CF following entry into therapeutic development agreement with Cystic Fibrosis Foundation -- -- Completed upsized $161 million public offering -- CAMBRIDGE, Mass., March 01, 2024 (GLOBE NEWSWIRE) -- 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, 2023 and provided a business update. “In 2024, we anticipate undergoing a significant transformation, maturing into a clinical-stage company and bringing the first-ever Prime Editing-based therapeutic candidate to patients. We look forward to filing our first IND or CTA in the months ahead, and to commencing our Phase 1 clinical trial in CGD, a serious, life-threatening disease that we believe is uniquely suited for treatment with a Prime Editing-based approach,” said Keith Gottesdiener, M.D., President and Chief Executive Officer of Prime Medicine. “In parallel, we continue to progress our broader pipeline, where we are advancing programs across our core areas of focus: hematology and immunology, liver, lung, ocular and neuromuscular disease. This year, we expect to advance our first liver and ocular disease programs into IND-enabling studies, while continuing to explore business development opportunities that can accelerate our existing work, enable us to pursue additional programs, and provide access to innovation that can further advance Prime Editing. Over time, we believe the modularity of the Prime Editing platform will allow us to quickly build on our current efforts, unlocking opportunities across a wide range of genetic and common diseases, which collectively impact millions of people.” Recent Business Updates Chronic Granulomatous Disease (CGD) In January 2024, Prime Medicine received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for PM359. Cystic Fibrosis (CF) In January 2024, Prime Medicine announced that the Cystic Fibrosis Foundation (CF Foundation) agreed to provide the Company with up to $15 million to support the development of Prime Editors for the treatment of CF. This funding will allow Prime Medicine to progress two distinct strategies for applying Prime Editing to treat CF: hotspot editing and PASSIGE™ (Prime Assisted Site Specific Integrase Gene Editing). Corporate In February 2024, the U.S. Patent and Trademark Office issued Prime Medicine’s fourth U.S. patent, No. 11,912,985, “Methods and Compositions for Simultaneous Editing of Both Strands of a Target Double-Stranded Nucleotide Sequence,” which covers dual flap Prime Editing systems.In February 2024, Prime Medicine closed an upsized underwritten public offering of common stock at a public offering price of $6.25 per share and, in lieu of common stock to certain investors, pre-funded warrants to purchase shares of common stock, at a public offering price of $6.24999 per pre-funded warrant. Gross proceeds to Prime Medicine from the offering, before deducting underwriting discounts and commissions and offering expenses, were approximately $161.0 million.In January 2024, Prime Medicine announced the appointment of Allan Reine, M.D., as the Company’s Chief Financial Officer. Dr. Reine, a seasoned financial executive with over twenty years’ experience in the biotechnology industry, will be responsible for the company’s financing strategy and investor relations, and will oversee all financial operations. Anticipated Upcoming Milestones Prime Medicine expects the following activities and next steps to drive Prime Medicine forward and support the company’s maturation into a clinical-stage company: Hematology and Immunology: Open investigational new drug (IND) application and/or clinical trial application (CTA) for Phase 1/2 study in CGD in the first half of 2024, with initial clinical data anticipated in 2025.Advance Shielded Hematopoietic Stem Cell (HSC) and Immunotherapy Pairs (SCIP) technology, establish proof-of-concept in HSC and immunotherapy and identify first clinical program(s) with this approach in 2024.Advance differentiated CAR-T program, using PASSIGE technology, into lead optimization. Liver: Continue to advance preclinical studies for three liver programs and initiate IND-enabling activities for at least one in 2024, leading to an IND and/or CTA in the second half of 2025 or first half of 2026. Ocular: Nominate development candidate for Retinitis Pigmentosa/Rhodopsin (RHO) and initiate IND-enabling activities in 2024. Neuromuscular: Continue to advance Friedreich’s Ataxia and advance one other program into lead optimization in 2024.In large animal studies, establish adeno-associated virus (AAV) delivery platform and route of administration for neuromuscular programs in 2024. Full Year 2023 Financial Results Research and Development (R&D) Expenses: R&D expenses were $147.9 million for the year ended December 31, 2023, as compared to $86.7 million for the year ended December 31, 2022. The increase in R&D expenses was driven by IND-enabling activities for the Company’s CGD program and expenses related to the advancement of the company’s pipeline and platform.General and Administrative (G&A) Expenses: G&A expenses were $43.4 million for the year ended December 31, 2023, as compared to $29.8 million for the year ended December 31, 2022.Net Loss: Net loss was $198.1 million for the year ended December 31, 2023, as compared to $121.8 million for the year ended December 31, 2022. Part of the increase was attributable to a one-time charge for the Company’s settlement with Myeloid Therapeutics, Inc.Cash Position: As of December 31, 2023, cash, cash equivalents, investments and restricted cash were $135.2 million, as compared to $307.4 million as of December 31, 2022. About Prime MedicinePrime 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 core areas of focus: hematology and immunology, liver, lung, ocular and neuromuscular. Across each core area, Prime Medicine’s initial focus is on genetic diseases with a fast, direct path to treating patients, and those with high unmet need not currently addressable using other gene editing approaches. Over time, the Company intends to maximize Prime Editing’s broad and versatile therapeutic potential to expand beyond the genetic diseases in its initial pipeline, potentially including 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. Forward Looking StatementsThis 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 initiation, timing, progress, and results of its research and development programs, preclinical studies and future clinical trials, and the release of data related thereto; the anticipated maturation into a clinical-stage company and bringing the first-ever Prime Editing-based therapeutic candidate to patients; progressing its broader pipeline across core areas of focus; exploring business development opportunities that could accelerate existing work and the benefits thereof; the modularity of the Prime Editing platform and the benefits thereof; certain activities and next steps to support the company’s maturation into a clinical-stage company, including opening IND and/or CTA applications, clinical data expectations, establishing proof of concept, advancing programs into lead optimization, advancing preclinical studies and initiating IND-enabling activities, nominating development candidates, and establishing delivery platform and rout of administration; its expectations regarding the breadth of Prime Editing technology and the implementation of its strategic plans for its business, programs, and technology; and the potential of Prime Editing to unlock opportunities across thousands of potential indications. 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 an IND or CTA filing and 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; and general economic, industry and market conditions, including rising interest rates, inflation, and adverse developments affecting the financial services industry. 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. © 2024 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. Investor ContactHannah DeresiewiczStern Investor Relations, Inc.212-362-1200hannah.deresiewicz@sternir.com Media ContactDan Budwick, 1ABdan@1ABmedia.com Condensed Consolidated Balance Sheet Data(unaudited) December 31,(in thousands) 2023 2022 Cash, cash equivalents, and investments$121,665 $293,921 Total assets$193,851 $360,314 Total liabilities$60,780 $44,044 Total stockholders’ equity$133,071 $316,270 Condensed Consolidated Statement of Operations(unaudited) Year Ended December 31,(in thousands, except share and per share amounts) 2023 2022 Operating expenses: Research and development$147,905 $86,725 Settlement payment — related party 13,500 — General and administrative 43,387 29,819 Total operating expenses 204,792 116,544 Loss from operations (204,792) (116,544)Other income (expense): Change in fair value of short-term investment — related party (2,382) (8,128)Other income, net 8,762 1,903 Total other income (expense), net 6,380 (6,225)Net loss before income taxes (198,412) (122,769)Benefit from income taxes 279 948 Net loss (198,133) (121,821)Cumulative dividend on preferred stock — (20,193)Net loss attributable to common stockholders$(198,133)$(142,014)Net loss per share attributable to common stockholders, basic and diluted$(2.18)$(4.19)Weighted-average common shares outstanding, basic and diluted 90,969,327 33,891,264

Before her arrival, Stefanski was an associate professor of pediatrics at the University of Minnesota and was actively involved in clinical care and research involving children with life-threatening blood and immune system disorders. One of her areas of focus was the use of cord blood units in stem cell transplants and other cellular therapy. She is board certified in both Pediatrics and Pediatric Hematology-Oncology. In the last two decades, there has been a rapid evolution in the diagnosis and treatment of primary immunodeficiencies and the recognition of immune dysregulation, could you explain a) why this is and b) what point we are at currently with the diagnosis and treatment? ​ We are more sophisticated with our molecular techniques of detecting genes in these disorders.  There are approximately 500 inborn errors of immunity causing genes and with the widely available sequencing methods this number continues to grow rapidly. Established treatment options currently consist of immune modulatory drugs, antimicrobial prophylaxis, immunoglobulin replacement therapy and, allogeneic hematopoietic stem cell transplantation (HSCT) as well as gene therapy. Could you explain what causes inborn errors of immunity? ​ Inborn errors of immunity (IEI) are caused by genetic mutations. They can be x-linked, autosomal dominant or autosomal recessive.  They can also be novel mutations that are not inherited. IEI present clinically as increased susceptibility to infections, autoimmunity, autoinflammatory diseases, allergy, bone marrow failure, and/or malignancy. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Until recently, management of treatment options were limited to prompt treatment of infections, gammaglobulin replacement and even bone marrow transplant depending on what was wrong. Could you outline the newer therapies including small molecule inhibitors, biologics, gene therapy etc? ​ In all types of gene therapy for IEI, ex vivo ​ gene therapy is used, in which a viral vector  is used to genetically modify cells from the patients with therapeutic intent. Gene editing can also be used where the DNA is repaired. Gene therapy has been used for multiple IEI including X-linked SCID, Artemis SCID, X-SCID, Wiskott-Aldrich Syndrome and Chronic Granulomatous Disease. What difference have these made to the patients? ​ These patients live longer, healthier lives and have a much better quality of life.  They are not hospitalized as frequently, they can attend school, they no longer need transfusions.  These therapies are life changing. What efforts have been made to increase awareness of IEI? ​ The advancement of genetic testing and diagnostic techniques have increased the awareness of IEI.  There are educational efforts to recruit young immunologists to the field as well as encouraging international collaborations. The development and widespread use of newborn screening have helped to identify severe combined immune deficiency (SCID) has also increased awareness.  These patients are identified immediately and have improved outcomes.  There are continual improvements and accessibility of genetic sequencing has accelerated identification of new IEI diseases. Advances and improvements in both gene therapy and hematopoietic stem cell transplant have made treatments possible in otherwise fatal diseases. Could you explain ‘newborn screening’ and the advantages or any disadvantages this may have? ​ Newborn screening identifies conditions that can affect a child’s long-term health or survival and is done within 24 hours after birth. Early detection, diagnosis, and intervention can prevent death or disability and enable children to reach their full potential.  The advantages are detecting life-threatening disorders early will impact that child’s health. Each year, new disorders, including IEI, can be detected on newborn screen.  The number of disorders detected varies by state. Where would you like to see this field in terms of development within the next decade or two? ​ A number of gene therapy trials using viral gene addition have been successful for ADA-SCID. Importantly, gene therapy approaches have become safer, more efficient and applicable to more IEI. Techniques for gene therapy continue to evolve and challenges include targeting the specific gene and minimizing the off-targets mutagenesis. The biggest obstacles remain cost and complex regulatory pieces. Where is the industry at with inborn errors of immunity? ​ We are continuing to improve gene therapy and expanding it to other IEIs.  We are making hematopoietic stem cell transplant safer for those that require transplant. The treatment for these disorders will change significantly in the next 10-20 years with more patients receiving gene therapy and additional IEIs being treated with gene therapy. We are truly on the cusp of novel therapies for these patients.

-- Presented new preclinical research across multiple programs, including proof-of-concept data from in vivo rodent and large animal studies, as well as updates on proprietary delivery systems -- -- Shared detailed safety evaluation of lead Prime Editors across multiple programs; preliminary off-target analyses did not identify off-target editing, supporting potential best-in-class safety pro -- Received U.S. FDA Rare Pediatric Drug designation for PM359 for CGD; initiated IND-enabling studies and remain on track to application in 2024 -- -- Further extended intellectual property portfolio; U.S. PTO issued Prime Medicine’s third patent, No. 11,795,452 -- CAMBRIDGE, Mass., Nov. 03, 2023 (GLOBE NEWSWIRE) -- 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 and provided business updates for the third quarter ended September 30, 2023. “In recent weeks, we announced compelling preclinical data across our pipeline, including our first in vivo demonstration of Prime Editing in non-human primates. The consistency of these data provides proof-of-concept that our technology can precisely and efficiently edit across a range of target tissues, correcting pathogenic mutations at levels that may be sufficient to reverse disease manifestations across severe genetic conditions,” said Keith Gottesdiener, M.D., President and Chief Executive Officer of Prime Medicine. “We also shared presentations detailing the power of our proprietary delivery systems, as well as new off-target analyses demonstrating the potentially best-in-class safety pro Prime Editors. Together, these encouraging results mark meaningful progress toward the clinic and support our strategy of simultaneously advancing multiple programs forward. We look forward to leveraging the modularity of our platform, as well as our many clinical, manufacturing and regulatory learnings, to inform further development of our pipeline with the goal of delivering one-time, curative therapies to transform the lives of patients with a wide spectrum of debilitating diseases.” Recent Business Updates Prime Medicine is advancing a strategic pipeline of eighteen programs. The Company is initially focused on indications with the opportunity for the fastest, most direct path to the clinic and technical success in humans, as well as indications that cannot be treated using other gene editing approaches. Chronic Granulomatous Disease (CGD) In August 2023, Prime Medicine received Rare Pediatric Drug designation (RPDD) from the U.S. Food and Drug Administration (FDA) for PM359. The FDA grants RPDD to medicines intended for the treatment of serious and life-threatening diseases that primarily affect children ages 18 years or younger and fewer than 200,000 people in the United States. Companies that receive approval for a New Drug Application or Biologics License Application for a rare pediatric disease may be eligible to receive a voucher for priority review of a subsequent marketing application for a different product. The priority review voucher may be used by the Company or sold to a third party. Glycogen Storage Disease 1b (GSD1b) In October 2023, Prime Medicine presented new in vivo data at the European Society of Gene and Cell Therapy 2023 Congress, demonstrating the ability of Prime Editors to precisely correct one of the most prevalent disease-causing mutations of GSD1b in both non-human primate (NHP) and mouse models. In these preclinical studies using single lipid nanoparticle (LNP) administration, Prime Editors showed up to 50% whole liver precise editing in NHPs (resulting in up to 83% of the key target cells, liver hepatocytes, edited), with no observed safety concerns. In addition, no detectable off-target effects were observed following a comprehensive in vitro off-target screening analysis. These data, the first evidence of Prime Editing in NHPs, provide proof-of-concept for Prime Medicine’s LNP liver-targeted delivery approach and support the further advancement of the Company’s Prime Editors for liver-targeted programs. Read the full data here. Retinitis Pigmentosa / Rhodopsin In October 2023, Prime Medicine presented new in vivo data at the International Symposium on Retinal Degeneration, demonstrating that Prime Editors can efficiently and precisely correct the predominant mutations that cause rhodopsin associated autosomal dominant retinitis pigmentosa (RHO adRP). In preclinical studies, single Prime Editors showed up to 70% precise correction in photoreceptors, as well as favorable tolerability. These data suggest that Prime Medicine’s proprietary dual adeno-associated virus platform can effectively deliver Prime Editors to the eye, with the potential to treat a range of retinal diseases. Read the full data here. Additional Pipeline and Prime Editing Platform Updates Prime Medicine presented additional preclinical data across its Prime Editing pipeline and technology at several healthcare industry conferences in October and has plans to share additional abstracts at medical meetings before year-end. Highlights of the conference presentations included: An overview of Prime Medicine’s comprehensive suite of assays to identify potential off-target events, which has been expanded to include new, unbiased genome-wide tools. These analyses continue to demonstrate minimal to no detectable off-target edits, chromosomal rearrangements or translocations. These preliminary analyses, across multiple editing programs, suggest potentially best-in-class safety; The first presentation on Prime Medicine’s universal LNP-RNA platform designed to deliver Prime Editors to correct pathogenic mutations in the liver; An update on using Prime Editors for the potential treatment of repeat expansion diseases, including an update on Fragile X syndrome; and Initial proof-of-concept data for Prime Medicine’s hotspot approach to developing Prime Editors to correct the CFTR gene in patients with Cystic Fibrosis, as well as new detail on Prime Medicine’s LNP and all-RNA delivery approaches for the lung. In December, Prime Medicine will present preclinical data showcasing the potential of the PASSIGE platform to multiplex edit CAR-T cells at the 65th American Society of Hematology (ASH) Annual Meeting, being held December 9-12, 2023, in San Diego, CA. Details of the poster presentation are as follows: Abstract Title: Multiplex Prime Editing and PASSIGE for Non-Viral Generation of an Allogeneic CAR-T Cell Product Date & Time: Monday, December 11, 6-8 PM PT Room: San Diego Convention Center, Halls G-H Session Title: Cellular Immunotherapies: Basic and Translational Presenter: Emily Pomeroy Corporate In October 2023, the U.S. Patent and Trademark Office issued Prime Medicine’s third patent, No. 11,795,452, “Methods and Compositions for Editing Nucleotide Sequences,” which covers Prime Editing systems that include a PEgRNA, Prime Editor protein, and, optionally, a recombinase. Anticipated Upcoming Milestones Year-to-date, Prime Medicine continues to make significant progress, executing against key initiatives to drive its Prime Editing platform forward. The Company initiated IND-enabling studies for PM359 in CGD, and expanded preclinical proof-of-concept data in vivo and in vitro across several programs and target tissue types. In addition, as evidenced by in vivo data shared in recent presentations, Prime Medicine continues to optimize its non-viral and viral delivery systems, and to demonstrate excellent off-target profiles for its Prime Editing programs. Prime Medicine expects the following activities and next steps to drive the Prime Editing platform forward in the coming months: Pipeline Complete first IND filing as early as 2024 with additional IND filings anticipated in 2025. Platform Expand Prime Editing using proprietary recombinase technologies for new and existing programs. Maximize Prime Editing’s broad therapeutic potential and create value through strategic business development that extends the reach and impact of Prime Editing to areas beyond Prime Medicine’s current areas of focus. Third Quarter 2023 Financial Results: R&D Expenses: Research and development (R&D) expenses were $41.0 million for the three months ended September 30, 2023, as compared to $25.0 million for the three months ended September 30, 2022. This increase was primarily due to increases in lab supplies, personnel, and facilities costs as the Company continues to expand and build out its R&D activities and function. G&A Expenses: General and administrative (G&A) expenses were $10.5 million for the three months ended September 30, 2023, as compared to $6.6 million for the three months ended September 30, 2022. This increase was primarily due to an increase in professional and consultant costs and personnel costs primarily attributable to the build-out of the Company’s G&A team to support its R&D function. Net Loss: Net loss was $50.7 million for the three months ended September 30, 2023, as compared to $29.4 million for the three months ended September 30, 2022. Cash Position: As of September 30, 2023, cash, cash equivalents, investments and restricted cash were $178.8 million, as compared to $307.4 million as of December 31, 2022. Financial Guidance Based on its current operating plans, Prime Medicine expects that its cash, cash equivalents and investments as of September 30, 2023, will be sufficient to fund its operating expenses and capital expenditure requirements through the end of 2024. 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 leveraging its proprietary Prime Editing platform, a versatile, precise and efficient gene editing technology, to develop a new class of differentiated, one-time, potentially 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. Prime Medicine is currently progressing a diversified portfolio of eighteen programs initially focused on genetic diseases with a fast, direct path to treating patients or with a high unmet need because they cannot be treated using other gene-editing approaches. Over time, the Company intends to maximize Prime Editing’s therapeutic potential and advance potentially curative therapeutic options to patients for a broad spectrum of diseases. For more information, please visit Cautionary Note Regarding 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 initiation, timing, progress, and results of its research and development programs, preclinical studies and future clinical trials, and the release of data related thereto, including its ability to expand preclinical proof-of-concept in vivo data; its ability to maintain Pediatric Drug designation for PM359 and the potential to use a priority review voucher or sell it to a third party; the timing of its regulatory filings, including its anticipated initial IND application submission for CGD as early as 2024 with additional filings anticipated in 2025; the potential of Prime Editors to reproducibly correct disease-causing genetic mutations across different tissues, organs and cell types, and the capacity of its PASSIGE technology to edit CAR-T cells for the treatment of certain cancers and immune diseases; its continued development and optimization of various non-viral and viral delivery systems; its ability to demonstrate superior off-target profiles for Prime Editing programs; its expansion of Prime Editing using proprietary recombinase and/or retrotransposon and other proprietary technologies; 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 areas of focus; 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 offer curative genetic therapies for a wide spectrum of diseases; and its estimates of expenses, capital requirements, and needs for additional financing and its expectations regarding the ability to fund its anticipated operating expenses and capital expenditure requirements through the end of 2024. 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 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; and general economic, industry and market conditions, including rising interest rates, inflation, and adverse developments affecting the financial services industry. 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. © 2023 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. Investor Contact Hannah Deresiewicz Stern Investor Relations, Inc. 212-362-1200 hannah.deresiewicz@sternir.com Media Contact Dan Budwick, 1AB dan@1ABmedia.com Condensed Consolidated Balance Sheet Data (unaudited) (in thousands) September 30, 2023 December 31, 2022 Cash, cash equivalents, and investments 165,317 293,921 Total assets 239,145 360,314 Total liabilities 45,188 44,044 Total stockholders’ equity 193,957 316,270 Condensed Consolidated Statement of Operations (unaudited) Three Months Ended September 30, (in thousands, except share and per share amounts) 2023 2022 Operating expenses: Research and development $ 40,967 $ 25,047 General and administrative 10,492 6,608 Total operating expenses 51,459 31,655 Loss from operations (51,459 ) (31,655 ) Other income (expense): Change in fair value of short-term investment — related party (1,579 ) 1,789 Other income, net 2,222 728 Total other income (expense), net 643 2,517 Net loss before income taxes (50,816 ) (29,138 ) (Provision for) benefit from income taxes 108 (212 ) Net loss $ (50,708 ) $ (29,350 ) Cumulative dividend on preferred stock — (6,362 ) Net loss attributable to common stockholders $ (50,708 ) $ (35,712 ) Net loss per share attributable to common stockholders, basic and diluted $ (0.55 ) $ (1.61 ) Weighted-average common shares outstanding, basic and diluted 91,846,835 22,226,301