Good afternoon and welcome to 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, Operator. Good afternoon, everyone, and welcome to Beam's conference call to review updated data from the BEACON trial of BEAM-101 in sickle cell disease, presented at this year's European Hematology Association 2025 Congress. 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 Ciaramella, our President; Dr. Amy Simon, our Chief Medical Officer; and Dr. Ashish Gupta from the University of Minnesota. Our Chief Commercial Officer, John Lo, will join for Q&A. 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 the 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 well as results 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 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.
Thanks, Holly. At Beam, we are reimagining what's possible in medicine. Our bold vision is to provide lifelong cures for patients suffering from serious diseases. We are pioneering a new class of one-time curative therapies, treatments designed not just to manage disease, but to potentially eliminate it at its source. Today, we're excited to share with you updated data from the BEACON trial of BEAM-101, which we believe has the potential to be a best-in-class option for people living with sickle cell disease. A poignant example of our vision in action can be found in Brandon's story. Brandon grew up with severe sickle cell disease and spent much of his childhood in and out of the hospital continuously with pain crises. In sixth grade, he had both of his hips replaced because of the damage caused by sickle inflammation.
By 17, he was having life-threatening acute chest syndrome attacks, where the sickle cells were blocking blood flow to the lungs, causing Brandon to miss his entire junior year of high school. In 2023, Brandon became the first person to receive BEAM-101. Since treatment, he has been healthy enough to experience many firsts that were previously unattainable due to his disease: graduating high school, his first job, planning for college, and exercising like a normal young adult. Beam has established a strong leadership position in the gene editing field, enabling us to pursue our vision of providing more of these kinds of outcomes for patients like Brandon. There are multiple factors that set us apart, including our clinically validated base editing platform with fully integrated manufacturing, two core high-value franchises, a dedication to rapidly executing our priority clinical programs, and an exciting 2025 with multiple anticipated key catalysts.
Underpinning this work is the strength of our balance sheet, with $1.2 billion in cash, cash equivalents, and marketable securities as of the end of the first quarter, which we expect to support our operating plans into 2028. Within the last six months, we've now established clinical proof of concept for base editing, as well as our ex-vivo and in-vivo delivery approaches spanning both of our franchises. With consistent translation from preclinical models to the clinic, we have now provided strong evidence for the power and versatility of our platform, and our internal GMP manufacturing capabilities have directly contributed to our clinical success. On the clinical and regulatory front, we continue to make significant progress in activating new sites in new countries, ramping up enrollment and dosing in our trials, and securing key regulatory designations to support the continued advancement of our programs.
Our two core franchises in hematology and liver genetic diseases each feature highly differentiated and potentially best-in-class lead programs. Our liver genetic disease portfolio represents a high-value strategic pillar of Beam's long-term growth. Our lead program is BEAM-302, a potential one-time treatment for alpha-1 antitrypsin deficiency aimed at addressing both lung and liver manifestations of the disease under normal gene regulation. Earlier this year, we established clinical proof of concept showing that BEAM-302 addresses the root cause of AATD, and operationally, we've made significant progress, having received IND clearance as well as RMAT and orphan drug designations from the FDA. In addition, we dosed the first patient in the phase I/II study of BEAM-301 for glycogen storage disease 1A. Looking ahead, we anticipate multiple clinical catalysts in 2025 with the potential to further validate our approach and unlock significant value.
Turning to hematology, which will be our focus for today, we believe we have a high-value franchise with potential best-in-class programs for sickle cell disease that have generated strong execution and momentum. I'm happy to report today that enrollment of both the adult and adolescent cohorts in the BEACON trial of BEAM-101 are now complete, with dosing progressing swiftly. Our next generation of ESCAPE antibody for non-genotoxic conditioning is also on track to enter the clinic later this year. To go deeper, let's step back and revisit our long-term strategy and commitment to developing safer, more effective, and more accessible treatments for people living with sickle cell disease. 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 force red blood cells into a sickle or crescent shape, blocking the flow of blood and oxygen throughout the body and causing pain crises, organ damage, and early mortality. Our vision is to bring functional cures to all patients with sickle cell disease with a series of complementary technologies, forming an integrated lifecycle strategy. Our wave one 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. Wave two uses the same BEAM-101 edit and incorporates our ESCAPE technology to enable non-genotoxic conditioning with antibodies.
If successful, ESCAPE would eliminate the need for chemotherapy conditioning, 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. Beyond this is wave three, where we are using our leading capabilities in lipid nanoparticles to explore the potential for in-vivo base editing for sickle cell disease, which would eliminate the need for transplantation. In-vivo delivery of base editing could be a maximally scalable delivery platform, enabling even broader patient access to these kinds of curative therapies, both here in the U.S. and around the world. In 2023, the first gene therapies were approved for the wave one market, aiming to revolutionize the treatment paradigm for the most severe sickle cell patients. Because they involve complex ex-vivo manufacturing and transplant, these products will take several years to fully operationalize.
However, we remain incredibly bullish on the commercial outlook for the wave one market in the U.S., with peak annual revenue potential of $3 billion-$4 billion. This aligns with CAR-T benchmarks, another complex cell therapy that took several years to operationalize, but where today, 10%-20% of clinically eligible patients receive these therapies, and the class has grown to a multi-billion dollar annual market. Unlike CAR-T, however, in severe sickle cell disease, existing pricing is around $2 million-$3 million per treatment, meaning that each patient is profitable and the reimbursement landscape is strong. To date, there have been no reported prior authorization rejections, and a new CMMI access model now covers 84% of eligible Medicaid patients. In addition, infrastructure is scaling as qualified centers are gaining experience with both therapy and reimbursement.
Patient experience metrics like mobilization, hospital stay, safety, and efficacy will shape provider capacity and therapy choice, and we believe BEAM-101 is uniquely positioned to differentiate in each of these categories. Already, there is evidence that demand is outpacing supply. To illustrate that last point, patient and site demand has been loud and clear from our market research, where KOLs have indicated significant interest from dozens to hundreds of their eligible patients, some of whom are on years-long waiting lists for their chance at a cure. The current landscape is also such that no single player can meet this demand on their own, and this makes our work to develop BEAM-101 all the more important.
We expect this market to continue to mature as operational improvements across suppliers, providers, and payers take effect, creating an opportunity for Beam to enter a much more established market in coming years. Our goal has been to bring forward a product with a highly differentiated profile. Based on data to date, including our updated data now presented at EHA, we believe we are achieving this goal, in part due to the underlying technology, as well as our ability to make and deliver this medicine quickly and efficiently. BEAM-101 uses base editing, a next-generation CRISPR technology that allows us to 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 the clinical experience with BEAM-101 to date exemplifies the best-in-class potential of this approach. Without double-stranded breaks or viral insertions in the DNA, we're seeing healthier cells and faster engraftment of the new edited cells. We also observe high levels of editing, and the uniformity of these edits within cells results in higher hemoglobin F production and lower residual S. Using this next-generation approach to gene editing, our goal for BEAM-101 is to achieve 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, a carrier with only one mutation who is typically asymptomatic. As shown on slide 14, total hemoglobin for a person with sickle cell disease has 100% HbS in circulation.
The disease threshold is exemplified by people with sickle cell trait, as these people generally have about 60% normal hemoglobin and only 40% HbS. This is a threshold that has not yet been achieved in the field of sickle cell gene therapy. Today, we're pleased to share that, consistent with data presented in December at ASH, all patients treated with BEAM-101 to date continue to achieve this profile with HbF levels above 60% and HbS levels below 40%, meeting or exceeding levels seen in sickle cell trait. We also observed full resolution of anemia, and markers of hemolysis and oxygen delivery were normalized or improved in all patients. In addition, our data continue to suggest the potential for needing less time in the hospital, with fewer average cycles of mobilization and rapid engraftment of edited cells following BEAM-101 treatment.
Beyond efficacy and safety markers, differentiation of BEAM-101 extends to our manufacturing process, which benefits from the scheduling flexibility of controlling our own facility, high yields enabled by base editing, plus a highly automated process. Pino will review our manufacturing process performance in more detail later in the call. Altogether, our goal is to deliver a high-quality product and improve the patient experience throughout the transplant process. Now, to review the latest clinical data in more detail, I'd like to introduce Dr. Ashish Gupta. Dr. Gupta is an investigator in the BEACON trial and a pediatric blood and marrow transplant physician at the University of Minnesota Health Masonic Children's Hospital. Dr. Gupta is also an assistant professor in the Department of Pediatrics and a faculty member in the Division of Blood and Marrow Transplantation at the University of Minnesota Medical School. Dr.
Gupta, thank you for being with us here today.
Thanks, John. I'm Ashish Gupta. I am an Associate Professor in the Division of Pediatric Blood and Marrow Transplant and Cellular Therapies at the University of Minnesota, and I'll be presenting the updated data from the BEACON trial, which is a phase I/II single-arm open-label study evaluating the safety and efficacy of a single dose of BEAM-101 in patients with sickle cell disease with frequent and severe vaso-occlusive crises. As we know, there is an unmet need in sickle cell disease for effective gene therapies that address the full spectrum of disease. BEAM-101 is an autologous stem cell-based therapy that uses a novel base editing mechanism to enable precision editing of HBG1/2 promoters without requiring double-stranded DNA breaks or disrupting downstream BCL11A pathways in order to upregulate fetal hemoglobin in patients with sickle cell disease.
Preclinical data have demonstrated that base editing results in highly efficient and predictable gene editing outcomes, leading to a more uniform induction of hemoglobin F and corresponding reduction in hemoglobin S, resulting in fewer sickle cells. The BEACON study is a phase I/II single-arm open-label study evaluating the safety and efficacy of this product. The study is ongoing with more than 40 patients past screening and enrollment, and here we present the data as of February 2025. The key eligibility criteria for the study include patients aged 12 to 35 years with sickle cell disease and history of at least four severe VOCs in the previous 24 months. Key safety and efficacy endpoints include proportion of patients with successful neutrophil and platelet engraftment, the time to engraftment, and the proportion of patients who are severe VOC-free for 12 consecutive months. We also evaluated the markers of hemoglobin and RBC function.
Further details about the RBC and hemoglobin function are on poster 1155, which will be presented on June 13th in the poster session one. The BEACON study involves four stages, shown on this slide, which can span from about six to eight months prior to dosing with BEAM-101. After confirming the eligibility, patients undergo mobilization and leukapheresis to collect their hematopoietic stem cells. This is done with the help of plerixafor without any GCSF in the mobilization. These HSCs are subsequently base edited ex vivo and then administered back to the patient after myeloablative conditioning with busulfan. Following engraftment, patients are discharged and follow up for up to 24 months on study before entering a long-term follow-up study. The baseline demographics and characteristics of patients treated with BEAM-101 are displayed here.
Seventeen patients have been dosed as of February 28, 2025, with a follow-up of between 0.2 months-15.1 months. The mean age of study participants is 22.9 years, and all but one patient has beta S, beta S. Median investigator-reported severe VOCs in the two years prior to the start of study is nine. On this slide, we present the mobilization and apheresis characteristics of BEAM-101 patients. Eleven patients required only one mobilization cycle, four required two cycles, and only two patients required three cycles for stem cell mobilization. During the mobilization, four patients were noted to have a reduction in platelet count, while three each had hypervolemia and hypomagnesemia. A median of three total mobilization days was required for drug product manufacturing. Patients who received BEAM-101 were noted to have rapid neutrophil and platelet engraftment with few days of severe neutropenia.
The median time to neutrophil engraftment in 16 out of the 17 patients was noted to be 16.5 days. The duration of severe neutropenia was noted to be seven days. Of the 17 patients, 14 patients achieved platelet engraftment by the time of data cut. The median time to platelet engraftment was noted to be 19.5 days. Of note, seven patients out of these 14 did not require a single platelet transfusion going through the process. In terms of the safety data, the BEAM-101 study was consistent with busulfan conditioning, autotransplant, and underlying sickle cell disease. There were no serious treatment emergent adverse events related to BEAM-101, and there were no AEs leading to discontinuation of the product.
One death was noted from respiratory failure approximately four months after BEAM-101 dosing, determined by the DMC not to be related to BEAM-101 and was likely related to busulfan conditioning. The common TAEs reported in at least three patients included stomatitis, febrile neutropenia, and other AEs as reported here. The swim lane plot here describes the VOCs pre and post BEAM-101 in patients who received the infusion. The gray bar here represents the baseline period, and each star represents a vaso-occlusive event that these patients had prior to infusion of BEAM-101. The blue bar on the right represents the RBC transfusion period, while the navy blue represents the post-infusion transfusion period. Of note, no patient was noted to have a severe VOC or a VOC post-engraftment.
Also, all patients achieved rapid and durable increases in hemoglobin F to greater than 60%, with a subsequent decrease in hemoglobin S as well. As noted on these bars, the navy blue ones are the hemoglobin F induction, while the teal bars are the hemoglobin S. As one can see, that hemoglobin F over F plus S, which is defined as the hemoglobin F percentage of the untransfused blood, was noted to be about 67% at one month in 13 patients, which remained consistent throughout. It was also noted that other than the rapid and robust increase in total hemoglobin as well as hemoglobin F, this increase was durable throughout the follow-up. This hemoglobin F was also noted to have a pancellular expression, and it was observed even following the elimination of the transfused blood.
Additionally, mean hemoglobin F reached a predictive threshold by month one and was sustained throughout the follow-up period, as noted on the bar on the right bottom. Also, of note, the erythropoietin levels were markedly decreased to normal or near normal, indicating adequate oxygen delivery to the tissues. Further details are on poster 1155, which described the RBC health and function post BEAM-101. We also looked at the hemolysis markers, which normalized or improved following BEAM-101. The graph here shows decrease in haptoglobin or normalization of haptoglobin, LDH, reticulocytes, and indirect bilirubin. In conclusion, the safety data from BEACON study supports continuation of the trial and demonstrates robust and sustained increase in hemoglobin F expression and resolution of anemia in patients with sickle cell disease. Again, further details about the efficient collection and manufacturing process are on poster 1165.
As we talked about before, there was a rapid and robust neutrophil and platelet engraftment that was noted. The ongoing safety data is consistent with busulfan conditioning and autotransplant. There were no severe VOCs or any VOCs that were reported by investigators post-engraftment. There was a rapid and robust increase in total hemoglobin as well as hemoglobin F with a pancellular distribution, which was maintained through the study follow-up. In parallel, there was a rapid and robust decrease in hemoglobin S, which was noted with resolution of anemia, and the markers of hemolysis normalized or improved in all patients. With that, I acknowledge all the study participants and their families and thank them for participation on this critical trial, as well as their caregivers and the study investigators for their contributions. Now, I will hand it over to Amy.
Thank you, Dr. Gupta. In addition to our primary BEACON clinical trial abstract, we're pleased to share data from an additional poster presentation that details the impact of BEAM-101 treatment on exploratory biomarker assessments of red blood cell hemoglobin expression and function from patients in the trial. As shown in orange, the presence of hemoglobin S in red blood cells results in multiple functional abnormalities in the cells due to polymerization of deoxygenated hemoglobin S, which leads to changes in cell shape, such as sickling, density, adherence to the vasculature, deformability, or the ability of the cell to pass through blood vessels, as well as lifespan. These red blood cell abnormalities underlie the pathophysiology of sickle cell disease, resulting in vascular occlusion, organ dysfunction, and systemic inflammation. Given that BEAM-101 treatment, as just shown by Dr.
Gupta, decreased sickling HbS to less than 40%, increased anti-sickling HbF to more than 60%, and decreased hemolysis, we wanted to explore the impact of BEAM-101 and other important aspects of red blood cell health and function, as outlined in green. Building on the initial data from two patients at ASH, we now have data from up to 13 patients treated with BEAM-101 demonstrating that post-treatment, 98% of their red blood cells expressed hemoglobin F as early as month one, with near complete elimination of red blood cells expressing solely hemoglobin S. These HbS-only cells are the cells which would be most likely to sickle under stress, such as in states of low oxygen or decreased temperature, causing pain crises, vascular occlusion, and organ damage. In addition, we evaluated the rate of red blood cell sickling.
On the left-hand side of the chart in yellow, you can see that at baseline, the blood from these patients has a high rate of sickling compared to the amount of sickling seen in the blood from healthy control individuals, shown in the dark blue on the right. After treatment, shown in green, you can see that there is a significant decrease in the rate of sickling in these patients compared to their baseline. Importantly, the rate of sickling post-BEAM-101 treatment is comparable to that seen in the blood obtained from sickle cell trait individuals, shown in light blue on the right. Also, as noted here, there were other improvements in red blood cell function, including an increase in deformability and a decrease in the percent of dense RBCs.
We also observed a decrease in systemic inflammation, as seen by reductions in serum CRP and IL-6 after treatment with BEAM-101. Shown on this slide is a striking visual of the impact of BEAM-101 on red blood cell number and morphology or shape. As you can see on the panel on the far left, this is what sickle cell red blood cells look like pre-treatment, with very few pale red blood cells reflecting the patient's underlying anemia, along with the presence of sickled cells and immature and misshapen red blood cells that look target-like or elongated. In subsequent images, you can see the resolution of the anemia with increased cell numbers that are no longer pale in color and no evidence of sickle cells or other abnormally shaped cells post-treatment was seen.
These data in up to 13 patients from the BEACON trial continue to suggest that treatment with BEAM-101 restored RBC health and function. In summary, following BEAM-101 treatment, 99% of non-transfused RBCs expressed hemoglobin F with near complete elimination of RBCs expressing solely hemoglobin F as early as month one post-treatment. Reductions in multiple sickling parameters were seen and were comparable to sickle trait. Cell adhesion was reduced to significantly below the critical sickle cell disease threshold, indicating a reduced risk for VOCs. The percentage of dense RBCs, RBC deformability, and systemic inflammation all improved. Finally, an increase in RBC cell number and resolution of abnormal RBC morphology was observed. With that, I'll turn the call over to Pino.
Thank you, Amy. As John outlined, there are multiple autologous gene therapies approved for sickle cell disease, which are administered using a fairly similar transplant process that Dr. Gupta described in detail. This is a complex and time-intensive journey, and with BEAM-101, we aim to streamline this process in multiple ways. First, with internal Beam GMP manufacturing, we can make it easier from the start with flexible scheduling of mobilization and CD34 isolations. Second, once we have the cells in hand, we use a closed automated manufacturing process that has resulted in high yields that pass high-quality standards. As of the data cutoff, our clinical experience shows that most patients require just one mobilization cycle. Finally, as Dr. Gupta noted, post-transplant, patients treated with BEAM-101 are engrafting rapidly, reaching neutrophil engraftment in just 16.5 days and platelet engraftment in 19.5 days.
This has the potential to translate to fewer neutropenic days and shorter hospital stays. The result is a potentially more efficient, better tolerated, and patient-friendly process that also puts less of a burden on hospital capacity. This could allow more patients to be treated over time and positions BEAM-101 as a differentiated and scalable solution in the gene therapy landscape. The manufacturing data being presented today at EHA gives insight into the consistency and robustness of our manufacturing process and of the base editing mechanism. Shown here are two example data points from the manufacturing poster presented today. In the left-hand panel, we show the robust and consistent clinical process performance that our team has achieved across 28 CD34 batches with a mean viability of 85%.
On the right, we show the strong and highly reproducible on-target editing rates being achieved by BEAM-101 base editing with a mean of 92% from 28 batches. Through the automation of every unit operation, we are able to ensure robust and repeatable process performance and produce consistently high-quality drug product. This manufacturing process has also allowed us to move incredibly fast. As John noted, we are now fully enrolled across both adult and adolescent cohorts. As of today, I'm happy to report that we've manufactured and released drug product for 34 patients, with 26 of those receiving BEAM-101 already. All of this has occurred in just under 18 months since the last patient was dosed with BEAM-101. We've also made regulatory progress, securing orphan drug designation for BEAM-101 just a few weeks ago.
We are well on our way to building a package for a future VLA submission for U.S. approval, and we look forward to continuing to update you along the way. Back to you, John.
Thanks, Pino. As you've heard from our team today, we continue to be energized by the emerging differentiated profile for BEAM-101, the efficiency of our manufacturing process, and the progress we're seeing in the established gene therapy market for sickle cell disease. We believe that we have a clear path toward a VLA submission with the potential to enter what we think will be a more established and growing market for sickle cell gene therapies with a best-in-class product. We look forward to continuing to advance this program to patients as quickly as possible. Building on the foundation of BEAM-101, we also look forward to advancing our suite of next-generation innovations in hematology: non-genotoxic conditioning with ESCAPE and in vivo LNP delivery to hematopoietic stem cells, which will further expand our sickle cell portfolio.
With the combined strengths of base editing and both ex vivo and in vivo delivery capabilities, we believe Beam is uniquely positioned to realize our vision of bringing the promise of functional cures to all patients with sickle cell disease. Everything we do at Beam is rooted in our mission to make a meaningful difference for patients. I want to thank the entire Beam team for their extraordinary dedication in advancing BEAM-101 from concept to clinic and for their unwavering focus on the patients who inspire this work every day. We are especially grateful to the individuals living with sickle cell disease who have made this progress possible through their courage, participation, and partnership. We also extend our thanks to the investigators, site teams, clinical and manufacturing collaborators, and advocacy organizations who have stood with us in pursuit of a better future for this community.
Operator, please open the line for Q&A.
Thank you. As a reminder to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please limit yourself to one question. Our first question comes from Rick Binkowski with Cantor Fitzg erald. You may proceed.
Hi all. Thanks for taking the questions and congrats on the data. I wanted to ask about the manufacturing time that you were seeing in the clinical trial. I do see that there's a median of one mobilization cycle, but I was hoping to get more detail around the actual length of time it takes from mobilization to dosing, and is this meaningfully different than what is being seen in the approved ex vivo products in the commercial setting?
Thanks, Rick, for the question, and I'll pass it on to Pino.
Hi, Rick. This is Pino. The time basically from, as you know, from the collection of the CD34 cells that occurs in the clinic, the cells basically are immediately shipped to us, and the process from that moment on takes approximately five days until we then store them in freezers, basically. We freeze them down. That is really the internal process. I'm not sure about the time from competition, obviously, but I would suspect that it is not too dissimilar from what others have seen.
Thank you. Our next question comes from Eric Joseph with JP Morgan. You may proceed.
Hey, guys. Thanks for the update here and taking the questions. Pretty forward-looking question from us in terms of the commercial outlook, just notwithstanding your comments, John, on access and reimbursements thus far with the existing approved products. We've heard anecdotally that some treatment centers have had trouble with commercial reimbursement going beyond the DRG, limiting their utilization. I'm just wondering along these lines whether you could talk about sort of relative manufacturing costs with BEAM-101 and whether price flexibility might be something that could be leveraged in order to kind of facilitate access and also take share. I might also have a follow-up.
Great. Thanks, Eric. Maybe I'll have John Lo, our Chief Commercial Officer, talk just a little bit about what we're seeing on access in general, and then maybe Pino, you can make a comment on relative cost of goods.
Yeah. Hi. Thanks, Eric, for a really great question. With regards to reimbursement, we have heard about this as well. I think it's an evolving landscape as commercial plans as well as Medicaid plans start adopting processes. It will be state by state or center by center. I'd say for the most part, what we've heard from most of the major transplant centers is that the reimbursement environment is improving whereby their states or their commercial plans are starting to input or implement processes. They're going away from single-case agreements to the more standardized plans. There are going to be some holdovers or some laggards, as you had referenced. We anticipate that over time that that'll all evolve. In fact, sort of by the time we launch, the reimbursement environment will greatly improve.
One example of that would be the CMMI rollout that John Evans had referenced earlier in the presentation, where 84% of the covered Medicaid sickle cell patients will be eligible for up to sort of down to two to three days reimbursed.
Yeah. Eric, this has been on your question about cost of goods. Obviously, we do not comment on the very specifics because, as you can appreciate, that is a competitive piece of information. One thing that I could say is that we expect every patient to be profitable, particularly if the price point can be, as you know, withstand $2 million per isolation per treatment or even higher, as you can see.
Yeah. I'd be willing to go a little further than that and just say I think I do expect we'll have a competitive cost of goods relative to others in the field, and we even have line of sight to continuing to make improvements on that over time.
Thank you. Our next question comes from Michael Yee with Jefferies. You may proceed.
Great. Maybe I can get one question for the doctor and one for the company. Maybe just for the doctor, in your experience or what you are seeing with patients who are getting treated with the commercial product as CASGEVY, is neutropenia a main gating factor for people being able to leave the hospital? Therefore, is that a material differentiation potential for the newer products and something to really keep an eye on? Also, for the company or for the doctor, perhaps, on the hemoglobin F levels, I see that one patient, number four, seemed to be sort of an outlier a bit just because they had maybe one or two points lower on average hemoglobin F. Was there anything particular about that patient or anything to note there on that chart? Thanks.
Hi, Michael.
Great. You too.
Yep. Sorry. I just jumped in quickly. Regarding the question for neutropenia, definitely it does make a difference because recovery from neutropenia is something that keeps those patients in the hospital and also heals as some of the pain issues are gone as the neutropenia is healing. That becomes a very important anchor there. What I would say is the focus is more on the duration of neutropenia rather than the neutropenic engraftment per se, which we are very impressed with the BEAM-101 data where we are seeing a median of about seven days of severe neutropenia. That does get into that factor of how quickly you recover from the treatment. Regarding the HbF levels, are you talking about patient three or patient four? I'm just a little not sure if you're confusing the two patients.
Four was sort of a light blue one that is about at hemoglobin F of about eight out to.
Can you guys hear me?
Do we have access? Hello?
Hello. Can you guys hear me?
Yeah, we can hear you fine. Yeah. I think Mike was saying it's the light blue patient number four, hemoglobin F around 8.
Yeah. So that patient actually is one of my patients. And I mean, that patient is doing very well and matches all other patients. I do not have a particular reason why that is a little bit down. Overall, what we are seeing is that at a month mark, there is a very robust hemoglobin F induction that is already happening, which is quite remarkable. It is sustained with a follow-up. Again, we have, if you see, just a couple of patients at the one-year mark on this data, but they continue to show the robust hemoglobin F induction.
Got it. Yep. Thank you.
Thank you. Our next question comes from Kostas Biliouris with BMO Capital Markets. You may proceed.
Congrats on the data, and thanks for taking our question. One high-level question from us for the company. Generally, the pushback we get from investors on CASGEVY is related to the lengthy process of treatment and delayed revenue booking. Given that BEAM-101 is also an ex vivo therapy, can you discuss high-level to what extent it can meaningfully address the current investor skepticism about CASGEVY and potentially how your follow-on treatments with a milder preconditioning and in vivo dosing can also address these skepticisms? Thank you.
Sure. Maybe I can just handle that one. I think, so for sure, it's a function of the ex vivo therapies that they are a longer process to get going, and then the revenue recognition comes in the tail end of that. That's primarily a dislocation, I would say, in market expectation on the beginning of the launch curve, and we're kind of living through that right now. That's obviously a focus area for investors. That will work itself out and gradually catch up. I don't think by the time we're launching, we expect that to be as much of an issue as I think it is today.
Certainly, we would be similar in terms of our process, notwithstanding the fact that our overall process from patient entry to dose may be faster based on some of the data we're seeing here, but it's still a process. ESCAPE ex vivo would be comparable. It's still that ex vivo process, again, probably more rapid than what we're seeing now, but still ex vivo manufacturing. In vivo, of course, would go faster, and that's one of the attractions to it. All that you're doing is you're shifting the timing of the revenue. I think the magnitude is still a function of the severity of the patients and the wave one market, and then our expansion to many more patients as we move to wave two and wave three.
Thank you. Our next question comes from Greg Harrison with Scotiabank. You may proceed.
Hi everybody. Thank you for taking our question. This is Joe Thomas on for Greg Harrison. I just had a quick one on the biomarker data around oxygen affinity for patients treated with BEAM-101. Have you seen any quality of life observations so far in the trial of this increased oxygen affinity? Are patients able to be more active or do anything that maybe they haven't been able to do previously? Thank you.
Yeah. Thank you. Maybe either Dr. Gupta, and maybe Amy, if you want to add on.
I can actually jump onto that, and I can share some of the patient experience there. Joe, we are very impressed with what we are seeing on the other end, just from the experience that we have with our patients. These are young men who are back to doing their workout, taking cold showers, which is unheard of in sickle cell patients, actually, because that can precipitate crises, and back to work, actually. The quality of life, again, I do not want to comment. There is a whole other study that is going on on that. Overall, we are very happy and impressed with what we are seeing in these young people, actually, who are living their lives now.
I'll just add just briefly across the study, and thank you, Ashish. That's wonderful to hear. We take cold showers for granted and some of the other things you said about going to work. This is wonderful. I do want to say we have a pretty robust amount of different PROs that we're collecting throughout the trial that will look at things like fatigue, one of the biggest complaints of people who have sickle cell because of the anemia. We also will be looking at different aspects of pain, looking at different pain medication usage, and very kind of common PROs or patient-reported outcome measures that are used in sickle cell and in general populations. It's too early given the duration of follow-up that we have right now to report on this.
We will plan to report on this usually after people have six months to 12 months of follow-up is when you start to report out more data. Stay tuned. We're looking forward to seeing that data.
Thank you. Our next question comes from Patrick Trucchio with H.C. Wainwright. You may proceed.
Thanks. Good afternoon and congrats on the data. Just a follow-up question around the regulatory piece. I'm wondering what discussions have occurred with the FDA around the regulatory path, particularly following recent personnel changes, including at CBER, and how those changes and today's data may potentially impact the path going forward.
Yeah. Thank you. Pino?
Yes. Thank you very much for the question. We continue to have very constructive interactions, frankly, with the FDA. I think even with the change of leadership, we are very encouraged by the comments that have been made with the new leadership that continue to see the opportunity for, frankly, transformative and curative therapies such as ours to really make a difference meaningfully to these patients and generating data that very clearly demonstrates that that's the case. We haven't yet confirmed, frankly, the path to the BLA yet. We plan to do that very shortly, but we have several interactions with them that would suggest certainly we already see a path with the experience of CASGEVY and LYFGENIA, for example, being an example that we can follow, so.
Thank you. Our next question comes from Alex Shenan with Bank of America. You may proceed.
Hey, guys. Thanks for taking our questions and congrats on the update here today. Maybe two quick ones from us. First, has anything changed with the busulfan conditioning since the update last year, either in terms of target exposure limits or monitoring? As a quick follow-up to that, any comments around the range you're seeing for average AUC of busulfan? I think it ranged from maybe 50-90 in the latest update, which is a little bit wider than what we saw at ASH last year. Thanks.
Thanks.
I'll comment first.
Dr. Gupta or Amy. Yeah. Go ahead.
I'll comment first, Ashish, and then you can go. We have not changed anything about our busulfan monitoring, which is basically very PK-driven. In general, as you know, we had an unfortunate event. Even that patient was within kind of what we were aiming for as far as the limits. That would not have been predicted. I feel like, again, all the monitoring is the same. I'll have Ashish comment on the range and compare it to what he's seen in his clinical practice.
Absolutely. Alex, good question, actually. The tricky piece with busulfan is that it is very center-dependent practice. Some centers would like to dose it once a day, like us. Other centers would like to dose it every six hours. The dosing is changed in real time based on the pharmacokinetic levels. That is where you see a lot of variability, actually, in the AUC for busulfan. I think the target is around 80 of AUC, which actually, if you're in that goal range, you are still able to maintain that target, which is a good myeloablative target. That's where you are seeing the variability on the AUC end, but how much it affects the clinical outcomes, actually, it is on the cumulative AUC where you are able to still maintain within the range. Busulfan has a wide range for myeloablation.
Anywhere between 60-90 is considered myeloblate. So till you're maintaining that range, you should be able to still get a good depletion of stem cells.
Thank you. Our next question comes from Samantha Semenkow with Citi. You may proceed.
Hi. Good afternoon. Thanks very much for taking the question and congrats on all the progress. I wanted to ask about the early signals that you're seeing that demand is outpacing supply. I guess, based on your understanding of this demand, how much of it would you say is or consider a bolus, or do you think this is something that will be enduring and continue to be demand that is there for you to capture potentially upon your launch? Just any context you could provide there would be very helpful. Thank you.
Yeah. Great. Maybe I'll have Dr. Gupta talk a little bit about what you're seeing yourself in terms of patient demand. Then maybe John, you can expand a little bit on how we're viewing that market and the sustainability over time.
Absolutely. Samantha, that's a really good question. As any new therapy comes to the market, there definitely is an initial bolus demand. This is an ongoing process as well. At my institution, we do maintain a list of patients who are not meeting the criteria yet. As time goes by, we do see actually that some of these patients eventually meet the criteria. There will be an ongoing need for sure. As John earlier pointed out, it's kind of like about 10% of the population, and we are still seeing a consistent flow of sickle cell patients. Again, depending on their response to different standard of care treatments, some of them will fall into this category of severe sickle cell disease. I do think that there will be a consistent demand.
It's hard to assess that at this point while we are still in that bolus phase. I like that word. I do think that there will be a consistent demand, as we are seeing on the clinical side, that there are patients who have severe disease continue to be there.
Yeah. And just to build on that, and thanks, Dr. Gupta, for your center's experience. We've talked to a number of the top transplanters across the country, and they would indicate that. I think two other points just to make. One, a waitlist is being built in a number of different centers. So it's unlikely that that would be depleted over the next X number of years before we launch. The other one is we are only projecting for the $3 billion-$4 billion market size a 10%-20% penetration of clinically eligible patients. And that balances roughly around sort of the incident patient population that would sort of age into the addressable patients. So we actually think there's a fairly long-term steady state that would also rely on sort of referrals from other centers into the major transplant centers.
Thank you. Our next question comes from Luca Issi with RBC Capital Markets. You may proceed.
Hi. Thanks for taking our question. This is Cassian for Luca. Congrats on a strong presence at EHA. We also have one question for company and one question for Dr. Gupta, if that's okay. Circling back on a prior question around the FDA, KalVista just announced that FDA will not meet the PDUFA date due to heavy workload and limited resources. When was the last meeting you had with FDA, and are you seeing any disruption there? Any comments there? Much appreciated. If Dr. Gupta, could you remind us the wave-based mix per kg dose for plerixafor support that you're using for apheresis? Thank you so much.
Sure. Maybe Dr. Gupta, do you want to answer that one first, and then we'll come back on the FDA?
I don't have the dosing on top of my head. If you want to answer the FDA, I can actually quickly get you the dose if that's okay.
That's much appreciated.
Great. Pino on the FDA?
Yeah. Just from our perspective, we haven't seen any dysfunction as you've made it. What I would note is that we have received several designations very recently, actually, even post some of the changes that have occurred. We obviously mentioned that we have an orphan drug designation for BEAM-101 just a few weeks ago. For our other program, BEAM-302, we've announced that we've received both an RMAT as well as orphan drug designation. That occurred, actually, in some cases, even faster than the deadline that they normally require. Our experience is all continues to move at the speed that it normally does. Obviously, we'll continue to see how it goes in future interactions.
Thank you. Our next question.
If I could just finish that question off, the plerixafor dosing is really based somewhat on the recommendations in the label, which then, if you go to the plerixafor label, gives guidance when people are under 85 kg. You can stay tuned. We will be presenting probably, hopefully, at a medical meeting in the future a little bit more about the plerixafor dosing and the outcomes.
Thank you. Our next question comes from Yanan Zhu with Wells Fargo Securities. You may proceed.
Great. Thanks for taking our questions and congrats on the data. A two-part question for Dr. Gupta, if we may. When you enroll patients into the study, is there also a decision to be made whether the patient would like to undergo commercial treatment? Do you think the differentiation or data from ASH has swayed patient decision in any way if there is such a decision point? Secondarily, could you comment on the total hemoglobin levels in these patients now that we have a few more patients? I think the earlier patients were on the higher end in terms of total hemoglobin. Anything of note now that there are more patients data to look at? Thank you.
Sure. Thank you for the question. From the decision standpoint, the way we practice over here is that we do what we call as a shared decision-making. I'm a transplant physician, and in consultation with the hematologist and the family, we discuss all options. It's not just one modality of gene therapy, but whatever is available. We discuss the pros and cons for each of the options and then make a decision. Again, recruitment on the clinical trial is based on after multiple consults with the patients and the families. Definitely, when that unfortunate event happened with the patient on the trial, which was presented at ASH, we did have discussion with the families. Also, the patients were already recruited on the trial as well. We discussed all the possibilities and how busulfan can play a role.
All the families and all the, I should say, all the patients, because these were all adults, consented on that, agreed, and we had a lot of discussion around it. I think it is always very upsetting to see any negative outcome, or especially a death, but also you have to put things in context where when you use a drug like busulfan, these things can unfortunately happen. Regarding your other question, yes, we do have more data than before. The total hemoglobin is, I'd say it is impressive, actually, where we have a good rapid induction of hemoglobin F. Your question regarding the high hemoglobin, we do not just consider just the high hemoglobin. You have to see what is the erythropoietin doing, what are the other markers doing. All in together, they are very impressive, and they are where we want it to be.
Regarding the high hemoglobin, there are no clinical concerns, actually, that we have. I have my patients, actually, who have high hemoglobin too. And they're doing fine. These are young men who are doing stuff that they were not able to do earlier on. We are monitoring them, but at the same time, there could be multiple factors for high hemoglobin. We are not seeing anything concerning on our end while continuing to monitor them.
Thank you. Our next question comes from Sami Corwin with William Blair. You may proceed.
Hey there. Congrats on the data, and thanks for taking my question. I was wondering if you could discuss your ex vivo manufacturing capabilities, specifically your current clinical scale of supply, what scale it might be necessary for future commercialization, and how easy it would be to switch BEAM-101 manufacturing to BEAM- 104. Thanks.
Yeah. Thank you very much for the question. The scale we are capable of supplying the clinical program pretty much fundamentally from North Carolina. The process is already pretty much a commercial process, so we can scale up very rapidly, and we have the ability to be able to satisfy the demand of the commercial setting from the North Carolina site. We feel very well placed to continue to progress this program all the way to commercial.
Thank you. Our next question comes from Manny Ferroja with Clear. You may proceed.
Hey, guys. We have Ryan on for Manny. Thanks for taking our question and congrats on the update. Maybe pivoting over to the ESCAPE program, wondering if you could just talk about what the regulatory pathway looks like for this post the healthy volunteer data. Then piggybacking off of that, just wanted your perspective on how mature this initial ESCAPE data has to be for you guys to feel confident reorienting your strategy around that approach. Thanks.
Yeah. Thank you. Thanks for the question. In terms of regulatory path, obviously, we need to continue to have the conversation with regulators, but we do plan for the healthy volunteer study that is scheduled for the second half of this year to provide a PK/PD analysis of the antibody and therefore guide our dosage in the patient setting that will come at a later time. The important thing there, as you know, is that the other part of that product is essentially BEAM-101. And therefore, the clinical sort of learning that we're making now will completely directly inform what we're going to do with the patients there. In terms of the change in the pivot, obviously, we will want to see more clinical data eventually with that setting in order to be able to determine whether that is worth a sort of consideration in terms of switching.
For the time being, we do believe that BEAM-101 is obviously the product that's moving forward. That, as I said, in any case, informs the future for a ESCAPE-type product anyway. There is a lot of synergy with moving BEAM-101 forward as we are.
Yeah. I'll just add to that to say the same thing, which is I think we don't view it as a reorientation. We view this as a single integrated life cycle strategy where BEAM-101 opens up with the severe patients, and then we look to ESCAPE to expand that to many more patients. Ultimately, in vivo, of course, is the maximally scalable option across the globe. Really, they build on each other, and they move together, and they have been for years.
Thank you. Our next question comes from Gena Wang with Barclays. You may proceed.
Thank you for taking my questions. I also wanted to congrats on the very consistent data. I wanted to go back to the patient three. I know it's a very unfortunate event. When we look at the slide 25, we did see the red blood cell transfusion period was very long. It was almost four months. Maybe any color there, and then also any color regarding the gene editing efficiency for that patient. For doctor, I wanted to ask you, if fast forward, all the three drugs on the market, BEAM-101, CASGEVY, and LYFGENIA, how would you use these three drugs?
Great. Thank you, Gina. I'll have Amy do the first question, and then Dr. Gupta, you can talk about across the three drugs.
Sure.
Thank you, Gina. Just to be clear about that patient who unfortunately had the untoward effect from busulfan, that patient had complete recovery and rapid engraftment like everybody else and was actually doing quite fine. In other words, stable hemoglobin, stable hemoglobin F above 60%, normal platelets, everything was well until the patient was then hospitalized. The transfusions and other things do not really start on that patient until after she becomes critically ill and is in the ICU. She was not someone who, for example, failed to engraft, had low hemoglobin F, etc. She had that same percentile, the greater than 60%, less than 40%, and was doing quite well. In fact, when people looked and examined her bone marrow, etc., and other things, that was also in complete recovery.
In fact, what you see with the transfusions, etc., is only after she became critically ill.
Yeah. I'll also add here that this is unfortunately consistent with when you have some busulfan-related toxicity. We do see this all the time in allo transplants where busulfan toxicity can put you in ICU, and that is where you require a lot of transfusions and stuff. That is kind of like where you are seeing data consistent around that. Your other question regarding the comparison, we are not there yet, but it will be a very interesting scenario. I would say that this is a—we are in the middle of a revolution where 10 years ago, we did not have that many options for these patients. Now we are talking about potentially three options plus throw a transplant in the mix. That will be great. It will be a good problem to have. I'll just leave it at that.
Hopefully, we'll have more data from Beam also, which will be very helpful to compare and see. I mean, at one size does not fit all. We have to see what issues the patients have and what would be the best product. Again, as I mentioned, it's a shared decision-making. We do need to have all those discussions when we are there. Again, a good problem to have.
Thank you. I would now like to turn the call back over to John Evans for any closing remarks.
Great. No, I think great conversation. We really appreciate the engagement. I just want to thank everybody for your time and for your attention. I certainly want to thank Dr. Gupta for a great presentation, and thank you for all the help. Thanks as well to all the patients and investigators and families who have been a part of this journey. We appreciate it and look forward to continuing to bring this product forward.
Thank you. This concludes the conference. Thank you for your participation. You may now disconnect.