Beam Therapeutics Inc.

Good morning and welcome to the BEAM Therapeutics conference call. At this time, all participants are in a listen-only mode. There will be a question and answer session at the end. Please be advised that this call is being recorded at BEAM's request. I would now like to turn the call over to Holly Manning, Vice President of Investor Relations and External Communications.

Thank you, operators. Good morning, everyone, and welcome to BEAM's conference call to review third quarter 2024 business updates, including abstracts accepted for presentation at the American Society of Hematology Annual Meeting. You can access slides for today's call by going to the investor section of our website, beamtx.com. With me on the call today with prepared remarks are John Evans, our Chief Executive Officer, Dr. Giuseppe Pino Taramella, 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 factor 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 FCC. 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.

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 AACD, 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 transplants. 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 developing candidates for our ESCAPE technology, which Pino will detail shortly. For our 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, and as I noted, we expect to share initial data for multiple cohorts in 2025. In addition, in June, we received US 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 today. I'll now turn to sickle cell disease. At the J.T. Morgan 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 B-Selfin 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 hundred 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 conditioning. 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- to four-fold. A little further out is wave three, 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 Dean 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 HBF, a deeper reduction of HBS, and normalization of hemoglobin and red blood cell function. 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 preclinical 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.