Iovance Biotherapeutics, Inc.

Good day, and thank you for standing by. Welcome to the Iovance Biotherapeutics first quarter 2025 financial results conference call. At this time, all participants are in a 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 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 1 1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Sarah Pellegrino, SVP, IR, and Corporate Communications. Please go ahead.

Good afternoon, and thank you for joining the IOVANCE conference call and webcast to discuss our first quarter 2025 financial results, as well as recent corporate updates. Dr. Fred Vogt, our Interim Chief Executive Officer and President, We'll provide an introduction and focus on the U.S. commercial launch of Amtagvi, including revenue and revenue guidance. Dan Kirby, Chief Commercial Officer, will discuss the Amtagvi commercial launch. Dr. Igor Balinski, our Chief Operating Officer, will provide a manufacturing update. John Mark Bellaman, our CFO, will review our financial results, including revenue and revenue guidance, gross margin and cash burn guidance. and Dr. Frederick Pinkenstein, our Chief Medical Officer, will summarize key pipeline programs. Additional members of our leadership team, including Dr. Raj Puri, our Chief Regulatory Officer, Dr. Brian Gassman, our EVP of Medical Affairs, will be available for the Q&A session. Earlier this afternoon, we issued a press release that is available on our corporate website at iovance.com. Before we start, I would like to remind everyone that statements made during this conference call will include forward-looking statements regarding IOAMS's goals, business focus, business plans and transactions, revenue and revenue guidance, commercial activities, clinical trials and results, regulatory approvals and interactions, plans and strategies, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interaction, licenses and collaboration, cash position and expense guidance, and future updates. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statements. With that, I will turn the call over to Fred.

Thank you, Sarah, and welcome to the I-Advanced first quarter 2025 conference call. We are four quarters into our U.S. launch of Antagni, the first FDA-approved kill cell therapy and the first treatment for patients with advanced melanoma who progress following anti-P1 treatment and, if appropriate, targeted therapy. In the first 12 months of our U.S. launch, we've executed towards our long-term goal, adoption goals, and generated more than $210 million in revenue. This includes infusions from nearly 300 Antagni patients in the first launch year, starting with our first infusions in April of 2024. Total first quarter product revenue was $49.3 million, including $43.6 million from more than 80 Antagni infusions and $5.7 million from Prolucan sales. Following steady growth throughout 2024, revenue was lower in the first quarter of this year, driven by three key contributors. First, our internal manufacturing facility, the ICTC, completed annual scheduled maintenance in December of last year, as we previously discussed on last quarter's call. As a result of limited production starts from multi-week antagonist manufacturing across our network, capacity was reduced by more than half for about one month. In addition, volume was impacted by higher rates of patient drop-off and lower manufacturing success rates, but it's since rebounded. Today, we are seeing healthy demand with a record number of production starts into the second quarter. Lower proleukin sales were the second factor contributing to lower first quarter revenue. We expect two of the three largest U.S. wholesalers to start replenishing proleukin in line with growing antagonism in the second quarter. We're also growing the other components of our franchise, including sales of proleukin to third parties for use with manufacturing and clinical research. The third contributor to first quarter revenue was the variable pace at which ATCs began treating patients, as this differs from center to center. For context, 16% of ATCs have treated more than 10 patients. Our ATCs have ample room to grow, and we anticipate near-term contributions from ATCs that came online in the latter half of 2024 into 2025. We are also confident in our growth prospects under our new Chief Commercial Officer, Dan Kirby. Dan brings invaluable leadership experience in cell therapy commercial organizations since the earliest developments in the field. In less than three months, Stan is already strengthening our commercial operations to drive ADC adoption and amplify earlier community referrals to our ADC network. The commercial team is working aggressively to implement key learnings from the first year as we continue to execute our U.S. launch. We are also excited about upcoming milestones related to our ex-U.S. launch expansion and pipeline development to lung cancer and beyond. We anticipate three potential approvals for AMTAGME in the United Kingdom, Canada, and the European Union. And additional regulatory submissions are also underway in Australia and Switzerland. We are on track to report updated data from our registrational trial of blephalusole and previously treated advanced non-small cell lung cancer and first clinical data in endometrial cancer. And we continue to advance our robust pipeline of next-generation toll cell therapies for patients with solid tumors. Looking ahead, I will briefly comment on our revised full-year revenue guidance and cash spend outlook. We revised our guidance to between $250 and $300 million in total product revenue for the full year 2025. We consider our experience with growth trajectories at the ATCs, timelines for new ATCs to begin treating their first patients, and expectations for large community practices and community referrals to drive momentum in the second half of 2025. These demand trends are consistent with the trajectory of other cell therapy launches moving from year one to year two. After aligning our manufacturing slot plans with our new demand forecast, we are maintaining our prior cash runway guidance into the second half of 2026. We remain confident in a peak sales opportunity of more than $1 billion in the U.S. and more than $2 billion globally for Ampagni and the current approved indication. We also continue to expect the gross margin can exceed 70% in the coming years. Ampagni and Perlucan are showing steady growth in the second quarter and will accelerate in the second half of the year. Current momentum is strong, and we project between 100 and 110 commercial patient infusions in the second quarter. We are also motivated by positive feedback from key opinion leaders and patient success stories that reinforce the unmet medical need and value of MTAGV. On a macro level, as Igor will describe, we are well prepared to supply ongoing demand to deliver commercial MTAGV, as well as our investigational tilt products to patients around the world. I-Advance is competitively positioned with a fully U.S.-based patent portfolio and manufacturing network. Tariff should have a minimal impact on Antagni and Prolucan. I'm happy to go into more detail during the Q&A, and we'll now turn the call to Dan Kirby for a detailed commercial launch update. Thank you, Fred.

Following my first 90 days at IOM, I'm excited about the potential for Antagni to benefit patients around the world. I've identified the strengths of our launch, as well as opportunities to optimize adoption and accelerate growth. Antagni is a game changer for patients who have failed first-line treatment in melanoma. mTagV is also the first cell therapy for patients with solid tumor cancers. I'll begin with my observations of what is going well. First, I'm very impressed by our competent and dedicated commercial organization and cross-functional field teams. These teams have established a solid foundation for mTagV by building awareness of the unmet need in advanced melanoma and strong clinical profile of mTagV, activating our 70 ATCs within our treatment network and preparing for the next wave of new centers, securing early inclusion in the NCCN guidelines and favorable reimbursement access for more than 95% of U.S.-covered lives. As a result of this execution, M-Type B is a successful cell therapy, the first of its kind in solid tumors. Today, I will discuss status and near-term initiatives to improve our performance across three key areas. First, our ATC network expansion and retention strategy. to drive adoption. A second area is to address plans to revamp engagements with medical oncologists to guide earlier consideration for antagony. And the third area is to further establish antagony within the U.S. community oncology networks. I'll start with our ATC strategy. In the first year of launch, we strategically prioritized 70 experienced cell therapy centers and most of the major cancer centers. Nearly all currently treated in Illinois patients and are within a two-hour drive of these ATCs. Current metrics amongst these 70 centers demonstrate ample growth performance and potential for MTAG. 79%, or 56 ATCs, have completed tumor resection, the starting material for TIL manufacturing. 69%, or 48 ATCs, have infused one or more patients. And 16%, or 11 ATCs, have infused more than 10 patients. ATC adoption is tracking in the right direction. We expect additional growth from the early launch centers with strong and steady patient volume. Newer centers, activated later in the launch, are currently contributing as they gain experience. For the next set of ATCs, we are currently in the process of activating more than 10 select high-quality centers, including those aligned to large community networks that have premier access to patients needing antagony as their second-line treatment. This next set of ATCs reflects lessons learned, best practices, incorporating clinic referral patterns. Meanwhile, we continuously collaborate with all of our active ATCs to support early referrals and best practices for procuring tumor samples. As we prepare to commercialize Antagni beyond the U.S., 10 international treatment centers are in process to become ATCs for our planned launches in the United Kingdom, Canada, and Europe. We remain on track to onboard 15 international centers as ATCs by Europe. Turning to the second area of focus, we have made it our goal in the last three months to better understand our physicians and how they view Antagni. In the initial launch, the team did a great job of educating the cell therapy community and key medical oncologists on the benefits of Antagni. From our market research, we see that those physicians view Antagni as second-line treatment. We also saw that there is a disconnect in Antagni treatment sequencing between our initial target physicians view MTAGV as a second-line treatment and referring medical oncologists in the community who consider MTAGV as third-liner later in therapy. This is a large market opportunity for MTAGV. Our number one goal is to establish MTAGV as the preferred option for all appropriate patients. To this end, we are educating referring medical oncologists to consider MTAGV early and bring forward the promise of cell therapy within current solid tumor treatment practices. We have a sizable patient population, and we have a tremendous potential to drive earlier patient referrals to our ATC. For example, a portion of our ATC, a portion of patients who initiate the MTAGV journey die or enter hospice prior to surgery shortly after committing to MTAGV. This is due to late referrals in the community. With our updated plans, we are doubling down on initiatives and medical education effort with community medical oncologists so we can drive earlier patient referrals and shift the treatment sequence. To do this, we will educate practitioners on the benefits of durable responses with one-time cell therapies like MTAGV versus temporary responses and ongoing side effects seen with other treatments. We will roll out new disease state educational efforts and amplify our presence at relevant medical meetings to provide a better understanding around TIL and cell therapy. For the first time in advanced melanoma and solid tumors, a cell therapy made from a patient's own immune cells has been shown to induce long-term benefit with curative intent. For the third area of focus, we are building relationships within community oncology networks that treat our target MTAGD patients. We are expanding resources within our community field team to increase frequency, speed, and overall timelines for referrals and to identify new ATC targets. Recently, we have seen increased momentum for patient referrals to current ATCs and identify new ATCs. Since my arrival, we've engaged with executive leadership in every major U.S. community cancer network. We are now collaborating with the top U.S. community clinic networks to identify and onboard several preferred centers for an antagonist. We are also focused on breaking down any remaining access barriers to adoption. For example, We're exploring alternative distribution channels that may offer flexibility and broader acceptance of one-time therapies like MTAGV while maintaining our current pricing strength. In addition to MTAGV, our commercial organization is dedicated to supporting ProLucan across three key business lines. Use with MTAGV, use in manufacturing, and clinical use. Aside from the main business tied to MTAGV, manufacturing and clinical use represent an existing base revenue for ProLucan. My team is focusing on opportunities to increase sales growth in all three areas. As Fred mentioned, strong public and sales in our main channel will resume throughout the remainder of 2025, including two distributors expected to reorder in the second quarter. In summary, I am energized to lead our commercial organization toward a bright future. Launching a first in-class therapy entails a unique set of opportunities to make a fundamental difference. I am deeply committed to the IVAN's vision of pioneering a new treatment paradigm for physicians who treat patients with solid tumors. We have barely scratched the surface of MTAGV's potential to globally address more than 30,000 melanoma patients annually. MTAGV has tremendous promise in solid tumor cancers, which represent 90% of all cancers. I will now pass the call to Igor Malinsky, our Chief Operating Officer, to highlight our manufacturing progress.

Thank you, Jim. Today, I will provide an update on our progress in manufacturing. Our Philadelphia-based manufacturing network consists of two FDA-approved facilities, our internal manufacturing facility, the Ivan Cell Therapy Center, or ICTC, and an American-owned contract manufacturer. This network serves commercial patients in the U.S., as well as clinical trial patients across Europe, Australia, and Asia. Our experience in supplying tilt cell therapies to clinical patients around the world is provides a strong foundation for delivering commercial product in the EU, UK, and Canada in the near term. Today, I'm pleased to report a major step forward in the ongoing review of our marketing authorization application, or MAA, for the European Union approval of MTAG. Recently, as part of the MAA process, the European Medicines Agency further validate our manufacturing network capabilities to meet regulatory standards from multiple healthcare authorities as we prepare to serve commercial patients in the European Union. As part of the ongoing launch, we steadily ramped up our staff manufacturing capacity to align with demand while tightly controlling expenses. As a result of our revised revenue guidance and updated demand forecast, as Fred described, realize additional cost savings by aligning our manufacturing capacity growth plans with demand. Owning our own manufacturing facility provides us with tremendous flexibility to scale up efficiently when needed. As mentioned previously, ICDC conducted and successfully completed annual scheduled maintenance. Given the three-week manufacturing process for Antagni, the network capacity was reduced by more than 50% maintenance production resumes successfully with full capacity available for Q2 MTIB infusions. I will also comment on our manufacturing success rate in the first quarter. Delivering final product within defined specifications is critical for treating patients. Throughout the first nine months of the U.S. launch, our commercial manufacturing experience was consistent with prior clinical experience. The rate of patient drop-off and out-of-spec rate in our cost of goods and gross margin, as Jean-Marc will further discuss. Following Q1, manufacturing success rate has since rebounded. During this year, we also expect to shorten our manufacturing turnaround time, which is currently 34 days from receipt of sales at the manufacturing facility to MTAG being ready for return shipment to the ADC. In addition, we continue to be in laser focus on driving operational efficiencies and economies cost of goods and improve gross margin over time. Shifting to the current macroeconomic and geopolitical environment, iBent is operating at a strategic advantage within the biopharma industry. We expect MTAG-B and Prolucan to see minimal impact from tariffs. Our intellectual property for MTAG-B and investigational till cell therapies is domiciled in the US. MTAG-B manufacturing is based in the US, Most of the antagonistic cost is U.S. based, with direct materials procured from ex-U.S. vendors currently representing less than 5% of the antagonistic cost of goods. For Prolucan, we have also brought sufficient Prolucan inventory to the U.S. that we expect to be sufficient for meeting demand into 2027. Our TIL self-therapy expertise and manufacturing capabilities are protected by a robust patent estate domiciled in the U.S. We own approximately 280 granted or allowed U.S. and international patents and patent rights, one category in other TILT-related technologies. We expect these patents to provide exclusivity through at least 2042. I'm available to answer questions during the Q&A, and I will now hand the call to Sean Mark, Deutsche Financial.

Thank you, Igor. Today, I will review our cash position and results for the first quarter of 2025. I will also highlight our financial outlook, including revenue, expense guidance, and gross margin. As of March 31st, 2025, our cash position was approximately $366 million. Our current cash position is sufficient to fund current and planned operations, including manufacturing expansion into the second half of 2026. I will now transition to our financial results. Net loss for the first quarter of 2025 was $116.2 million, or $0.36 per share, compared to a net loss of $113 million, or $0.42 per share, for the first quarter of 2024. Total product revenue consists of MTAGV infusion in the U.S. and pro-looking sales. Total product revenue was $49.3 million for the first quarter of 2025, including $43.6 million for MTAG-V and $5.7 million for Proloquing, compared to total product revenue of $0.7 million for the first quarter of 2024 for Proloquing. The US commercial launch of MTAG-V and Proloquing sales drove the revenue increase in the first quarter of this year over the prior year period. I will now highlight our cost of sales, which includes cost of inventory, overhead, and related cash and non-cash expenses that are directly associated with sales of Antagvy and Prolucane, as well as manufacturing costs for Antagvy. Cost of sales for the first quarter of 2025 was $49.7 million, including $15 million in period costs associated with patient drop-off and manufacturing success rates, an increased quarter-over-quarter, as Igor previously described. $5.4 million for non-cash expenses, including fair market value step-up and intangible asset amortization, and $1.3 million in royalties payable on product sales. During the first quarter of 2024, cost of sales was $7.3 million, primarily related to non-cash amortization for acquired intangible assets. The increase in cost of sales in the first quarter of 2025 over the prior year period was primarily attributable to cash and non-cash expenses associated with MTAGI product sales tied to the U.S. launch, along with period costs associated with patient drop-off and manufacturing success rates. Average standard gross margin is 32% for the first four launch quarters. Standard gross margin for the first quarter of 2025 was 10%, or $5 million, compared to total product revenue of $49.3 million. First quarter was negatively impacted by lower revenue and higher cost of sales, as previously described. As we increase volume and capacity utilization, We expect gross margin to surpass 70% in the coming years. Our priorities are to drive revenue while optimizing our cost of sales with a correspondingly higher gross margin. As we expand our manufacturing, coordinate and continue our focus on ATC engagement and training, and realize efficiencies in manufacturing and release testing. I will now shift to our operating expenses. Research and development expenses were $76.9 million for the first quarter of 2025, a decrease of 4% compared to $79.8 million for the same prior year period that was primarily attributable to the transition of MTAGRI from clinical to commercial manufacturing. This decrease was partially offset by higher ad count and related costs, including staff-based compensation and clinical trial costs resulting from continued enrollment in existing trials. Selling, general, and administrative expenses were $43.9 million for the first quarter of 2025, an increase of 40% compared to $31.4 million for the prior year period. Higher selling, general, and administrative expenses were primarily attributable to increases in headcount and related costs including stock-based compensation to support the growth in the overall business and related corporate infrastructure, marketing and legal costs, and costs to support the commercialization of MTAG-V and ProLoki. Looking ahead, we revised our guidance to between $250 and $300 million in total product revenue for the full year 2025. After aligning our manufacturing slot expansion strategy with our new demand forecast, we are maintaining our current cash runaway guidance into the second half of 2026. Cash burn for full year 2025 is expected to remain in line with prior guidance of less than $300 million, with a strong focus on optimizing spending and reducing expenses throughout the organization, including flat expenses related to MTAGV manufacturing at current expansion for the latter half of 2025. As we grow revenue and as gross margin improves, we expect further reduction in our net cash spend, with ample flexibility to control both capital and operating expenses as we approach break-even. For additional information, please see the company's selected consolidated balance sheet and statements of operation in this afternoon's press release and our form 10-Q to be filed later today. I will now end the call to Frederick, our chief medical officer, to discuss our clinical pipeline.

Thank you, Jean-Marc. Building on the team's comments about MTAGV, the durability of responses following a one-time treatment is a key differentiator from other available and emerging therapies. We will present five-year results from our CE14401 trial at the American Society of Clinical Oncology, or ASCO, annual meeting on June 2nd. Compared to prior data updates, these results show consistent trends for overall survival and durability over a five-year period. Our clinical programs and next-generation approaches are the next frontier for child cell therapy and solid tumors, which represent more than 90% of all diagnosed cancers in the US. Future growth drivers include global label expansion for Lifolucel into frontline advanced melanoma, other solid tumor types such as non-small cell lung cancer, and next-generation therapies. Today, I will summarize our latest pipeline updates. First, we are making progress towards the broader commercial opportunity for MTAGV in frontline advanced melanoma. Our global registrational phase 3 trial, TILBAN301, remains on track to support accelerated and full approvals of Emtagli in combination with Pembrolizumab in frontline advanced melanoma, as well as regular approval of Emtagli in our initial indication in post-anti-PD-1 melanoma. The proof-of-concept cohort is also investigating Lysolusil in combination with Nivolumab and Rilatilumab in the U.S. Our registrational program in advanced non-small-cell lung cancer The single-arm phase II IOV LUN202 clinical study is designed to show efficacy and safety of lysolutal monotherapy in patients progressing after anti-PD-1 therapy. There is a significant unmet medical need as most patients progress in chemotherapy. The current standard of care in this treatment setting provides limited rate and duration of responses. remain on track as planned to share additional data from IOV LUN202 in the second half of 2025. The trial is designed with the potential to support a potential regulatory decision on U.S. accelerated approval in post-anti-PD-1 non-small cell lung cancer in 2027. In frontline non-small cell lung cancer, our strategy is to establish a new regimen Consisting of lifelucel plus pembrolizumab following standard-of-care chemotherapy pembrolizumab, multiple cohorts are investigating patients with EGFR wild-type non-small cell lung cancer who are the majority of patients with an unmet medical need in this treatment setting. Turning to another significant opportunity, advanced endometrial cancer, our IOV END201 clinical trial is investigating lysoleucel after frontline standard of care of chemotherapy and anti-PD-1. We look forward to sharing initial data from END201 in the second half of this year. As the leader in TIL cell therapy, IOV is also at the forefront of next-generation approaches to optimize TIL and TIL treatment regimens. I'll briefly summarize our three lead next-generation programs. Our PD-1 inactivated tilt cell therapy, IOV4001, continues to enroll patients in a trial that previously treated advanced melanoma or non-small cell lung cancer. Building on our successful Prolucan franchise, we are treating patients in a Phase I-II clinical trial of IOV3001, a second-generation modified IL-2 analog for use with the TIL cell therapy treatment regimen. And lastly, ILV5001 is a genetically engineered, inducible, and tethered IL-12 TIL cell therapy with potential for enhanced activity, which could facilitate expansion into a wide range of common solid tumor cancers beyond our current pipeline with significant market opportunity. We plan to submit an investigational new drug application to FDA this year for IL-B5001. I'm happy to address questions about these programs and additional trials during the Q&A session. I now turn the call over to the operator to begin the question and answer session.

As a reminder, to ask a question, please 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. In the interest of time, we ask that you please lend yourself to one question and you may rejoin the queue. Please stand by while we compile the Q&A roster. Our first question comes from Andrew Tsai with Jefferies. Your line is open.

Hey, thanks. Good afternoon. Thanks for taking my question. Appreciate the update. My question is around the line of sight you're having. amidst the revised guidance, presumably you do have some direct line of sight maybe at least a month in advance into the number of patients who are waiting to get dosed in the queue. Can you confirm whether you're seeing or have seen a spike or an inflection in patient uptake as of today to give you the confidence around your guidance of 110 patients for Q2? Thank you.

So Andrew, this is Dan. Thank you very much. Yes, we're confident in that number, and we are seeing demand, as we stated in the script, in quarter two be strong.

Thank you. Our next question comes from Tyler Van Buren with TD Callen. Your line is open.

Hey, guys. Thanks very much for all the information. So for the 11 ATCs that have infused more than 10 patients, Were most of them involved in the clinical program and it's just a matter of getting the other ones that weren't up to speed? You know, maybe you could discuss the barriers of the other 37 ATCs that have infused more than one patient but haven't infused 10 plus and what tactics you're employing to get them to increase their utilization.

Yeah, Todd, I'll start and I'll pass over to Dan and give you a little bit more on the second part of that question. On the trial, only a few of those ATCs were actually involved in the trial. It's not necessarily a correlation between the clinical trial unit of the site and their experience and what the site does with commercial antagony. A lot of times it's different people, and we have to work closely with that unit at each ATC to get them up to speed. So there is some learning there, but we're able to overcome it. Obviously, we're learning quite a bit ourselves about how to do that, and we're getting better and better all the time. And that's why we have confidence that many of those other ATCs are going to come along quickly. In fact, we're seeing that today. But Dan, do you want to take the second part of the question? Sure.

And looking at just with cell therapy in general, there's actually patients coming into treatment, and there's a cell therapy experience level at these centers. So what we'll say is that the larger centers that got off to a quicker start, those are the ones with the infrastructure from various cell therapy launches that were ready for MTAG-B to enter in. The other ones are ramping up to speed. They're doing this with other cell therapies as well. But infrastructures such as billing mechanisms, cell therapy lab, et cetera, are coming online with that. So we are seeing them increase their ramp a lot quicker once they get that infrastructure in place. Does that answer your question? Yep, thank you.

Thank you.

Thank you. Our next question comes from Salim Saeed with Mizuho. Your line is open.

Great. Thanks for the question, guys, and the color of the day. I guess on your guidance kind of going forward here for 25, if I'm doing my math correctly here and assuming something like 20% Prolucan, sort of backing into the balance of the year, you're going to have something like 250 or 325. uh 325 uh infusions um so roughly like call it 100 110 something like 100 per quarter roughly is is that a correct way to sort of think about this which essentially apply you know no growth versus uh no growth versus like the the 2q number no absolutely that's that's not how you want to think about it we're actually right now as you know we did 164 million in revenue last year

including quite a bit of proleukin. And what we're projecting is 250 to 300 this year, which is some growth there, obviously. That's fiscal year-aligned. If you want to think of it as just infusions, though, you can look at the four quarters. We infused our first two patients back in April of 2024, and through to the end of March, we were about 280-some patients infused. Our guidance implies that in this year, we'll probably get over 500 patients infused, And that's in the four quarters of the fiscal year. And of course, there'll be another quarter into 2026 that will grow more. So you are looking at like a 50% or more growth rate there as you go through this time period year over year. And there's a lot of upside there as well.

Dave, do you want to add to that? Sure. So what I would say is the way you can look at this is that we expect continued growth throughout this year. So it will not be flatlining. It will continue to grow. That's driven by two factors. One, as we talked about, the increase of adoption in our centers, both the ones that started at the very beginning and the ones that ramped up through 2024, and the addition of new ATCs that have enhanced referral networks within the community to get patients not only in quantity but also quality, meaning they're getting earlier referrals.

Okay. Thank you so much. Thank you. Our next question comes from Andrea Newkirk with Goldman Sachs. Your line is open.

Good afternoon. Thanks for taking the question. Maybe a follow-up there, Fred, on what your guidance is implying per infusions. I just wanted to make sure I understood this, but are you suggesting that 500 infusions should be on top for 2025? And if that's the case, then what are you assuming for proleukin through the remainder of this year, even after the uptick expected in 2Q?

So if you just take the guidance we gave, subtract off a number like what Saleem just gave you for proleukin, and divide that through by 550 or so, you're going to get something in the high 400s, close to 500, depending. And if you think there's some upside here, there could be some upside, too, on top of that. Does that answer the question?

OK. And then just really quickly, Igor, could you just speak to what drove the higher patient drops or lower manufacturing success in the quarter, and what gives you the confidence that this will reverse on the forward?

So some of this, thanks for the question, Andrea, some of this or much of this is related to patient selection and the tumor procurement technique. And as I mentioned, we already saw the return to normal rebound in the Q2 so far. What gives us confidence is the success rate trends that we see among ATCs who've been up and running for a long time and the experience curve that they've been able to achieve. So that gives us confidence that it's teachable and can be translated to other ATCs across the network.

Thank you. Our next question comes from Yanen Zhu with Wells Fargo. Your line is open.

Thanks for taking our questions. First, a clarifying question. I must be missing something. So assuming each MTAG-V product is roughly north of $500,000, that's half a million. And then if there's 500 patients infused this year, that alone will be $250 million, which is the lower bound of the guidance. So if that's the case, then you know, adding IL-2 on top of that, the lower bound of guidance should really be above 250. So I'm trying to see if my assumption for per patient, you know, price, you know, off. And my, thank you for clarifying. My actual question is on COGS. And can you talk about the, you know, it seems like COGS has, you know, ratio of revenue has increased over the last quarter. Just wanted to understand what proportion of the COGS is due to patient attrition, i.e., patient passing away, cannot get the product, or manufacturing failure, if you can give us some color there. Thank you.

Yes, Yan, on the first part, our guidance, we consider this guidance to be fairly conservative. So as you go and do your math there, there is going to be some upside of what we're giving here. But if we get to 500 infusions, it might be above 300 on the upper end. And that's something that we really want to, with this new guidance, we really want to show that we can actually exceed guidance here and do well here with this launch. So it's not going to work out exactly to where you might think. Maybe it's 450 patients if you want to be more conservative. However, it's still growth. It's still growth over the first three quarters of the launch. If you want to look at it on a fiscal year basis or four quarters, you want to look at it on a launch year basis. But again, the first four quarters of our launch, we treated about 280-some patients. Now, for the cognitive question, let me ask, and that's the ratio of Scrap and Jean-Marc, and maybe Igor might need to help out with that one.

Can I just say something? Go ahead. So one of the things, I mean, first, the quarter, the $250 million is a 50% growth over 2024 sales. So that is definitely a growth in the lower end for it, and yes, they're The second part, when you talk about patient health, I just want to clarify that statement. Those are patients who went to hospice or died prior to the manufacturing process starting, meaning they went there before we had tumor procurement. So, therefore, they would not be affecting COGS. And, Igor, do you want to take the COGS question? I think John Mark may need to take that.

Yeah. I'm happy to take the COGS question. So, yes, you're correct. And the overall cost of sales together, as Igor mentioned during the script, is that we see a spike in the out-of-spec on the first quarter that we know will improve over time, but you have to think also relative to the overall revenue. So yes, the cost of goods and the cost of sales has increased in Q1, particularly related to revenue, but we know this will definitely improve in Q2. And our standard gross margin remains positive in Q1, as you heard me say.

Got it. Thanks for the cover.

Thank you. Our next question comes from Colleen Cousy with Bayard. Your line is open.

Good afternoon. Thanks for taking our questions. You report that patient drop-off and out-of-spec rate together, but can we assume that that out-of-spec rate went up? And if so, what drove that? Was it anything to do with the annual maintenance? And then would we expect that same one-month interruption going forward every year? Thank you.

Colleen, thanks for the question. So, again, regarding the patient drop-offs and manufacturing success rate, these closely relate to each ATC's track record and patient selection and tumor tissue procurement. And again, the increase we saw in Q1, we believe it to be transient. It's already normalized in Q2 to date. So that's what we believe is driving it. We have new ATCs, new surgeons, and some of that needs to be optimized over time, which our teams are working on. What was the second part of the question?

Just the annual maintenance, whether that will be a similar one month 50% reduction in capacity every year.

So annual maintenance, so we are now completing build out of the shell space at ICTC. Once that shell space is operational, which will not be this year, that should be later on, once that shell space is operational, then we don't need to, the maintenance will only affect part of the ICTC facility, not all.

It will have less impact. It will have less impact. But yes, Colleen, it is an annual event. You have to do it.

But for now, this year, we'll still need to do it. But in the subsequent years, once the ICDC is fully built out and fully up and running, we will not see that effect.

Helpful. Thank you.

Thank you. Our next question comes from Peter Lawson at Barclays. Your line is open.

Great. Thank you so much. Just Going back to kind of manufacturing success, has that returned back to normal levels? And was that also related to the, I thought you had a problem in 4Q as well, associated with the same thing. Is the same thing kind of spread into 1Q or a separate issue?

We're not really sure, Peter, what you're asking out there. The important point is, we didn't talk about that in the last quarter at all. What we did mention back then is there was going to be a shutdown, and we were in the process of, at that point, actually hitting the shutdown.

But no, we don't, that doesn't resonate. There was no issue with manufacturing success rate Q4. No, Q4 was actually a good quarter.

Now, the important thing to remember here, Peter, is rebounded already. Again, we think it has to do with individual activities in some of the ATCs and how they procure tumor as well as some some things that we can learn from throughout the entire process and how we can improve those things. And it looks like it's already rebounded pretty well. We're back in the zone where we think we were during the first part of the launch.

Got you. Thank you. And is there any way of breaking out sort of the revenue weakness you had and lower guidance, kind of how much of that's due to demand uncertainty and or manufacturing uncertainty?

No, I don't really think there's a way of doing that. No, that would be very complicated to analyze that. Dan or Igor?

I mean, we see demand being consistent and growing, especially with the new centers coming on with it, not the ones ramping up. So demand is not an issue for that part of it, and I think Igor had addressed it.

Again, the guidance computer is really driven by ATC launch dynamics more than anything. It's not really about uncertainty in those areas.

Got you. Okay. Thanks so much.

Thank you. Our next question comes from Rennie Benjamin with Citizens. Your line is open.

Hey, guys. Thanks for taking the questions. Igor, you had mentioned that these different ATCs are different. doing things slightly different. I'm kind of curious, what are the strategies, the different strategies that you guys are employing right now to kind of get all these ATCs rowing in the same direction to improve all these, you know, improve the various manufacturing things and, you know, to help improve kind of the overall processes there? And then just as a second question, it's revised guidance I guess we were all kind of surprised to begin with when last year you provided guidance for this year. I'm kind of curious as to, you know, I get being conservative now. Why provide guidance for 2025 way back in 2024 to begin with?

So the first part we have to then get out, sir? Sure. I can also throw over to Brian for that. One of the things we're seeing for the tumor tissue procurement that's happening at the centers, and replicating the successes that we're seeing with the surgeons that are doing it better than others. We actually have our field teams out there now that are really focused and actually from the medical affairs side, so I'll hand to Brian. But Brian, can you talk about how your field teams are addressing that?

Yeah, I think one of the things that's happening is we recognize that these centers continue to grow internally. They keep adding new members and what we've been doing really, we call it a white glove service where we're getting in there and actually certainly for the newer surgeons to actually go from, we call it the start program or start to finish program, where we actually go in and we'll walk through the surgery and beyond with them to try to make sure that every case is as successful as possible. We've had very good feedback. They're enjoying it, especially the new centers and the new surgeons, and we're hoping to try to really speed up those learning curves for our newest ADCs so that they can learn from the successes of our best ADCs that have been around a long time.

I guess I can get the second part of your question ready. Back in August, we were trying to give investors our best line of sight to what we thought was going to happen. At that point, we were very well aware of the high demand for the product, and we were ramping up our manufacturing as fast as we could. So we built our model on the back of how many manufacturing slots we would make available at maximum ramp. Now, as we've gone, we've learned a lot about the launch. especially recently as we've watched some of the dynamics with the ATCs. We looked at our experience with growth trajectories there. We looked at the timelines it takes for new ATCs to come on board and begin treating their first patients and how they work through their processes. We're onboarding these large community practices, which takes some time, and we're doing the community referral process, which takes a lot of time, too. And as we looked at that, we just decided that it was better and more accurate for us to forecast guidance that we gave today to show you that we can still make this product grow very, very substantially But now what we're going to do is we're just going to limit some of our manufacturing slots. It ends up being essentially almost a neutral one with respect to how we use our cash. And we'll roll forward and we'll continue to succeed on the launch. But we think we'll do it on terms that are, I think, a little bit more in line with what we actually see at the ATCs.

Thank you. Our next question comes from Astika Goonwarden with Truth. Your line is open.

Hi, this is Karina. Thanks for taking the questions. What percentage of the product is currently being manufactured at the ICT versus contract manufacturer? And then also, again, lower manufacturing success rate. Some of the clinicians, they noted that there's a need for a larger amount of tissue to improve success rate. Can you comment on that? Thanks.

So I'll take the first part. ICTC, our internal manufacturing facility, is responsible for most of the manufacturing volume and has significantly higher capacity than our contract manufacturer. And then the second part, perhaps I'll turn it over to Brian.

Yeah, I mean, we've made a lot of guidance changes in terms of best surgical practices. It goes from volume of tumor to handling of tumor in general and preparing it before it's being sent. To be honest with you, you know, the Do we need all the tumor that we get sent? Not always, but we generally guide towards what I would call the average ATC, the average surgeon, because the best surgeons probably don't need any guidance and probably the below average need a lot of guidance. And so in general, we do try to ask them for as much tumor that reasonably fits into the vial that we give them.

All right, thank you.

Thank you. I'm showing no further questions at this time. I would now like to turn it back to Fred Vogt, interim president and CEO, for closing remarks.

Thank you again for joining the IVANS Biotherapeutics first quarter 2025 financial results and corporate updates conference call. We look forward to providing future updates on our growing commercial and clinical portfolio, including our data presentation and investor event at the upcoming ASCO annual meeting in Chicago. We are motivated by the stories we continue to hear about the patients who benefit from IVANs and tel-cell therapies in our clinical trials and commercial setting. I'm confident that IVANs will remain the global leader in innovating, developing, and delivering current and future generations of tel-cell therapies for patients with cancer. As always, we are thankful to the patients, healthcare, and advocacy communities, our partners, and our exceptional IVANs team. I'd also like to thank our shareholders and covering analysts for their support. Thank you.

This concludes today's conference call. Thank you for participating. You may now disconnect.