Iovance Biotherapeutics Inc
NASDAQ:IOVA
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Iovance Biotherapeutics Inc
Earnings Call Analysis
Q2-2024 Analysis
Iovance Biotherapeutics Inc
Iovance Biotherapeutics is reporting a successful start to the commercial launch of their innovative therapeutic, Amtagvi, designed for patients with advanced melanoma. The second quarter product revenue reached $31.1 million, driven primarily by Amtagvi and Proleukin sales. This launch is notable not only for its revenue impact but as a significant step in addressing unmet medical needs in cancer treatment. The demand seen thus far demonstrates a positive response from healthcare providers and patients alike.
Looking ahead, Iovance has provided optimistic revenue guidance. For Q3 2024, they expect total product revenue to be between $53 million and $55 million. For the full year of 2024, product revenue is anticipated in the range of $160 million to $165 million, reflecting continued growth as adoption of Amtagvi accelerates. For 2025, the company projects a significant revenue increase, targeting between $450 million and $475 million, benefiting from an expanding network of authorized treatment centers (ATCs) and increased referrals from the medical community.
As Iovance ramps up its operations, gross margins are expected to improve to over 70% in the coming years. This increase is enabled by scaling up manufacturing efficiency and optimizing operational processes. Currently, the cash burn guidance indicates a range of $320 million to $340 million for 2024, but the robust revenue projections suggest the firm is positioned to manage its expenses effectively while capturing significant revenue growth.
Iovance is not just reliant on Amtagvi for its growth. The company is actively developing additional therapies and has started two registrational trials for their TIL cell therapy, lifileucel, which aims to address front-line advanced melanoma among other indications. There's a clear pathway outlined for expanding the application of their therapies across broader types of cancers, including non-small cell lung cancer, which could further enhance their market positioning.
The authorized treatment center network is expanding rapidly, projected to reach at least 70 centers by year-end 2024, up from over 50 currently. This will help facilitate quicker patient access to treatments. Iovance's ability to reduce the time from patient opt-in to infusion—currently about 3 to 4 weeks—plays a key role in enhancing patient experiences and outcomes. As the feedback from ATCs continues to be positive regarding patient benefits, this establishes a promising trajectory for ongoing treatment adoption.
Iovance's unaudited cash position is approximately $449.6 million, aided by recent equity financing. This substantial cash reserve is expected to sustain the company's operations through 2026, shielding it from short-term market fluctuations while it continues to grow its business and expand its product offerings. Investors can find comfort in the company’s strong financial backing alongside promising product revenue projections.
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Welcome to the Iovance Biotherapeutics conference call to discuss second quarter 2024 results and recent corporate updates. My name is Daniel, and I will be your operator for today's call. [Operator Instructions] Please note that this conference is being recorded. I will now turn the call over to Sara Pellegrino, Senior Vice President, Investor Relations and Corporate Communications at Iovance. Sara, you may begin.
Thank you, operator. Good afternoon, and welcome to Iovance's conference call and webcast to discuss our Second Quarter and First Half 2024 results and corporate update.
Dr. Fred Vogt, our Interim President and Chief Executive Officer, will provide an introduction and summarize key updates for our U.S. commercial launch Amtagvi, including revenue guidance and our pipeline program. Jim Ziegler, EVP Commercial, will highlight additional details of the U.S. commercial launch of Amtagvi in advanced melanoma. Dr. Igor Bilinsky, Chief Operating Officer, will comment on our commercial manufacturing experience and capacity expansion plan. Jean-Marc Bellemin, CFO, will review our financial results, including revenue and financial outlook; and Dr. Friedrich Finckenstein, Chief Medical Officer, will review key clinical pipeline update. Dr. Brian Gastman, EVP Medical Affairs; and Dr. Raj Puri, EVP, Regulatory Affairs, are also on the call and available for the Q&A session.
Earlier this afternoon, we issued a press release that could be found on our corporate website at iovance.com.
Before we start, I'd like to remind everyone that statements made during this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans and transactions, revenue and revenue guidance, commercial activity, 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 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, Sara. I'm pleased to host this afternoon's conference call to discuss our 2024 Second Quarter and First Half results. We've had a productive year so far at Iovance following our first FDA approval and a successful start the U.S. commercial launch of Amtagvi for patients with advanced melanoma. First, we are very pleased with the exceptional demand for Amtagvi.
Our second quarter product revenue was $31.1 million, inclusive of recognized revenue for Amtagvi and Proleukin. Amtagvi revenue is recognized upon infusion, while Proleukin revenue is recognized upon delivery, typically a few months prior to Amtagvi infusion, providing a strong leading indicator of demand of future Amtagvi revenue.
The initial quarter of product revenue from our U.S. launch demonstrates early success from our team's execution as well as the unmet need, high awareness, broad patient access and motivated authorized treatment centers or ATCs. With the Amtagvi already showing a meaningful benefit for patients treated in the commercial setting, we expect continued launch momentum, which I'll return to in a moment.
As Jim will discuss, we have a very engaged network of more than 50 current ATCs. These ATCs are proving that they have the training, infrastructure and capabilities to treat patients with Amtagvi. We also remain on track to have at least 70 ATCs by the end of the year, representing the largest ever initial ATC network for a cell therapy launch.
We've also started our community referral activities to drive additional demand for these ATCs. Through early success with reimbursement and a strong logistics and scheduling collaboration between Iovance and the ATCs, time to treatment is also becoming faster for patients. In addition, our commercial manufacturing capabilities are successfully delivering Amtagvi at an increasing pace. The key takeaways, Ziegler will summarize, but that we are staffed to provide manufacturing slots to meet current and expected demand. We are scaling up manufacturing according to our growth projections. We have increased capacity and headcount each month since launch and continue ramping up to match ongoing demand growth.
Turning back to launch momentum. This afternoon's press release. We also introduced revenue guidance for the third quarter of full year 2024 and for 2025. This guidance is based upon our ongoing experience and confidence in the strong uptake and significant quarter-over-quarter growth in the Amtagvi demand and corresponding Proleukin sales for the foreseeable future. We used our visibility to the growth rate of infusions, adoption across our ATC network, manufacturing capacity and additional launch dynamics to prepare this guidance.
In the third quarter, we expect total product revenue within the range of $53 million to $55 million. Notably, more than 55 patients have been infused with Amtagvi since the first commercial infusion in April 2024, including 25 patients infused in the second quarter. More than 30 patients have already been infused and distributors are restocking Proleukin since the start of the third quarter. Many more infusions are scheduled or anticipated before quarter end in support of our guidance.
For full year 2024, we anticipate total product revenue for Amtagvi and Proleukin of $160 million to $165 million. We expect the full year 2024 will reflect continued demand growth for Amtagvi and corresponding sales for Proleukin. For full year 2025, the first calendar year of our U.S. launch first full calendar year over U.S. launch, we expect significant year-over-year growth driven by scale-up in existing and new ATCs and robust community referral networks contributing to additional demand. As a result, we anticipate total product revenue will increase to $450 million to $475 million in the full year of 2025.
In 2026 and beyond, Amtagvi and Proleukin are expected to continue to drive significant additional revenue growth. These products represent more than $1 billion peak opportunity in the U.S. market in the currently approved indication alone. Future revenue growth drivers also include a wider geographic footprint for Amtagvi in previously treated advanced melanoma as well as U.S. and global label expansions to the front line advanced melanoma, non-small cell lung cancer and other indications as we'll discuss later in the call.
Gross margins are also expected to increase to greater than 70% over the next several years. This reflects the long-term commercial strength for Amtagvi and Proleukin and highlights a strong future for Iovance. Globally, Amtagvi represents a multibillion-dollar opportunity to address more than 20,000 previously treated advanced melanoma patients annually across the U.S. in our initial planned geographic footprint.
Following our recent regulatory submission in the European Union, we remain on track for additional submissions in the U.K. and Canada this year and Australia and Switzerland in 2025, with commercial launches to follow. Iovance is well positioned to build upon our existing commercial success and continue growing globally.
In addition to Amtagvi, our robust and exciting pipeline may help even more patients with solid tumors pain potentially curative medicines. Our programs include 2 registrational trials and other indications, and we are continuously innovating with next-generation cell therapies. Friedrich will discuss our pipeline in further detail on this call.
The first approval launch in large-scale manufacturing with TIL cell therapy, together with our intellectual property position and deep pipeline provide us with distinct competitive advantages. As a fully integrated company, Iovance is well positioned to maintain the global leader in innovating, developing and delivering TIL cell therapies for patients with cancer.
I'll now hand over to Jim, our Executive Vice President of Commercial, who will summarize our U.S. commercial activities. Jim?
Thank you, Fred. We are excited about the potential for our U.S. launch of Amtagvi to improve the lives of patients with advanced melanoma. As more and more patients are treated with commercial Amtagvi, An increasing number of our ATCs are sharing positive feedback and posting stories about their patients who have benefited from Amtagvi in the early months since approval.
My objectives today are to highlight our U.S. launch priorities and progress, including adoption and utilization within our expanding ATC network, community referrals, reimbursement and patient access and streamlining and expediting the patient journey. First, our ATC network is scaling and expanding as planned, which is a key driver of demand and we expect robust demand to continue.
Today, onboarding is complete at more than 50 U.S. ATCs. The centers who were active at approval are scaling up and many have treated multiple patients. Newer ATCs that have recently completed onboarding, including major U.S. cancer centers are beginning or preparing to treat patients. As we look to bring treatment closer to patients, our goal is to have approximately 70 ATCs in total by year-end. Beyond this number, many additional centers have expressed interest in joining our network.
Currently, more than 90% of treated patients are located within 200 miles of an ATC, with 70 ATCs, nearly all melanoma patients will be within a 2-hour drive to the closest center. Community referrals are also driving growth in patient volume and demand within the ATCs. An increasing number of ATCs are proactively building awareness about Amtagvi across their community referral networks.
Iovance is rolling out initiatives to further support awareness and referrals by deploying direct outreach and resources into the community. The size and scope of our ATCs and these community referral networks are a testament to the significant unmet need in advanced melanoma, each center's dedication to offer Amtagvi and interest among community oncologists.
In addition to ATC demand, patient access is critical for adoption and uptake. Our launch data indicates that approximately 75% of Amtagvi patients are covered by private payers as expected. Favorable medical coverage policies and reimbursement are facilitating broad access to Amtagvi.
First, Amtagvi's inclusion in the National Comprehensive Cancer Network or NCCN guidelines reinforced clinical data and support broad payer coverage. We have also achieved significant accomplishments with positive payer coverage in only 5 months since approval. As of today, payers responsible for more than 225 million lives or more than 85% of U.S. covered lives have already implemented positive medical coverage policies that are consistent with label, clinical trials and the NCCN guidelines.
Successful reimbursement is also driving faster time to treatment. The current average time to financial clearance is approximately 3 weeks, which is a significant reduction from the 4 to 6 weeks at initial launch. Improved efficiencies at ATCs, including scheduling in parallel with financial clearance are also speeding up time to treatment. We expect the trends towards shorter time to treatment to continue as more ATCs gain experience.
In summary, we are extremely pleased with the early launch performance. There is strong demand at our ATCs, payer coverage policies are in place and favorable and time to treatment is becoming faster. These dynamics support the strong growth projections in our product revenue guidance for Amtagvi and Proleukin. I would also like to acknowledge our very talented cross-functional team who works tirelessly to ensure broad and timely access to Amtagvi.
I will now pass the call to Igor Bilinsky our Chief Operating Officer, to highlight our manufacturing progress.
Thank you, Jim. Today, I'd like to highlight our commercial and clinical manufacturing capabilities, the progress of our commercial launch as well as our ongoing capacity expansion efforts.
Manufacturing is a core competency of Iovance. We are laser focused on quality from incoming receipt of tumor samples through manufacturing and product release to outbound shipments of the final product. Our established internal manufacturing facility, the Iovance Cell Therapy Center, or iCTC, is the core of our manufacturing network. Located in Philadelphia, iCTC is one of the world's largest cell therapy manufacturing facilities and the only one specifically designed for TIL manufacturing.
The iCTC has a fully integrated and committed team with deep cell therapy experience. This facility is approved by the FDA for Amtagvi commercial manufacturing and has been supplying Amtagvi to patients since approval while continuing to serve patients in our global clinical trials. We are actively hiring at iCTC to support the continued ramp in the U.S. commercial demand and our clinical pipeline. The iCTC location in Philadelphia provides access to an experienced workforce with cell and gene therapy experience as well as to innovative partnerships with local colleges and trade groups.
Within our manufacturing network, a contract manufacturer site is also approved by the FDA for commercial manufacturing of Amtagvi and provides additional capacity and flexibility to closely match supply and demand.
Turning to commercial manufacturing updates. Our experience to date has been consistent with our expectations and with prior clinical experience. We are executing and scaling up as planned. Since the FDA approval in February, we have been continuously increasing our staff manufacturing capacity month-over-month to closely align it with the growing commercial demand. We have sufficient capacity and staffing available in our manufacturing network to meet the increasing Amtagvi demand.
We are now running our manufacturing network at high capacity utilization while ensuring slot availability for our ATCs. In addition, the turnaround time for Amtagvi has been on target with our launch plans of approximately 34 days from receipt of patient cells at our manufacturing facility to return shipment of the product to the ATC. As we scale up, we're also focused on improving cost of goods over time through economies of scale and operational efficiencies and by leveraging our competitive advantage and unique position as the leader in the TIL cell therapy.
Turning to our facility expansion efforts. They are closely aligned with our demand growth projections. iCTC is built today has the capacity to provide TIL therapies for more than 2,000 patients per year. Following the recent EU regulatory submission and additional planned ex-U.S. filings, we expect iCTC to provide commercial Amtagvi patients in Europe and beyond upon potential approvals in those geographies. We're in the process of building out the existing shelf space at iCTC, so this facility can supply TIL therapies for more than 5,000 patients annually in the next few years.
Longer term, our vision is to supply TIL cell therapies for over 10,000 patients annually from the iCTC campus. We have an option to construct another building on the adjacent lot and plan to drive additional efficiencies by incorporating increased automation in our manufacturing process. Importantly, our manufacturing capabilities are protected by a robust intellectual property portfolio. Iovance currently owns more than 210 granted or allowed U.S. and international patents and patent rights for Amtagvi and other TIL-related technologies that are expected to provide exclusivity through at least 2042.
In summary, the Ivan's team is excited and firmly committed to manufacturing and delivering Amtagvi in our investigational TIL cell therapies for patients with cancer. I'm available to answer additional questions during the Q&A, and I will now hand the call over to Jean-Marc, our Chief Financial Officer.
Thank you, Igor. Today, I will review our current cash position as well as our results for the second quarter and first half ended on June 30, 2024. I will also highlight our financial outlook, including revenue and expense guidance.
As of July 24, 2024, Iovance had an unaudited cash position of approximately $449.6 million, which includes net proceeds of approximately $200 million raised from an at-the-market equity financing facility during the second and third quarter of 2024. The current cash position and anticipated product revenue are expected to be sufficient to fund current and planned operation into 2026. Iovance had $346.3 million in cash, cash equivalents, investments and restricted cash at the end of December 31, 2023.
I will now transition to our second quarter and year-to-date financial results. Net loss for the second quarter of 2024 was $97.1 million or $0.34 per share compared to a net loss of $106.5 million or $0.47 per share for the second quarter ended June 30, 2023. Net loss for the first half of 2024 was $210.1 million or $0.76 per share compared to a net loss of $213.9 million or $0.98 per share for the 6 months period ended June 30, 2023.
Revenue was $31.1 million for the second quarter of 2024 and consisted of product revenue from the initial quarter of Amtagvi sales as well as recurring revenue from Proleukin. We recognized revenue of $12.8 million from completed Amtagvi infusion. We also recognized $18.3 million in global revenue from Proleukin during our initial quarter in supplying U.S. specialty distributors.
Revenue for the first half of 2024 was $31.8 million and consisted of product revenue from both Proleukin and Amtagvi. Revenue for the first half of 2023 was $0.2 million for global sales of Proleukin, which we began to recognize during the 3 months period ended June 30, 2023.
Revenue increases in the second quarter and first half of 2024 over the prior year periods were primarily attributable to the U.S. launch for Amtagvi as well as significant growth in U.S. Proleukin revenue for use in the Amtagvi treatment regimen. As Fred mentioned, Proleukin is a strong leading indicator for near-term Amtagvi growth. Revenue recognition for Proleukin is a few months earlier than Amtagvi when specialty distributors and ATCs purchased Proleukin in advance of Amtagvi infusions. Notably, Proleukin second quarter revenue surpassed annual global revenue for Proleukin in 2023, reflecting strong demand for use with Amtagvi.
In addition, specialty distributors who purchased Proleukin in the second quarter have already started restocking and is another positive signal of the strong Amtagvi launch and increasing demand for Proleukin used with Amtagvi.
Cost of sales for the 3 and 6 months ended June 30, 2024, was $31.4 million and $38.6 million, respectively, primarily related to costs associated with sales of Amtagvi and Proleukin, certain costs associated with patient drop off and manufacturing success rates, non-cash amortization expense for intangible assets and royalties payable on product sales.
Cost of sales for both the 3 and 6 months ended June 30, 2023, was $2.1 million, primarily related to non-cash amortization for intangible assets. The increase in cost of sales in the second quarter and first half of 2024 over the prior year periods were primarily attributable to the initiation of commercial manufacturing and related costs for the U.S. launch of Amtagvi during the first half of 2024. Cost of sales is a function of volume and capacity utilization, which is already improving as we scale up our available capacity.
In addition, education and training to optimize patient selection and tumor samples resections, as well as our continued focus on operational efficiencies are expected to optimize cost of sales over time as we aim to reach our target gross margin of more than 70% over the next several years.
Research and development expenses were $62.1 million for the second quarter of 2024, a decrease of $24.2 million compared to $86.3 million for the same period ended June 30, 2023. Research and development expenses were $141.9 million for the 6 months ended June 30, 2023, a decrease of $27.2 million compared to $169.1 million for the same period ended June 30, 2023.
The decreases in research and development expenses in the second quarter and first half of '24 over the period -- the prior year periods were primarily attributable to the transition of Amtagvi to commercial manufacturing, decreased the cost associated with certain clinical activities in the first half of 2024 and the completion of pre-commercial qualification activities in 2023. This decrease in research and development were partially offset by increase in stock-based compensation, resulting from growth in headcount.
Selling, general and administrative expenses were $39.6 million for the second quarter of June 2024, an increase of $17.7 million compared to $21.9 million for the same period ended June 2023. Selling, general and administrative expenses were $71 million for the first half of '24 and an increase of $21 million compared to $50 million for the same 6-month period ended June 30, 2023.
The increase in selling, general and administrative expenses in the second quarter and first half of 2024 compared to the prior year period was primarily attributable to the increase in headcount and related costs, including stock-based compensation to support the growth in the overall business and related corporate infrastructure as well as legal costs and costs incurred to support the commercialization of Amtagvi and Proleukin.
Next, I would like to cover our financial outlook for the Amtagvi launch and future expenses. As Fred highlighted earlier in his introduction around revenue guidance, we expect quarter-over-quarter and annual growth in product revenue to continue for the next several years with the steepening U.S. adoption curve for Amtagvi. Geographic and label expansion as well as new product approvals, we also add to our growth trajectory in 2026 and beyond.
I will highlight our guidance numbers again as a reminder. In the third quarter of 2024, we expect total product revenue within the range of $53 million to $55 million. We anticipate total product revenue for the full year of 2024 within the range of $160 million to $165 million. In the full year 2025, we expect a significant year-over-year increase in annual product revenue to $450 million to $475 million. In addition, as Fred mentioned, gross margins are expected to increase to greater than 70% over the next several years.
Regarding our expense outlook, we continue to reiterate full year 2024 cash burn guidance in the range of $320 million to $340 million, excluding one-time expenses. We will also continue to leverage the opportunities to optimize spending. For additional information, please see the company's selected combined consolidated balance sheet and statement of operations in this afternoon's press release and our Form 10-Q to be filed later today.
I will now hand the call to Friedrich, our Chief Medical Officer, to discuss our clinical pipeline.
Thank you so much. As my colleagues have conveyed Amtagvi is only the tip of the iceberg for the potential of TIL cell therapy in solid tumors which represents more than 90% of all diagnosed cancers in the U.S.
I would like to acknowledge my own personal excitement and the rewarding experience for our Iovance clinical development teams as we hear frequent ATC feedback about patients benefiting from Amtagvi in the commercial setting. This is great news that also motivates our clinical teams to develop and deliver TIL cell therapy to cancer patients in additional therapeutic settings and with additional tumor types.
Today, I will focus on key clinical pipeline highlights, including 2 ongoing registrational trials from this afternoon's press release. I'll begin with the frontline advanced melanoma setting. The key priority with the potential for lifileucel to address thousands of additional patients. Our global registrational Phase III trial TILVANCE-301 remains on track to support accelerated and full approvals of Amtagvi in combination with pembrolizumab in frontline advanced melanoma as well as regular approval of Amtagvi in post anti-PD-1 melanoma.
Enrollment is strong across geographies with high enthusiasm for site participation. More than 40 sites are currently active across 10 countries, including the U.S., Canada, Europe and Australia, with 60 additional sites selected across 18 countries globally. Iovance does careful feasibility assessment for each site selection at which time the sites also commit to participate. Site activation includes institutional ethics board approvals and scientific review of the TILVANCE trial design, including the pembrolizumab monotherapy control arm and its fit with local standards of care for the enrolled patient population.
We also believe the option to cross over to TIL therapy from the control arm is attractive to patients. As a reminder, TILVANCE-301 is supported by previously published data on TIL monotherapy in the pre-immune checkpoint inhibitor era and importantly, lifileucel data in advanced melanoma patients who were naive to immune checkpoint inhibitors in Cohort 1A of our IOV-COM-202 trial in solid tumors.
In our after oral presentation in a minute, updated Cohort 1A data demonstrated an unprecedented rate depth and durability of responses including a more than 60% over and 30% comes from complete response rate and a differentiated safety profile.
The new proof-of-concept Cohort 1D is also beginning in the IOV-COM-202 trial to investigate lifileucel in combination with nivolumab and relatlimab in patients with frontline advanced melanoma. This novel combination represents another potential best-in-class frontline alternative for physicians and patients.
Shifting to non-small cell lung cancer. Enrollment continues to accelerate with strong demand in our single-arm registrational Phase II trial IOV-LUN-202 in post anti-PD-1 non-small cell lung cancer. We expect to complete enrollment and report topline data for the IOV-LUN-202 registrational cohort in 2025 and submit a potential supplemental biologics license application to the FDA in 2026.
We are confident in the IOV-LUN-202 trial based on the positive preliminary data. Also, the FDA provided positive regulatory feedback on our proposed potency matrix as well as the single-arm trial design to support accelerated approval of lifileucel post anti-PD-1 on small cell lung cancer.
We have also initiated the multicenter IOV-END-201 Phase II trial to investigate lifileucel post-anti-PD-1 endometrial cancer patients regardless of mismatch repair or MMR status. There is an unmet medical need and no currently approved treatment options for the vast majority of patients with endometrial cancer in the post anti-PD-1 treatment setting. This unmet need will become more relevant as immune checkpoint inhibitors move into the frontline setting in combination with chemotherapy. Combined with the enthusiasm from gynecological oncologists, we expect IOV-END-201 to enroll quickly, and we look forward to presenting initial data soon.
As the leader in TIL cell therapy, Iovance is at the forefront of next-generation approaches to optimize TIL and TIL treatment regimens. We are investigating a next-generation PD-1 inactivated TIL cell therapy, IOV-4001 in the clinical trial in previously treated advanced melanoma or non-small cell lung cancer patients.
Two additional next-generation programs are in IND-enabling studies and are approaching clinical trials in the near term. IOV-3001 is the next-generation Interleukin-2 or IL-2 analog for use with the TIL treatment regimen. Preclinical data support the potential for improved safety with robust effects or T cell expansion driven by IOV-3001. IOV-5001 is a genetically engineered TIL cell therapy with inducible Interleukin-12 or IL-12. IOV-5001 has augmented TIL antitumor activity in preclinical studies and may improve safety via the tethering of IL-2 to the TIL.
As noted in this afternoon's press release, we renewed our Cooperative Research and Development Agreement, or CRADA, to collaborate with the U.S. National Cancer Institute or NCI, on preclinical and clinical development of enhanced tumor reactive TIL products. Additional details about our development programs are included in today's press release as well as the corporate slide deck and scientific presentations on our website. I'm happy to address questions about these programs and additional trials during the Q&A session.
I'll now turn the call over to the operator to begin the question-and-answer session.
[Operator Instructions] Our first question comes from Michael Yee with Jefferies.
Congrats on a good execution of the launch and good guidance. We just wanted to ask 2 questions on the guidance. Does the guidance number include Proleukin revenues built into that? I know it's not a huge amount, but I just want to make it square and accurate.
And then can you talk to the $18 million of Proleukin as a leading indicator, does that imply a certain amount of patients or a certain amount of time? Or is it just distributors buying it up? We try to back into that as maybe a queue of demand. And so I just want to think about your numbers on Proleukin and perhaps related to that, if I may just ask differently, do you have any numbers on the patient enrollment forms to think about the queue?
Yes, Mike, the guidance does include Proleukin. So all the guidance numbers that we put out include Proleukin revenues as well as Amtagvi revenues. Now on the Proleukin revenue number for this quarter, that represents sort of the leading indicator for what we think will be Amtagvi demand over the next couple of quarters. You can model it any way you see fit. It's a large number of infusions. We've given you the number of infusions through -- recently, it's more than 55 now, and you can use that to kind of estimate where we're going.
But the whole point was giving guidance is so that you can -- you can rely on our internal understanding of infusions and Proleukin demand and see what the upswing is going to look like here. It's a very positive uptake of both Proleukin and especially Amtagvi.
Yes. So to clarify, it's a buying up of a certain amount from distributors, but not like a one-for-one or a certain amount of time. It's just -- it's an indicator.
It's just an indicator, and they've already started restocking. I can't stress that more. They've already started reloading because they've sold a lot of that product already.
Our next question comes from Peter Lawson with Barclays.
Thanks for the guidance, Fred, and congrats on the progress. The Q3 guidance, what's the breakout of IL-2 versus TIL? Same question for the full year as well. And then for the IL-2 revenues this quarter, what was the proportion of that IL-2 that was used for TIL therapy?
Yes. We don't have -- we're not going to provide guidance on the individual products. We're just going to provide the aggregate guidance. You can probably model it by understanding the amount of Proleukin that you use for Amtagvi patient because I'm going to answer your second question at the time here. We don't know exactly how much of our Proleukin gets used in the Amtagvi regimen. But you can hear from Jean-Marc's comments earlier and from the experience of Proleukin in the industry for many years, it's got to be the vast majority of it getting used for Amtagvi. We have no way of tracking that from an accounting perspective, but it's being, obviously, the massive upswing of Proleukin sales is driven by Amtagvi.
Our next question comes from Andrea Tan with Goldman Sachs.
Fred, I'm curious here, just given where you stand in the launch and your 6-months and what is driving your confidence for full year '25 guidance, given where you are now? And then just curious if you plan on providing metrics around demand, such as the patient enrollment or screening as you have in past quarters?
Andrea, we may provide some additional guidance on -- we're not -- you won't hear us talking about enrollments anymore. It's really not relevant anymore. All that matters now is infusions, which is the revenue-generating event. So we may talk a bit about that as we go over the next whatever 4, 5 quarters here. But really, what we're trying to do with the guidance is give you the big numbers, you don't have to worry about enrollments and that sort of thing you can figure out exactly what we're seeing in terms of infusions.
What's giving us confidence on that fiscal year '25 guidance, the full year '25 guidance? We can see the launch. We see how we're doing. We know all the dynamics. We know how many ATCs are coming on board. We know what we think they're going to do. We know our manufacturing capacity and all the details around that stuff that would be very difficult, I think, for the Street to model in some cases. So we're going to provide it for you. So you have clarity on what we're seeing. And we're very, very confident in that guidance based on what we're seeing so far in the initial part of the launch because we've got such a good picture of launch dynamics right now.
Our next question comes from Yanan Zhu with Wells Fargo Securities.
Great. Congrats on the progress here. So I guess I have a couple of questions on patient numbers. You gave the patient infused -- the infusion -- number of infusions for -- since the start of this quarter, which is 30 patients. Given that there will be -- you have talked about month-to-month increase and quarter-over-quarter increase, can we assume that over the next 2 months, within the current quarter, you will have patient numbers that will exceed the 30 patient number there?
And -- also on patient number, just wanted to understand, has there been patients that have been reflected around the same time as the 30 patients and who did not receive the product, i.e., trying to get a sense of the ongoing attrition rate, whether that's due to manufacturing issues or patient progression? If you can give some color there, that would be super helpful.
Yes. To answer your second question first, the patient dropout rate and manufacturing success rate remained consistent with what we saw in the clinical trial experience. So we're seeing that today. We can obviously further optimize that, and we're working on that. Part of the reason we're giving guidance is so that you don't have to necessarily fact that all in, we can see that pretty clearly and understand that. And as we go, we may provide more details on that once we have a larger [ MMR ] data set here, but right now, we feel very good about those numbers.
And then to answer your question, I couldn't fully understand what you're getting out with the patient numbers. We've already done more than 30 patients this quarter, meaning third quarter, in the quarter we currently sit in, that we did in the quarter -- second quarter that we're reporting for. We expect that to obviously accelerate considerably such that by the end of the third quarter, the numbers are going to be much higher. I'm not sure if that answers your question or if you want to phrase it differently, I can try it again.
Right. So given that you infused more than 30 patients, this quarter, but this quarter is -- still have a couple of months to go, right? So I'm just trying to understand what's your assumption for this quarter, the patient number for this quarter, given that you only gave the revenue guidance, which includes Proleukin. And at this current rate, I think it's a little hard for us to understand the Proleukin revenue contribution because there's a lot of stocking going on. So it's hard for us to see the patient number. If you can help us understand the patient number for this quarter, that would be helpful.
Estimated, we have an estimated number for this quarter that's a lot higher than 30. I can't give you that number today. I can tell you that it will be significantly higher, and it will track out the way we think it will track out to give you $53 million to $55 million in revenue with a good portion of that being Proleukin, especially restocking of Proleukin. That's the most color I can give you right now.
Our next question comes from Tyler Van Buren with TD Cowen.
Just a couple. So you gave basically some metrics on time to -- of manufacturing, which is consistent in reimbursement. But what's the average time from the beginning from opt-in to infusion? And then the second one is around kind of how much you're netting per infusion and gross margins. I suppose if you guide to target gross margin of 70% over the next few years. That would assume roughly [ 3 60 ] on the [ 5 15 ] list. So it has to be lower currently, and we're getting some inbounds with cost of sales being the same as product revenue for this quarter. So more color on that and how much is fixed versus variable and how it might evolve over time would be super helpful.
Sure. We currently, right now, Tyler, see the entire enrollment process. The reimbursement approval, financial single case agreement, all the stuff we talked about endlessly on our earnings calls as well as scheduling and getting in line for resection. The whole thing takes about 3 to 4-weeks right now, right? So that -- I hope that answers the first part of your question there. That's where it is today, and that's getting quite close to where we wanted to be long term.
On the netting, I think with respect to gross margin, we've obviously given you the number -- are you asking about gross to net on the product on Amtagvi? Because you mentioned discounting, and I'm not sure exactly what you're talking about from a financial perspective. Gross to net of the product is very low.
Yes, currently, how much you're netting with each infusion and how you expect that to evolve in the coming quarters?
All right. So gross to net right now is less than 0.5%, and we expect it to stay around there. less than 0.5%.
But I guess the question is cost of sales are the same as product revenue. So there's a lot I mean, is a lot of that fixed. I mean -- and obviously, if it's a 70% gross margin, it's not half currently, right -- 0.5% currently.
I think -- so I'm going to probably need Jean-Marc's help here, but maybe this is -- some of this is lost in the definition of cost of sales that we have. Jean-Marc, do you want to comment?
Yes, just chiming in and trying to answer Tyler's question. So what you will see in the 10-Q and all the detail is obviously our cost of sales in total which is $38 million. If you look at year-to-date June 2024. We don't have any specific gross margin to give for product or product-by-product because it's a total, but just note that on the cost of sales, you will have, of course, other things than only cost of product, cost of goods sold itself because you have intangible assets that you need to take into account, you have royalty to take into account. So you cannot do exactly what's the conclusion on the gross margin.
But we are committed, again, in the next several years to reach this 70% because we believe that where we stand today in terms of cost of sales for our product, make us confident for reaching the 70% in the next few years.
Our next question comes from Ben Burnett with Stifel.
And again, I appreciate -- congrats on all the progress on a great quarter. A question just on the cash guidance that Jean-Marc you were talking about. To what extent do you consider product revenue when calculating the cash runway?
Yes. We do take into account the product revenue, but to be honest with you, Ben, we are very conservative. So that's why we're confident into saying with the recent $200 million we just -- we just wait to be able to go into 2026. And that includes all the spending in terms of investment in terms of increasing manufacturing capability and capacity and all our operational spend. So we are very conservative and very confident about that.
Okay. And so just to clarify, so when thinking about kind of the spending going forward, we shouldn't just assume that, that cash guidance is assuming the product guidance exactly -- product revenue guide?
We do take into account, what we are telling you, around the $450 million to $475 million in 2025, obviously, this is our baseline to look into our cash burn for the cash overall situation for next year. But that's the topline. After you have to take into account also some one-time expenses we may have into increasing capability and capacity at iCTC, for example. But again, very confident into giving the guidance into 2026 as a cash in that.
Excellent. Okay. And maybe just one follow-up. What is kind of the timeframe for expanding the manufacturing capacity to 5,000?
Igor, do you want to handle that one?
Happy to. So right now, the network is built to a couple of thousand patients per year capacity. And within the existing iCTC facility. As you recall, we have shelf space that we're now building out and that build-out will bring iCTC to over 5,000 patients per year capacity. And that build-out should be completed in a couple of years.
Our next question comes from Colleen Kusy with Baird.
Congrats on the progress. Can you comment on the manufacturing success rate and just kind of what happens when there is an unsuccessful manufacturing run? Does that just get filtered into COGS? And then for the fiscal year 2025 guidance, how much of -- is the contribution expected to be from Europe?
Yes. Jean-Marc, do you want to talk a little bit about how it works with the manufacturing like an out-of-spec and how that goes into cost?
Yes. So Colleen, thanks for the question. I appreciate that. The out of spec and all the scrap will go and you will see that in the queue as part of our cost of sales because when the product is not being infused by the patient because of patient health or other situations like that and out of spec, of course, we have to take it into account what stage of production it was. So it will be taken into account as part of cost of sales. If it is going into potentially some kind of -- and its case-by-case situation, clinical use, then we will switch into OpEx. We will switch it back to OpEx as part of our clinical spend in that case.
And Colleen, I can answer. No, the European revenue is not factored in anything right now, that will come online. As I said in my remarks a little bit later, we expect and will give us even more tailwinds in 2026 and beyond.
Our next question comes from Asthika Goonewardene with Truist.
I appreciate all the color and the patience with all our questions today on this. I'm going to ask one more on the guidance here. Maybe you can give a little color if the proportion of the product revenue guidance that is attributable to Proleukin? Is that right to assume that the contribution slides down with each progressing period? Or is it a fixed component each period? And then -- each period provided, and then of the 25 patients that were treated in 2Q, what proportion of these patients was reimbursement sought on a single case basis? And how has that shifted into the 30 patients already treated today in 3Q?
Yes. So Asthika, the way to think about it is Amtagvi has a price, Proleukin has a price, you multiply the Proleukin price by the number of vials you expect, you're going to get to what I think you referred to as a fixed combination, which is a fixed percentage. So ultimately, Amtagvi patients that get Proleukin, there's going to be a percentage between the total cost of those 2 drugs, what percentage Proleukin contributes or what percentage Amtagvi contribute, you calculate pretty easily. It's roughly in the ballpark of about 15%.
We could calculate that out in more detail for you, but you can do the math. For the 25 patients is the single case agreement, we do single case agreements for every patient. They just go faster and faster. Maybe Jim, could you add a little bit color on how that help improve for those 25 patients?
Yes. Thanks, Fred. So the payer mix that we're seeing currently in the early days of launch, mirrors what we had previously shared prior to launch. So prior authorizations and single-case agreements primarily applied to the private payers, which you will recall was about 3/4 of the patients. That's what we're seeing right now. In the early months of launch, our payer mix that's very consistent, so about 75%.
Our next question comes from Reni Benjamin with Citizens JMP.
Congratulations on a great quarter and great guidance. A couple for us. Maybe just starting off, can you talk a little bit about how you're managing and working with ATC especially as it comes to maybe constraints and how they're dealing with prioritizing CAR Ts versus TIL infusions and how that's looking kind of going forward.
And I guess also, we heard a lot of arguments this quarter. patients were dying before they get the infusion. Maybe you can talk a little bit about how -- what the patients are kind of looking at now as they're being enrolled? Is it -- has it changed any? Are they healthier, less lines of therapy? And then the other argument -- as you guys didn't have enough slot that there was just a backlog and then people were waiting for cells to get process. Can you talk maybe a little bit about that, whether or not there was a backlog?
Jim, do you want to take the first part of that, maybe Brian can take the second part?
Yes. Sure. So thanks, Reni. As we work with the ATCs, we work with them almost on a daily basis, especially the top ATCs, how they decide and allocate beds between CAR Ts and TILs I'm not exactly sure of, but I do know that in terms of demand and scheduling patients for Amtagvi, that doesn't seem to be a concern. Just as prior to launch, there was a lot of concern around the lack of hospital beds, it does not appear to be any type of restraint at all.
In terms of patients dying before infusions, I guess what I would say is similar to other CAR-Ts where there's a high unmet need and the lack of available treatments. Yes, you do have some patients that may progress or may dive before therapy. But as we are well into launch now into our fifth and sixth months, I think patient selection is getting much better, and we're not seeing those same trends. I would just reiterate that the demand that we're seeing at the ATCs, the operational readiness looks really, really good, and it reinforces the confidence behind our guidance. Brian?
Yes. I would second everything you said, Jim. One thing that we've done at Iovance, I think it's not the only one of its kind. It's certainly rather unique, it's developed as --we call it peer-to-peer, which is really former healthcare providers speaking to current healthcare providers and assessing patients as a partnership. We're all -- we've all learned about the current commercial patient population out there. And I think what's really made the biggest improvement is patient selection, people understanding who are the most appropriate and even more so that these authorized treatment centers are speaking to the referring doctors, try to get them to understand earlier when it's best to send it -- send the patients to them so that we can move this process up and make patients who right now may not be the best candidate.
There is a point in their -- earlier in their journey when they were better candidates. I think this relationship that we have with all the authorized treatment centers is starting to bear fruit. And that's why I think you're seeing less and less of what you were describing.
Thank you. I'm showing no further questions at this time. I would now like to turn it back to Fred Vogt for closing remarks.
Thank you again for joining the Iovance Biotherapeutics Second Quarter and First Half 2024 Financial Results and Corporate Update Conference Call. We're honored to disclose the first revenue for the first commercial TIL cell therapy and look forward to providing further updates on the progress of our Amtagvi launch as well as continued developments in our pipeline and future outdates.
It's already been a monumental year for Iovance. We continue to be motivated as we hear media and social media, Amtagvi is providing hope to patients with metastatic melanoma. As always, we are thankful for the patients, healthcare and efficacy communities, our partners and our exceptional Iovance team. I'd also like to thank our shareholders and covering analysts for their support. Please feel free to reach out to our Investor Relations team for follow-up. Thank you.
This concludes today's conference call. Thank you for participating. You may now disconnect.