Thank you for standing by, and welcome to today's program entitled Lyfgenia FDA Approval Call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you'll need to press star one one on your telephone. If you wish to remove yourself from the queue, simply press star one one again. Today's program is being recorded. Now I'd like to introduce you our host for today's program, Courtney O'Leary, Director of Investor Relations. Please go ahead. Good afternoon, everyone, and thank you for joining today's presentation. My name is Courtney O'Leary, Director of Investor Relations at bluebird bio. Before we begin, let me review our safe harbor statement. Today's discussion contains statements that are forward-looking under the Private Securities Litigation Reform Act of 1995, including expectations regarding the therapeutic potential of our therapies, our commercialization plans, business operations, and financial position. Such statements are based on current expectations and assumptions that are subject to risks and uncertainties and involve a number of risk factors that could cause actual results to differ materially from projected results. A description of these risks is contained in our filings with the SEC, which are available on the Investor Relations section of our website, www.bluebirdbio.com. On today's call, you'll hear from Bluebird bio's CEO, Andrew Obenshain, followed by Rich Colvin, Chief Medical Officer, who will walk through the clinical data and label, and Tom Klima, Chief Commercial and Operating Officer, who will discuss the Lyfgenia commercial launch. Andrew will then discuss the company's business and financial position before opening up for Q&A. With that, I will turn the call over to Andrew. Thank you, Courtney, and good afternoon, everyone. I want to start by recognizing what an incredible moment this is. Yes, for the field of gene therapy and yes, for Bluebird, but most importantly, for the sickle cell community, a community that has long been stigmatized, underserved, and has historically been impacted by significant underinvestment. Bluebird is dedicated to the discovery, development, and delivery of gene therapies to bring patients and their families more Bluebird days. Today, we are one step closer to realizing that mission with the approval of Lyfgenia, also known as lovo-cel, for patients with sickle cell disease, 12 and over, who have a history of vaso-occlusive events or VOEs. This is Bluebird's third FDA approval for LVV gene therapy in less than 18 months, and we believe Lyfgenia has the potential to be our most substantial launch yet and to propel our company forward. But most importantly, it means sickle cell warriors now have a new, potentially curative option for this complicated and devastating disease. Now, I will turn it over to Rich to talk through the label and clinical data. Thanks, Andrew, and good afternoon, everyone. I want to start by echoing Andrew's comments about what an incredible moment this is and to express our gratitude for the brave sickle cell warriors who participated in our lovo-cel clinical trials, as well as the caregivers, providers, and researchers who made this milestone possible. Living with sickle cell disease affects every aspect of a person's life and oftentimes their family's lives as well. Beyond the debilitating and unpredictable vaso-occlusive events that are most associated with the disease, individuals face irreversible damage to vital organs, severely diminished quality of life, and early death. 50%-60% of adults with sickle cell disease have end organ damage, with almost a quarter experiencing damage in multiple organs. Additionally, one in four people with sickle cell disease have a stroke by age 45. The physical costs are devastating, but the financial implications of the disease also have a significant impact on individuals and their families. With an average of $4 million-$6 million in direct lifetime medical costs, despite a median age of death of just 45 years of age, this does not include patients' incurred out-of-pocket costs or the financial impact on caregivers. sickle cell disease also robs patients and caregivers of economic, academic, and social opportunities. Research has shown that approximately two-thirds of patients have had to give up a job due to their disease. With the approval of Lyfgenia, we now have the opportunity to unlock new possibilities for these individuals. Lyfgenia is the most deeply studied gene therapy for sickle cell disease, built on decades of LVV gene therapy research. Our LVV gene addition technology is traceable, giving us a deep understanding of our therapies and the ability to conduct rigorous monitoring. We understand LVVs and can measure how we modify the cell and can monitor the effects over time. Lyfgenia is a one-time, single-dose, autologous gene addition therapy that treats patients at the genetic level. A functional beta AT87Q gene, referred to as beta AT87Q, is added to the patient's own hematopoietic stem cells using a lentiviral vector. These cells are then infused back into the patient, and engraftment occurs over a median of 20 days. After a single Lyfgenia infusion and following successful engraftment, the expression of hemoglobin AT87Q has the potential to be lifelong. Lyfgenia has the most robust and longest follow-up of any gene therapy program for sickle cell disease, with 59 patients treated and up to eight years of follow-up across the entire clinical development program. In fact, this weekend, we'll be presenting sickle cell data at ASH from the podium for the seventh year in a row. Lyfgenia is indicated for the treatment of sickle cell disease in patients ages 12 and older who have a history of vaso-occlusive events. The label for Lyfgenia is based on efficacy results from 36 patients from the HGB-206 study Group C cohort, with a median of 38 months of follow-up. 32 patients depicted on this swim lane plot on this slide were evaluable for resolution of debilitating severe vaso-occlusive events. These were eliminated for 30 of 32, or 94% of the evaluable patients, and all vaso-occlusive events were resolved for 28 of 32, or 88% of patients, within the 6 month- 18 month assessment period. In this population, the majority of adverse events were attributed to underlying sickle cell disease or conditioning with busulfan. The label includes a boxed warning for hematologic malignancy. This is due to two cases of AML that occurred in our clinical trials using an earlier treatment process. These events have been well-described in the medical literature, and neither of these cases are due to insertional oncogenesis. We believe that healthcare providers value transparency sickle cell disease community as much as we do, and we are prepared to appropriately characterize this risk with it, and they are appropriately prepared to characterize this risk with their patients. In summary, people with sickle cell disease have been waiting impatiently for new therapies, and the approval of Lyfgenia is a transformational moment for this community and science. Now, over to Tom to walk through the Lyfgenia commercial launch plans. Thanks, Rich. We have been preparing for this monumental occasion for over a decade. As you saw in our press release, and as we've been hearing all day long, there is a lot of excitement for the launch of Lyfgenia, and with our 18-month head start, is proving to be an important differentiator. We are pleased with the early approval, and we are ready and excited to launch, starting today. In fact, this weekend, we will have both a medical and a commercial Lyfgenia presence at ASH, where we will begin engaging key stakeholders, and our field will be trained and in the field next week. You've heard us talk many times about 3 pillars of a gene therapy launch: patient demand, our qualified treatment center or QTC network, and payer access. Today, I want to provide a more in-depth look at all three of these and how we are set up to successfully bring Lyfgenia to individuals living with sickle cell disease in 2024 and beyond. As I mentioned, we are capitalizing on our 18-month head start in the market with Zynteglo. We've talked a lot about our QTC strategy, and I'm excited to announce today that we have activated 35 QTCs for Zynteglo. Of those 35 QTCs, 100% of them have already started the activation process for Lyfgenia. Even more exciting, 27 sites are ready today to receive patient referrals for Lyfgenia, and we anticipate that our network will be fully activated for both Zynteglo and Lyfgenia by the end of Q1. Additionally, we anticipate our first patient start for cell collection to also occur in Q1. We have gained immense experience with our Zynteglo launch, and our foundational strategy of synergizing our QTC network is starting to materialize. We believe we remain on track to onboarding 40 or more QTCs by the end of this year, and we look forward to further expansion in 2024, bringing our therapies closer to patients. Switching to access and reimbursement. bluebird has long been a leader within this space, and our leadership is continuing with our approach to timely and equitable access for Lyfgenia. We have been engaged with payers for more than five years, earning credibility and gaining critical experience to inform our approach. They understand the significant burden of sickle cell disease and have acknowledged the urgency to ensure patients have meaningful access to this therapy in the coming weeks and months, and we at bluebird understand their priorities. Today, we announced a list price for Lyfgenia of $3.1 million. Keep in mind that there is a reason why patients in the U.S. have access to gene therapy, and it's because the value gene therapy offers to patients and to the system is recognized. We have priced Lyfgenia according to that value. First and foremost, the robust and sustained clinical benefit our therapy provides, and secondly, in recognition of the positive impact it can have on the healthcare utilization and opportunity for people with sickle cell disease. Building on our partnership with payers and our established track record, we are offering innovative payment models to ensure timely access consistent with our label. Importantly, these agreements were uniquely designed for Lyfgenia and sickle cell disease. Specifically, bluebird's outcomes-based offering for Lyfgenia are tied to VOE-related hospitalizations. This is a claims-based metric that is directly correlated with an important clinical benefit, which is key for both patients and for payers. Under terms of these agreements, patients will be followed for three years, offering payers meaningful risk-sharing. We have developed a second contracting option specifically for state Medicaid agencies based on direct input that predictability and operational ease are essential for states who are grappling with resource constraints. We anticipate throughout the first year, Medicaid may primarily rely on the medical exceptions process to grant access to our therapy... We are in advanced discussions with the nation's largest payers and more than 15 Medicaid agencies, representing 80% of patients with sickle cell disease in the U.S. One final point on access. Through the Zynteglo and Skysona launches, we have learned that in addition to payer access, solutions at the QTC level are also critical. We have established solutions to help overcome challenges that QTCs may face in providing timely, equitable access. Our goal is to build confidence across all stakeholders so that access is not seen as a barrier for this important therapy. We estimate that approximately 20,000 individuals living with sickle cell disease in the U.S. may be appropriate candidates for gene therapy. This takes into account eligibility based on our label and patients who are fit for gene therapy. Our commercial team is among the most experienced in cell and gene therapy, with a deep understanding of the sickle cell disease market and a clear strategy for capturing the significant patient demand. Within this large patient population, there is strong interest in gene therapy. In fact, in over seven years of market research, we have seen that over 70% of patients would consider gene therapy if recommended by their doctor. Importantly, we know where these patients are today. Approximately 90% of the target population for gene therapy are connected to the healthcare system already, and we have designed our QTC network with proximity to patients in mind. To sum up, we believe our experienced commercial team is well poised to launch Lyfgenia and capitalize on this multi-billion-dollar opportunity in front of us. We have a strong commercial strategy with clear patient and physician demand, an 18-month head start from the Zynteglo launch, and with our extensive gene therapy experience, including over 350 years of gene therapy expertise in our field team, our manufacturing expertise, and our established commercial, commercial infrastructure, we are ready to go, and we are excited to be bringing this therapy to patients. Now back to Andrew to walk through the treatment process and provide some closing comments. Thanks, Tom, for walking us through the commercialization launch plans. I want to take a minute to walk you through the process a patient goes through when they receive Lyfgenia. Guided by our experience and a deep understanding of the needs of patients and providers, our focus is on getting it right the first time and building a positive experience for the QTC and for the patient. You may be familiar with this slide from our Zynteglo experience. Much like Zynteglo, for individuals treated with Lyfgenia, cells are collected through apheresis, shipped to a manufacturing site for drug product manufacturing, and then shipped back to the QTC, where the QTC schedules the patient for infusion. There are, however, some notable differences. In the consultation and preparation phase, patients with sickle cell disease need to be transfused and prepared for apheresis to calm the bone marrow in advance of cell collection. This step, which was implemented as an improvement to our clinical development program, is a key learning from earlier-stage studies and has since been adopted by others in the field. The process takes on average 2 months. In some cases, this will happen after a confirmation of payer approval for therapy, and in other cases, it may occur concurrently. We are already aware of patients who have initiated transfusions in anticipation of treatment. Drug product manufacturing is also long, between 70-105 days. This is specifically due to an anti-sickling assay, which is required by the FDA. Lastly, re-collections are a reality for any gene therapy. In the case of sickle cell disease, where the cells can inherently be more challenging to collect and where we are only able to use one mobilization agent, this occurs more frequently. In clinical trials, patient underwent a median of two mobilization cycles. In terms of this process translating to revenue, as with our other therapies, we will bill the QTC when Lyfgenia is shipped and recognize revenue at infusion. We expect this process to continue to become more efficient over time as the process is completed in the commercial setting. Our priority and commitment to the sickle cell community is getting this process right the first time and building a positive experience for patients and for the QTC. Before we open for Q&A, I want to address Bluebird's financials. I know there have been a lot of questions on this today. In October, we announced that Bluebird had entered into an agreement to sell a priority review voucher, if received. Today, we updated that we did not receive a PRV as part of the review of Lyfgenia. We are currently evaluating the FDA's denial of our PRV request, and we will be discussing this matter with the agency. We look forward to working with the FDA to address its feedback and to achieving a potentially positive outcome. We currently have a cash runway into Q2 of next year, and of course, we are always exploring additional financing opportunities. Our focus is on what an incredible achievement it is to have made this therapy available for individuals living with sickle cell disease. To close out, I want to thank the many stakeholders who have carried us to this milestone approval. The bluebird bio employees, both past and present, the investors that have stuck with us through the ups and downs of the last few years, and the healthcare professionals and investigators who have been our partners since the inception of this journey, and most importantly, the sickle cell warriors, their families, and caregivers. This community has participated in our clinical trials. They've been our partners every step of the way, and we have been, and continue to be, committed to understanding their experiences and raising up their voices. Without our decade-long collaboration, this approval would not have been possible. I'm excited to continue this partnership in the commercial setting and together bring a new reality to this deserving community. With that, I'd like to ask Tom and Rich to rejoin me and open it up for questions. Operator? Certainly. One moment for our first question. ... Our first question comes from the line of Jason Gerberry from Bank of America. Your question, please. Hi, everyone. This is Dina on for Jason. Just I wanted to say huge congratulations on the approval, and thank you so much for taking our question. So I guess on just a quick one for us on the lack of PRV grant, maybe could you provide any additional color on, you know, why that wasn't granted? You mentioned the FDA denied it first for a couple of reasons, and just maybe your confidence in getting it granted. And then, you know, what are, you know, your other options for capital to support the sickle disease, sickle cell disease launch? Thank you so much. Yes. So we're very early on in the process of evaluating the FDA's refusal, refusal of the PRV, so I'm really not going to say much more on that, other than that we will be discussing the matter with the FDA to find a path forward. In terms of, of financing, of course, we are always exploring additional financing opportunity. The PRV was always one of a multipronged approach to, to raising money, so we'll continue to explore other financing opportunities. Thank you. Thank you. One moment for our next question. Our next question comes from the line of Eric Joseph from JPMorgan. Your question, please. Hi, congrats on the approval, and thanks for taking our questions. I'm trying to get a sense of Eric, if you could get closer to the mic. Sorry, we can't hear you. Sorry about that. Hopefully, this is a little bit better. That's better. It's better. Okay. Congrats on the approval, and thanks for taking our questions. Do you expect the presence of a box warning to, I guess, have an impression? Or how do you expect physicians to receive the presence of a box warning with Lyfgenia, relative to Casgevy? Not only physician impressions, but also impressions by QTCs. Did you test for sort of physician market perception around a box warning in your market research? Do you expect it to have an impact on sort of pricing negotiations with payers? Yeah, thanks for the question. I'm gonna ask Rich to talk to the clinician's perspective, and then I'm gonna hand it to Tom to talk about the QTC and payer perspective. Yeah, thanks, Andrew, and thanks, Eric. So as we've reported before, hematologic malignancy has occurred in patients who receive Lyfgenia in clinical studies. This is an important risk that all patients must be aware of, counseled on, and if they're considering getting gene therapy. One thing to remember, though, that's very important, is that there have been no cases of insertional oncogenesis that have been observed, and that this risk of this type of malignancy is not unique to Lyfgenia. The AML case that occurred in our studies used a process to manufacture the cells that we no longer use, and we characterized it very carefully in the medical and scientific literature. And we've talked about it with the physician community, the QTC community, and we've published it in the New England Journal of Medicine. In fact, what we learned from our program has informed not only the development program for Lyfgenia, but the broader gene therapy field, especially in sickle cell disease. The potential for a box warning was something we anticipated, and it was built into our commercial projections. And with that, I'll pass it over to Tom. Yeah. Hey, Eric, good afternoon, it's Tom Klima. You know, we've really been extremely transparent with our data throughout the entire process, including in market research, where we actually tested different target product profiles throughout the years. We've consistently tested the risk for hematologic malignancy, especially as Rich mentioned, as our data matured. And our current projections actually reflect feedback from QTCs throughout market research. The second thing I will say is that these risks are pretty well characterized with transplant physicians. They're familiar with complex procedures, and we wouldn't expect to have many surprises from QTCs or transplant physicians, or much of an impact on the curve other than what we've already projected. Secondly, with payers, I would just say we've been working with payers for approximately five years now, where we've been very transparent with them on our data. We would not expect the box warning to have an impact on negotiations or discussions with payers. Okay, thanks. I appreciate the color. Maybe just one follow-up, if I could. Just given the pretty, you know, wide difference in gross pricing, gross list pricing between, Lyfgenia and Casgevy, perhaps you could take us through the, sort of your, the, some of your pricing strategy, what clinical or manufacturing factors might support that premium? Or should we maybe expect net pricing ultimately to be, you know, fairly in line between the two products over the long run? Thank you. Yeah. Go ahead, Tom. Yeah, it's a good question. So we obviously don't comment on others' pricing strategies, nor do we have any insight into the pricing strategy, and we'll have to see how it pans out over time. But I can tell you that we feel very confident in our value-based approach for how we price all three of our gene therapies now. We ran a very similar process for Lyfgenia that we ran for both Zynteglo and Skysona, and obviously looking at a potentially curative therapy for such a devastating disease like sickle cell disease becomes very important. So obviously, we take a data-driven approach. We took a very heavy feedback approach when it comes to our outcomes-based agreement with payers, and we expect that the outcomes-based agreement will be a key part of the strategy to ensure rapid access and access consistent with our label. ... Okay. Well, great. Thanks for taking the questions and congrats again. Thanks, sir. Thank you. One moment for our next question. Our next question comes from the line of Gena Wang from Barclays. Your question, please. Thank you. Sorry about background noise. So I have two questions. One is also wanted to ask about the pricing, about $3.1 million. I'm more thinking about competitive landscape, you know, regarding if the other drug is $3.2 billion, and how the payer would choose between the two. And the second question is regarding the monitoring schedule. It seems that every six months, you will need to do the analysis of the integration analysis. Can you walk us through the process regarding, say, the cell collection tests that need to be run and the cost of running the test and analysis, and as well as the time that you need to spend to do the monitoring? Yeah. So Tom, why don't you address the pricing question? We'll switch over to Rich for the monitoring question. Yeah, sure. Hi, Gina. It's Tom Klima. Again, we feel very confident in how we priced Lyfgenia, and we've worked with payers throughout the course of the last five years to come up with our approach. Keep in mind, obviously, the lifetime benefit that a therapy like Lyfgenia can provide is a massive difference to the healthcare system and for patients in their lives, and we think the payers are well aware of this and will recognize that. We've actually already been engaged with payers and have not seen any significant pushback. So our teams are working very closely right now to make sure that patients who are entitled to get Lyfgenia have access to Lyfgenia. Yeah. Thanks, Tom, and hi, Gina. In talking about Insertion Site Analysis testing and how it's done, well, first of all, in the registry program, remember, those are 15-year studies, and it's not every 6 months for the whole 15 years. That's the first thing. The second thing is with respect to Insertion Site Analysis or ISA testing, it's done on just a blood test, right? So you just take the blood out of the person's arm and you can test it from there. And that has become, we do that with a vendor who's been developing it, who's been the experts in developing that test. And that test is continuously being improved, worked on, and the efficiencies continue to increase. So, you know, this is something that's going to be built into our registry study that we're covering, and we'll go from there. Thank you. Thank you. One moment for our next question. Our next question comes from the line of Jeff Hung from Morgan Stanley. Your question please. Congratulations on the approval, and thanks for taking my questions. You walked through the multiple steps patients undergo to reach the infusion of the drug. Can you just talk about your expectations for time from script to infusion to improve? You know, that, is that going to improve over time and how long that might take, or what are the gating factors? And then based on the feedback that you've heard from clinicians and payers, what do you expect to be the profile of patients who are more likely to be treated in the early months of launch? Thanks. Great. So I'll take... Thanks for the question. I think the first question was about whether we could shorten the 105 days- 120 days. And is that correct? Yeah, that's right. Sorry, 70 days-105 days. 70 days-105 days. The, so that's based on a release assay, that is unlikely to change dramatically. However, remember, these patients, they're not like CAR T patients or oncology patients, where needle to needle is of the utmost essence, right? These are patients that can be scheduled in. I will say that what we are focused on is making that experience for the patient better and better. One of the ways we will do that is to focus on reducing the number of times they have to come in for apheresis. So our patients have to come in multiple times for apheresis, and we do believe that we have methodologies to actually improve the collection, the number of collections. So we will be focused there. Let me hand the second part of the question over to Rich. Yeah, great. Thanks, Jeff. And if I understand you right, you wanted to understand who the first patients who are going to be lined up to get therapy with Lyfgenia, correct? Right. Right. You mentioned that the first patient collection is probably in the first quarter, so I was just curious if there are certain, you know, profile patients that are more likely to be the ones that physicians and payers are likely to, you know, have go first? Yeah, and when we think about it, it's, they're going to be the patients who fit in what we've done in the clinical trial. So meaning that patients who are treated in the clinical trials tend to be patients who are 12 and up. So somebody in that range, it will be somebody who's had a history of vaso-occlusive events and who is going to be healthy enough to undergo an autologous transplant. And that applies to a good number of patients with sickle cell disease. And we know, and Tom could comment on this, that there are patients who are, as I say, impatiently waiting for this kind of therapy because they've seen how it could transform the lives of others. Yeah, just to add to that, this is Tom. Thanks for the question, Jeff. You know, we've heard from QTCs, and we've heard from patients that there's a group of patients that are really excited for a transformational therapy like this, who are lined up for gene therapy. So, I'm a little hesitant to give you an exact patient type because what we've seen with Zynteglo so far is that it's a wide range of patients who are actively seeking treatment. But it's exactly what Rich said, kind of consistent with our clinical trials, have a champion in the QTC and really are actively seeking new alternatives and pretty unhappy with their current therapy. Thank you. Thank you. One moment for our next question. Our next question comes from the line of Rick Bienkowski from Cantor Fitzgerald. Your question, please. ... Hey, guys, congrats on the approval, and thank you for taking the questions. So first, I had a follow-up question on the insertion site analysis testing. I was hoping you can go into a little bit more detail about how easy it is for QTCs to perform this analysis, and if the infrastructure is already in place for every QTC to conduct this analysis. And second, my question is about the outcomes-based pricing agreement. Could you just go into a little bit more detail here? I was wondering how much of the total payment would be at risk under these agreements. Rich, go ahead on the testing question. Yeah. Thanks, Rick. And thanks for the follow-up on the ISA. And one of the great things about Lyfgenia treatment and all of our LVV therapies is that we can actually trace them and follow where the gene integrates, so we can follow that over time. And that's what we're doing with ISA. And in terms of infrastructure, it's just, it's literally phlebotomy that the patients they need to do. And then they send the sample to the testing facility, which is just a lab here in Burlington, Massachusetts. Yeah. Yeah. Hi, good afternoon. So we've been very transparent about our outcomes-based agreements, and we're excited today to announce that we've been working on, obviously, a very unique outcomes-based agreement for Lyfgenia. The two most important things, I think number one is that it's a meaningful outcome in that it's tied to VOE-related hospitalizations. Obviously, hospitalizations are devastating for patients and for families, but also very costly to the system. And then the second part of it is that we'll track these through claims data, which are easy to track and less burdensome for payers to track. Hopefully, you can appreciate that we're not giving additional details beyond that because they're somewhat competitively sensitive. But payers have given us great feedback to the outcomes-based agreement. In fact, we're in advanced negotiations, as I mentioned, with some of the largest U.S. payers and with 15 different state Medicaid agencies. I got it. One follow-up question, if I can. Could you talk to if any patients have started the preconditioning process yet? Go ahead, Tom. You know, I hate to comment on that. Those, we don't really get into patient-specific details, especially at a QTC level. But I can tell you that we have a lot of interest from QTCs and some very excited patients to get treated. I got it. Congrats on the approval again, and thanks for taking the question. Thank you. Thank you. Thank you. One moment for our next question. Our next question comes from the line of Mani Forooha r from Leerink Partners. Your question, please. Hey, congratulations on the approval, and thanks for taking my question as well. I wanted to focus a little bit on just the financial practicalities. Can you revisit again how we should think about the range over time and the conversions of an individual patient to cash in hand for you guys? How are you gonna be treating, from an accounting perspective, the uncertainty around the outcome-based contracts? Should we be expecting that to flow through revenue? Is it as a contra asset? Should we expecting that to be a reserve? And I have a quick follow-up. Yeah, absolutely. So just on the cash in general, so we send the invoice to the QTC when we ship the product. The revenue is recognized when the patient is infused. And the outcomes-based agreement has a three-year measure on that, so we will hold a reserve account against revenue for the potential amount that we would have to pay back in an outcomes-based agreement. So you'll see it in... even though it won't be a direct cash impact right away, you'll see it in a gross to net calculation. And just to add to that, this is Tom. Although the outcomes-based agreement for Lyfgenia is structurally different because of the population that we're looking at for Lyfgenia than Zynteglo, I would say for modeling purposes, you can model it somewhat consistent with how you've modeled your Zynteglo model. Okay. And I guess the quick follow-up here, we really touched on the time to cash in hand, but how should we think about where you guys are on cash runway now, and based upon the margin profile that you guys are expecting in the first couple years of launch, like, what scale of revenue needs to happen to extend your cash runway to closer to breakeven? Like, is there a certain scale number of patients? Are we thinking about this as in terms of absolute dollar level? Just trying to understand the path to get you guys out of sort of, you know, what has been an overhang on the stock, on the balance sheet for an extended period of time. Yeah. Manny, I appreciate the question. I'm not gonna give you comments on kind of what the patient number is, et cetera. I would just repeat that we are on a path to profitability. It is nice to have revenue, you know, by coming in from two therapies right now, soon to be added with a third. We have, as a leadership team, come together and been very, very focused on that path to profitability for the last two years. So it's something that we talk about quite a bit with us and our board. Unfortunately, I can't give you any more granularity than that. Well, you can't but you can try. Thanks and congrats again. One moment for our next question. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your question please. Hi, this is Lydia on for Salveen Richte r. Congrats on the approval, and thanks so much for taking our question. Could you just provide some sort of update on how conversations are progressing with both commercial payers as well as Medicaid agencies? ... Yep, go ahead, Tom. Yeah. Hi, good afternoon, everybody. So as I mentioned, we've been in long-term negotiations and discussions with payers. We've received tremendously positive feedback when it comes to the structure of our outcomes-based agreements. And also, you know, payers understand the unmet medical need and the burden of sickle cell disease. And so far, we've seen very positive feedback from both commercial payers but also from state Medicaid agencies. As I mentioned, we are in advanced negotiation with 15 different state Medicaid agencies and with the largest payers in the U.S., representing about 80% of patients who have sickle cell disease. Thanks so much. Thank you. One moment for our next question. Our next question comes from the line of Yinan Zhu from Wells Fargo Securities. Your question, please. You might be on mute. We can't hear the question. Yeah. All right. Just as a quick reminder, if you do have a question, please press star, then one. One moment. I think that probably brings us to the end of our questions. I want to thank everyone for joining us today and for all of your very thoughtful questions. I just want to say what an exciting time it is for the field of gene therapy, not only for sickle cell patients today with two approved therapies, but really we're starting to see the first wave of gene therapies come, and hopefully that these will bode for many, many more innovations in the future for all sorts of diseases. So thanks everyone for your time. Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day!