Glycogen Storage Disease Type I

iStock, PhonlamaiPhoto Beam Therapeutics and Verve Therapeutics have each built their lead candidates on a technique billed as a safer alternative to conventional CRISPR. Clinical results have so far been promising. Nine years ago this month, researchers led by Harvard University’s David Liu reported on a new gene editing technique, a variation on CRISPR/Cas9 that they dubbed base editing. Today, preliminary but encouraging results are trickling out from clinical trials on the first base editing therapies. Just last month, Beam Therapeutics announced that its candidate BEAM-302 can correct the disease-causing mutation in patients with alpha-1 antitrypsin deficiency. Weeks later, Verve Therapeutics released initial results from a Phase Ib trial showing that its VERVE-102 gene therapy reduced LDL cholesterol levels by half, on average, in four participants who received the highest dose. “I think the prospects and outlook [for base editing] look very positive right now,” Sami Corwin, an analyst at William Blair, told BioSpace . “We’ve seen it de-risked in three indications so far”—AATD, familial hypercholesterolemia and sickle cell disease (SCD). Beam owns the intellectual property behind base editing and, so far, has only licensed it to Verve, Beam President Giuseppe Ciaramella told BioSpace . But that may change: “Once you show success, I’m sure there are going to be some other companies that are going to be trying to use base editing to essentially do their own product,” he said. Base Editing Basics With CRISPR/Cas9 gene editing, researchers construct a guide RNA (gRNA) complementary to a targeted stretch of DNA. The gRNA is tethered to a Cas9 enzyme that snips a double-stranded break at the target, which is then repaired by the cell’s own machinery. It’s a process that carries risks, including that off-target breaks could be created and that breaks may not be properly repaired, creating unwanted mutations. “The problem is that [with] all of the nucleases, the only thing that they could do when they landed on the spot of DNA was making a double-stranded break, and . . . basically everything else is now left to the cell to sort out,” Ciaramella said. Double-stranded breaks “need to occur only under very controlled conditions when the cells are replicating because otherwise they can lead to all sorts of unpredictable editing outcomes.” The only CRISPR/Cas9-based therapy approved so far, Vertex and CRISPR Therapeutics’ Casgevy, relies on extracting bone marrow cells from a patient with SCD and editing them outside the body to disable a gene that suppresses production of fetal hemoglobin. The cells are then expanded and transplanted back into the patient, where they produce red blood cells with fetal hemoglobin as a stand-in for the adult hemoglobin that’s mutated in the disease. Casgevy is also approved for transfusion-dependent beta thalassemia. Base editing, like the original CRISPR/Cas9, uses a gRNA. However, it leverages a modified Cas9 that, rather than creating a double-strand break in the DNA, can chemically change an adenosine (A) base to a guanine (G) or a cytosine (C) to a thymine (T). Researchers can target either the coding DNA strand or its complementary partner for these edits, Ciaramella noted, which opens up more possibilities. “Essentially, we can achieve four edits with the two base editors that we’ve got.” Base editing is “actually much more versatile than maybe even people anticipated at the beginning,” when it was viewed mainly as a way to correct point mutations, Ciaramella added. For example, by making a change in the regulatory rather than the coding region of a gene, researchers can activate that gene. Beam: Running the Gamut After his group devised base editing, Liu and CRISPR pioneer Feng Zhang co-founded Beam specifically to develop therapeutics based on the technique. The company emerged from stealth in 2018 with $87 million in series A funding. The company has not confined itself to particular kinds of disorders or means of delivery. It has both in vivo and ex vivo programs for SCD and beta thalassemia alongside in vivo programs in alpha-1 antitrypsin deficiency (AATD) and glycogen storage disease 1a (GSD1a). Beam also has collaborations with Apellis and Pfizer, about which it’s revealed little. The candidate at the center of Beam’s March 10 announcement , BEAM-302, corrects a mutation that causes the body to produce a form of the AAT protein known as Z-AAT rather than the functional form, M-AAT. Z-AAT has deleterious effects on both the lungs and liver. BEAM-302 delivers base editing machinery to the liver, where AAT is made, via lipid nanoparticles. At sites in Australia, New Zealand, the Netherlands and the U.K., the company tested single intravenous doses of 15 mg, 30 mg and 60 mg in three-patient cohorts and found dose-dependent, durable increases in total AAT and decreases in Z-AAT, along with only minor adverse events. Total circulating AAT levels were high enough in the highest-dose group that those patients can be considered to no longer have progressive disease, Ciaramella said. He added, however, that these were only interim results and that the company is testing higher doses and considering redosing some patients. The AATD data “confirmed that the sensitivity and efficacy of the base editing technology was there,” Corwin said. Since the treatment was well-tolerated even at higher doses, the readout also suggested that an inflammatory response to another base editing candidate reported earlier by Verve was due to the lipid nanoparticle vehicle rather than the base editing machinery itself, she added. Other analysts also took note. Jefferies’ Michael Yee said in a note to investors that “safety has been a major area of focus in the context of issues from other LNP products for gene editing,” but that “BEAM safety looks clean.” He added that BEAM-302 “looks to have important benefits that differentiate from RNA editing and plasma-derived AAT therapy. . . . [W]e are seeing ‘correction’ of the disease with a one-time therapy.” With another program, Beam is seeking to set itself apart in the sickle cell disease space. Both bone marrow transplants and Casgevy treatment require patients to undergo a course of the chemotherapy drug busulfan to open up space in the marrow for the new blood-making cells that will be introduced. The treatment has side effects, including the possibility of impaired fertility. Beam’s ex vivo SCD candidate, BEAM-101, edits cells so that not only is fetal hemoglobin production switched on, but a receptor is tweaked to confer resistance to an antibody Beam devised. Rather than busulfan, patients are treated with the antibody, which starves unedited bone marrow cells of a growth factor needed to proliferate. “We can confer advantages of survival to the edited cells over unedited cells simply by changing a single amino acid in this receptor,” Ciaramella said. Beam presented positive safety and efficacy data on the first seven patients treated with BEAM-101 in a U.S.-based study at the American Society of Hematology meeting in December. Verve: A Focus on the Heart Boston-based Verve’s origin story begins with a competition entry that wasn’t selected, said CEO and co-founder Sek Kathiresan. The 2016 contest, run by the American Heart Association, promised $75 million in funding for an idea to tackle coronary heart disease. Kathiresan, then a professor at Harvard Medical School and director of Massachusetts General Hospital’s Center for Genomic Medicine, said he took inspiration from natural mutations that keep cholesterol levels low and thus protect people carrying the mutations from developing heart disease. Kathiresan wanted to develop a therapy that mimicked natural protective mutations. “The proposal was really: well, we understand what causes disease, which is cholesterol. We know a key way to stop this disease, which is to get cholesterol down and keep it down for a long time,” he told BioSpace . When the application was turned down, he forged ahead anyway, gathering the investors and initial team needed to found Verve in 2018. The company tested both base editing and traditional CRISPR/Cas9 on target genes in preclinical research, and “what ultimately led us to choose base editing was the possibility of it being a fair bit safer because it did not cut DNA in both strands, but rather just tried to make the single spelling change A to G at one spot,” he said. The editing was also precise: “we’re not really seeing any off targets elsewhere in the genome.” But for another of its programs, Verve settled on a different gene editor because it found base editing wasn’t the most effective way forward. The company now has three base editors in clinical trials, although the trial of VERVE-101 was paused last April after one patient developed grade 3 drug-induced thrombocytopenia within days of dosing. Verve, like Corwin, has since attributed those abnormalities to the lipid nanoparticle vector. Verve said at the time that it would instead prioritize VERVE-102, which like VERVE-101 treats heterozygous familial hypercholesterolemia, a genetic propensity to high cholesterol. VERVE-102 uses a different lipid nanoparticle from VERVE-101 that targets the PCSK9 gene for inactivation in liver cells. Last month, Verve announced IND clearance for VERVE-102 based on initial clinical data from outside the U.S. showing the therapy was well-tolerated. In its April 14 press release , the company reported a dose-dependent response and no serious adverse events in a Phase Ib trial, with a maximum LDL cholesterol reduction of 69% in the highest-dose cohort. Verve is now testing a still-higher dose and plans to begin a Phase II trial in the second half of this year, per its announcement. Meanwhile, VERVE-201, which targets the ANGPTL3 gene in liver cells, is in trials for the homozygous version of the condition as well as for patients whose hypercholesterolemia is not responding to other therapies. The first patient was dosed with VERVE-201 in a Phase Ib trial in Canada and the U.K. in November 2024. Getting this far has required breaking new ground in a few ways, Kathiresan said, from devising the mRNA and gRNA that would go into treatments to interfacing with the FDA. “We were actually the first to go in front of the U.S. FDA and propose in vivo gene editing in humans,” he notes, as other companies in the space have so far run their early trials in other countries, just as Verve did for VERVE-102. Gene editing and other gene therapies are usually associated with rare disease, often those with no other effective treatments. High cholesterol is both common and treatable, but Kathiresan argued gene editing could nonetheless fill an important unmet need. “Theoretically, current medicines can lower LDL at a single time point [by] 40, 50, 60%. . . . But the challenge is discontinuation. A year out after starting any cardiovascular medication, a third to 50% of people have discontinued,” he said. In contrast, with base editing, “you basically lower LDL and then keep it low for your whole life. And that can really have a dramatic impact on your risk for heart attack.” Ultimately, though, Kathiresan characterized base editing not as a silver bullet but as one tool companies can consider. “I think base editing will have a place. . . . But there will be other technologies as well that I think may be even better suited for a given target,” he said. “So I think right now the focus is really on the targets and the disease indications, and then, at least for us, finding the right gene editing tool for that target.”

Delivery of Prime Editors with a proprietary, universal liver-targeted LNP was well tolerated, with no safety concerns or detectable off-target edits observed across multiple preclinical studies On track to initiate IND-enabling activities for Wilson’s Disease program in 4Q 2024, with IND and/or CTA filing expected in 1H 2026 CAMBRIDGE, Mass., Oct. 24, 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 presented data from multiple studies showcasing the potential of its proprietary, universal lipid nanoparticle (LNP) platform to precisely deliver Prime Editors to correct disease-causing mutations in the liver. The in vivo proof-of-concept data shared at the European Society of Gene and Cell Therapy (ESGCT) 31st Annual Congress demonstrated successful correction of disease-causing mutations in Wilson’s Disease in both mouse and non-human primate (NHP) models. Additionally, the Company highlighted the ability of its universal liver-targeted LNP platform to deliver Prime Editors to correct the underlying mutational cause of Glycogen Storage Disease Type 1b (GSD1b) in humanized mice and NHPs, reinforcing the potential for its modular LNP to support future programs in rare and non-rare liver indications. “Our liver-targeted LNP platform represents a significant step forward in gene editing, providing a novel framework that can be used repeatedly to generate candidates that we believe can safely and precisely correct pathogenic mutations across a range of liver diseases,” said Jeremy Duffield, M.D., Ph.D., Chief Scientific Officer of Prime Medicine. “We believe the modularity of our LNP platform allows us to seamlessly introduce alternative guide RNAs that address different genetic targets, while the shared components of the LNP platform enable increased potency, as well as an improved safety profile and biodistribution compared to other commonly used LNPs in development. The preclinical data from our GSD1b program played a critical role in validating our universal LNP approach, and findings from this work laid the groundwork for our current efforts in Wilson’s Disease, where we believe we can efficiently advance our program into the clinic with the potential to deliver benefit to thousands of patients.” Dr. Duffield continued, “At ESGCT, we will present the first in vivo data from our Wilson’s Disease program. We are very encouraged by these interim results, which show that LNP delivery of our Prime Editors results in efficient editing, well above the threshold anticipated to be necessary to reverse disease manifestations. As we continue to optimize toward our final drug candidate, we expect to share updated data and initiate IND-enabling activities by year end. We remain confident in the potential for our universal LNP to deliver transformative treatments not only for Wilson’s Disease and GSD1b, but also for other rare and non-rare liver indications.” Prime Medicine’s universal LNP contains a GalNAc-targeting ligand (GalNAc-LNP), a validated mechanism for liver-specific delivery of gene editors. In preclinical studies, delivery of Prime Editors using a GalNAc-LNP has demonstrated increased potency and both an improved safety profile and biodistribution when benchmarked against other LNPs that have gone into the clinic. Preclinical studies in GSD1b animal models, including new data presented at ESGCT, demonstrated that delivery of GalNAc-LNP Prime Editors restored glycogen metabolism in a humanized mouse model and achieved up to 85% precise liver cell editing of the L348 mutation in NHPs at a dose that was well tolerated and durable up to 44 weeks, with an excellent safety profile, and no detectable off-target edits or unintended edits at the target site. The Company believes these findings validate Prime Medicine’s LNP platform and support its continued evaluation in other liver-related diseases, including Wilson’s Disease. Wilson’s Disease is a rare and severe disorder caused by excess copper accumulation in the liver and brain that can lead to liver failure and neurocognitive decline, and without liver transplant can be fatal. Research suggests that correcting a Wilson’s Disease mutation in 20-30% of hepatocytes could be potentially curative. To address Wilson’s Disease, Prime Medicine is advancing its GalNAc-LNP Prime Editor program that targets two prevalent mutations in the ATP7B gene – H1069Q and R778L – which combined account for up to 50% of Wilson’s Disease patients. In the data presented today, GalNAc-LNP delivery of Prime Editors targeting the H1069Q mutation in Wilson’s Disease demonstrated up to 80% precise correction of the H1069Q mutation and restoration of ATP7B mRNA to wild-type levels in a humanized mouse model, as well as precise editing of liver cells in NHPs, with up to 51% precise editing with a surrogate H1069Q Prime Editor. In preclinical studies completed to-date, Prime Medicine observed significant reductions in copper accumulation in the livers of humanized mice. In both mouse and NHP studies, no detectable off-target edits or unintended edits at the target site were observed. Prime Medicine is completing the final stages of lead optimization and expects to initiate IND-enabling activities of its Wilson’s Disease program by year-end, with an IND and/or CTA filing expected in the first half of 2026. Details of the presentations are as follows: Presentation Title: LNP delivered Prime Editors restore glycemic control in humanized rodent models of Glycogen Storage Disease Type 1b (GSD1b)Date & Time: October 24, 2024, 5:00 p.m. CEST Poster Title: Prime Editing advancements enable in vivo therapeutic correction of ATP7B p.H1069Q and p.R778L mutations in Wilson’s DiseaseDate & Time: October 24, 2024, 6:00 – 7:30 p.m. CEST About Wilson’s DiseaseWilson’s Disease is a devastating rare disease of the liver, with manifestations throughout the body, that is caused by copper accumulation. Most people are diagnosed between ages five and 35 years. With reported prevalence rates ranging between 1 in 10,000 and 1 in 30,000, Wilson’s Disease is believed to affect upwards of 35,000 to 100,000 patients in the United States and Europe. Normally, excessive copper is excreted through the liver in bile. For patients with Wilson’s Disease, copper is not eliminated correctly and accumulates to toxic levels. While the key site of pathology is the liver, and many patients present with liver disease, patients often show persistent neurological problems including involuntary movements, tremor, and gait disturbance, as well as kidney, hematological or psychiatric problems. Wilson’s Disease is caused by mutations, including H1069Q and R778L, in both genomic copies of the ATP7B gene, which encodes a copper transporter that removes excess copper. Prime Medicine is advancing a liver-directed Prime Editor program that aims to correct mutations in ATP7B to restore copper metabolism. 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 our 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. © 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. 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 timing, progress, and results of its Wilson’s Disease program, including the timing of the release of updated data, IND-enabling activities, and the opening of an IND and/or CTA application; the potential for its modular universal LNP platform to precisely deliver Prime Editors, correct disease-causing mutations in the liver, and deliver transformative treatments for Wilson’s Disease, GSD1b, and other rare and non-rare liver indications; the modular universal LNP platform’s ability to be used repeatedly to generate candidates that offer an improved safety profile and biodistribution compared to other LNPs in development; the potential for the treatment of Wilson’s Disease with Prime Editors to result in efficient editing well above the threshold anticipated to be necessary to reverse disease manifestations; the safety profile, tolerability, and durability of its universal LNP; the initiation, timing, progress, and results of its research and development programs, preclinical studies and future clinical trials; 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 potential of Prime Editors to reproducibly correct disease-causing genetic mutations across different tissues, organs and cell types; 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: 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; and the effect of unfavorable macroeconomic conditions or market volatility resulting from 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 and Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, 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 ContactHannah DeresiewiczPrecision AQ212-362-1200hannah.deresiewicz@precisionaq.com Media ContactDan Budwick, 1ABdan@1ABmedia.com

-- On-track to initiate IND-enabling activities for Wilson’s Disease program in 4Q 2024, with IND or CTA filing expected in 1H 2026 -- CAMBRIDGE, Mass., Oct. 15, 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 announced the Company will highlight advances from across its Prime Editing pipeline and platform at the upcoming European Society of Gene and Cell Therapy (ESGCT) 31st Annual Congress, being held October 22-25, 2024 in Rome, and the American Association for the Study of Liver Diseases (AASLD), being held November 15-19, 2024 in San Diego. “At the ESGCT and AASLD meetings, we will present new preclinical data from across our pipeline, including from our efforts in liver disease,” said Jeremy Duffield, M.D., Ph.D., Chief Scientific Officer of Prime Medicine. “We are particularly excited to share in vivo data from our Wilson’s Disease program, as well as from our universal liver-directed lipid nanoparticle (LNP) platform. Together, these data reinforce our strategy of prioritizing Wilson’s Disease – a large, genetically defined condition for which there are no currently approved disease-modifying treatments, and which we believe is uniquely suited to a Prime Editing-based approach – and reinforce the potential for our modular universal LNP to be used broadly across current and future programs. We look forward to advancing our Wilson’s Disease program into IND-enabling studies later this year and, longer term, to potentially leveraging the modularity of our platform to expand into numerous follow-on indications.” Details of the presentations are as follows: European Society of Gene and Cell Therapy 31st Annual Congress (ESGCT); October 22-25, 2024 in Rome Presentation Title: LNP delivered Prime Editors restore glycemic control in humanized rodent models of Glycogen Storage Disease Type 1b (GSD1b)Date & Time: October 24, 2024, 2:00 p.m. CEST Poster Title: Development of PM359, a Prime Edited CD34+ cell drug product for the treatment of p47phox Chronic Granulomatous DiseaseDate & Time: October 24, 2024, 2:00 – 2:30 p.m. CEST Poster Title: An all-Prime Editing one-step approach for non-viral generation of a multiplex-edited allogeneic CAR-T cell productDate & Time: October 24, 2024, 2:00 – 2:30 p.m. CEST Poster Title: Methods for genome-wide detection of single strand breaks induced by gene editors reveals the specificity of SpCas9 nuclease domains and provides comprehensive lists of potential off-targets for Prime EditorsDate & Time: October 24, 2024, 2:00 – 2:30 p.m. CEST Poster Title: Exploring the roles of DNA repair processes across diverse Prime Editing strategies with pooled screens and Knock-Knock PrimeDate & Time: October 24, 2024, 6:00 – 7:30 p.m. CEST Poster Title: Prime Editing advancements enable in vivo therapeutic correction of ATP7B p.H1069Q and p.R778L mutations in Wilson’s DiseaseDate & Time: October 24, 2024, 6:00 – 7:30 p.m. CEST Poster Title: Prime Editors precisely correct pathogenic mutations in RHO and USH2A associated Retinitis Pigmentosa and prevent retinal degenerationDate & Time: October 24, 2024, 6:00 – 7:30 p.m. CEST American Association for the Study of Liver Diseases (AASLD); November 15-19, 2024 in San Diego Presentation Title: LNP delivered Prime Editors restore glycemic control in humanized rodent models of Glycogen Storage Disease Type 1b (GSD1b)Date & Time: Sunday, November 17, 2024, 5:00 – 6:30 p.m. PT Presentation Title: Advances in Prime Editing enable in vivo therapeutic correction of the ATP7B p.H1069Q and p.R778L mutations causing Wilson’s DiseaseDate & Time: Monday, November 18, 2024, 8:00 – 9:30 a.m. PT 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 our 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. © 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. 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 timing, progress, and results of its Wilson’s Disease program, including the timing of IND-enabling activities and opening an IND and/or CTA application; the initiation, timing, progress, and results of its research and development programs, preclinical studies and future clinical trials; the modularity of the Prime Editing platform and the benefits thereof; the potential for its modular universal LNP to be used broadly across current and future programs; 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 potential of Prime Editors to reproducibly correct disease-causing genetic mutations across different tissues, organs and cell types; 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: 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; and the effect of unfavorable macroeconomic conditions or market volatility resulting from 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 and Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, 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 ContactHannah DeresiewiczPrecision AQ212-362-1200hannah.deresiewicz@precisionaq.com Media ContactDan Budwick, 1ABdan@1ABmedia.com