BEAM

-- IND and CTA clearances in the United States and New Zealand establish a global Phase 1/2 program for PM577a in Wilson disease; study startup activities underway, with initial clinical data in 2027 -- -- Favorable arbitration resolution with Beam Therapeutics affirms Prime Medicine’s rights to PM647 in Alpha-1 Antitrypsin Deficiency; IND and/or CTA submission expected in 3Q 2026, with initial clinical data in 2027 -- -- FDA grants Regenerative Medicine Advanced Therapy designation to PM359; continued regulatory engagement with the FDA toward a BLA submission for PM359 in 1H 2027 -- -- Cash, cash equivalents, investments, and restricted cash of $108.8 million as of June 30, 2026, providing cash runway into 2027 -- CAMBRIDGE, Mass., Aug. 06, 2026 (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 quarter ended June 30, 2026 and provided a business update. "We have continued to deliver on the focused strategy we laid out last year," said Allan Reine, M.D., Chief Executive Officer of Prime Medicine. "Wilson disease is now cleared to enter the clinic in two geographies. Our rights in Alpha-1 Antitrypsin Deficiency are secure, and the program is advancing toward regulatory submission. And in CGD, where Prime Editing has already shown it can correct disease in humans, we are working toward a BLA filing, and delivering this therapy to patients in need. The opportunity ahead of us is to demonstrate that same potential effect in vivo, in two of the largest genetic diseases targeting the liver." Dr. Reine continued, “We are now entering a transformative phase of growth and value creation potential that extends well beyond this year. We expect to initiate our global Phase 1/2 study of PM577a in the second half of 2026 and to submit an IND and/or CTA for PM647 in the third quarter, with initial clinical data from both programs anticipated in 2027. Alongside our progress toward a potential BLA for PM359, these milestones have the potential to significantly expand the clinical evidence supporting Prime Editing and advance our goal of bringing the first Prime Editing therapies to patients.” Prime Medicine’s Pipeline: Prime Medicine is advancing in vivo programs to cure two of the largest genetic diseases originating in the liver, Wilson disease (WD) and Alpha-1 Antitrypsin Deficiency (AATD). Following clearance of the Company’s Investigational New Drug (IND) application in the United States and Clinical Trial Application (CTA) in New Zealand, PM577a is progressing into a global Phase 1/2 program and study startup activities are underway. Additionally, Prime Medicine expects to submit an IND and/or CTA for PM647 in AATD in the third quarter of 2026. Initial clinical data from both programs are expected in 2027. Prime Medicine is also advancing an in vivo Cystic Fibrosis (CF) program with support from the Cystic Fibrosis Foundation and Prime Edited CAR-T products for hematology, immunology and oncology in partnership with Bristol Myers Squibb. Additionally, 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), and the recent grant of Regenerative Medicine Advanced Therapy (RMAT) designation, Prime Medicine continues to engage in regulatory dialogue with the U.S. Food and Drug Administration (FDA) toward a potential Biologics License Application (BLA) filing for PM359. Recent Corporate Updates: Wilson Disease (PM577a) In June 2026, the New Zealand Medicines and Medical Devices Safety Authority (Medsafe) cleared the Company’s CTA for PM577a, the first clinical authorization for an in vivo Prime Editing therapy from Prime Medicine. In July 2026, the FDA cleared the Company’s IND application for PM577a, opening participation to patients in the United States, where the ATP7B H1069Q variant that PM577a targets is the single most common cause of WD. Together, the two clearances establish a global Phase 1/2 program. The open-label, first-in-human study will evaluate the safety, tolerability, biological activity and efficacy of ascending doses of PM577a in adults and adolescents with WD, initially enrolling adults who are clinically stable on standard-of-care therapy. Prime Medicine has initiated study startup activities, with initial clinical data anticipated in 2027. Alpha-1 Antitrypsin Deficiency (PM647) In July 2026, Prime Medicine announced a positive, binding resolution of its previously disclosed arbitration with Beam Therapeutics, Inc. relating to the parties’ 2019 Collaboration and License Agreement. The Tribunal declared that PM647 is within Prime Medicine’s “Field” as defined by the agreement, that Prime Medicine did not breach the agreement, and that Prime Medicine owes no monetary damages. PM647 leverages Prime Medicine’s universal liver lipid nanoparticle (LNP) to correct the E342K (PiZ) mutation in the SERPINA1* gene, the most prevalent disease-causing mutation in AATD. In fully humanized mouse models, treatment with PM647 achieved high levels of editing efficiency and restored the corrected protein isoform (M-AAT) into the healthy human range at clinically relevant doses. PM647 is built on the same universal liver LNP delivery approach that underpins PM577a. Prime Medicine expects to draw on its experience with PM577a as it advances PM647 toward the clinic, and to benefit from the efficiencies and learnings enabled by its modular approach. Prime Medicine expects to submit an IND and/or CTA for PM647 in the third quarter of 2026, with initial clinical data expected in 2027. Chronic Granulomatous Disease (PM359) In June 2026, the FDA granted RMAT designation to PM359 based on Phase 1/2 clinical data, including data previously published in The New England Journal of Medicine. RMAT provides the benefits of intensive FDA guidance and expedited review, including discussions on surrogate or intermediate endpoints that may support accelerated approval and eligibility for rolling and priority review of a future BLA. PM359 has now received RMAT, Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the FDA. Prime Medicine continues to engage with the FDA on the most efficient path to a BLA submission planned for the first half of 2027. Upcoming Milestones Continue study startup activities for the global Phase 1/2 clinical trial of PM577a in WD, initial clinical data in 2027. Submission of an IND and/or CTA for PM647 in AATD in the third quarter of 2026, initial clinical data in 2027. Continued regulatory engagement with the FDA toward a BLA submission for PM359 in the first half of 2027. Second Quarter 2026 Financial Results Research and Development (R&D) Expenses: R&D expenses were $33.4 million for the three months ended June 30, 2026, as compared to $41.4 million for the three months ended June 30, 2025. The decrease in R&D expenses was driven primarily by fewer R&D personnel-related costs resulting from the workforce reduction announced in May 2025, and facility cost savings realized from bringing the Company’s vivarium in-house. General and Administrative (G&A) Expenses: G&A expenses were $11.0 million for the three months ended June 30, 2026, as compared to $13.1 million for the three months ended June 30, 2025. The decrease in G&A expenses was primarily driven by a decrease in personnel costs resulting from one-time severance charges recorded in Q2 2025 and a decrease in stock compensation expense, and lower corporate legal fees. Net Loss: Net loss was $42.1 million for the three months ended June 30, 2026, as compared to $52.6 million for the three months ended June 30, 2025. Cash Position: As of June 30, 2026, cash, cash equivalents, investments, and restricted cash were $108.8 million, as compared to $191.4 million as of December 31, 2025. Financial Guidance Based on its current operating plans, Prime Medicine expects that its cash, cash equivalents and investments as of June 30, 2026 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 our core areas of focus: liver, lung, and immunology and oncology. 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, its 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 its WD, AATD and CF programs, including the anticipated timing of filing an IND and/or CTA application for PM647 in 3Q of 2026, the initiation of the global Phase 1/2 clinical trial of PM577a in the second half of 2026, and initial clinical data for PM647 and PM577a in 2027; the potential of Prime Editing to correct the causative mutations of, and to cure, diseases, including WD, AATD, CF and CGD; the ongoing regulatory engagement with the FDA based on the data from its Phase 1/2 trial of PM359 and the outcomes of such engagement, including the planned submission of a BLA filing in H1 2027; the potential benefits of RMAT designation for PM359, including discussions that may support expedited approval and eligibility for rolling and priority review of a future BLA; the effect of the resolution of the arbitration with Beam Therapeutics, Inc. on the Company’s rights to develop and commercialize PM647; the modularity of the Prime Editing platform and the benefits thereof; its expectations regarding the breadth of Prime Editing technology and the implementation of its strategic plans for its business, programs, and technology; and its expected cash runway. 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 DearbornPrime [email protected] Hannah DeresiewiczPrecision [email protected]

Updated BEAM-302 Phase 1/2 Clinical Data Selected for Late-Breaking Oral Presentation at the European Respiratory Society (ERS) Congress 2026 Dosing Complete for All Adult and Adolescent Patients in Phase 1/2 BEACON Trial of Risto-cel in Sickle Cell Disease; U.S. Biologics License Application (BLA) Submission Expected as Early as Year-End 2026 Clinical Trial Start-up Activities Underway Following U.S. FDA Clearance of Investigational New Drug (IND) Application for BEAM-304 in Phenylketonuria (PKU) Ended Second Quarter 2026 with $1.2 Billion in Cash, Cash Equivalents and Marketable Securities; Cash Runway Expected to Support Operating Plans into mid-2029 CAMBRIDGE, Mass., Aug. 04, 2026 (GLOBE NEWSWIRE) -- Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, today reported second quarter 2026 financial results and provided updates across the company’s hematology and genetic disease franchises. “The second quarter marked another period of rapid progress and disciplined execution on the clinical, regulatory and operational milestones we set for Beam,” said John Evans, chief executive officer of Beam Therapeutics. “Importantly, this progress enabled dosing of the first patient in the global pivotal cohort evaluating BEAM-302, the most advanced genetic medicine in development for AATD, which has the potential to fundamentally change the treatment paradigm for patients. In addition, we completed dosing for all adult and adolescent SCD patients in the BEACON trial of risto-cel and received FDA clearance of the IND for BEAM-304 in PKU, paving the way to the clinic for this next potentially high-value franchise. Looking ahead, we believe Beam is positioned to achieve several important milestones, including updated clinical data for BEAM-302 at the ERS Congress, rapid enrollment in the BEAM-302 pivotal cohort, first-in-human data for BEAM-301 in GSDIa, and the expected BLA submission for risto-cel. With the continued expansion and advancement of our base editing pipeline, we have the potential to deliver transformative therapies for many patients with serious genetic diseases.” Second Quarter 2026 and Recent Progress and Anticipated Milestones Liver-targeted Genetic Disease Franchise BEAM-302: Beam’s lead genetic disease program is designed to be a best-in-class and first-in-class liver-targeting therapy for alpha-1 antitrypsin deficiency (AATD) that directly corrects the root cause of the disease and therefore has the potential to address both liver and lung manifestations of AATD. In July, Beam dosed the first patient in the global pivotal cohort of the ongoing Phase 1/2 trial evaluating BEAM-302 in patients with AATD-associated lung disease, with or without liver disease. The cohort is designed to support a potential accelerated approval path in the United States. Detailed and updated clinical data for BEAM-302 were selected for a late-breaking oral presentation at the European Respiratory Society (ERS) Congress, taking place September 5-9, 2026, in Barcelona, Spain. BEAM-304: BEAM-304 is designed to leverage Beam’s proprietary and clinically validated base editing technology and lipid nanoparticle (LNP) delivery capabilities to directly and durably correct mutations in the phenylalanine hydroxylase (PAH) gene that cause phenylketonuria (PKU). Beam aims to advance BEAM-304 using an innovative platform approach with the goal of creating mutation-specific base editors for the majority of patients with PKU. In June, Beam announced that the U.S. Food and Drug Administration (FDA) cleared the investigational new drug (IND) application for BEAM-304. Beam has initiated clinical start-up activities for the planned Phase 1/2 trial for BEAM-304. The trial will initially evaluate safety, tolerability, and reduction of blood Phe levels in PKU patients with the R408W mutation, one of the most prevalent disease-causing mutations among patients with PKU in the U.S., with a goal of establishing clinical proof of concept for base editing in PKU. The trial will subsequently evaluate base editors for additional mutations within a single clinical program. In July, updated preclinical data for BEAM-304 were presented at the Federation of American Societies for Experimental Biology (FASEB) Genome Engineering: Research and Applications Conference. The presentation is available on the Presentation and Publications page of Beam’s website beamtx.com. BEAM-301: BEAM-301 aims to correct one of the most common disease-causing mutations, R83C, in patients with glycogen storage disease type Ia (GSDIa). BEAM-301 is currently being evaluated in an open-label Phase 1/2 dose-exploration trial in patients with GSDIa. Beam expects to report initial clinical data in 2026. Hematology Franchise Risto-cel: Ristoglogene autogetemcel (risto-cel, formerly known as BEAM-101) is an investigational autologous cell therapy with a potential best-in-class profile for the treatment of sickle cell disease (SCD). Dosing is complete in all adult and adolescent patients enrolled in the Phase 1/2 BEACON trial. Beam expects to report updated data for the BEACON trial by year-end 2026 and submit a biologics license application (BLA) for risto-cel as early as year-end 2026. Next-generation Programs in Sickle Cell Disease and Hematology: Beam completed enrollment and dosing in the Phase 1 healthy volunteer clinical trial of BEAM-103, an anti-CD117 monoclonal antibody with the potential to enable non-genotoxic ex vivo and in vivo therapies for SCD. Treatment with BEAM-103 was well tolerated across all doses tested. Beam continues to make significant investments in developing targeted LNPs to deliver gene editing to hematopoietic stem cells (HSCs). Targeted LNPs for HSC delivery have been identified and are in lead optimization. Second Quarter 2026 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $1.2 billion as of June 30, 2026, compared to $1.2 billion as of December 31, 2025. Research & Development (R&D) Expenses: R&D expenses were $95.1 million for the second quarter of 2026, compared to $101.8 million for the second quarter of 2025. General & Administrative (G&A) Expenses: G&A expenses were $31.9 million for the second quarter of 2026, compared to $26.9 million for the second quarter of 2025. Net Income (Loss): Net loss was $122.7 million, or $1.18 per share, for the second quarter of 2026, compared to net loss of $102.1 million, or $1.00 per share, for the second quarter of 2025. Cash RunwayBeam expects that its cash, cash equivalents and marketable securities as of June 30, 2026, together with an additional $200 million expected to be drawn from the company’s facility with Sixth Street, will fund anticipated operating expenses and capital expenditure requirements into mid-2029, funding the company through the anticipated launch of risto-cel in SCD, execution of the BEAM-302 pivotal development plan in AATD, and clinical proof of concept for BEAM-304 in PKU. About Beam TherapeuticsBeam Therapeutics (Nasdaq: BEAM) is a biotechnology company committed to establishing the leading, fully integrated platform for precision genetic medicines. To achieve this vision, Beam has assembled a platform with integrated gene editing, delivery and internal manufacturing capabilities. Beam’s suite of gene editing technologies is anchored by base editing, a proprietary technology that is designed to enable precise, predictable and efficient single base changes, at targeted genomic sequences, without making double-stranded breaks in the DNA. This has the potential to enable a wide range of therapeutic editing strategies that Beam is using to advance a diversified portfolio of base editing programs. Beam is a values-driven organization committed to its people, cutting-edge science, and a vision of providing lifelong cures to patients suffering from serious diseases. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Investors are cautioned not to place undue reliance on these forward-looking statements, including, but not limited to, statements related to: the therapeutic applications and potential of our technology, including with respect to SCD, AATD, PKU and GSDIa; our plans, and anticipated timing, to advance our programs and present data from ongoing clinical trials; the clinical trial designs and expectations for risto-cel, BEAM-103, BEAM-301, BEAM-302 and BEAM-304; our planned submission of a BLA for risto-cel; our expectations regarding the anticipated launch of risto-cel; the potential for an accelerated approval path for BEAM-302; our expected presentations at upcoming medical conferences, including at the ERS Congress; our anticipated regulatory interactions and filings; our expectations regarding the funds that will be available to draw under our credit facility; the sufficiency of our capital resources to fund operating expenses and capital expenditure requirements and the period in which such resources are expected to be available; and our ability to develop lifelong, curative, precision genetic medicines for patients through base editing. Each forward-looking statement is subject to important risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement, including, without limitation, risks and uncertainties related to: our ability to develop, obtain regulatory approval for, and commercialize our product candidates, which may take longer or cost more than planned; our ability to raise additional funding, which may not be available; our ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; the uncertainty that our product candidates will receive regulatory approval necessary to initiate or continue human clinical trials; that preclinical testing of our product candidates and preliminary or interim data from preclinical studies and clinical trials may not be predictive of the results or success of ongoing or later clinical trials; that initiation and enrollment of, and anticipated timing to advance, our clinical trials may take longer than expected; that our product candidates, including the delivery modalities we rely on to administer them, may cause serious adverse events; that we may not achieve the funding milestones under our credit facility; that our product candidates may experience manufacturing or supply interruptions or failures; risks related to competitive products; and the other risks and uncertainties identified under the headings “Risk Factors Summary” and “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2025, and in any subsequent filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by applicable law. Contacts: Investors:Holly ManningBeam [email protected] Media:Josie [email protected]

A week ago, Beam Therapeutics Inc. (NASDAQ:BEAM) came out with a strong set of quarterly numbers that could potentially lead to a re-rate of the stock. Revenues of US$32m beat estimates by a substantial 160% margin. Unfortunately, Beam Therapeutics also reported a statutory loss of US$0.91 per share, which at least was smaller than the analysts expected. Earnings are an important time for investors, as they can track a company's performance, look at what the analysts are forecasting for next year, and see if there's been a change in sentiment towards the company. With this in mind, we've gathered the latest statutory forecasts to see what the analysts are expecting for next year. This technology could replace computers: discover the 20 stocks are working to make quantum computing a reality. Taking into account the latest results, the 14 analysts covering Beam Therapeutics provided consensus estimates of US$74.0m revenue in 2026, which would reflect a substantial 55% decline over the past 12 months. Per-share losses are expected to explode, reaching US$4.41 per share. Before this earnings announcement, the analysts had been modelling revenues of US$48.3m and losses of US$4.33 per share in 2026. So there's definitely been a change in sentiment in this update, with the analysts upgrading this year's revenue estimates, while at the same time holding losses per share steady. See our latest analysis for Beam Therapeutics There were no major changes to the US$51.13consensus price target despite the higher revenue estimates, with the analysts seeming to believe that ongoing losses have a larger impact on the valuation. It could also be instructive to look at the range of analyst estimates, to evaluate how different the outlier opinions are from the mean. The most optimistic Beam Therapeutics analyst has a price target of US$80.00 per share, while the most pessimistic values it at US$26.00. With such a wide range in price targets, analysts are almost certainly betting on widely divergent outcomes in the underlying business. As a result it might not be a great idea to make decisions based on the consensus price target, which is after all just an average of this wide range of estimates. Of course, another way to look at these forecasts is to place them into context against the industry itself. These estimates imply that revenue is expected to slow, with a forecast annualised decline of 65% by the end of 2026. This indicates a significant reduction from annual growth of 26% over the last five years. By contrast, our data suggests that other companies (with analyst coverage) in the same industry are forecast to see their revenue grow 22% annually for the foreseeable future. It's pretty clear that Beam Therapeutics' revenues are expected to perform substantially worse than the wider industry. The most obvious conclusion is that the analysts made no changes to their forecasts for a loss next year. Fortunately, they also upgraded their revenue estimates, although our data indicates it is expected to perform worse than the wider industry. The consensus price target held steady at US$51.13, with the latest estimates not enough to have an impact on their price targets. With that said, the long-term trajectory of the company's earnings is a lot more important than next year. We have estimates - from multiple Beam Therapeutics analysts - going out to 2028, and you can see them free on our platform here. We don't want to rain on the parade too much, but we did also find 2 warning signs for Beam Therapeutics (1 is a bit concerning!) that you need to be mindful of. Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team (at) simplywallst.com. This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

Recent BEAM-302 Topline Data in Alpha-1 Antitrypsin Deficiency (AATD) Demonstrate Strong Single-dose Safety and Efficacy Profile, with 60 mg Selected as Optimal Biological Dose; Global Pivotal Cohort Expected to Initiate in Second Half of 2026 Data from Phase 1/2 BEACON Clinical Trial of Risto-cel in Sickle Cell Disease Published in April 1 Issue of the New England Journal of Medicine; U.S. Biologics License Application (BLA) Submission Expected as Early as Year-End 2026 Investigational New Drug (IND) Application for BEAM-304 in PKU and Data from BEAM-301 in GSDIa Anticipated in 2026 Ended First Quarter 2026 with $1.2 Billion in Cash, Cash Equivalents and Marketable Securities; Cash Runway Expected to Support Operating Plans into mid-2029 CAMBRIDGE, Mass., May 07, 2026 (GLOBE NEWSWIRE) -- Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, today reported first quarter 2026 financial results and provided updates across the company’s hematology and genetic disease franchises. “The first quarter of 2026 was a defining period for Beam, marked by meaningful clinical advances across our portfolio and key steps toward becoming a commercial-stage company. The updated topline data from BEAM-302 – including robust increases in total AAT and a well-tolerated safety profile – give us high confidence in the 60 mg optimal biological dose and a clear path to initiating the pivotal cohort in the second half of this year,” said John Evans, chief executive officer of Beam Therapeutics. “Publication of the BEACON trial data in the New England Journal of Medicine underscores the differentiated profile of risto-cel, and we remain on track to submit our BLA as early as year-end 2026, a milestone toward bringing a potentially transformative treatment to patients with sickle cell disease. With BEAM-304 in PKU, we are extending the reach of our clinically validated base editing platform to directly correct disease-causing mutations in a new indication, further demonstrating the breadth of what precision genetic medicine can achieve. With a strong cash position extending our runway into mid-2029, we have the financial foundation to execute across all of these priorities and deliver on our mission to bring precision genetic medicines to patients who need them most.” First Quarter 2026 and Recent Progress and Anticipated Milestones Corporate Beam Therapeutics has been selected for the TIME100 Most Influential Companies list by TIME Magazine, highlighting 100 companies making an extraordinary impact around the world. In February, John Evans, chief executive officer of Beam, was recognized as part of the TIME100 Health list, TIME’s list honoring leaders who are advancing care, shaping policy and driving innovations that transform lives. Liver-targeted Genetic Disease Franchise BEAM-302: Beam’s lead genetic disease program is designed to be a best-in-class and first-in-class liver-targeting therapy for alpha-1 antitrypsin deficiency (AATD) that addresses the underlying pathophysiology of both liver and lung disease. In March, Beam announced updated safety and efficacy data from the ongoing Phase 1/2 trial of BEAM-302. Treatment with BEAM-302 led to rapid and durable increases of total and functional AAT, decreases in mutant Z-AAT, and new production of corrected M-AAT, with a well-tolerated safety profile across single doses up to 75 mg. Amy Simon, M.D., chief medical officer of Beam, will give a presentation on translating scientific discovery in gene editing to clinical progress for patients with lung disease, featuring the recent clinical data from the BEAM-302 trial, at the upcoming American Thoracic Society (ATS) International Conference 2026, being held in Orlando, Florida, May 15-20. The presentation will be included in the scientific symposium titled “Rewriting the Code: Precision Delivery Vectors and Gene Therapy for Pulmonary Vascular Diseases” at 3:30 p.m. ET on Monday, May 18, 2026. Based on feedback from the U.S. Food and Drug Administration (FDA), Beam intends to pursue an accelerated approval pathway for BEAM-302. To support a future biologics licensing application (BLA) submission, the company anticipates enrolling approximately 50 additional patients with AATD-associated lung disease, with or without liver disease, in an expansion of the ongoing open-label Phase 1/2 trial. Beam expects to initiate this pivotal cohort in the second half of 2026. In addition, Beam expects to present detailed and updated BEAM-302 data at a medical congress in 2026. BEAM-304: BEAM-304 leverages Beam’s proprietary and clinically validated base editing technology and lipid nanoparticle (LNP) delivery capabilities to directly and durably correct mutations in the phenylalanine hydroxylase (PAH) gene that cause phenylketonuria (PKU). A planned Phase 1/2 trial will initially evaluate safety, tolerability, and reduction of blood Phe levels in PKU patients with the R408W mutation, followed thereafter by a base editor for a second mutation, with a goal of establishing clinical proof of concept for base editing in PKU. Beam expects to file an investigational new drug (IND) application with the FDA for BEAM-304 in 2026 following completion of pre-IND activities. BEAM-301: BEAM-301 aims to correct the most common disease-causing mutation, R83C, in patients with glycogen storage disease type Ia (GSDIa). BEAM-301 is currently being evaluated in an open-label Phase 1/2 dose-exploration trial in patients with GSDIa. Beam expects to report initial clinical data in 2026. Hematology Franchise Risto-cel: Ristoglogene autogetemcel (risto-cel, formerly known as BEAM-101) is an investigational autologous cell therapy with a potential best-in-class profile for the treatment of sickle cell disease (SCD). Data from the ongoing Phase 1/2 BEACON clinical trial evaluating risto-cel for the treatment of SCD with severe vaso-occlusive crises (VOCs) were published in the New England Journal of Medicine. Data demonstrate risto-cel’s differentiated profile, including deep resolution of SCD markers, rapid engraftment, reduced hospitalization, and a predictable manufacturing process that may improve patient experience and treatment center capacity and reduce the length of the transplant process. Beam expects to submit a BLA for risto-cel as early as year-end 2026. Next-generation Programs in Sickle Cell Disease and Hematology: The ongoing Phase 1 healthy volunteer clinical trial of BEAM-103, an anti-CD117 monoclonal antibody that enables ESCAPE, is expected to complete dosing in the first half of 2026. First Quarter 2026 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $1.2 billion as of March 31, 2026, compared to $1.2 billion as of December 31, 2025. Research & Development (R&D) Expenses: R&D expenses were $104.5 million for the first quarter of 2026, compared to $98.8 million for the first quarter of 2025. General & Administrative (G&A) Expenses: G&A expenses were $34.4 million for the first quarter of 2026, compared to $27.9 million for the first quarter of 2025. Net Income (Loss): Net loss was $94.3 million, or $0.91 per share, for the first quarter of 2026, compared to net losses of $108.3 million, or $1.23 per share, for the first quarter of 2025. Cash Runway Beam expects that its cash, cash equivalents and marketable securities as of March 31, 2026, which includes $100 million from the close of the company’s financing agreement with Sixth Street, along with an anticipated additional $100 million from the Sixth Street facility, will fund anticipated operating expenses and capital expenditure requirements into mid-2029, funding the company through the anticipated launch of risto-cel in SCD, execution of the BEAM-302 pivotal development plan in AATD, and clinical proof of concept for BEAM-304 in PKU. About Beam Therapeutics Beam Therapeutics (Nasdaq: BEAM) is a biotechnology company committed to establishing the leading, fully integrated platform for precision genetic medicines. To achieve this vision, Beam has assembled a platform with integrated gene editing, delivery and internal manufacturing capabilities. Beam’s suite of gene editing technologies is anchored by base editing, a proprietary technology that is designed to enable precise, predictable and efficient single base changes, at targeted genomic sequences, without making double-stranded breaks in the DNA. This has the potential to enable a wide range of potential therapeutic editing strategies that Beam is using to advance a diversified portfolio of base editing programs. Beam is a values-driven organization committed to its people, cutting-edge science, and a vision of providing lifelong cures to patients suffering from serious diseases. 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. Investors are cautioned not to place undue reliance on these forward-looking statements, including, but not limited to, statements related to: the therapeutic applications and potential of our technology, including with respect to SCD, AATD, PKU, ESCAPE and GSDIa; our plans, and anticipated timing, to advance our programs and present data from ongoing clinical trials; the clinical trial designs and expectations for risto-cel, BEAM-103, BEAM-301, BEAM-302 and BEAM-304; our planned submission of a BLA for risto-cel; our expected presentations at upcoming medical conferences, including at ATS 2026; our anticipated regulatory interactions and filings; the sufficiency of our capital resources to fund operating expenses and capital expenditure requirements and the period in which such resources are expected to be available; and our ability to develop lifelong, curative, precision genetic medicines for patients through base editing. Each forward-looking statement is subject to important risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement, including, without limitation, risks and uncertainties related to: our ability to develop, obtain regulatory approval for, and commercialize our product candidates, which may take longer or cost more than planned; our ability to raise additional funding, which may not be available; our ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; the uncertainty that our product candidates will receive regulatory approval necessary to initiate or continue human clinical trials; that preclinical testing of our product candidates and preliminary or interim data from preclinical studies and clinical trials may not be predictive of the results or success of ongoing or later clinical trials; that initiation and enrollment of, and anticipated timing to advance, our clinical trials may take longer than expected; that our product candidates, including the delivery modalities we rely on to administer them, may cause serious adverse events; that our product candidates may experience manufacturing or supply interruptions or failures; risks related to competitive products; and the other risks and uncertainties identified under the headings “Risk Factors Summary” and “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2025, and in any subsequent filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by applicable law. Contacts: Investors: Holly Manning Beam Therapeutics [email protected] Media: Josie Butler 1AB [email protected]

This article first appeared on GuruFocus. Cash and Equivalents: Ended 2025 with $1.25 billion in cash equivalents and marketable securities. Strategic Financing Agreement: Up to $500 million in long-term non-dilutive capital from Sixth Street, including $100 million funded at close. Financial Runway: Expected to extend into mid-2029 with the anticipated minimum draw of $200 million from the Sixth Street facility. Warning! GuruFocus has detected 6 Warning Signs with BEAM. Is BEAM fairly valued? Test your thesis with our free DCF calculator. Release Date: February 24, 2026 For the complete transcript of the earnings call, please refer to the full earnings call transcript. Beam Therapeutics Inc (NASDAQ:BEAM) is leveraging its platform to develop a new program for phenylketonuria (PKU), showcasing the scalability of its base editing technology. The company has solidified its balance sheet with a strategic financing agreement providing up to $500 million, supporting the anticipated commercialization of Ristoel for sickle cell disease. Beam Therapeutics Inc (NASDAQ:BEAM) has built significant expertise in lipid nanoparticle (LNP) delivery systems, enhancing its ability to efficiently target liver diseases. The company has completed productive pre-IND interactions with the FDA for its Beam 304 program, indicating regulatory support for its innovative approach. Beam Therapeutics Inc (NASDAQ:BEAM) ended 2025 with $1.25 billion in cash equivalents and marketable securities, extending its financial runway into mid-2029. The company faces significant challenges in addressing the wide spectrum of PKU mutations, requiring a tailored approach for each variant. Current treatments for PKU are not curative and impose a significant burden on patients, highlighting the need for more effective therapies. The regulatory path for addressing multiple mutations in PKU remains complex, requiring adaptive trial designs and ongoing collaboration with the FDA. Beam Therapeutics Inc (NASDAQ:BEAM) must navigate the competitive landscape in sickle cell disease, where existing therapies have set high benchmarks for efficacy and safety. The development of personalized gene editing therapies for ultra-rare diseases presents regulatory and logistical challenges, requiring innovative solutions and real-time development capabilities. Q: Can you discuss the regulatory path forward for addressing multiple mutations in PKU and how the strategic financing for Risto cell impacts your ability to fund additional programs? A: John Evans, CEO, explained that Beam Therapeutics is already working on additional mutations beyond the initial R408W mutation. The platform approach allows for faster and more efficient development of subsequent mutations. Sravan Emany, CFO, added that the strategic financing provides flexibility to support the commercial launch of Risto cell and enhances the ability to redirect capital to pipeline growth. Q: Is there intellectual property associated with the base editing for PKU mutations, and how does the delivery system for Beam 304 compare to other programs? A: John Evans, CEO, confirmed that Beam Therapeutics has access to the necessary intellectual property. The delivery system for Beam 304 uses similar lipid nanoparticle (LNP) approaches as Beam 302 and 301, leveraging the company's proprietary ionizable lipids and internal manufacturing capabilities. Q: With the FDA's new draft guidance for individualized therapy, how does this impact the PKU program, and what are the technical specifics of Beam 304? A: Kiran Musunuru, a collaborator, noted that the FDA's guidance primarily addresses ultra-rare diseases, and there's some ambiguity regarding PKU's qualification. Gopi Shanker, President, explained that Beam 304 will use unique guide RNAs for each mutation, and the company is confident in the on-target editing and benefit-risk profile. Q: How do you view the market potential for Risto cell in sickle cell disease, given the recent financing and market dynamics? A: Giuseppe Ciaramella, President, highlighted the significant demand for Risto cell, noting that no patients have been refused payment despite high treatment costs. The optimized manufacturing process allows for efficient mobilization, positioning Risto cell as a competitive product to meet market demand. Q: What are the expectations for the upcoming readout in the AATD program, and how confident are you in moving forward with the pivotal trial? A: John Evans, CEO, stated that the upcoming data will be comprehensive, including dose and schedule exploration. The company expects to have sufficient insight to finalize the dose and schedule for the pivotal trial, with the accelerated approval cohort already being operationalized. For the complete transcript of the earnings call, please refer to the full earnings call transcript.

The new BEAM-304 program for Phenylketonuria (PKU) serves as a strategic expansion of the liver-targeted portfolio, utilizing the same clinically validated LNP delivery system as prior programs. Management attributes the selection of PKU to its high addressability via base editing, as the disease is primarily caused by single-point mutations in hepatocytes reachable by LNPs. The platform's modularity allows for a 'flywheel' effect where only the guide RNA needs to be changed to address different mutations, significantly reducing incremental R&D costs and development risk. Strategic positioning focuses on the 'power of predictability,' aiming for reproducible outcomes across a growing pipeline rather than relying on a single-asset success story. Operational efficiency is driven by internal GMP manufacturing capabilities in North Carolina, which support the transition from research to IND-enabling activities in under two years. The PKU program targets a significant unmet need, particularly in adults where adherence to restrictive diets and current therapies like enzyme replacements is low. Beam plans to utilize an 'umbrella' clinical trial design, allowing multiple mutation-specific base editors to be developed and potentially approved within a single clinical program. The regulatory path for BEAM-304 is anchored by the established precedent of blood Phe reduction as a surrogate endpoint for full approval in both the U.S. and Europe. Management expects to file the IND for BEAM-304 in 2026, following the completion of pre-IND activities and productive initial interactions with the FDA. Financial guidance includes a cash runway extending into mid-2029, supported by a $500 million strategic financing agreement with Sixth Street to fund the risto-cel launch. The Phase I/II study for BEAM-304 will be an open-label, single ascending dose trial initially focusing on the R408W mutation to establish early clinical proof-of-concept. A $500 million financing facility with Sixth Street provides long-term non-dilutive capital, with $100 million funded at close and $300 million tied to risto-cel milestones. The financing is intended to preserve balance sheet flexibility, allowing Beam to redirect existing capital toward liver-targeted pipeline growth while preparing for commercialization. Management highlighted the 'plausible mechanism' draft guidance from the FDA as a potential future pathway for platform-based approvals in ultra-rare diseases. Risks include the high discontinuation rates of current PKU standards of care due to immune reactions, which Beam's one-time therapy aims to circumvent. Our analysts just identified a stock with the potential to be the next Nvidia. Tell us how you invest and we'll show you why it's our #1 pick. Tap here. Management confirmed the FDA is supportive of an adaptive trial design where multiple variants are treated under a single IND application. This approach allows for the addition of new variants in real-time using in vitro data, potentially bypassing the need for new animal data for every mutation. Beam's process typically requires only one mobilization cycle, whereas competitors often require several, which limits system capacity and delays patient dosing. The absence of double-stranded DNA breaks in base editing is cited as a key factor in maintaining cell health and improving manufacturing efficiency. PKU is a recessive loss-of-function disease, meaning only modest levels of enzyme restoration (correcting one copy of the PAH gene) are needed to normalize Phe levels. Preclinical data showed therapeutic thresholds were met at relatively low LNP doses, suggesting an efficient path for clinical dose-finding. In vivo LNP delivery has been prioritized because it can reach a larger patient population more easily than ex vivo approaches if efficacy is proven comparable. Beam is leveraging its ESCAPE technology to potentially enhance the engraftment of in vivo edited cells, providing a competitive edge in the genetic medicine market. One stock. Nvidia-level potential. 30M+ investors trust Moby to find it first. Get the pick. Tap here.

Beam Therapeutics (BEAM) just released new BEACON trial data on its sickle cell therapy risto cel, showing durable hemoglobin F gains, lower hemoglobin S, and anemia resolution that help explain the stock’s recent momentum. See our latest analysis for Beam Therapeutics. That BEACON update lands after a sharp run, with a 30 day share price return of about 22 percent and a 90 day share price return near 36 percent. However, the three year total shareholder return remains deeply negative, so momentum is clearly rebuilding from a low base. If this kind of clinical inflection has your attention, it could be a good time to see what else is moving across healthcare stocks as the market reprices healthcare risk and opportunity. With the stock still trading at a steep discount to analyst targets even after a big run, the debate now shifts from science to valuation: is Beam Therapeutics still mispriced or already discounting years of future growth? According to davidlsander, the narrative fair value of 150 dollars sits far above Beam Therapeutics last close near 27 dollars, framing a highly asymmetric setup if the platform delivers. This sum-of-the-parts rNPV analysis of only the two lead assets (BEAM-101 and BEAM-302) derives a base-case intrinsic value of 65 dollars per share. This valuation is based on the following key assumptions from the report: Read the complete narrative. Curious how two programs and a cash pile alone can justify more than double the current price, while everything else is treated as pure upside option value? The narrative leans on aggressive revenue expansion, premium pricing, and robust profitability metrics that look more like a mature platform company than a clinical-stage biotech. Want to see the exact assumptions powering that leap? Dive into the full narrative to unpack the numbers behind this bold valuation call. Result: Fair Value of $150 (UNDERVALUED) Have a read of the narrative in full and understand what's behind the forecasts. However, investors still face meaningful risk if ESCAPE underperforms or if payers resist multimillion dollar pricing, which could compress margins and stall multiple expansion. Find out about the key risks to this Beam Therapeutics narrative. That bold 150 dollar fair value contrasts sharply with a simpler check using the price to sales ratio. Beam trades around 48 times sales, roughly double peers at 22.3 times and far above a fair ratio near zero, which implies the market already prices in a lot of success. See what the numbers say about this price — find out in our valuation breakdown. If you see the story differently or want to stress test these assumptions with your own inputs, you can build a personalized valuation narrative in just minutes at Do it your way. A great starting point for your Beam Therapeutics research is our analysis highlighting 1 key reward and 4 important warning signs that could impact your investment decision. Beam might be your starting point, but you could miss some of the market’s most compelling opportunities if you stop your research here, so keep going. Capture potential re-rating opportunities by scanning these 907 undervalued stocks based on cash flows that the market has not fully appreciated yet. Explore structural tech shifts by targeting these 26 AI penny stocks positioned to benefit from accelerating AI adoption. Strengthen your cash flow with these 15 dividend stocks with yields > 3% offering income potential alongside business fundamentals. This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned. Companies discussed in this article include BEAM. Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email [email protected]

It has been about a month since the last earnings report for Beam Therapeutics Inc. (BEAM). Shares have added about 15.9% in that time frame, outperforming the S&P 500. But investors have to be wondering, will the recent positive trend continue leading up to its next earnings release, or is Beam Therapeutics due for a pullback? Before we dive into how investors and analysts have reacted as of late, let's take a quick look at its most recent earnings report in order to get a better handle on the important drivers. Beam Therapeutics incurred a loss of $1.10 per share in the third quarter of 2025, which was wider than the Zacks Consensus Estimate of a loss of 98 cents. The company had reported a loss of $1.17 per share in the year-ago quarter. Total revenues, comprising license and collaboration revenues, came in at $9.7 million in the third quarter compared with $14.3 million reported a year ago. The top line also fell short of the Zacks Consensus Estimate of $13 million. Research and development expenses were $109.8 million in the third quarter, up around 16.5% from the year-ago quarter. General and administrative expenses totaled $26.7 million, inching up 0.8% year over year. As of Sept. 30, 2025, Beam Therapeutics had cash, cash equivalents and marketable securities worth $1.1 billion compared with $1.2 billion as of June 30, 2025. The company expects its existing cash balance to fund its operating expenses into 2028. Since the earnings release, investors have witnessed a downward trend in estimates revision. The consensus estimate has shifted -10.57% due to these changes. Currently, Beam Therapeutics has a subpar Growth Score of D, though it is lagging a bit on the Momentum Score front with an F. Following the exact same course, the stock was allocated a grade of F on the value side, putting it in the bottom 20% quintile for value investors. Overall, the stock has an aggregate VGM Score of F. If you aren't focused on one strategy, this score is the one you should be interested in. Estimates have been broadly trending downward for the stock, and the magnitude of these revisions indicates a downward shift. Interestingly, Beam Therapeutics has a Zacks Rank #3 (Hold). We expect an in-line return from the stock in the next few months. Beam Therapeutics belongs to the Zacks Medical - Biomedical and Genetics industry. Another stock from the same industry, Regeneron (REGN), has gained 12.3% over the past month. More than a month has passed since the company reported results for the quarter ended September 2025. Regeneron reported revenues of $3.75 billion in the last reported quarter, representing a year-over-year change of +0.9%. EPS of $11.83 for the same period compares with $12.46 a year ago. For the current quarter, Regeneron is expected to post earnings of $10.65 per share, indicating a change of -11.8% from the year-ago quarter. The Zacks Consensus Estimate has changed -0.6% over the last 30 days. The overall direction and magnitude of estimate revisions translate into a Zacks Rank #3 (Hold) for Regeneron. Also, the stock has a VGM Score of B. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Beam Therapeutics Inc. (BEAM) : Free Stock Analysis Report Regeneron Pharmaceuticals, Inc. (REGN) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research

Image source: The Motley Fool. Tuesday, November 5, 2024 at 11:54 a.m. ET Chief Executive Officer — John Evans President — Dr. Giuseppe Ciaramella Chief Medical Officer — Dr. Amy Simon Need a quote from a Motley Fool analyst? Email [email protected] John Evans, our Chief Executive Officer; Dr. Giuseppe Ciaramella, our President; and Dr. Amy Simon, our Chief Medical Officer. Before we get started, I would like to remind everyone that some of the statements we make on this call will include forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual events and results could differ materially from those expressed or implied by any forward looking statements as a result of various risks, uncertainties and other factors, including those set forth in the Risk Factors section of our most recent annual report on Form 10-K, as updated by our quarterly reports on Form 10-Q and any other filings that we may make with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon, as representing our views as of any subsequent date. Except as required by law, Beam specifically disclaims any obligation to update or revise any forward-looking statements even if our views change. With that, I will turn the call over to John. John Evans: Thanks, Holly. Good morning, everyone, and thank you for joining us for this exciting moment for Beam, for our employees and for the patients we aim to serve. At Beam, our vision is to provide lifelong cures for patients suffering from serious diseases. This vision has never felt more tangible than it does today, as we report the first clinical data from our portfolio of one-time treatments. From the beginning of Beam, we saw an opportunity to advance the gene editing field. CRISPR nucleases are able to precisely target a location in the DNA, but they lack the ability to precisely edit genes. With our innovative next generation technology called base editing, we can now make more precise single base changes at specific locations in genes, resulting in predictable edits in all cells, without needing to damage or make double stranded breaks in the DNA. The central hypothesis behind Beam is that this breakthrough could provide a superior way to modify genes and could open up entirely new applications in gene editing for a wide range of severe diseases. Given the incredible breadth of potential applications for base editing, it was critical to sharpen our focus and execution on areas where we can have the greatest impact in the near-term. This led to our two core franchises in hematology and liver genetic diseases. In both cases, we are advancing highly differentiated and potentially best-in-class lead programs with BEAM-101 in sickle cell disease and BEAM-302 in alpha-1 antitrypsin deficiency or AATD, each of which have increased probability of technical success based on strong preclinical validation as well as recent advances in the field. In sickle cell disease, we have a validated regulatory pathway available for BEAM-101, which the BEACON trial is designed to pursue. We also have a next generation program using our ESCAPE technology designed to expand the addressable patient population by eliminating chemotherapy from transplant. Beginning today and continuing at ASH, we're reporting the first clinical data from our hematology franchise. Initial data from our BEACON Phase 1/2 trial support the potential for meaningful clinical differentiation of BEAM-101 compared to currently available treatments for sickle cell disease. We will also be reporting non-human primate data for our ESCAPE technology that validate our vision of enabling gene editing and stem cell transplant, using only antibody based conditioning avoiding chemotherapy altogether. In our liver franchise, BEAM-302 also has the potential for rapid proof-of-concept in the clinic and represents the first program with potential to be a one-time treatment with benefit for both lung and liver manifestations of the disease. We expect to report the first clinical data from our ongoing Phase 1/2 trial of BEAM-302 in patients with AATD in 2025, marking another potentially transformative event for the company, our platform and for patients. I'd like to highlight several important updates from our third quarter financial results press release. To-date, we have exceeded enrollment expectations in the BEACON trial with 35 sickle cell patients enrolled. Of these, eight patients have been treated with BEAM-101 with the remainder going through pre transplant stages including cell collection and drug product manufacturing. We are also excited to share that we have nominated development candidates for our ESCAPE technology, which Pino will detail shortly. For in-vivo therapies, this summer we dosed the first patient with BEAM-302 in AATD and have continued to enroll and treat patients while opening new sites globally. As of last month, we have completed dosing in the first cohort of the study. As I noted, we expect to share initial data for multiple cohorts in 2025. In addition, in June, we received U.S. IND clearance for our second in-vivo program BEAM-301 for the treatment of glycogen storage disease 1a or GSD1a. Since then, our team has been preparing to advance BEAM-301 into the clinic with site activation underway and patient dosing expected to commence in early 2025. And importantly, we continue to be in a strong financial position. Turning now to ASH. We are honored to have four abstracts accepted for presentation at the meeting in December. These include two oral presentations, one featuring initial clinical data from the BEACON trial and one with our non-human primate data for our ESCAPE technology as well as poster presentations showcasing exploratory biomarker data for BEAM-101 and preliminary clinical data for BEAM-201, our quad edited CAR-T cell for T-cell malignancies. Abstracts will be available on the ASH website at 9 A.M. Eastern Day. I'll now turn to sickle cell disease. At the JPMorgan Conference in January, I asked the question, what if we could develop better one-time therapies for people living with sickle cell disease. I'm pleased today to report that, yes we believe we are on the road to do just that. For sickle cell disease, we are pursuing a long-term stage development strategy that envisions three waves of innovation to progressively reach broader subsets of patients over time. Our Wave 1 approach is BEAM-101, a genetically modified investigational cell therapy administered via hematopoietic stem cell transplantation with busulfan conditioning. We believe BEAM-101 has the potential to be a best-in-class option for the roughly 10% of sickle cell patients, who have severe disease despite receiving standard of care treatments and are considered appropriate for a chemotherapy based transplant. Though the market for autologous genetic therapies in sickle cell disease is just getting started, it is important to note that allogeneic transplants for patients with severe sickle cell disease are already a reality with several 100 conducted annually in the U.S. And that number only represents those patients, who could find a suitable matched donor, which we know, represents a small minority of total eligible patients. And finally, we know that autologous transplants are expected to have real advantages over allogeneic transplants, including a lack of graft versus host disease and no need to coordinate the procedure with a donor. Wave 2 takes the same BEAM-101 platform and now incorporates our ESCAPE technology to enable non-genotoxic condition. If successful, ESCAPE would eliminate chemotherapy, which we believe is one of the main hurdles for patients considering a transplant based therapy and thus meaningfully expand the patient population for ex-vivo gene editing by three-fold to two-fold. A little further out is Wave 3, where we are using our leading capabilities in lipid nanoparticles to explore the potential for in-vivo based editing for sickle cell disease, which would eliminate the need for transplantation, thus enabling even broader patient access around the world. Now, let's start by reviewing BEAM-101. Sickle cell disease is a genetic disorder that affects hemoglobin, which delivers oxygen to cells throughout the body. People with this disease make abnormal hemoglobin molecules called hemoglobin S or HbS. This abnormal HbS can form stiff polymers, which distort red blood cells into a sickle or crescent shape, blocking the flow of blood and oxygen throughout the body. Sickle cell disease begins in early childhood and leads to anemia, infections and episodes of severe pain, which can manifest as vaso-occlusive crises or VOCs. Patients also can experience life threatening complications such as stroke and significant organ damage, resulting in decreased life expectancy. While recently approved gene therapies have been shown to significantly reduce VOCs, patients are still generally left with HbS of more than 50%, suggesting there are opportunities for further improvement. Elevating a protective form of hemoglobin called fetal hemoglobin or HbF is a clinically validated strategy to prevent the consequences of sickle cell disease by preventing HbS from polymerizing, thereby preventing red blood cell destruction and organ damage. BEAM-101 was designed to induce a more efficient editing leading to greater and more uniform induction of HbS, a deeper reduction of HbS and normalization of hemoglobin and red blood cell function. Moving to an ideal outcome what would an ideal outcome from genetic correction look like. As shown on Slide 13, total hemoglobin for a person with sickle cell disease has 100% HbS in circulation, which causes sickling and results in decreased red blood cell lifespan, anemia, pain crises and organ damage. The disease threshold is exemplified by people with sickle cell trait or carriers with only one mutation and are typically asymptomatic. These people generally have about 60% normal hemoglobin and only 40% HbS. The recently approved gene therapies for sickle cell disease, though clearly providing significant benefit to patients, do not achieve this threshold. With base editing, we are aiming for a deeper correction of the hemoglobin profile that is at least on par with or even better than that of a typical person with sickle cell trait. HbF also has the additional biochemical benefit of being anti-sickling, which may provide additional protection. In pre-clinical models, BEAM-101 achieved these goals, potently inducing HbF to more than 60% and proportionally reducing sickle HbF to less than 40% without the need to make double stranded DNA breaks. Today, we are reporting the first data from our ongoing clinical trial at BEAM-101 in patients with sickle cell disease that validate our preclinical findings and support our goals for this program. Let me now turn the call over to Amy to review the BEACON trial and the initial clinical data in our ASH abstract. Amy Simon: Thanks, John. Starting with the trial design, BEACON is a single-arm open-label study evaluating the safety and efficacy of a single dose of BEAM-101 in patients with sickle cell disease and severe VOCs. The trial is enrolling adult patients 18 to 35 years old with sickle cell disease, who have experienced four or more severe VOCs in the two years prior to screening. Patients are mobilized using plerixafor, after which autologous CD-34 positive hematopoietic stem and progenitor cells are collected by leukapheresis and genetically modified with our adenine based editor. Patients then receive myeloablative conditioning with busulfan, followed by a single infusion of BEAM-101. Key endpoints are outlined here on Slide 16. As John highlighted to date, we've exceeded enrollment projections with 35 patients having cleared screening and enrolled in the study. The data we'll review today are as of July 2, 2024 data cut and includes six patients in the safety analyses and four patients in the efficacy analyses. In our presentation at ASH, we'll share additional data with more patients and longer follow-up. Baseline demographics are shown on Slide 17 and were as follows. Five of the six patients were beta-S genotype and one patient was beta-S beta-zero genotype. All were self-reported as Black African American, 50% were female and ages ranged from 19 to 27 years. The BEAM-101 manufacturing process allows for efficient dose production with all six patients requiring just one or two cycles of mobilization to achieve a dose with a mean of 1.5 cycles. As a reminder, minimizing the number of cycles of mobilization is a key goal for both patients and providers to reduce days in hospital and the overall time required to manufacture a dose. Safety data were captured for all six patients. BEAM-101 was considered generally well tolerated and demonstrated a safety profile consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant. Of note, one patient died due to respiratory failure four months after their BEAM-101 infusion, which was determined by the investigator to be likely related to busulfan conditioning. Busulfan is a cytotoxic drug used in a transplant setting and is known to be associated with significant side effects, including lung injury and death. This is a complex case and the unfortunate outcome while rare has been reported previously with stem cell transplant. The event was determined to be unrelated to BEAM-101 by the investigator. The case was reviewed by both the Data Safety Monitoring Committee and the FDA. In all patients dosed, there was no Grade B or higher adverse events or serious adverse events related to BEAM-101. As shown on Slide 19, time to engraftment is for the four patients with a follow-up period of one month or more. Rapid neutrophil engraftment was observed for all patients after BEAM-101 treatment with a median of 17 days and a range of 15 to 19 days. Platelet engraftment was achieved at a median of 20 days with a range of 11 to 34 days. These data are similar to what is seen in patients undergoing allogeneic stem cell transplantation with unedited stem cells. Neutrophil engraftment is particularly important, as this is one of the key factors that determine the length of hospital stay in patients after undergoing a transplant. Minimizing time to neutrophil engraftment is another important goal of transplant therapy in sickle cell disease because not only can it result in reduced hospital stays, but also to potentially decrease risk of developing opportunistic infections. On Slide 20, we detailed total hemoglobin for the four patients included in the efficacy analyses, where patients had six, five, two and one month of follow-up, respectively. After treatment with BEAM-101, we observed an early end market induction of HbF and a significant increase in total hemoglobin. The patient's total hemoglobin increased from a mean baseline of 9.3 grams per deciliter to 17.9, 18.2, 11 and 11.8 grams per deciliter at the last time point. No symptoms or interventions were undertaken for the patients with mild elevated total hemoglobin. Notably, all four patients achieved greater than 60% HbF of non-transfused hemoglobin at month one and sustained its elevation at the last time point. The percent of HbF in non-transfused blood dropped to less than 40% in all four patients, which again was sustained to the last time point as of the data cutoff. Importantly, these data are consistent with our pre-clinical results and was seen in individuals with sickle cell trait, whereas John mentioned, patients generally have 60% normal hemoglobin and 40% sickle globin. In addition, markers of hemolysis including lactate dehydrogenase, indirect bilirubin, haptoglobin and reticulocyte counts were seen to normalize or improve in all four patients. No VOCs were reported by investigators following BEAM-101 treatment. Collectively, these findings represent a deep correction of the hemoglobin profile of the blood after BEAM-101 treatment. In addition to our primary BEACON clinical abstract, we have an additional abstract detailing exploratory biomarker assessment of red blood cells' hemoglobin expression, health and function. As shown on Slide 22, for the first two patients included in the analysis, 98% of red blood cells expressed HbF as early as month one with near complete elimination of red blood cells expressing solely HbF post treatment with BEAM-101. These HbS only cells are the cells, which would be most likely to sickle and cause pain crises and organ damage over time. Biomarker data also show that treatment with BEAM-101 restored red blood cell function across a range of parameters. As shown on Slide 23, maximum sickling was significantly reduced for the first two patients treated with BEAM-101 below the levels associated with sickle trait blood samples. Other improvements in blood function include decreased dense red blood cells, decreased hemolysis and decreased red blood cell adhesion, all of which are associated with disease severity. In summary, we're encouraged by this emerging BEAM-101 clinical data, which we believe are consistent with our preclinical findings and demonstrate the potential for differentiation from other cell and gene therapies as outlined in the key takeaways on Slide 24. Beam cell collection and manufacturing process were efficient, resulting in just one to two mobilization cycles. BEAM-101 was generally well tolerated with the safety profile consistent with the known effects of myeloblative conditioning and stem cell transplant. Neutrophil engraftment is rapid with all patients engrafting in under 20 days. Both in grafting timing and cell collection efficiency contribute to shorter hospital stays and a faster path for treatment for patients. BEAM-101 effectively induced HbF to greater than 60% with HbF meaningfully reduced to less than 40% consistent with the profile of individuals with sickle cell trait. And finally, multiple biomarkers show the near elimination of HbF only cells and improved red blood cell health and functions following BEAM-101 treatment. Taken together, we believe this initial data set demonstrates BEAM-101 has the potential to be best-in-class, one-time treatment for people living with sickle cell disease. We look forward to reporting data from a more recent data cut from our BEACON trial in oral presentation at ASH on December 8, which will feature additional patients and longer follow-up. I'll now pass the call over to Pino to go through our initial ESCAPE data. Giuseppe Ciaramella: Thank you, Amy. Returning to our overall vision for bringing new options to patients with sickle cell disease, ESCAPE forms the foundation of our Wave 2 sickle cell disease strategy, which aims to provide the same transformative efficacy potential seen with Wave 1, but with an alternative to genotoxic conditioning during the transplant process. This approach offers significant upside, including the potential to improve patient safety and overall treatment experience and become a compelling option, not only for severe patients but also for more moderate disease patients. As a result, we believe that such a product would expand the eligible patient population for gene editing therapies by up to four-fold. So why is conditioning so important? Conditioning is a critical component of a transplant. It is necessary to make space in a patient's body to receive the ex-vivo edited cells that need to graft in the patient's bone marrow in order to be effective. The field of stem cell transplant has generated dramatic outcomes for many hematology patients with upwards of 22,000 transplants now occurring in the U.S. and even. However, all such transplants still rely on chemotherapy, most commonly busulfan to enable the replacement of blood cells. Busulfan was first approved in 1950s. And as Amy mentioned, it's associated with both acute and chronic toxicity that include infertility, the potential for increased rates of malignancy and in rare instances can be fatal. Improving upon that option represents the next frontier in hematology and could bring the transformative impact of transplant to many more patients with many more diseases. The ESCAPE technology has the potential to finally enable the vision of a non-genotoxic conditioner approach, thus bringing about the paradigm shift in transplant medicine for the first time in nearly 70 years. Our ESCAPE program consists of two investigational therapies, which we named the BEAM-103 and BEAM-104 as part of our development candidate nomination announced today. BEAM-103 is our conditioning antibody, designed to bind unedited hematopoietic cells in the marrow and eliminate them. BEAM-104 is a multiplex based edited cell product that includes two edits. The first is the same therapeutic edit as in BEAM-101 to elevate fetal hemoglobin. The second is an additional edit to introduce a mid-sense mutation in the extracellular domain of CD117, a receptor expressed by hematopoietic stem and progenitor cells that regulates survival proliferation and differentiation of the cells. The CD117 edit does not alter CD170 biology, but only disrupts the binding of BEAM-103 to the receptor. This allows edited cells to ESCAPE the antibody with the goal of enabling engraftment in growth of edited cells and clearance of disease cells. In the data shown on the right, you can see that, in the presence of a mixed population of unedited and edited cells, increasing levels against about the cost of cell population to shift to become completely edited cells. We have evaluated the system extensively in mice, but to establish true growth concept, we wanted to conduct a comprehensive study in non-human primates. We are collaborating with multiple leading experts in the field and this initial study was conducted by Dr. John Tisdale of the NIH, a pre-eminent leader in autologous transplant and non-human primates model to a transplant. The data to be presented by Dr. Tisdale at ASH seek to answer two key fundamental questions: Can engraftment of hematopoietic stem cells be achieved without chemotherapy? And can a therapeutic level of fetal hemoglobin be achieved? As detailed on the right side of Slide 30, the monkey autologous transplant process being conducted here is comparable to an ex-vivo gene editing product in humans, with the caveat that by necessity various steps in the process have not been optimized to the same degree that we have done for humans. We mobilized CD34 cells from two reasons macaque monkeys and edited them ex-vivo, incorporating both the HbF edit and the CD117 ESCAPE edit. The animals were conditioned with BEAM-103, CD117 antibody and then infused with the BM-104 edited cell product. Subsequently, these animals received monthly antibody treatments after transplantation to maximize the competitive advantage of edited cells and continue suppression of unedited cells. The BEAM-103 antibody was well tolerated both doses and no supportive care was necessary for the antibody condition of animals. Importantly, they did not go through a period of myelobrasion, as is steady seen in chemotherapy condition. Remarkably, we observed significant reduction of HbF at 30-time points post-transplant. As cell levels rose to 61% in the periphery, as early as eight weeks post-transplant in one of the animals and stabilized at approximately 85% at week 35 for both animals. Early induction of HbF was also observed in the level of surpassing 50% in both animals in both ends. These unprecedented results established preclinical proof-of-concept for condition with a CD117 antibody and non-chemotherapy, leading to robust long-term engraftment and high levels of HbF expression for ex-vivo edited CD34 cell. If replicated in humans, these results will achieve our Wave 2 vision of non-genotoxin condition for gene editing in hematology. Intriguingly, the lack of myeloplation also suggests the possibility that the transplant of ESCAPE edited CD34 cells could eventually become an outpatient procedure, further enhancing the access and scalability of these products for patients. On the back of the strong preclinical results, we are now accelerating the development of our ESCAPE technology towards the clinic. We're currently conducting additional NHP studies to explore antibody dosing regimens, dose response and cannibalism and we're on track to initiate Phase I enabling studies by the end of the year. Once complete, we plan to conduct a Phase 1 healthy volunteer study of the BEAM-103 antibody before moving into studies of both BEAM-103 and BEAM-104 in sickle cell disease and beta thalassemia patients. As we now look forward to the development of this promising technology, I want to highlight the strong synergies between BEAM-101 and ESCAPE. With an identical edit and underlying base editing technology, today's BEAM-101 clinical data are also derisking for ESCAPE. In each investment and advancement, we make in manufacturing, clinical, regulatory and commercial preparedness for BEAM-101, a direct applicability to accelerate and derisk the future success of ESCAPE. The two programs therefore form a single integrated franchise, which we believe can deliver successful improvements to patients with sickle cell disease. I'll now turn the call back over to John to wrap up. John Evans: Thanks, Pino. As you can see, we are very encouraged by these emerging data sets. First, for BEAM-101 in patients with sickle cell disease, we are so far achieving a potentially differentiated clinical profile using base editing, consistent with our preclinical data and comparable to sickle cell trait, while also potentially requiring fewer days in the hospital for both mobilization and engraftment. Second, with ESCAPE achieving robust preclinical proof-of-concept and now moving rapidly towards the clinic, we are opening up the potential for non-genotoxic conditioning and transplant, which would expand the initial BEAM-101 market to reach a broader group of patients with a less myeloablative profile that even has the potential to become an outpatient procedure for conditioning and transplant. And finally, these data sets support that base editing does appear to have significant advantages in predictability, efficiency and lack of double strand breaks with strong translation from preclinical to clinical data, minimal impact on cell viability and promising efficacy outcomes. Before I close, I'll provide a brief review of the clinical data on BEAM-201, which will be in a poster at ASH. Initial clinical data for BEAM-201, which is the first quadruplex edited allogeneic CAR T-cell therapy candidate in clinical development establishes clinical proof-of-concept for a high level of multiplex based editing. The safety profile of BEAM-201 was consistent with these patients' advanced underlying disease as well as with lymphodepletion and CAR T-therapy. We also observed early evidence of clinical efficacy with two of three patients treated with BEAM-201 achieving a complete response, allowing them to pursue transplant, which is potentially curative. While not a priority program given our decision to focus on hematology and liver-genetic diseases, we continue to seek a path forward for BEAM-201 with a partner and look forward to supporting the future advancement as well as other potential applications of multiplex-based editing in cell therapy. Wrapping up, as you've heard, 2024 has been an incredibly fruitful time at Beam with broad-based execution and validating data across our portfolio of base editing programs. We have a number of meaningful catalysts on the horizon, starting with updated data at ASH in December. Again, I'd like thank the Beam team for their continued hard work and dedication to our shared vision, the patients and physicians, who participated in our clinical trials and to each of you for your continued support of Beam. With that, operator, please open the line for Q&A. Operator: [Operator Instructions] Our first question comes from Gena Wang with Barclays. Gena Wang: Thank you. Really impressive update. I have so many questions. Since I can only ask one question, maybe I'll ask a less exciting question. That's the safety. One patient’s death just a little bit puzzling. Why after four months and that patient die? And then, why that will could be due to the busulfan? If you can give a little bit more color there? John Evans: Sure. Maybe I'll start and then I'll have Amy give a little color on the time course and what we know about busulfan. Yes, it's a very sad outcome, of course. I think what it shows maybe at a high level is the very real risks of transplant and chemotherapy. We're using busulfan in this case that we use the same protocol and dosing regimen of busulfan as others do in the field, obviously, informed by world experts on our trial. But we know that chemotherapy and transplant do have significant toxicity and in rare cases can have mortality, something that the field continues to optimize, but it's a real choice that patients have to think about. At the same time, I'd like to say that I think this also underscores the severity of severe sickle cell disease. We've seen sickle cell survival rates improve to about 50 years on median here in the U.S., but that's median. The most severe 10% are much sicker than that. And so, the severity of the disease really is what makes that transplant potentially compelling option despite the risks. Importantly, as Amy will outline, the case is consistent with our prior experience with busulfan and with transplant. So, we don't see any change in the risk benefit profile of our agent or of the field based on this. Our goal with BEAM-101 is ultimately to give a better option to patients and transplanters, who are seeking transplant that begins with the shift from allo to auto, which is happening now. And of course, with the data we're showing today, we believe that BEAM-101 is potentially best-in-class profile out of the autologous therapies. So maybe with that preamble, I'll ask Amy to say just a little bit about what we know about busulfan and the time course of this kind of toxicity. Amy Simon: Sure. So it turns out busulfan is, as John mentioned, a chemotherapeutic and cytotoxic agent and it is known to be associated with dose dependent pulmonary toxicity. As you go up in higher doses, more toxicity and in some cases can actually be fatal. In general, myeloblade conditioning with agents such as busulfan can cause something that we refer to as the idiopathic pneumonia syndrome. This can occur in up to 6% of patients who have autologous transplant. And this idiopathic pneumonia syndrome really represents a spectrum of pulmonary diseases, including lung injury, respiratory failure that tend to start around day 20 or 30 post transplant and kind of manifest through about day 100. The rates, as I mentioned, are up to 6% and these can often wind up with multi kind of – multilobar opacities in the lung, respiratory failure and in some cases, as I mentioned be fatal. I think that the team at the site did an extensive workup. And usually, what you'll do is rule out other potential contributing causes, which they did, such as infection or other types of etiologies for pulmonary dysfunction. In the end, the timing of this dysfunction as well as the extensive clinical workup really point to the fact that, this is consistent with what has been seen previously in busulfan both in what is reported in the label as well as the literature about stem cell transplantation, complications with busulfan and other literature. Notably, the patient's blood was corrected and normalizing in line with what was seen in other patients. So while it's an unfortunate case, it is a known complication that myeloablative conditioning can have really kind of profound effects, even though it is required for a successful transplantation. And I think investigators take this into account, when thinking about selecting patients, who are appropriate for a risk benefit profile as well as talking with their patients, so that it's clear that the patients understand the risk benefit and that, they're signing up for something that they understand what they're getting into. Operator: Our next question comes from [Yanin Zhu]. Unidentified Analyst: Thanks for taking our questions and congrats on the data. Again a very impressive HbF induction. I was wondering, how would the higher HbF induction translate into additional clinical benefit compared with approved product and also other upcoming products in the pipeline? If you can shed some light, because I guess VOC has been -- data has been pretty strong for the approved product. So wondering where could we see additional clinical benefit? John Evans: Sure. I'd like to Pino to cover this one. Giuseppe Ciaramella: Yes. As you can see, really, we do believe that this higher hemoglobin F is also associated with a concomitant decline of hemoglobin S to levels less than 40%. That 60 to 40 ratio is really the ratio that you typically see in sickle trait individuals, who obviously do not have symptoms unless in very sort of severe condition. We do feel that, that combination of 60 to 40 can be like a sickle trait and potentially even better since hemoglobin S is anticycline as opposed to hemoglobin A. So that should lead to a variety of deeper resolution. We share some biomarkers that show that the blood is function is normalized to the extent that we can measure it. We also show that we have almost completely eliminated cells that express hemoglobin S on its own. These are really the cells that potentially can cause sickling under some severe conditions. And so even though it is great to see a strong resolution of VOCs in the launch product so far, I think we have also potentially the opportunity to improve even upon that. And so, the overall combination of the parameters that we have really for the first time, reproduce the sickle trait that others have not yet done. Operator: Our next question comes from Dae Gon Ha with Stifel. DaeGonHa: Thanks for taking our questions and I'll add my congrats on the initial data as well. Look forward to your 302 update next year. Circling back on the efficacy side, question for either John or Amy. Patients three and four, the female patients, just wondering if you can comment on the progress you're seeing there, specifically on the fetal hemoglobin induction. And when you look at both across the board, it seems like month two seems to be sort of the start of a plateau, if you will, on the total hemoglobin. So just wondering how we should think about sort of a longer-term efficacy for these two patients and specifically on the patient floor side? John Evans: I think there's not much to see between the patients. There's going to be some variability. All of these patients have what I would consider to be a robust early induction of F. In patients three and four, it's also worth noting, they received their last transfusion closer to the month one-time point, which means you have more transfused blood around. That has to clear before the marrow is going to turn on its endogenous production quite as strongly. That's a subtle variable. I think ultimately, we'll just wait for a longer follow-up and we should be able to compare these datasets. Operator: Our next question comes from Eric Joseph with JPMorgan. Eric Joseph: Thanks for taking the questions. Just digging into the first two patients of one and two that the total hemoglobin count is fairly high at least at months five and six. So just wondering how we -- whether there's any concern about the total hemoglobin counts being sort of where they are, whether you sort of normalize or come back down with time. Any sort of concern, I guess, with long-term follow-up with persisting hemoglobin around that level? John Evans: Yes. Thanks, Eric. Amy? Amy Simon: Yes. Two patients, as you noted, have experienced mild elevations in hemoglobin. Importantly, there have been no clinical signs or symptoms from those patients or medical interventions required. These are really considered laboratory abnormalities at this point by the investigators and have not even been considered as adverse events. Importantly, as Pino alluded to recently, with the elevated hemoglobin F to S ratio of 60 to 40, we feel that these patients are no longer patients who have sickle cell disease but in fact, with editing their blood health and function have improved to what would be similar to that of a trait or a healthy person. And those include, as I already mentioned, the hemoglobin F to S ratio, the improvements or normalization in hemolysis, the decreased RBC sickling, RBC density and RBC adhesion. And for all those reasons, there has been really no concern by the investigators of these mild elevations seen to date. And as you mentioned, we'll continue to follow these, but at this point in time, this reflects really just a lab abnormality. Eric Joseph: Appreciate it. Maybe just one quick follow-up, if I could, on the safety front. Any changes to either screening criteria or modifications to the conditioning regimen as a result of the unfortunate death attributed to busulfan? Amy Simon: Yes. There's been no change to our eligibility criteria. It was determined by the DMC and concurred with the FDA that the safety profile of the study had not changed after this event. However, we already had in place what's called therapeutic drug monitoring for busulfan, and that type of therapeutic monitoring is often done when there's a narrow therapeutic window for a drug. This is typically done by all the various studies in gene editing as well as investigators who use busulfan for conditioning. And just to note that the patient's busulfan level was within the target range that we were basically trying to obtain -- to try to ensure both conditioning was appropriately done, but at the same time trying to guarantee safety. Operator: Our next question comes from Kostas Biliouris with BMO Capital Markets. Kostas Biliouris: Thanks for taking our question and congrats on the progress and the data here. One clarification and one question from us, please. I think you already kind of described that, but can you clarify whether you have observed any off target editing or busulfan editing in the patient who died? I know there is no clinical evidence for that, but this is a question that comes up from investors. And then a second question on commercialization of 101 and ESCAPE. How are you thinking about the sequencing of commercializing these two products and potential cannibalization of 111 from ESCAPE? John Evans: So I'll let Pino answer the first question and then I'll do the second. Giuseppe Ciaramella: Yes, we have not noted any off target biology of concern in any of the studies that we've done. Specifically, we do not do off target biology on every single drug product but as part of our pre-clinical package, you do extensive off-target biology on several donors, including the adjustment in silico of looking at different genomic background, which was the context of the cash JV advisory board conversation that added. And through none of that activity, there was any off target biology of concern emerged. John Evans: Yes, and then, on the market perspective, I think our plan has always been -- we consider this a lifecycle strategy across this franchise. So beginning with BEAM-101 then leading to ESCAPE, now BEAM-103 and 104 and ultimately, thinking about in-vivo as well. So we see this as a progression. I think if ESCAPE fully achieves its profile, which would be efficacy comparable to 101 or other gene therapies in the field, but without chemotherapy, I would expect that to overtake and replace 100 million of the market, but of course we'll have to see the profiles and consider that at the time. In terms of the market progression, I think we've talked about this as well, and I had it in my slides, but we continue to believe that, the market for these sort of Wave 1 therapies as we call them is about 1 in 10 patients, really those patients who are severe enough to consider a transplant and there our goal is to give transplant as a better option. It's quite clear that autologous will be preferred over allogeneic. There's already several 100 allogeneic transplants that occur every year in the U.S. for sickle cell patients with severe disease and that's after including the fact that most of those patients who might seek a transplant can't find a match seek a transplant can't find a match. So, I think that implies a certain market size that we expect will be there and we believe with today's data, assuming it holds up over time, we'll show that BEAM-101 is the best-in-class option for patients in this first market. Once we can bring ESCAPE forward, of course, that really changes the game because now you have, of course, eliminated a lot of the risks of transplant and chemotherapy. You've also expanded the addressable patient population, so that many more patients who might not have been a good fit for transplant before now can come in. And as Pino said, we think that leads to an addressable population that's up to 4x larger. Final point to make in terms of the staging of the programs is the one that Pino highlighted as well, which is the ESCAPE program is almost identical to BEAM-101 plus one-single guide RNA to get to the CD117 edit and of course the antibody. So from a regulatory preclinical package, the clinical trial sites and design, regulatory strategy and endpoints and ultimately even commercial infrastructure, all of that is shared between the two programs, which will make for a much more efficient development program and I think ultimately will accelerate what we can do with ESCAPE. Operator: The next question comes from Samantha Semenkow with Citi. Samantha Semenkow: Thank you for taking the question. Sort of expanding on that last question, the NHP data that you shared today for ESCAPE, they look pretty encouraging on both engraftment and HbF injection. But given the safety advantage with avoiding chemotherapy, I'm just curious on your thoughts on the potential trade-off for a slightly less efficacious profile on the trade-off for the better safety profile. And then relatedly for BEAM-103, the CD117 antibody, are there any safety concerns for targeting CD117 that we should be aware of? John Evans: Yes. Maybe I'll have Pino answer the second question. I'll just highlight on the first question. I think, of course, if you have a safety advantage but lose some efficacy, then there's more of a debate to be had. I think what you see from the data that Pino shared is, we're achieving fairly full efficacy with ESCAPE and then we get that safety advantage. So, so far that looks quite compelling. Obviously, as I noted, it will take some time to evolve the full product profile, but maybe I'll hand over to Pino to expand on that. Giuseppe Ciaramella: I'm sorry, could you repeat the second question just for a moment? Samantha Semenkow: Yes, of course. I was just thinking about as you move, BEAM-103 into the Phase 1 healthy volunteer study next year, Are there any safety concerns of targeting 117 that we should be aware of? Giuseppe Ciaramella: Yes. There have been actually several studies already conducted with antibodies against CD117. Actually, Celldex was the latest company to reveal some of the data they're using anti CD117 for the treatment of urticaria. And basically what you see in those individuals is that, you see a transient but mild neutropenia being the major sort of outcome that you'll see. And so, really, these antibodies do not lead to myelblation, as you would see with chemotherapy. And that's why as John mentioned earlier, it opens the possibility actually that this kind of treatment may even become in the future outpatient treatment paradigm, because obviously they do not run the risk of opportunistic infections due to neutropenia. So, we think that, it really the healthy volunteer is a very healthy volunteer is a very expeditious and efficient way of quickly getting to a PK/PD understanding of the antibody, and then it gives us a more assured essentially dosing regimen for us to go into the sickle cell and beta thalassemia patient without having to have extensive, sort of treatment options, tested during those trials. Operator: Our next question comes from Sami Corwin with William Blair. Sami Corwin: Congrats on the data and thank you for taking my questions. Pino, you just mentioned this and I noticed on the slide that you plan on exploring the ESCAPE technology and beta thalassemia in addition to sickle cell disease. I guess I was curious, what kind of prompted that expansion? And then, as you're thinking about the clinical trials for the ESCAPE platform, are you thinking about running those in the U.S. or would those likely be conducted ex-U.S.? Giuseppe Ciaramella: So, a couple of things on there. In terms of the beta thalassemia consideration, it's really a fact that, we think that ESCAPE essentially alters the risk benefit profile and in particular reduces the risk to the point that even in the beta thalassemia patients, a transplant might be justified, particularly in the broader beta thalassemia patient, which goes beyond the transfusion dependent thalassemia patients, which as you know is a relatively small number of patients, obviously very sick, but we think that ESCAPE opens up the opportunity to treat even beyond TDP. And so, that's fundamentally the main reason to consider that. And then in terms of the various places where we'll go, the healthy volunteers, we have not yet decided exactly where U.S. or ex-U.S. We will just be really efficiency and rapid exploration of that Phase 1 is really what's going to guide us in the choice that we make. Operator: Our next question comes from Luca Issi with RBC Capital. Luca Issi: Thanks so much for taking my question. Maybe John, big picture, it feels to me that ESCAPE is becoming increasingly more important now, especially in the context of the debt today, kind of reminding us the risk associated with busulfan. If a scenario where escape is actually not game-changing, are you still committed to commercialize BEAM-101 solo or would you be open to partner BEAM-101 or out license it similar to what Editas has recently communicated? Any color there. Much appreciated. John Evans: Yes. I think as you noted, we are playing the long game here in hematology and we see very exciting progression of technology that takes advantage of base editing, not to mention our now significant capabilities in CD34 manufacturing and these sorts of blood therapies to create a lot of impact for patients over time. And it is a progression that begins with 101 as potentially best-in-class product for this Wave 1 market leading to ESCAPE, which is no question, incredibly exciting and would be a really revolutionary product in the conditioning field, expanding us from sickle cells also include beta thalassemia, et cetera. As I have noted before, I think a lot of the capabilities we build along the way there, now adding the ability to change your blood system potentially without chemotherapy could lead to a lot of other places, right? So, we see a lot of growth opportunity here in hematology over the long-term. That's why it's one of our two core pillars. So, I think when it comes to partnering, I think we've always said that we have the luxury here of we don't have to partner for financial reasons. We would only partner strategically. And so, the partnership would be considered if a party could help us reach more patients more quickly than we could do ourselves and then it would be something that we would consider. To your hypothetical, I think if some of the elements of that pillar were to start to change, if we didn't have the ESCAPE technology for instance or it didn't work in some fundamental way, I do think that would change the long-term outlook in hematology that might change the balance of our strategic thinking. But in the near-term, I don't think it would change the value we have with BEAM-101 to potentially help a lot of patients who need help. So I think the calculus would basically be the same. It would be these are products that I think can make a big impact for patients and generate sustainable revenue and market value. If there's a party out there who can help us do any of this better without getting in the way of what we need to build that's a conversation that we'll entertain. Otherwise, we're prepared and well financed to do this ourselves. Operator: Our next question comes from Michael Yee with Jefferies. Michael Yee: If I may, since this is an earnings call as well, right, there are some other pipeline developments. You did announce that you had completed dosing the first cohort in AAT, which I think is a big achievement. Could you just remind us to what extent you believe that there would be material enough information to disclose and at what time point, given my understanding is the AAT levels should be rising pretty quickly. And certainly based on today's data, I'm sure you have more confidence in the editing here in-vivo. So at what point, would there be enough proof-of-concept for you to disclose and given you've already dosed three patients already? John Evans: So, you're absolutely right. We have a lot going on in the portfolio. We're very excited about the progress on liver side as well, as I noted in the Q results. With alpha-1, obviously, first cohort completed and now moving forward with that dose escalation. It is true as a reminder to everybody, we have dose escalating beginning at a low dose, but a low dose that is nonetheless expected to have biological activity that's important ethically and then we will seek to understand the optimal biological range, as we go. We've guided to a 2025 data release on that program. I feel confident in that guidance. I think when we will narrow that as we can, obviously. I think what we've always said is, we would look to bring out data when there is a clear profile of the drug. And I think that, I think clearly means at least multiple cohorts, exactly how we define that will be TBD. But we'll be watching it closely. And as you know, this is a program that does have the potential for early clinical proof-of-concept based on levels of alpha-1 normal, M alpha-1 going up based on Z protein hopefully going down. And then, of course, we'll be looking at safety in a Phase 1 study. So stay tuned, but that's certainly an update that we'll be looking forward to in 2025. Operator: Our next question comes from Rick Bienkowski with Cantor Fitzgerald. Rick Bienkowski: Congrats on the update and thanks for taking the question. I was just hoping to get a little more color on the expected pace of dosing in BEACON. I believe you said there were 35 patients enrolled in the study and eight patients dosed to date. If we can just get a little more detail on where we are for cell collection of the 27 patients, who weren't dosed yet and the potential timeline for all of these patients to be dosed? John Evans: Yes. So, I think as you rightly noted that we're quite pleased with the enrollment. It's actually exceeded expectations at this point. 35 patients now fully enrolled. That does not include additional patients who are in screening and consenting. So, it's a pretty robust pipeline and moving quite quickly now. As we had hoped, I think when we set up the clinical program that we did and thanks to Amy and her team for driving it. Dosing is now -- basically, as you know, it takes a long time to create the dose. At this point, we have doses rolling off the line fairly regularly. So, there is going to be a big uptick in doses in the near future as that trial commences. As a reminder, the overall trial, we're looking for 45 total patients, who will be dosed here. Clearly, we're well on our way to that. Also interestingly, we've always designed this trial as a potential to be a registration trial and our best understanding of that package based on the benchmark set by the XL program was 30 patients followed for about 15 months to get their endpoint assessed. And so, clearly, in this 35 patients, we've already got those patients moving. So, the clock has started at this point as we execute on these doses and look to enable, what could be a potential filing package for 101. Operator: Our next question comes from Debjit Chattopadhyay with Guggenheim. Unidentified Analyst: This is [Rai Forsathon] on for Debjit. What are your human translational expectations from the NHP ESCAPE data? Do you expect outperformance or underperformance relative to 101? And does having BEAM-101 clinical data help bolster your confidence in escape's clinical performance? John Evans: Yes. Pino? Giuseppe Ciaramella: Yes. We expect frankly equivalent, if not better performance in human and that's driven by the sequence of the guide that we use is -- and the antibody being cross reactive actually between non-human primates and human. So, obviously, we are refining a little bit the treatment paradigm of the antibody, so that we can optimize it even further, but I think this non-human primate data gives us tremendous confidence that we can move forward to the clinical studies. Operator: Our final question comes from Mani Foroohar with Leerink Partners. Mani Foroohar: Thanks for taking the question, guys. A quick follow-up on Mike's question on AATD. As we think about the market opportunity in this indication, this is obviously a fairly heterogeneous population. How should we think about the path forward both in terms of enrollment and clinical data and then ultimate sort of commercial opportunity between patients with a predominantly lung phenotype and those with a liver phenotype? And how will your enrollment strategy reflect the opportunity set across those? John Evans: So, alpha-1, it is a somewhat heterogeneous population. You have, of course, the majority of patients are primarily lung involved a minority have primary liver involvement, and of course, there's a spectrum of patients who share both. The beauty of BEAM-302 is that it addresses both sides of that equation. So for every allele we add it, we are going to start secreting normal protein, which should benefit the lungs and be under normal regulation and we're going to decrease the production of this toxic C protein that is causing so much trouble to liver. So I think at the end of the day, we don't need to choose. Now in the trial itself, we're initially studying this in patients, who are primarily lung just to make sure we have a clean profile given this is a liver delivered therapy, then, we will treat patients who have much more liver involvement. But our expectation based on pre-clinical data and our goal would be to deliver a single dose that is usable across the entire population and develop the drug across the entire population. I think by the time we get to considering market potential, ultimately, all patients are in view here, both currently diagnosed and then continuing to identify additional patients, who have that Z phenotype and are in really severe need of new therapeutic options. Mani Foroohar: Can I get a quick follow-up here? It makes a lot of sense to me that the technology can address the underlying genetic cause of disease and therefore address the molecular genetics to drive all of these phenotypes. That makes a lot of sense to me, biologically and clinically. But from a regulatory perspective, the time horizon approval endpoints for these two phenotypes aren't necessarily aligned. If you give us a little bit of color on how you think about -- how to get approved for treatment for liver, mixed, long, et cetera, what that looks like from a regulatory practical perspective? John Evans: Yes, understood. And I mean, look, I think our first job here is to deliver a hopefully compelling Phase 1 data set, right, which shows the kind of fundamental correction of the gene in the body for the first time. That's step one. That of course, that data opens the door to the conversation with the regulators for a lot of the different options here. You're right that formally a lung endpoint may have a certain set of requirements and characteristics that may be different than a liver endpoint. Of course, the RNAi knockdown therapies have been exploring the liver pathway. We can learn from that. And so, certainly for the different kinds of patients, we may explore both. At the same time across both of them, there's the opportunity to consider the use of just the biomarkers themselves and the protein deficiency, which defines this disease, as endpoints and markers of benefit that we would be exploring as well and that of course would be universal across patients. So, I definitely grant your point. I think it's early days. There's a lot to work through. I think our first step is to generate a compelling data set that will then drive the conversations with regulators and investigators on how to develop the drug. Operator: This concludes the question-and-answer session. Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Ever feel like you missed the boat in buying the most successful stocks? Then you’ll want to hear this. On rare occasions, our expert team of analysts issues a “Double Down” stock recommendation for companies that they think are about to pop. If you’re worried you’ve already missed your chance to invest, now is the best time to buy before it’s too late. 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