Legend Biotech Corporation

Good day and thank you for standing by. Welcome to the Legend Biotech first quarter 2025 earnings 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 the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would like to hand the conference over to your first speaker today, Caroline Paul, Associate Director of Investor Relations. Please go ahead.

Good morning. This is Caroline Paul, Associate Director of Investor Relations at Legend Biotech. Thank you for joining our conference call today to review our first quarter of 2025 performance. Prior to this call, we issued a press release announcing our financial results for the quarter. You can find the press release on our IR website at legendbiotech.com. Joining me on today's call are Ying Huang, the company's chief executive officer, Alan Bash, the company's president of Carvete, and Jesse Young, the company's interim chief financial officer. Following the prepared remarks, we will open up the call for Q&A. We have our President of R&D, Go Wei Fang, and Chief Medical Officer, Maifeili Kaneru, joining the Q&A session. During today's call, we will be making forward-looking statements, which are subject to risks and uncertainties that may cause our actual results to differ materially from those expressed or implied here within. These forward-looking statements are discussed in greater detail in our SEC filings, which we encourage you to read and can be found under the investor section of our company website. In addition, adjusted net loss is a non-IFRS metric. This non-IFRS financial measure is in addition to and not a substitute for or superior to measures of financial performance prepared in accordance with IFRS. There are a number of limitations related to the use of these non-IFRS financial measures versus their closest IFRS equivalents. However, we believe that providing information concerning adjusted net loss and adjusted net loss per share enhances an investor's understanding of our financial performance. We use adjusted net loss as a performance metric that guides management in its operation of and planning for the future of the business. We believe that adjusted net loss provides a useful measure of our operating performance from period to period by excluding certain items that we believe are not representative of our core business. Our press release includes IFRS to non-IFRS reconciliations for these measures. With that, I will now turn the call over to Yang.

Hello, everyone.

Thank you for joining us today. During the first quarter, we continued executing on our strategic priorities by increasing the number of global ATCs and patients treated with CARVICTI in partnership with J&J, delivering operational efficiency and making continued investment. We continue to anticipate achieving operational break-even for CARVICTI by the end of 2025 and company-wide profitability in 2026, excluding unrealized foreign exchange gains or losses. Regarding CARVIC-T performance during the first quarter, net trade sales were approximately $369 million, which is a 135% increase year over year. We have now treated over 6,000 patients with CARVIC-T, and our CARVIC-T launch remains the strongest CAR-T launch to date. In the U.S., more than half of our utilization is now in the earlier line setting. In a recent 50-respondent survey, After presenting CART2-4 data to 86% of physicians from the community setting, preference for CARVICTI in early-line multiple myeloma rose from 34% to 55%. On this note, we're very pleased that overall survival was added to CARVICTI's EMA label based on the CHMP-positive opinion of data from CART2-4. We're also pleased that Australia's regulator, has now approved CARVICTI in the second line plus setting. We're looking forward to bringing CARVICTI to more patients outside the U.S. who might benefit from its differentiated efficacy. CARVICTI's unique profile continues to be demonstrated through extensive data, and we continue to facilitate best practice sharing as we treat more and more patients and generate additional safety data. For example, we've already incorporated additional safety measures in our ongoing CARTITUDE programs And new data is constantly being generated about CARVICTI's benefit versus risk profile. As a result of the posters presented at the meeting, and given that patients are already doing routine blood work, the majority of centers administrating CARVICTI have implemented monitoring for absolute lymphocyte count, followed by dexamethasone intervention as needed. We'll continue highlighting new safety data to the oncology community as it is reported. On the clinical front for CARVICTI, we continue to expect to complete enrollment for CARVICTI 6 this year. We believe the CARVICTI 5 and 6 trials are key to moving CARVICTI into the frontline setting. Looking at long-term growth for Legend, in addition to moving CARVICTI into the frontline, we remain focused on building out our pipeline programs. As part of our mission to serve more patients around the world through innovative cell therapies, We're investing in research and development where we can bring to bear our industry-leading expertise to drive the advancement of innovative new assets. This includes in vivo CAR T delivery, which we believe represents an important opportunity to strengthen our cell therapy leadership. We are excited about the new research facility currently being built in Philadelphia, where in vivo delivery will be one of its key focuses. positioning us well to pursue this area of innovation with the right infrastructure and resources. We believe this next generation approach to off-the-shelf therapy holds a lot of promise for incurable diseases. By reprogramming immune cells directly in the body through direct infusion, the need for ex vivo cell engineering and manufacturing is eliminated. No lymphodepletion apheresis are necessary for in vivo delivery, enabling even more scalable manufacturing. We're excited to be embarking on this next frontier of cell therapy innovation, and we look forward to providing additional updates as we make progress on this front. Turning to our upcoming anticipated company milestones, we anticipate growth to be driven by capacity expansion in Belgium and in New Jersey, which Alan will detail in just a moment. In addition to increasing our manufacturing capacity, we continue to work towards the overall survival benefit being included in the U.S. label, now that it's already in the European label. To sum up, regardless of the current macroeconomic uncertainties, Legend endures as the largest stand-alone cell therapy company with over 6,000 patients treated by Carvicti as we forge the path to cure. With a cash position of approximately $1 billion, we are investing in our core differentiators and remain focused on delivering operational efficiency in order to ensure durable long-term growth. With that, I'll pass it over to Alan to provide an update on Carvicti.

Thanks, Ying.

Moving on to Carvicti's performance, as Ying mentioned, net trade sales of Carvicti were approximately $369 million, which is a 135% increase year over year and a 10% increase from the fourth quarter. Our global growth was driven by continued share gains and capacity expansion. U.S. net trade sales of $318 million grew 127% year over year and 5% quarter over quarter. In the U.S., we continue to certify more hospitals as authorized treatment centers, and the total number of U.S. hospitals that are certified to treat with the CARB-XD is now 114. We remain pleased with the progress we have made in the outpatient setting and continue to anticipate that a majority of our volume will be coming from outpatient use by the end of this year. Regarding OUS performance, which was notably strong, we had sales of $51 million, which is more than double compared to the same period a year ago and represents a 65% increase quarter over quarter. Our OUS performance was driven by expansion in Germany, Switzerland, Austria, and Brazil, and we are pleased to be bringing Carvicti to more eligible patients in Spain, the UK, Denmark, Belgium, and Israel, where we recently launched. To this end, we're excited to share that Tech Lane initiated clinical production in Ghent during the first quarter and remains on track to initiate commercial production there later this year. This is another critical component of our plans for serving patients in Europe to meet the increasing demand. And to meet additional demand in the United States, we expect to receive approval for our physical expansion in Raritan in the second half of the year. The progress we've made in executing our manufacturing plan and investments has enabled us to be among the best in class. We now have a 97% manufacturing success rate, which we believe is the highest in the CAR-T industry. 95% of the time, we deliver CAR-VIC-T on or before the promised delivery date, and our median turnaround time has been consistently declining and now stands at 30 days. We believe this turnaround time is more than sufficient based on our conversations with physicians. As physicians place their orders, they are mindful that bridging therapy alone takes multiple weeks for a number of patients. Going forward, we expect to continue to reduce out-of-spec rates and increase our efficiency and expect further declines in our turnaround time. Now it's time to take a closer look at the financials, so I will turn the call over to Jessi.

Thank you, Alan, and good morning, everyone. During the first quarter, we delivered solid financial results with capacity net sales of 135% year-over-year. Total revenues were $195 million, driven by collaboration revenue growth of 137% year-over-year. Q1 delivered a $101 million net loss and a $27 million adjusted net loss. after excluding items that are not representative of the company's core business, such as a $52 million unrealized foreign exchange loss due to our treasury center based in Ireland. Importantly, our operating loss of $118 million in the same period one year ago was reduced by over half to an operating loss of $51 million. The meaningful improvement in operating results was driven by our operational efficiency, and discipline expense management. Even though we continue to invest in a robust pipeline and supporting the second line indication launch as well as our manufacturing capacity, our first quarter growth margin on net product sales was 63%, improving from 59% in Q4. As expected, R&D expense on an IFRS basis grew only 1% year over year, and SG&A on an IFRS basis only grew 29% from the prior year to $72 million. Overall, we believe we have been making strides towards positive operating cash flow generation and profitability. Our adjusted denoted earnings per share were negative $0.07 compared to negative $0.23 for the same period last year. Now turning to capital allocation. We continue to have a strong balance sheet with $1 billion in cash and equivalents and time deposits. We believe this is a competitive advantage for us in our industry, and we will continue to prioritize disciplined expense management as we fund our operating and capital expenditures, including future innovation, until we achieve profitability, which we anticipate in 2026, excluding unrealized foreign exchange gains or losses. In summary, our first quarter results demonstrate the durability of our standalone cell therapy platform. We are pleased with our performance and the advancements of many impactful initiatives, along with increasing operational efficiency in 2025. And now it's time to take your questions. Operator, we are ready for the first question, please.

Thank you. At this time, we'll conduct a question and answer session. As a reminder to ask a question, you will need to press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. And our first question comes from the line of Gina Wang of Barclays. Your line is now open.

Thank you for taking my questions. I have three quick questions. First one is regarding the CAR-VD. price differences between U.S. and the ex-U.S., if you can give any color there. And the second is regarding the new Rarrington section approval in second half 25. Would you be able to walk us through the steps you need FDA sign-offs and any concern on FDA on-time execution? And lastly, very quickly, I know you have multiple pipeline assets. Just give us a a rough idea, when should we see which program first in the coming years or 2025, we will see additional data.

Hi, Gina. It's Alan. The price differential between the U.S. and ex-U.S. is approximately 30%. Obviously, it varies country to country. In terms of the Raritan approval in the second half, we're confident that we will be able to achieve the approval from FDA in terms of capacity expansion, and that is based on the filings with them and the CB30 with that process.

So, in terms of pipeline, our focus are on two different technology platforms, in vivo cell therapy platform for oncology indication and the adigeneric cell platform for autoimmune diseases. We are looking forward to a multiple clinical readout later this year. For in vivo CAR-T platform, we expect to have first patient dose. in our investigator-initiated study in June or July, and expect to have preliminary clinical results towards the end of this year. On the ELO platform side, we expect to have clinical results in the second half of this year, again, through the investigator-initiated study. Autoimmune, currently, we are running some IIT trials. in China using the triple-targeting or target-cell therapy product, targeting CD19, CD20, CD22, to try to drive a deeper response. And we also expect to have clinical results in the later part of the year. Lastly, on the U.S. side, we have two ongoing phase one programs, targeting CAUD18.2 for gastric cancer and DL3 for Again, we are reading out of the Phase 1 dose escalation data for both programs.

Yeah, I can expand on that a little bit. For the DLL3 program, we have an oral presentation at ASGCT next week, and both the DLL3 programs and the Quadrant 18.2 programs have ASCO posters that you may have seen from the titles that were released back in April.

Hi, Gina. This is Dean. Maybe I'll supplement the answers by pointing out two things. First of all, I know you guys are all looking at the price difference, right? So you're pretty much aware that in the United States, there are three types of customers that we pay a mandatory federal required rebate. So it's Medicaid, 340B hospitals, and also VA hospitals, right? We provided 23.1% rebate to those customers from the list price. And this is why we don't see a really significant difference between the U.S. price and those types of customer in the U.S. So we don't see a big impact regarding, you know, some of the proposals from the administration here. And then on FDA approval, I know people are concerned that you're seeing some reduction agency, but based on our current interaction with FDA on the expansion at Raritan, Like animation, FDA agreed that we'll use the so-called CB30 pathway. That is, once we and J&J file the application in writing, within 30 days, if we don't hear from the agency, it's deemed approval, or if there's any request during that 30 days we can answer, then, again, we don't expect any delays here. So, we fully expect the on-time approval from FDA for the physical expansion for . And right now, we're still on track to achieve that by end of this year.

Thank you. Thank you. One moment for our next question. And our next question comes from the line of Jessica Fye of JPMorgan. Your line is now open.

Hey, guys. Good morning. Thanks for taking my question. I was wondering if you could just take a minute to kind of make the case to investors that Carvicti will successfully penetrate the community. The reason I ask is one pushback we hear from investors is that when they do KOL calls, so, you know, with key centers, the physicians indicate they don't have a backlog, and thus I think some investors come away thinking that demand is largely satisfied and there's limited growth ahead. So just hoping you can spend a minute on kind of making the case about why you have conviction this product can get into the community. Thank you.

Based on many of the discussions we've had, both with the KOLs in the authorized treatment centers, as well as physicians out in the community, there is a high demand for providing CAR-50 as an option for patients in earlier lines. And what we hear is that the benefits based on the profile of extending survival, extending long-term remission to these patients is very attractive. And there are obviously, as you know, the majority, nearly 80% of the patients out there in the community. What we have done is, and based on the feedback we've received, is we've increased our investment and efforts along with J&J in terms of educating the community, going out and reaching all the major community sites, and we're in the process of doing that, and not only raising awareness. There's already high awareness of CARBICTI as an option, but actually where we see more opportunity is to raise awareness and increase that call to action in terms of referring patients into the authorized treatment centers. The 2nd thing we're doing is we are connecting the experts in the authorized treatment centers with the experts out in the community. And this is getting a lot of great traction, a lot of increased dialogue, a lot of really good opportunities for those referrals to happen. And then, thirdly, we are explaining to the community. that those patients are going to be coming back to them and we are building a platform around transition of support so that those patients actually will need to get back to their community physician for ongoing monitoring, other health checks, and so that the community understands that they will not be losing those patients. So the profile of the product, the outpatient administration, the overall survival benefit, the unique differentiated benefit, these are all things that we see gaining traction in the community.

Maybe I'll just add one more point to Alan's comments. We will present some long-term data at ASCO. In fact, you will see the abstract coming out next week. And we and J&J are extremely pleased with the results. And we think this will be actually another impetus for the community to take up CARBIG in the second line, given the unprecedented benefits. Also, I'm happy to report that our overall survival result was just added officially into the label in Europe. following the positive CHMP opinion already. So again, in both the US market and European markets, we will be able to promote on the merit of overall survival and also the significant results from CAR-4 that demonstrates both clinically meaningful and also statistically significant superiority in survival over standard of care. So that will help the community uptake.

Thank you.

Thank you. One moment for our next question. Our next question comes from the line of Aaron Werber of TD Calendly. Your line is now open.

Great. Thanks so much. I have two quick questions. Number one, in terms of capacity for Q2, now that Obelisk is online and continuing to sort of you're pushing volume through it, Can you give us a sense, we're expecting obviously a step up in terms of quarter-over-quarter growth over Q1, but is that going to be more European-centric than U.S.? And then secondly, it sounds like you do not need to get the new Raritan facility inspected, the new expansion. Can you just confirm that? Thank you.

Yeah, so in terms of Obelisk, you're absolutely right. It came online in September of last year, and it is now delivering for Europe. So we do expect that that will continue to improve our ability to supply Europe. And we do expect modest growth in Q2 with more sequential growth and acceleration in the back half of the year, supported by not only Obelisk, but also the U.S. capacity expansions, as we've outlined previously with Raritan, as well as Novartis coming online in the first half of this year. In terms of the Raritan physical plant expansion, as Ying described, at this point, we do not expect that there will be required any inspections relative to that CB30 process and the approval there.

Thank you. One moment for our next question. And our next question comes from the line of Costas Bellaris of BMO Capital Markets. Your line is now open.

Good morning, everyone. Thanks for taking our questions. Can you remind us, please, what is the difference between high-risk patients and functional high-risk patients? What is the percentage of functional high-risk patients in multiple myeloma? And what percentage of the patients treated with CARVICT in early lines correspond to functional high-risk patients? Thank you.

Sure. When we refer to high-risk patients, we are referring to patients with certain cytogenetic factors, whereas the definition of functional high risk is more related to the concept that they progress quickly after sort of a frontline setting. So, it's more related to how the patients respond to a particular therapy. In terms of the CARTITUDE IV study, As the abstract titles show for ASCO, we will be having data coming out on the subgroup analysis on these various patients in CARTITUDE 4. But in general, CARTITUDE 4 has shown very strong you know, both PSS and OS in the population in these early lines of patients. So, we feel confident that both of these populations, both high-risk and functional high-risk, do very well with cilta cell administration.

And in terms of cardicti uptake in early lines, what dynamics do you see there with functional high-risk patients? Is this a high percentage of That's patients in the update that you see that in lines.

Yeah, I think in the early lines, namely the 2nd through 4th line, we do see that we're physicians tend to start are in these categories that might just describe the functional high risk and the high risk patients. That's a natural place for them to begin to think about as an option. But we've also, in our conversations, heard that many physicians, once they've gotten comfortable there and they have started to use it in that population, will then expand. So I think, to your point, this is a progression from utilizing CARVICT in the early lines for the patients who are either fast progressors or have the high size of genetic risk and then moving on from there.

Thank you.

Thank you. We'll move on for our next question. And our next question comes from Kelly Shai of Jefferies. Your line is now open.

Hi, good morning. This is Clara for Kelly. Thanks for taking our question. So you just initiated CardoT clinical production. That's a tackling facility. So just wondering if you can Give us a little bit more color about the manufacturing expansion moving forward and also just want to quickly touch upon the in vivo cartoon initiative. You mentioned wondering, where do you see the differentiations might land in this novel space? Thank you.

Yes, as you mentioned, we achieved approval for the clinical production and began that. in Tech Lane, and that sets us up well for the ability to start commercial production in Tech Lane by the end of this year, and we're on track for that. So between Tech Lane and the Obelisk facility, which is already approved in commercial, we are quite significantly ramping there to support the European launches. And just to remind you, the European launches are across Germany, Switzerland, Austria, Denmark, And then throughout the world, we have the UK in private market, Israel in private market, and Brazil as well. And as you saw from the release, Australia is now achieving approval. Reimbursement and launch will come later. Just to add to the two facilities, again, as we've already mentioned, we've talked about the railroading expansion. And the Novartis commercial production, which started the first part of this year in January, is also starting to meaningfully contribute in Q2 here and then Q3 and beyond. In addition, let me just mention, because we have talked about the fact that there is an investment in TechLane that the companies have jointly approved. And so that speaks to the additional capacity that we plan to build in TechLane to the tune of $150 million jointly by the collaborations.

So, in terms of in vivo card T approach, this is a platform where you, we use molecular engineering, the 90 virus that can specifically recognize the immune cell. In this case, she's in the body of patient at the same time. We also engineer virus to reduce the generic or non specific transduction to normal tissue and. We are expecting the first patient dosing in June and July this year. In terms of the advantage of in vivo CAR-T compared to conventional ex vivo manufactured cell therapy, there are a few key areas. One is those T cells are engineered, recognized engineered in the body of patient, and therefore, in general, it have better cell phenotype based on our preclinical data. Second is completely offshore without the need for depreciation, so there's no delay in terms of administering therapy. And no need for depreciation also provide additional safety benefit to the patient. Lastly, it's a scalable manufacturer due to the nature of antivirus being the drug product. So those are the few key areas.

Thank you. One moment for our next question. And our next question comes from the line of John Miller of Everchorus. Your line is now open.

Hi, guys. Thanks so much for taking the question. A couple of clarifications, if I may start with those. I know you already spoke about the general price difference, US versus XUS, but what's the price delta between the US and the lowest cost anywhere else in the world, not just the average difference, A? And secondly, B, you talked a little bit about penetrating the community, Ying, but most of the stuff that you were talking about is how to get referrals into academic centers. I know you've also talked about... getting actual CAR T infusion into select community centers this year. Can you give us an update on how that process is going and how rapidly you expect to be able to deliver CAR T in the community itself? And then maybe lastly on those in vivo CAR T differentiators that you just spoke of, that makes sense relative to an ex vivo CAR T. But how do you feel differentiated for your approach in in vivo space relative to other in vivo players who are also working on similar Lenti-based approaches? Thank you.

This is Alan. I don't think we'll be commenting on the specific lowest price, but I do want to just remind you that we have a band, a pricing band at J&J. given their pricing policy does adhere to. So we don't go below that price. And that's supported basically based on the costs and other factors, obviously speaking to the value of carbon safety in the marketplace as well. So there is a price band there. You're absolutely right that I was speaking to the penetrating of the community in terms of referral base. But to add to that, we are also in active discussions around having Perfectly closer to the patient and administered in the community setting. We have several, I would say sort of demonstration projects and initial plans with certain community centers this year in the works. Nothing to announce as of yet, but we do expect that this year we'll have at least 1, if not 2 or more. community, large community networks starting to administer CARB-ICT in some of their centers. And then the third leg of that journey, if you will, is actually bringing it to even more sites around the country and having CARB-ICT adopted in the community setting as well. So we are on that journey starting with some centers this year.

Yeah. Getting to your second question in terms of differentiation of our in vivo approach versus our peer groups approach across the industry. This is a novel platform and rapidly evolving. We began to invest in this platform three years ago. We think that there are probably four or five areas of key differentiation that we actually set up from the get-go. One is the T-cell recognition method. So, there are many different ways to recognize T-cell and then induce the transduction. We are testing multiple mechanisms of T cell recognition and to drive the transduction efficiency as well as to control the safety signal. Those approach we invested well played out in the clinical setting. The second area of differentiation is really about the engineering of the antivirus, reducing the generic transduction capacity of virus. We have specific point mutations. with our own IEP position to really reduce the generic transduction and therefore expand the potential therapeutic window between the T-cell recognition and non-specific recognition. The third area is the car design. We have large experience and expertise in optimizing the car design. combined with armored mechanisms. I think that's a key area that can drive the differentiation and the activity of the in vivo CAR-T. The fourth area is another area we have a tremendous expertise coming from CAR-T's experience. That is the CMC, the process development, process robustness, and ability to scale up. From Gallagher, our goal is to optimize the CMC process so that we can not only support the initial IET tribe, but also have ability to further develop down the road. And then last area, the fifth area of differentiation, we focus on is really the execution for clinical validation for those platforms. We have end-to-end capacity in clinical development on the ground in China. We can execute IIT tried very efficiently. Our first development candidate for in vivo platform was selected last December, and six months later, we are looking forward to first patient dosing. So that speaks to the speed and efficiency of our clinical development process. All those, I think, will bring value to our in vivo platform.

Thank you. One moment for our next question. And our next question comes from the line of Leonid Temerjev of RBC. Your line is now open.

Hey, thanks, guys. Thanks for taking my question. I wondered if you could talk a bit more about the community referral process. I guess I'm wondering how much brand awareness and stickiness actually is there in the community for Carvicti specifically versus that decision being made at other centers, I guess. Effectively, are you laying the groundwork for Carvicti or for all CAR-Ts, including, I guess, future and current competitors? And then related to that, I guess, what's the messaging from you and your partner in the community, given that your commercialization partner also has buy-specific offerings, which are pretty popular in the community? Thanks.

Yeah, there's growing awareness of CAR-T and specifically CAR-VICT in the community. We estimate, we do some surveys, that about 70% of community oncologists are aware of CAR-VICT. Where we see more opportunity is actually to get them to kind of go from awareness to action based on the earlier line approval of the CARTITUDE-4 program. population. But we are certainly laying the groundwork for that in the ways that I described earlier in terms of strong education through our field teams, through medical education, through connecting the experts at the treatment centers to the community, and making sure that the community understands that they will be getting their patients back for a transition of support and monitoring and ongoing care. In terms of, I think that was the answer on that. Oh, the messaging with the partner, yeah. So, we and our partners are very committed to the fact that cell therapy, specifically BCMA CAR T, is the very best option for patients in terms of earlier lines. We have the overall survival data, we have the durability, and the IMWG recommendations are very clear that for patients who are eligible for both bispecifics and CAR T should really be evaluated for CAR T first. and that's based on the clinical profile. J&J is committed to this, and I should just remind you that we have our own teams out in the field, our own sales teams dedicated to Carvicti, both on the J&J side and on the Legend side, making this case.

Thank you. One moment for our next question. And our next question comes from the line up of Morgan Stanley. Your line is now open.

Hi, good morning. Thank you for taking our questions. We had two. So first, could you just kind of walk us through your initial thoughts on the recently appointed leadership at CBER and what you see as the potential implications and key considerations here that we should keep in mind for the Curvix development program? And then secondly, related to an earlier question, Could you remind us what portion of cardiac use is currently in the carditude for population and and where do you see that trending over the course of the next year? Thank you.

It just answer your 2nd question. 1st, we see that nearly 60% of our patients, and this is based on our ordering system. nearly 60% are coming from that CART or 2.4 population. We expect that to continue to evolve in that direction and get to about three quarters, either by the end of this year or certainly before our competitor in this space is launched. So again, as they get into the market in a later line population, we will have significantly evolved our business into the earlier lines.

Hey, Vikram. So I'll answer the question about the new CBER leadership at FDA. You know, we're happy to see that Dr. Prasad has been appointed the director of CBER, which regulates all the cell and gene therapy approvals. First of all, we agree with Dr. Prasad's point that in any cancer trial, you should use gold standard of survival benefit. And to that end, we're happy to report that, first of all, we will report long-term, minimum five-year follow-up from CAR-21. And you guys will see the data at ASCO. In fact, the abstract is coming out next week. So you will see the unprecedented benefit we bring to this population, and that is survival, which is a hard endpoint, right? Secondly, I think if you look at the history of cardiac approval, we did secure FDA approval back in February of 2022 based on the primary endpoint of overall response rate. However, when we started this trial back in 2018, 2019, these patients have exhausted all the available therapy to them, so it represents a very significant unmathematical need Today, of course, you can argue things are different, because you have two BCMA targeting CAR T available as commercial therapy, and three, soon to be four, biopsy antibodies, again, indicated for myeloma. So, it's very different. But since we conducted that CAR T1 trial, we have demonstrated the survival benefit. We have demonstrated the PFS, which is nearly three years from historically about four to five months in this patient population. So, that is the hard evidence we demonstrated. We also secured both FDA and also EMA approval based on PFS endpoint. However, in September of last year, we demonstrated, again, clinically meaningful and also statistically significant benefit in survival with a hazard ratio of 0.55, which means 45% improvement in survival from standard of care. So we think CARB-A-T comes with a very, very strong benefit in terms of clinical outcome, which is survival. And then that's also accompanied by the surrogate endpoint, such as PFS, and overall response rates, right? That is why Legend and also J&J stands by the best-in-class profile. So we welcome Dr. Prasad as the CBER leadership because we have clearly demonstrated the survival benefit here. Now, I know there are questions from investors about MRD inactivity. So we think that, you know, given the support from ODAC last year, using MRD as a starting endpoint, we plan to sit down with the FDA to explore the possibility of using MRT activity as a potential endpoint for accelerated approval. We think this is a good setting in the first line setting because, as you know, today if a newly diagnosed multiple myeloma patient is treated, expected survival is probably over five to seven years. Therefore, in this setting, a surrogate endpoint makes perfect sense. Now, in last line or even second line, if you look at our data from CAR4, right, The standard of cure had a PFS of shorter than one year. So in that setting, we're not sure whether, you know, a surrogate endpoint makes sense or not under the leadership of Dr. Persaud. As I mentioned, again, we agree that, you know, in oncology settings, survival should be the gold standard, and we're happy to report that CARB-XT does bring that life-saving benefit to patients.

Great. Thanks so much.

Thank you. We'll move it for our next question. And our next question comes from the line of James Shen of DV. Your line is now open.

Hey, good morning, guys. Thank you for taking our question. I want to kind of piggyback on the Dr. Prasad question. I know base case for CAR2-6 is to lean on PFS, and it sounds like you have engaged on possibly exploring MRD. But any thoughts on, like, competitors or, you know, the utilization of percentage of patients completing 12 months of follow-up? And then for Alan, what is the status on, like, I believe there was an industry coalition for lowering community-based CAR T accreditation. Is that, I guess, call it a bottleneck for community adoption right now?

Thank you. Regarding your first question, unfortunately, we do not comment on competitors. I can't say what they are doing. We're confident about our approach and discussions that we will be having with the FDA on our CART6 study?

Yeah, the industry discussions around providing some sort of fact light accreditation are ongoing. There are some centers we are in discussions with that, and they are affiliated with the larger academic centers around the country. So, that I would say is in process, and that should potentially unlock some of the opportunity in the community as well.

In addition, just to add to the Carditude 6, as I mentioned, we have a clear plan to have conversations with the FDA, and we intend on meeting with them in about a two-month time frame.

Thank you. One moment for our next question. And our next question comes from the line of Mitchell Kapoor of 18 Way Right. Your line is now open.

Hey, everyone. Thanks for taking the questions. I wanted to ask one about outpatient volume. I think last quarter you had mentioned that it comprised over half of all volume for CARVIC-D. Can you quantify that trend now and just give us a little bit of the direction of where that is heading? And then secondly, can you talk through your assumptions and pipeline efforts for cash runway through second quarter of 2026? Would you need to seek some avenues of non-diluted capital to bridge yourself like well into profitability? Or do you think that maybe there's some other opportunities you might see?

In terms of outpatient volume, we see that growing steadily but slowly also because as new centers come on, sometimes they start in the inpatient. Our latest claims data continues to show that it's a little over half. We do see growth each quarter, but it's kind of in the single-digit percentage points. I expect that over time we will continue to see continued move to the outpatient setting. Again, this might be center-specific or it might be patient-specific, depending on the patient characteristics. But I would say, you know, we'd probably get into kind of the two-thirds one-third outpatient versus inpatient over time with the treatment centers that we have now and the ones that will be coming on board in the future.

And Mitchell, as you know, we have many reasons to be optimistic about Allegiant's future, and we are the market leader with the fastest launch in the CAR T space, and we continue to expect Carvicti will break even operationally by the end of 2025, and we anticipate profitability in 2026, excluding FX fluctuations. We have $1 billion in of cash on hand and that will reach profitability when we, that will last through 2026. So we don't have any present needs to raise capital. And we have a joint investment with J&J on CapEx for $150 million that will last through 2028 for the tech phase two expansion and that is included in our cash runway. Thank you.

Great. Thank you, guys.

Thank you. One moment for our next question. Our next question comes from the line of Jeet Mukherjee of BTIG. Your line is now open.

Great. Thanks for taking my questions. Just two from me. First, coming back to integrating CAR T therapy into the community setting, when it comes to the tertiary and regional centers, what are the biggest infrastructure hurdles for them currently, and what are you doing to facilitate this? And second, on the DLL3 and CLOD and 18.2 datasets we're expecting, Will the data be as part of the conference abstracts, or will they perhaps be saved for the conference presentations themselves? Thank you.

In terms of infrastructure, you know, certainly capacity and chair space and staff are some of the factors that we look at, but again, speaking to the prior question around outpatient, we do see that over half of our patients are getting Pervicti in the outpatient setting, and that's based on a couple of factors, one of which importantly is our profile around the time of onset for CRS. And that gives the centers confidence to safely infuse it in the community and then monitor patients. And that opportunity for outpatient is one of the ways that we overcome some of the infrastructure hurdles there. One of the other infrastructure hurdles that we are monitoring and we keep a close conversation on with our centers is any capacity limits in terms of pickups and apheresis and cryopreservation. Again, there are multiple ways that centers around the country are addressing this. including use of third-party suppliers for apheresis pickup as well as cryopreservation. And we're engaging those companies to help make sure that those infrastructure hurdles are not a limit to patients getting apheresis.

Regarding DLL3 and Claudine 18.2, as I mentioned, DLL3 will have an oral presentation at ASGCT next week. Regarding the ASCO-ASTRAC, There will be key data from the dose escalation in both studies that will be available next week when the abstracts are released and look forward to providing more details at the conference itself.

Thank you. One moment for our next question. And our next question comes from the line of Ash Burma of UBS. The line is now open.

Yeah, thanks for taking our questions. So maybe just on Kavikti, I know you've talked about second quarter as a step up since the know-how to supply comes online. Is that a step up more of the magnitude what we saw in the third quarter of last year, which was a pretty robust sequential growth quarter for you? And then secondly, any thoughts you can share on the potential upcoming clinical data from RSLX? We saw 98 patients of data at the ASH conference and presumably now getting 19 additional patients with more than 2 months of follow up. So do you think that there can be any non icons near talks that can show up in the upcoming update?

Thanks.

As a step up for Novartis is now starting to contribute to our capacity expansion towards our goal of 10,000 doses by the end of this year. And we feel very confident with that target of. Providing the ability to supply 10,000 annualized patient doses in terms of size of the step ups and size of growth. I think we're, we're, we're projecting that Q2 will be another modest step up in terms of our growth based on demand and supply. with sequential growth and then further acceleration in the back half of the year. Just in terms of some of the dynamics for Q1, I think one of the reasons why we saw a solid 10% growth, not only because of the European markets coming online, but also based on some of the improvements we saw out of spec with turnaround time and our obelisk facility ramping a little bit faster than we expected. This is just great execution from our team in Europe to supply the European launches, and that helped pull in some of the revenue from what we were projecting for Q2 into Q1 for a solid Q1 performance.

Regarding your second question on the clinical data from RSLX, I can't comment on what's going to be presented. Besides just the title abstract that we are aware of at ASCO and what I can say is that or whether they'll have any evidence of neurotoxin in their studies. They are obviously starting a phase three randomized study. And so I think that will be very telling about more of their safety profile. What I can say is, regarding our study, we're very excited about the actual presentation of Accreditude One long-term data set. I think you'll be pleasantly excited as well when you see the data being presented. In addition, I can also say that, you know, that our monitoring of the absolute lymphocyte count, or ALC, and use of prophylaxis steroids with ALC counts of greater than 3,000 is being further incorporated into major academic centers as well as in our CARTITUDE studies. And we're seeing, you know, good response from the KOLs who are implementing this, and we expect additional data to come out. later this year. So we will report on that in the near future.

Thank you. One moment for our next question. And our next question comes from the line of George Farmer of Scotia Bank. Your line is now open.

Hi. Good morning. This is Chloe on for George. Thank you for squeezing us in, a couple from us. So, I wanted to double click on the survey number that you mentioned earlier about the preference from Hume-Onc's second line, prescribing the second line rising from 34 to 55%. I was wondering if you could provide a little bit more color here on the diversity or the geographic location or volume of the centers where these hemungs are operating at and what they need to see to keep pushing beyond that 55%. And if you could also comment on uptake in this early aligned setting in the EU, if you expect the updated label to have a significant impact there on early aligned use. Also wanted to ask about outpatient administration. You did say it's a little over 50% now. And could you maybe break that down for us between the earlier and the end stage disease? Like in your second to fourth line patients, what proportion of those are being treated in outpatient versus inpatient? And how does that compare to the end stage patients? And a last question, if I may. Just to clarify, when you specify the DGN turnaround time is around 30 days for CAR-VT. Are you using that kind of interchangeably with vein-to-vein time here?

Yeah, so first of all, in terms of the EU, we do expect that the updated label will support the use in the earlier lines, and that's the feedback we've been getting from the centers in Germany that are now online, and in the other European markets, as we mentioned. So, we do expect that it's the overall survival data that is very compelling, and this will enable patients, much like it has in the U.S., to sort of move into the earlier treatment settings with CARBICTI. In terms of outpatient, we don't have a specific breakdown between how much of the outpatient use is in the earlier line versus the end stage, But, you know, qualitatively, I will tell you that as we get into more patients receiving Curvic D in the earlier lines, that does correlate somewhat with the ability and the comfort level with physicians to administer in the outpatient setting. Although the outpatient setting is more a factor of, you know, sort of safety monitoring, and we do see, again, in the earlier lines, lower rates of CRS and lower rates of MNTs, and so these are the things that physicians do gain comfort with as they move to earlier lives. In terms of turnaround time, our median 30 days, you know, everyone uses a bit of a different definition in terms of what vein-to-vein is, but we think this is the most relevant way to think about our ability to deliver to physicians because this is the point at which they A, freeze the patient, and then when is the product available for them to take it back and infuse patients. And as we discussed on the presentation, because of bridging therapy, this is a very acceptable, I wouldn't say even acceptable, I would say comfortable place for physicians to be by the time they get through the bridging therapy that most patients are going to receive, whether that's in later lines or in earlier lines. We're really at the 30-day mark, and so turnaround time is quite competitive to where physicians need it to be at this point, but we do expect that we'll continue to be able to reduce that over time.

Yeah, I mean, you heard from Adam how much improvement we have seen in our manufacturing process. In fact, the latest data from Raritan suggests that the median efficiency delivery time is about 27 days now. And then, Chloe, I want to answer a question about the publication. So, it's a paper. published actually from Cardinal Health with collaboration with Vanderbilt University Medical Center. And it was based on the response from 50 chematologists and oncologists. In terms of the breakdown of the surveyed physicians, it's about 86% in the community practice and then 14% in the academic setting. It's also very well distributed in terms of geographic distribution of these doctors. So it's 28% from the south. 28% from the western area, 24% Midwest, 20% Northeast. So if you want to know more about this paper on the survey of 50 physicians on CAR4 data, we're happy to send you the paper, but it's a very well representative sample set here.

Okay. Thanks, Ying. I'm wondering if you could maybe comment on what feedback you got from them on what, well, I guess, what are you hearing and what is needed to further improve kind of their approval ratings in the second line prescriber setting?

So what we're hearing anecdotally from the field is that obviously the community-based hematologists and oncologists are really excited about survival. When we survey them on the three most important decision factors when they choose a medicine for second life, they rank in such an order, right? Survival, followed by PFS, and then followed by response rate, including complete response rate. So that shows you there's a divergence here because in the academic setting, the physicians in tertiary hospital tend to put PFS on par with OS, but in the community setting, clearly there's a very strong preference on survival here. That's what we're finding out in the community setting. And like I said, We fully expect the FDA to approve our survival data in the label in the fall of this year. We have a due date here. And, you know, this survival benefit will also be augmented by our ASCO presentation in the next month. So, you will see that once we have the detailed data, and the physicians, I'm sure, will be excited about the long-term follow-up data in terms of the long-term remission.

Got it. Thank you so much. Thank you. One moment for our next question. And our next question comes from the line of Shawn McCutcheon of Raymond James. Your line is now open.

Hi, guys. Thanks for squeezing me in. Can you speak to the BAR to take the CLAD in 18.2 program forward? We've seen some decent results from CARS-Gen with some entry frontline signals in sequence with chemo and But the durability for the second line setting looks like it could be more of a question. And maybe it's restricted to the cloud and 18.2 high expressors. And secondarily, should we expect a similar approach on the development compared to the DLL3 program, meaning would you want to take it forward with a partner? Thanks.

Thank you for your question. So regarding the cloud and 18.2 study, We are, as discussed earlier, going to be presenting some data at ASCO. We anticipate the dose escalation to be complete, you know, later at the end of summer, and then we anticipate the expansions to begin at that time. We have, obviously, cloud in 18.2 is important, both in gastric cancer, but also pancreatic cancer. I think it's also, while there is an antibody approved in the frontline setting in gastric cancer, the expression, the clouded expression is quite high in order for people to use that antibody. I think in general, we've seen that CAR T cells tend to have more sensitivity for lower-expressing cells. So, there's, I think, an opportunity to pursue CAR-T in this space, both in gastric cancer and pancreatic cancer. So, we'll have to wait and see how the completion of the safety dose escalation is, but we are excited for the opportunity to explore this further in the expansion.

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