Iovance Biotherapeutics, Inc. Price & Performance (IOVA)

And Doctor. Frederic Graf Finkenstein, our Chief Medical Officer will summarize key pipeline programs including our two registrational programs in frontline melanoma and Iovance Hodg cell lung cancer. Additional members of our leadership team including Doctor. Brian Gasman, our Executive Vice President of Medical Affairs, will be available for the question and answer session. Earlier this afternoon, we issued a press release that can be found on our corporate website at iovance.com. Before we start, I would like to remind everyone that statements made during this conference call include forward looking statements regarding Iovance'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 technology, manufacturing capabilities, regulatory feedback and guidance, payer interactions, 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.

I'm pleased to host this afternoon's conference call to discuss our financial results. For the fourth quarter and full year of 2024, as well as our recent corporate highlights, Earlier this month, we marked the one year anniversary of the historic approval of MTAGV, the first FDA approved Till cell therapy and the first treatment for patients with advanced melanoma progressed following anti PD-one treatment and appropriate targeted therapy. In 2024, iovance fully transformed into a commercial company. We executed a strong start to the AMTAG, The U. S. Launch, reinvigorated global for lukein sales growth and gained significant traction in our efforts to launch into new markets. Meanwhile, we advanced our robust pipeline of current and future generation telcelther across all stages of development to address tens of thousands of patients with solid tumors. Today, I'm pleased to highlight continued growth in total product revenue both AMPAGNY and Proleukin. Total product revenue was $73,700,000 in the fourth quarter and $164,100,000 in the full year 2024. Importantly, our full year revenue achieved the upper end of our 2024 guidance range, $160,000,000 to $165,000,000 and we finished above the full year Street consensus. Total revenue consisted of $48,700,000 from Tagby and $25,000,000 for Proleukin in the fourth quarter, with $103,600,000 for Amtag being $60,500,000 for Proleukin, in the full year period.

Our full year product revenue reflects more than 200 patients already treated with AMPAGNY in the partial first year of launch. We are pleased with the robust initial uptake and increasing strong demand for AMPaggy as well as continuing momentum in global ProLukin sales, Our team's successful execution as well as the unmet need the advanced melanoma, high awareness broad patient access and a motivated expanding network of authorized treatment centers or ATCs continue to drive increasing demand for AMTAGNY and 1,200 patients per year and continue to scale up for additional U. S. And global launch growth. In the back half of last year, we augmented our investment in focused community referral These efforts in the field are targeted at driving additional demand in our ATCs to scale up treat more patients. Looking ahead, we are reiterating our full year 2025 guidance of $450,000,000 to $475,000,000 in total product revenue. We expect a significant increase in year over year growth in both AMPADVI and Proleukin as ATC's broadened utilization. While new ATCs as wealth community referral networks are expected to contribute increasing demand through the year. Our fourth quarter gross margin again improved quarter over quarter and is our well over halfway towards our target to surpass 70% over the next several years.

And continued increases in revenue and gross margin will also correspond significant decrease in our annual cash burn. While maintaining our pipeline of future indications and products. We were judicious in managing our balance sheet 2024 and expect cash burn including one time items. To continue to decrease as we execute the launch and drive towards breakeven and profitability. Longer term, we remain confident in significant revenue growth in 2026 and beyond. For the currently approved advanced melanoma indication, the peak sales opportunity is more than $2,000,000,000 in The U. S. Market alone. And more than $2,000,000,000 globally.

Our ex U. S. Ex launch expansion plans are on track potential to gain three new approvals and provide early access to AMTAGNY in several new markets.

IVAN has distinct competitive advantages with the first approval launch and large scale manufacturing of Till cell therapy combined with strong intellectual property positions and a deep pipeline. Future growth drivers include global label extensions into frontline Iovance melanoma, other solid tumor types such as non small cell lung cancer and next generation therapy. As we transition today's commercial update, I would like to welcome and introduce Dan Kirby, on his first quarterly call as a member of the Iovance team. Dan joined us earlier this month in the newly created role of Chief Commercial Officer. As an instrumental leader in cell therapy commercial organizations since the earliest developments in the field, and is a perfect fit for Chief Commercial Officer as we grow the MTAGV launch and expand our prelukin sales. I'm pleased to begin the call to him to discuss our commercial updates. Thank you, Fred.

I'm very excited to be part of the Iovance team. Like many others in Celin Gene, I have been following the ENTYV launch I'm currently impressed by the progress the team has made in the first year.

And Tag B has the potential to improve lives thousands of patients with advanced melanoma and to advance into other solid tumors as well.

I came to Iovance because I believe it impacted me and the patient focused mission at Iovance.

My objectives today are to highlight the additional details the commercial progress that Fred summarized.

To begin, favorable medical coverage policies and broad reimbursement is critical for success in patient access for Intacty.

Approximately seventy five percent of NTAG B patients are covered by private payers and AMTAG B is also covered under the Medicare cell therapy DRG-one 80. Overall, more than two fifty million lives greater than ninety five percent of The U. S. Covered lives currently have access to reimbursement for Entegi Early inclusion in the National Comprehensive Cancer Network or NCCN guidelines combined with strong clinical data have also supported patient access. Throughout 2024, we scaled up our ATC network meet the growing patient demand fulfill significant interest among healthcare providers to offer NTAGV to their patients. After launching with an unprecedented 30 ATCs, on day one, we reached our target of approximately 70 ATCs at the end of twenty twenty four. Our ACC network now spans 32 states in nearly all treated melanoma patients, within a two hour drive of the closest center. We treated more than 200 patients with commercial MTAGI within the first three quarters of launch EmtekMe is positioned for significant growth across our ATC network in 2025 and beyond. Amongst the 70 current ATCs, seventy six percent completed tumor resection.

Sixty four percent infused ntagli, fifty three percent infused two or more patients, and thirteen percent infused more than ten patients.

These metrics demonstrate significant growth potential as our ACC scale up to accommodate growing patient demand.

New ATCs are preparing to treat initial patients Our more experienced ATCs are steadily growing or plan to increase utilization throughout 2025.

And we expect new ADCs will follow similar trends as we add steadily throughout 2025.

These additional ATCs will be selected for high quality and volume of eligible patients. Including large community practice [indiscernible] earlier patient identification and higher referral volume into our DTC network ioVend's field teams are actively engaging top community oncologists and large community practices with a focus on high volume markets.

Additionally, we are aligned with leadership at key community organizations on their preferred ATCs for patient referrals.

As more patients embark on their treatment journey, we are making steady progress to speed up the time to impact the infusion. Financial clearance currently averages approximately three weeks continues to improve. ATCs are saving up to two additional weeks by scheduling in parallel with financial clearance and or initiating the preconditioning regimen in conjunction with products for Allo. And we expect to decrease turnaround time for manufacturing and release Globally, NTAG B may address more than twenty thousand melanoma patients annually in The U. S. And our targeted international markets. In all future markets, AMTAGNY has the potential to be the first and only improved therapy for the treatment of adult patients with advanced melanoma previously treated with the PD-one and targeted therapy. Three regulatory dossiers are currently under review for potential approvals in 2025. Beginning with The United Kingdom in the first half, then Canada in midyear, and the European Union in the second half of the year. We also plan to provide early access for INTEGVY In The UK France, Germany, Canada, Switzerland and Australia.

In preparation for our initial ex U. S. Launch, we plan to onboard 15 international treatment centers by year end. Additional regulatory submissions remain on track including Australia in the first half and Switzerland in the second half of twenty twenty five.

In addition to ONTAGBI, our commercial organization is dedicated to supporting Proleukin, across three key lines of business. Which include for use in the IMPACT B treatment regimen, for use in manufacturing clinical trials and for clinical trial use where appropriate. During the fourth quarter, activated and provided initial stock for a third and final plan for a Logan distributor. Orders are now being fulfilled at all three major U. S. Wholesalers, with healthy ordering patterns, including restocking. We expect demand for Probuphine to continue to increase across each of these three key business lines throughout the year. In summary, I am extremely pleased with The U. S. Launch for and the momentum we are building to catalyze and expand the PAGNY adoption while growing prelukin sales within The U. S. And beyond.

I'm fully committed to the opportunity to impact thousands of patients' lives and drive toward $2 plus billion peak sales around the world. I will now pass the call over to Igor Balinski, our Chief Operating Officer, to highlight our manufacturing progress.

Thank you, Tim. Today, I would like to build on Fred's introductory comments with an update on our commercial and clinical manufacturing network as well as our capacity expansion. Our manufacturing network consists of our internal manufacturing facility, the Iovance Cell Therapy Center or ICTC, and the contract manufacturer helps ensure flexibility and ample capacity for both commercial and clinical production. To support growing commercial demand for AMTIG B, we are steadily ramping up our manufacturing capacity month over month while actively hiring manufacturing, quality control and support staff.

Within our manufacturing network, the staff capacity is currently at more than 1,200 patients annually. Throughout 2025, we will continue growing staff capacity in alignment with demand while operating at a high capacity utilization. Each of our facilities is currently required to schedule a brief annual maintenance which entails a short pause in production. I'm pleased to report that ICDC successfully completed annual maintenance and resumed production promptly at full volume with no issues. We expect the same positive outcome following the upcoming scheduled maintenance at our contract manufacturer. Our commercial manufacturing experience continues to be positive and consistent with prior clinical experience. The medical affairs and commercial teams are effectively sharing best practices among ATCs and contributing to improvements in manufacturing success rates and gross margin over time.

The turnaround time is consistently thirty four days from receiving cells at the manufacturing facility Emtek we've been ready for return shipments to the ATC. Our team is planning to shorten the turnaround time in 2025. Our Philadelphia manufacturing currently serves patients in our clinical trials in Europe, Australia and other geographies. We are now establishing logistics and distribution to provide access to commercial product in new markets in The EU, UK and Canada in anticipation of potential approvals this year. We are also expanding capacity to full our longer term vision The ICDC is built today, it has capacity for more than 2,000 patients [indiscernible] Once we complete the ongoing build out of existing shelf space, we expect the ICTC to have total capacity for over 5,000 patients annually within a few years. Additional expansion of our ICTC manufacturing campus along with process optimization and automation is expected to provide capacity for over 10,000 patients annually. As we draw our manufacturing network, we are focused on through economies of scale and operational efficiencies as well as by leveraging our unique competitive advantage as the leader in the Till cell therapy. Our Till cell therapy expertise and manufacturing capabilities are protected by a robust intellectual property portfolio.

We currently own more than two fifty granted or allowed U. S. And international patents and patent rights for MTAGV and other Till related technologies, that are expected to provide exclusivity through at least two thousand and forty two I'm available to answer additional questions during the Q and A and I will now hand the call to Jean Marc, our Chief Financial Officer. Thank you, Hugo.

Today, I will review our current cash position as well as our results for the fourth quarter and full year 2024.

I will also highlight our financial outlook including revenue expense guidance, 2024, our cash position was $330,100,000 As of February 26, 2025, our unaudited cash position was approximately $422,000,000 Our current cash position is sufficient to fund current and planned operations including manufacturing expansion into the second half of twenty twenty six. I will now transition to our financial results. Net loss for the fourth quarter of twenty twenty four was $78,600,000 or $0.26 per share compared to a net loss of $116,400,000 or $0.45 per share for the fourth quarter ended 12/31/2023. Net loss for the full year 2024 was $372,200,000 or $1.28 per share compared to a net loss of $444,000,000 or $1.89 per share Total product revenue consists of Emtagli Infusion In The U. S, and global sales of Prolukin within three different lines of business as Dan described.

Total product revenue was $73,700,000 for the fourth quarter of twenty twenty four including $48,700,000 for AntagV and $25,000,000 for Colleukin. For the full year 2024, we achieved the higher end of our product revenue guidance range of $160,000,000 to $165,000,000 Total product revenue for the full year 2024 was $164,100,000 and consisted of $103,600,000 for Amtech V and $60,500,000 for Proluton. Revenue increases in the fourth quarter and full year 2024 over the prior year periods were primarily driven by The U. S. Commercial launch of AMTACD and strong demand from global product in sales. 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 ENTYK V and Prolucine as well as manufacturing costs for AntagV. Cost of sales for the fourth quarter was $45,500,000 including $9,100,000 in period cost associated with patient drop off and manufacturing success rates which decreased quarter over quarter as a percentage of total revenue. Dollars 5,900,000.0 for non cash expenses including fair market value step up and intangible asset amortization $6,000,000 in royalty payable on product sales. In the prior year three months period, cost of sales was $4,400,000 primarily related to non cash amortization for intangibles assets.

Cost of sales for the full year 2024 was $124,000,000 including $26,300,000 in certain costs associated with patient drop off and manufacturing success rates dollars 26,200,000.0 in non cash expenses including fair market value step up and intangible asset amortization, and $14,200,000 in royalties payable on product sales. In the prior full year, cost of sales was $10,800,000 primarily related to non cash amortization for intangible assets. The increase in cost of sales in the fourth quarter and full year twenty twenty twenty four over the prior year's periods primarily attributable to The U. S. Commercialization and sales of AMTACBI as well as pro looking sales growth following the initiation of product sales in The U. S. Commercial manufacturing and related cash and non cash expenses tied to MTAGV and Prolucine. Our standard gross margin for the fourth quarter twenty twenty four was 46% or $34,000,000 compared to the total product revenue of $73,700,000 Cost of sales has improved over time as we increased volume and capacity utilization throughout the launch ramp up. The higher gross margin over the previous quarters reflect our ongoing focus on profitability, and is well over halfway towards our target for gross margin to surpass 70% the coming years Our ongoing manufacturing expansion strong coordination with the ATCs and efficiencies in manufacturing and release testing are expected to further optimize our cost of sales with a correspondingly higher gross margin.

I will now shift to our operating expenses. For the full year 2024, our total cash burn excluding one time expenses was within our guidance range of $320,000,000 to $340,000,000 Research and development expenses were $72,200,000 for the fourth quarter of twenty twenty four, a decrease of $15,300,000 compared to $87,500,000 for the same period prior year period. Research and development expenses were $282,300,000 for the full year 2024 a decrease of $61,800,000 compared to $344,100,000 for the full year 2020. The decrease in research and development expenses in the fourth quarter and full year 2024 over the prior year period was primarily attributable to the transition of MTAGV from clinical to commercial manufacturing. This decrease was partially offset by increase in headcount and related costs including stock based compensation, and clinical trial costs. Selling, general and administrative expenses were $42,500,000 for the fourth quarter of twenty twenty four, increase of $12,600,000 compared to $29,900,000 for the prior year period. Selling, general and administrative expenses were $153,000,000 for the full year 2024 an increase of $46,100,000 compared to $106,900,000 for the full year 2023. The increase in selling and general administrative expenses in the fourth quarter and full year 2024 compared to the prior year periods was primarily attributable to increasing net count and related costs including stock based compensation, to support our overall growth as well as legal and commercial related costs.

Looking ahead, we continue to reiterate our prior total product revenue guidance within the range of $450,000,000 to $475,000,000 for the full year 2025.

In addition, we anticipate our cash burn for the full year 2025 to be less than $300,000,000 including investment in our I [indiscernible] Over time, we expect cash burn to decrease as we continue to grow revenue as gross margin improves. We also plan to keep leveraging additional opportunities to further optimize spending this year.

For additional information, please see the company's selected consolidated balance sheets and statement of operation in this afternoon's press release and our Form 10 ks to be filed later today. I will now hand the call to Frederic our Chief Medical Officer to discuss our clinical pipeline.

Thank you so much.

We continue to be excited about the potential of Till cell therapy in solid tumors which represent more than ninety percent of all diagnosed cancers in The U. S. Today, I will summarize key updates for our clinical program, as well as our exciting next generation pipeline.

Expanding the commercial opportunity for a tagvi Our global registrational Phase three trial TILVAN-three zero one remains on track to support accelerated and full approvals of ENTYVY in combination with pembrolizumab in frontline advanced melanoma.

As well as regular approval of amtagb in our initial indication and post anti PD-one melanoma. Strong momentum with enrollment and high enthusiasm continue among participating in planned clinical sites.

As a reminder, Till then three zero one is supported by positive results lifeluzil plus pembrolizumab from IOV COM202 cohort 1a in patients with advanced melanoma naive to immune checkpoint inhibitors. To explore another potential best in [indiscernible] melanoma for U. S. Physicians and patients cohort 1D in IOV COM2 We'll investigate lifegutro in combination with nivolumab and brinabab. Our second registrational program is investigating liferlutin monotherapy in the single arm registrational Phase II IOV LUN two zero two clinical trial to address unmet medical need among patients non small cell lung cancer who progressed after anti PD-one therapy. Single agent chemotherapy, the current standard of care in this setting provides limited rate and duration of responses. We expect to share additional data from IOV LUN202 in the second half of twenty twenty five. Enrollment continues with high demand at clinical sites in multiple countries to support a potential accelerated approval of liferusil in post anti PD-one non small cell lung cancer in The U. S. With an anticipated regulatory decision in 2027. We also continue to pursue earlier treatment settings in non small cell lung cancer. In frontline advanced non small cell lung cancer, our strategy is to establish a new frontline regimen of lisoutel plus pembrolizumab following standard of care chemo pembrolizumab for patients with EGFR wild type non small cell lung cancer who represent the majority of patients with an unmet medical needs in this setting.

We will investigate this regimen in cohort three d in the IOV COM202 clinical trial to inform a registrational and confirmatory trial design in frontline advanced non small cell lung cancer. Our goal is to further augment the strong efficacy seen in Cohort 3a with lifeluzil in combination with pembrolizumab in patients who were not previously treated with immune checkpoint inhibitor therapy. Moving along the pipeline, we are excited about our first clinical trial in Iovance endometrial cancer. A significant new opportunity for Till Till therapy in an additional post anti PD-one setting.

Our IOV END-two zero one clinical trial is investigating lifileusil after frontline standard of care of chemotherapy and anti PD-one therapy in patients with endometrial cancer. Regardless of mismatch repair or MMR status. Recent approvals of immune checkpoint inhibitors in combination with chemotherapy for frontline endometrial cancer have created an unmet need. There are no currently approved therapies for patients who progress. We look forward to sharing initial data from END-two zero one in the second half of this year. As the leader in tilt cell therapy, Iovance is also at the forefront of next generation approaches to optimize Till and Till treatment regimens. I'll briefly summarize our three main programs in this area. Our next generation PD-one in [indiscernible] is investigated in the Phase two efficacy stage of our IOVGM-one clinical trial Multiple centers are enrolling at an increasing pace across two Phase two cohorts of patients with previously treated advanced melanoma, non small cell lung cancer. Building on our successful PORELUCON franchise, we recently initiated a Phase onetwo clinical trial of IOV-three thousand and one a second generation modified IL-two analog for use with the Till cell therapy treatment regimen. IOV-three thousand and one may result in a better safety profile and support less frequent dosing.

Compared to Proleukin. Lastly, we plan to submit an IND to FDA this a genetically engineered, inducible and tethered IL-twelve Till cell therapy A clinical trial of a prior generation IL-twelve IL12 Till therapy at the National Cancer Institute showed improved efficacy with low cell doses without the use of IO2 and provides the rationale for the modifications in IOV-five thousand and one. To enhance Till efficacy while optimizing safety. IOV-five thousand and one could facilitate expansion into a wide range of common solid tumor cancers, beyond our current pipeline with significant market opportunity. I'm happy to address questions about these programs in additional trials during the Q and A session. I look forward to sharing additional updates this year as we continue to work to deliver Till cell therapy to cancer patients in additional therapeutic settings and with additional tumor types. Thank you to the talented, multidisciplinary team and research partner who make this possible.

I'll now turn the call over to the operator to begin the question and answer session. Operator?

In the interest of time, ask that you please limit yourself Our first question comes from Andrea Newkirk with Goldman Sachs. Your line is open.

Good afternoon. Thanks for taking my questions. Fred, on prior calls, you've provided an update on the number of patients infused thus far in the quarter. Just wondering if you'd be willing to share where you stand as of today? And then just remind us or help us understand what gives you the confidence that the range for full year '25, which was set when you were only one quarter into the launch is still intact? Thanks so much.

Yes, sure Andrew. We're not from the press release and in the call, we're not going to be providing the infusions right now. We're not sure how useful that metric was to long investors in as some of you know, it was prone to over interpretation. We provide some different metrics this time around, including the potential for growth at the ATC's net actually is a part of the answer to your second question. If you look at our press release and heard Dan's commentary, within the 70 ATCs that we have right now, only thirteen percent have infused more than 10 patients. Gives you a very good idea of the upside that we're expecting unique acceleration we're expecting in the second half and second quarter of twenty twenty five here as we go through. So we still have confidence in those numbers because the growth curve for this type of product can accelerate quite a bit and we see that happening across our ATC network right now. We see the potential for that in this ATC Thank you. Our next question comes from Peter Lawson with Barclays. Your line is open. Peter, your line is open. Please check your mute button.

Great. Thank you so much for taking the question.

As we think about the IO2 revenues, kind of they had a nice spike this quarter Is that should we view that as a signal for future tail demand or is that kind of a stock in from distributors? And how should we think about the IoT sales going forward? What component of 25 revenues, could that be? Thank you.

Yes. So we continue to believe and continue to talk about revenue as being a leading indicator for AMTAGNY sales like we've been saying for quite some time now. And I think what you're seeing there is you're seeing the uptake by all the STs now in United States As Dan pointed out, we we restocked two of them and sold block to a third. And I think you'll see in 2025, we'll be restarting again and it will represent a significant portion of the four fifty to April guidance that we have out there. It can be as close, $80,000,000 to $100,000,000 or more.

We think it's a fantastic business. That's why we acquired it.

It's performing very well right now. So we're very happy with that number.

Thank you. Our next question comes from Ben Burnett with Stifel. Your line is open.

Hey, great. Thanks so much. I guess question for us is what are physicians saying about sort of the evolving landscape and just the potential for a new entrant later this year?

I think many of your colleagues have written notes about this lately and there's been a lot of discussion about this. We view the potential entrant as basically being very similar to a currently marketed product known as TBEC. We're not really sure what the differentiation is between that. We've also have a lot of information on how that product launched. View the clinical data is not being comparable to ours. They're patient population is much, much earlier sixty five percent of their patients have one or two prior lines. They had quarter patients with adjuvant PD-one only in the study. And we're looking at sixty five percent of our patients with three or more prior lines much more real world population in metastatic melanoma. So we we don't really see this being any kind of significant impact on our launch. We're out there with what we think is the premier product and we're looking to grow our market, launch outside The U. S. And get other indications as soon as we can.

Okay. Appreciate that color. Thank you.

Thank you. Our next question comes from Collyn Koozie with Baird.

Your line is open.

Great. Thanks for taking our questions. Understand you're not giving inter quarter updates going forward, but since you did provide in 4Q, can you speak was there a slowdown in fusions in the back half of the quarter? And did you see any seasonality Collyn, no, we don't see any seasonality.

As Igor mentioned, we did have a a manufacturing maintenance period there. So we have those kind of things cell therapy. If you look at the launch curves for BEKMA, YASCARTA and CARBICT, you'll see there's there's little peaks and dips and valleys in those. As things like that happen. So but nothing in terms of a holiday seasonality that's what you're asking?

Great. Thanks for taking our question.

Thank you. Our next question comes from Tyler Van Buren with TD Thanks very much for taking our question. This is Nick on for Tyler. Thinking about guidance, 2025 guidance, is the potential price increase currently included in that guidance? And also how should we think about the global ex U. S. Expansion having a potential impact on guidance? Thanks. Yes. The price increase that's coming in April has been factored into that guidance. Any contribution from HUS. Thank you. Thank you. Our next question comes from Yanan Xu with Wells Fargo Securities. Great.

Thanks for taking our questions. I was wondering how many infusions were performed in 4Q and the quarter over quarter growth over the prior quarter, which was 82 infusions, How does that compare with your expectation And do you think that growth will either be the same or be be different for Wangchuk over [indiscernible] Thanks.

Yes, Yan, it's about 95 revenue infusions. There's other infusions that occur with single patient INDs and that kind of thing that still generate revenue of Probuqin sales, for example. That's about 95 Iovance infusions is what we're reporting for fourth quarter. I think the quarter over quarter growth is quite strong.

Seeing the growth that we need to see. It's going to go up and down as we go. Just like I said with the CAR T products, if you look back at their growth they were there was Our intention is to drive growth and we have tremendous opportunity at the ATCs that we have right now do that as well as as we get to the community.

Great. [indiscernible] Thank you. Our next question comes from Astika Gooneworden with Truist. Your line is open.

Hey guys, thanks for taking my question. That you provided, the end of quarter data that you provided, up to 70 ADCs that are online, what proportion have reached their steady state I'm wondering does that align with the thirteen percent of ADCs that have already treated more than 10 patients Thanks.

So I think it's a very low number. I can't tell you But it's probably ten percent or less of each state at this point. We know that the vast majority of the 78 DCs have tremendous upside. Maybe I'll ask Dan to comment a little bit on what we've seen so far on the the potential upside of those ATCs. Sure, Fred. And I think one of the things that you look at the ATCs, you look at the ones that are doing plus I don't really think they're saturated with it because our strategy is again to increase referrals in the community into those. They're the ones that have developed expertise within TagMe and we have other ones that are inching towards that 10 plus confusion number with it. Those are really our centers of excellence that are leading the way not only the other centers, but also for our activities in driving referrals to those centers.

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

Hey guys, thanks for taking the questions and congratulations on the quarter.

Maybe just one from me from the pipeline for Frederick. We have data coming out in the second half of this year. Can you talk a little bit about or set expectations for both non small cell and endonutrial, how many patients worth of data and I guess with this data, is this the registrational set Do we need to enroll even more patients before filing for accelerated approval in both non small cell and endometrial? Or do we need to start another cohort that ultimately becomes the registrational data set?

Any color would be great.

Yes. So to start with LION-two zero two, thanks for the question. Obviously, we're going to to time our data disclosure with an appropriate venue and we'll time our cut with that. Where we are in regards to enrollment will really depend on the timing, and I can't really comment on this at this point. This will be an update On what what is obviously of the priority interest, which is the data from cohorts one and two, which are the registrational cohorts there's not going to be additional cohorts or anything that we would be reporting out because we think that that is probably not that that relevant. About timing of the the registrational plan, I said in my script, timing will be that we're expecting a registrational decision by the end of twenty twenty seven. We are enrolling currently. We're seeing good momentum and and we are on track with that. I hope that answers your question. Around endometrial, similarly, I can't really commit to a specific patient number here, but it's going to be a meaningful initial idea around the signals that we're seeing in this trial. We find this important enough to share an early data set this year still.

Thank you.

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

Hi.

This is Bennett Porcellin. Thanks so much for taking our question and congratulations on the quarter and all the progress. So also on the registrational Phase two trial in post anti PD-one non small cell lung cancer, could you remind us what's the goal there [indiscernible] sits around 30%, but I'm not sure if that's the best competitor here or if you can just talk a little bit about that bogey and the bar here? Yes, I can start. Maybe, Frederic, can get the rest of that. So first of all, we can run FDA has told us we can run a single arm trial We're not running randomized against docetaxel. What we will look at is we with that BLA submission, the FDA would look at available care for those patients and that includes the Rabelle study, which is REMS remaciramaprilizodexel or docetaxel MOS therapy. And there you're looking at response rates in the the low 20s, but very short durability. With Till therapy, we have much longer durability. So we're thinking if we come in with response rates in the mid-20s like we showed before, with the durability like we've been seeing, we should be fine in terms of getting approval on this product based on what FDA has told us today and they've told us quite a bit about this.

And Frederic, if you're online, you're welcome to add that.

No, that's exactly right. The one thing to add here is it's really the it's really the durability that is the limitation here. For the standard of care. For dolutexel plus plus REMU, Although again, as Fred mentioned, it's it's about twenty percent response rate. PFS is about four months and Duration of response data has never been shared. So I think that is indicating that this the the limitations and the challenges that we are with lysosomal therapy. Just as a reminder, the data that we had previously shared from ElU-one-two indicated a response rate in the mid twenty percent twenty six percent and then in a follow-up communication around it, we saw that seventy one percent of the confirmed risk responders had DORR of of more than six months, which in this population is very meaningful.

Thank you.

Thank you. Our next question comes from David Dye with UBS. Your line is open.

Hey, great. Thanks Latim. My question Fred, I know you mentioned that you didn't see any seasonality, as for the holiday break. I'm just wondering if you see any kind of spillover impact from holidays on Starform or receptions? Could you repeat that, David?

Reception seasonality on receptions?

No, no, no, just wondering if there's any spillover impact from holidays on kind of start worms or any kind of tumor restrictions if that makes sense?

Yes, I'm not following you. We haven't maybe I can try answer more generally. We didn't really see any slowdown in terms of the ATCs just for the holidays. That's what you're asking for any other operations because they are generally running through the Christmas holidays without any interruption for cancer patients.

So of course, there could be one or two patients here or there.

And actually just carrying on top of that Fred, I think for seasonality, we didn't notice it from my understanding in the clinical trial. But as we go commercially, we're just finishing our first year So we're going to look at those trends and patterns as we go forward to see if there is seasonality. Right now, we're not seeing it in the data. Hopefully, that helps you, David. But that is something we're looking at.

All right. Thank you so much.

Thank you. Our next question comes from Andrew Tsai with Jefferies. Your line is open.

Hey, thanks. Good afternoon. Appreciate the updates. Look forward to 2025. So a quick one is, in terms of the launch uptake, what exactly would you say is the bottleneck at this juncture if it's not patient demand nor supply chain nor even beds at sites what is the gating factor to seeing an acceleration?

For 2025 like you guided. Thanks.

So I think above all the ATCs that are starting up now have to get their feet out of them and get running. We've got some ATCs that are performing very, very well right now. We've got a lot more that are working their way up. I think in each ATC, there's a difference. Each individual ATC has its own little bottlenecks or whatever it might be. Some of them have staffing issues, some of them have financial clearance challenges that we're helping out with. But all these things are pretty easily resolvable and we've been able to show that a good portion of our ATCs can really fly right now and we think we can get a lot more there pretty soon. Dan?

Sure.

And Andrew, I think one of the things I top of what Fred said.

Regarding not really a bottleneck, but there's a process they go through. They have to make sure they operationally can do it. Again, we're the first till in the market. So there's a learning curve there. As you see, we said 13% have hit 10 or more That number continues to grow. So once they hit that wave where they understand how to use the product with it, then the lever really is to pull the referrals drive more patients in there and that's where we're working the community not only at the clinic level, but also the leadership level and community to make sure that those centers are getting to see the most patients. Makes sense. Thanks.

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 Iovance Biotherapeutics fourth quarter and full year twenty twenty four financial results and corporate updates conference call.

As we close the first calendar year of our first commercial cell therapy launch, we look forward to providing future updates on our growing commercial and clinical portfolio. We continue to be motivated as we hear frequent feedback from ACCs about advanced melanoma patients and finding hope in TEGDNA in the commercial setting. I'm confident that IVS is poised to maintain our global leadership in innovating, developing and delivering current and future generations of Till cell therapies for patients with cancer.

As always, we are thankful for the patients, healthcare and advocacy communities our partners and our exceptional Iovance team. I'd also like to thank our shareholders and analysts for their support. Thank you.

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