Earnings Call Transcript - BEAM Q3 2024

Operator, Operator

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.

Holly Manning, Vice President of Investor Relations and External Communications

Thank you, operator. Good morning, everyone, and welcome to Beam's conference call to review the third-quarter 2024 business update, 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 Investors section of our website, bmtx.com. With me on the call today with prepared remarks are 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, CEO

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 another 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 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, thus meaningfully expanding 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 HbF, 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? 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 benefits 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 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, Chief Medical Officer

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. 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, and include six patients in the safety analyses and four patients in the efficacy analyses. Baseline demographics 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. Notably, 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. 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 were no Grade B or higher adverse events or serious adverse events related to BEAM-101. As shown, 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. 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. 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. Importantly, these data are consistent with our preclinical results and were seen in individuals with sickle cell trait. 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, 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 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. 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.

Giuseppe Ciaramella, President

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. 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. However, all such transplants still rely on chemotherapy, most commonly busulfan to enable the replacement of blood cells. 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 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 cells. The CD117 edit does not alter CD117 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. We have evaluated the system extensively in mice, but to establish true growth concepts, we wanted to conduct a comprehensive study in non-human primates. We are collaborating with multiple leading experts in the field. The preliminary data 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 cells. If replicated in humans, these results will achieve our Wave 2 vision of non-genotoxic conditioning for gene editing in hematology.

John Evans, CEO

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. 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.

Operator, Operator

Our first question comes from Gena Wang with Barclays.

Gena Wang, Analyst

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 did that patient die? And then, why that could be due to the busulfan? If you can give a little bit more color there?

John Evans, CEO

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. What it shows at a high level is the very real risks of transplant and chemotherapy. We're using busulfan in this case, and 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 lead to mortality, something that the field continues to optimize, but it's a real choice that patients have to think about. 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 transplant physicians, who are seeking transplant that begins with the shift from allogeneic to autologous, which is happening now. And of course, with the data we're showing today, we believe that BEAM-101 has a 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, Chief Medical Officer

Sure. It turns out busulfan is, as John mentioned, a chemotherapeutic and cytotoxic agent and is known to be associated with dose-dependent pulmonary toxicity. As you go up in higher doses, more toxicity can occur, and in some cases, it can indeed be fatal. Myeloablative conditioning with agents such as busulfan can cause something referred to as idiopathic pneumonia syndrome, which can occur in up to 6% of patients who have autologous transplant. The rates are up to 6%. The timing of this dysfunction, as well as the extensive clinical workup really points to this being consistent with what has been seen with busulfan both in what is reported in the label as well as the literature about stem cell transplantation. The patient's blood was corrected and normalizing in line with what was seen in other patients. While it's an unfortunate case, it is a known complication.

Operator, Operator

Our next question comes from Yanin Zhu.

Unidentified Analyst, 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 products and other upcoming products in the pipeline? If you can shed some light, because I guess VOC data has been pretty strong for the approved product. So wondering where could we see additional clinical benefit?

John Evans, CEO

Sure. I'd like to have Pino cover this one.

Giuseppe Ciaramella, President

Yes. As you can see, 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 severe conditions. We do feel that this combination of 60 to 40 can be like a sickle trait and potentially even better since hemoglobin S is anti-sickling as opposed to hemoglobin A. We believe this can lead to a variety of deeper resolutions. We share some biomarkers that show that the blood function is normalized to the extent that we can measure it. 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.

Operator, Operator

Our next question comes from Dae Gon Ha with Stifel.

Dae Gon Ha, Analyst

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, a 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 four side?

John Evans, CEO

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 HbF. In patients three and four, it's 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.

Operator, Operator

Our next question comes from Eric Joseph with JPMorgan.

Eric Joseph, Analyst

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 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 over time. Any concern, I guess, with long-term follow-up with persisting hemoglobin around that level?

John Evans, CEO

Yes. Thanks, Eric. Amy?

Amy Simon, Chief Medical Officer

Yes. Those two patients experienced mild elevations in hemoglobin. Importantly, there have been no clinical signs or symptoms from those patients or medical interventions required. These are considered laboratory abnormalities at this point by the investigators and have not even been considered as adverse events. Importantly, as Pino mentioned, with the elevated hemoglobin F to S ratio of 60 to 40, we feel 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.

Operator, Operator

Our next question comes from Kostas Biliouris with BMO Capital Markets.

Kostas Biliouris, Analyst

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 101 from ESCAPE?

Giuseppe Ciaramella, President

We have not noted any off-target biology of concern in any of the studies that we've done. Through extensive off-target biology, no off-target biology of concern emerged.

John Evans, CEO

From the market perspective, our plan has always been to view this as a lifecycle strategy across this franchise. It begins with BEAM-101, leads to ESCAPE, and now includes BEAM-103 and 104, with the potential for in-vivo applications as well. We see this as a progression. If ESCAPE achieves its intended profile, with efficacy comparable to 101 or other gene therapies in the field but without chemotherapy, I expect it to overtake and replace 101 in the market. Once we advance ESCAPE, it changes the dynamics significantly because it eliminates many of the risks associated with transplant and chemotherapy, thereby expanding the patient population we can address, which we believe could be up to four times larger. The regulatory preclinical package, clinical trial systems and design, regulatory strategy, and endpoints for both programs are aligned, resulting in a more efficient development program.

Operator, Operator

Our next question comes from Samantha Semenkow with Citi.

Samantha Semenkow, Analyst

Thank you for taking the question. Sort of expanding on that last question, the NHP data that you shared today for ESCAPE look pretty encouraging on both engraftment and HbF induction. 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, CEO

Maybe I'll have Pino answer the second question. On the first question, I think 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.

Giuseppe Ciaramella, President

Yes. There have been several studies already conducted with antibodies against CD117. And in those individuals, you see a transient but mild neutropenia being the major outcome. These antibodies do not lead to myeloablative conditions as you would see with chemotherapy. The healthy volunteer study will be a very efficient way of getting to a PK/PD understanding of the antibody.

Operator, Operator

Our next question comes from Sami Corwin with William Blair.

Sami Corwin, Analyst

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 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, President

In terms of the beta thalassemia consideration, we think that ESCAPE alters the risk-benefit profile and reduces the risk to the point that even in beta thalassemia patients, a transplant might be justified, particularly in the broader beta thalassemia patient population. We are still deciding where we'll deploy for the healthy volunteers. Efficiency and rapid exploration of that Phase 1 are what's going to guide us.

Operator, Operator

Our next question comes from Luca Issi with RBC Capital.

Luca Issi, Analyst

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 data today, kind of reminding us of the risk associated with busulfan. If a scenario where ESCAPE is actually not game-changing, are you still committed to commercializing BEAM-101 solo or would you be open to partner BEAM-101 or out license it similar to what Editas has recently communicated?

John Evans, CEO

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 capabilities in CD34 manufacturing to create a lot of impact for patients over time. We see a lot of growth opportunity here in hematology over the long term. We've always said we have the luxury of not having to partner for financial reasons. We would only partner strategically. If some elements of that were to start to change, it would likely change the long-term outlook in hematology, but in the near-term, I don't think it would change the value we have with BEAM-101.

Operator, Operator

Our next question comes from Michael Yee with Jefferies.

Michael Yee, Analyst

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?

John Evans, CEO

So, you're absolutely right. We have a lot going on in the portfolio. We’re excited about the progress on the liver side as well. With alpha-1, we have planned dose escalation beginning at a low dose but a dose that is expected to have biological activity that is important ethically. We’ve guided to a 2025 data release on that program. Our goal would be to deliver a single dose that is usable across the entire population and develop the drug across that population. I think by the time we get to considering market potential, ultimately, all patients are in view.

Operator, Operator

Our next question comes from Rick Bienkowski with Cantor Fitzgerald.

Rick Bienkowski, Analyst

Congrats on the update. 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, CEO

Yes. You’re right. We're quite pleased with the enrollment, which is already exceeding expectations. We have 35 patients enrolled, which includes some additional patients in screening and consenting. Dosing is now rolling off the line regularly. So, there will be an uptick in doses in the near future as that trial commences. The overall trial looks for 45 total patients to be dosed. We expect to see significant movement soon as we have already begun to clock on that front.

Operator, Operator

Our next question comes from Debjit Chattopadhyay with Guggenheim.

Unidentified Analyst, Analyst

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, CEO

Yes. Pino?

Giuseppe Ciaramella, President

We expect frankly equivalent, if not better performance in human clinical trials. The data gives us tremendous confidence that we can move forward and conduct these studies.

Operator, Operator

Our final question comes from Mani Foroohar with Leerink Partners.

Mani Foroohar, Analyst

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 the ultimate commercial opportunity between patients with a predominantly lung phenotype and those with a liver phenotype?

John Evans, CEO

Alpha-1 is a somewhat heterogeneous population. You have the majority of patients primarily lung-involved and then the minority have primary liver involvement. The beauty of BEAM-302 is that it addresses both sides of that equation. We don’t need to choose. In the trial itself, we're initially studying this in patients who are primarily lung-affected just to ensure a clean profile. We ultimately will treat patients across the spectrum including liver involvement.

Operator, Operator

This concludes the question-and-answer session. Thank you for your participation in today's conference. This concludes the program. You may now disconnect.