Cuộc họp công bố kết quả kinh doanh quý 3/2026 của Iovance (IOVA): Doanh thu tăng 80%, tái khẳng định định hướng

Điểm nhấn chính

• Doanh thu quý 3/2026 đạt mức kỷ lục khoảng 122 triệu USD, tăng 80% so với cùng kỳ năm trước và tăng 22% so với quý trước.
• Amtagvi mang lại doanh thu khoảng 102 triệu USD, tăng 77% so với cùng kỳ năm trước và tăng 12% so với quý trước. Hơn 1.000 bệnh nhân thương mại đã được điều trị kể từ khi thuốc ra mắt.
• Biên lợi nhuận gộp tăng lên mức kỷ lục khoảng 60%, trong khi chi phí R&D giảm 16% so với quý trước xuống còn khoảng 49 triệu USD và chi phí SG&A đi ngang ở mức khoảng 39 triệu USD.
• Iovance tái khẳng định dự báo doanh thu cả năm 2026 trong khoảng từ 410 triệu đến 420 triệu USD. Ban lãnh đạo kỳ vọng nguồn tiền mặt và doanh thu của công ty sẽ đủ tài trợ cho các hoạt động tới tận năm 2029.
• Trong thử nghiệm Lung 202, lifileucel đạt tỷ lệ đáp ứng khách quan 24,6% ở 69 bệnh nhân ung thư phổi không tế bào nhỏ di căn, không vảy, từng được điều trị trước đó. Iovance có kế hoạch nộp hồ sơ sBLA vào năm 2027.
• Một phân nhóm có chọn lọc dấu ấn sinh học trong thử nghiệm Lung 202 đạt tỷ lệ đáp ứng 59,1%. Nhóm thuần tập Positivity được xác định theo phương pháp tiền cứu đang hướng tới mục tiêu 80 bệnh nhân và dự kiến bắt đầu tuyển bệnh nhân vào tháng 11/2026.

Dữ liệu tài chính quan trọng

Kết quả kinh doanh và hoạt động

Amtagvi tiếp tục là động lực tăng trưởng chính. Ban lãnh đạo cho biết tính bền vững của hiệu quả điều trị là lý do hàng đầu khiến các bác sĩ lựa chọn liệu pháp này, với hơn 80% bác sĩ mục tiêu đánh giá cao độ bền vững trong nghiên cứu thị trường của công ty.

Iovance kết thúc quý với hơn 100 trung tâm điều trị được ủy quyền (ATC) và tiếp tục duy trì lộ trình đạt ít nhất 110 trung tâm vào cuối năm. Các trung tâm cộng đồng chiếm hơn một phần ba mạng lưới này. Hiện tại, khoảng hai phần ba số ca truyền thuốc diễn ra tại các trung tâm học thuật và một phần ba tại các trung tâm cộng đồng, nhưng ban lãnh đạo kỳ vọng các cơ sở cộng đồng cuối cùng sẽ chiếm hơn một nửa.

Thời gian chu chuyển sản xuất là từ 30 ngày trở xuống đối với hầu hết các lô. Ban lãnh đạo cũng cho biết tác động từ hoạt động bảo trì cơ sở trước đây dự kiến sẽ không còn làm gián đoạn hoạt động sau khi chuyển sang mô hình sản xuất dạng mô-đun.

Trên bình diện quốc tế, Amtagvi đã được phê duyệt tại Canada và Úc đối với bệnh u hắc tố từng được điều trị trước đó. Các trung tâm ATC ban đầu đã sẵn sàng tại Canada và đang được triển khai tại Úc, mặc dù khả năng tiếp cận rộng rãi còn phụ thuộc vào việc thanh toán bảo hiểm y tế công. Ban lãnh đạo cho biết khả năng được phê duyệt tại Anh và Thụy Sĩ có thể diễn ra vào quý 1/2027. Iovance cũng có kế hoạch nộp hồ sơ tại Brazil và nộp lại hồ sơ tại EU vào năm 2027.

Cập nhật danh mục sản phẩm đang phát triển

Trong thử nghiệm Lung 202, 17 trong số 69 bệnh nhân ung thư phổi không tế bào nhỏ di căn, không vảy, từng được điều trị trước đó đã đạt đáp ứng một phần hoặc hoàn toàn, tương đương tỷ lệ đáp ứng khách quan khoảng 25%. Khoảng một nửa số bệnh nhân có đáp ứng vẫn duy trì hiệu quả. Ban lãnh đạo cho biết việc giảm liều làm suy giảm tế bào lympho đã cải thiện độ an toàn trong khi vẫn duy trì tỷ lệ đáp ứng và mức độ bền vững tương đương.

Quá trình tuyển bệnh nhân trong nhóm thuần tập 1 và 2 đang tiến gần đến mục tiêu khoảng 80 bệnh nhân. Iovance đang tiến hành các đánh giá độc lập, thảo luận với FDA và thực hiện các công việc chuẩn bị khác trước kế hoạch nộp đơn sBLA vào năm 2027.

Công ty cũng đang đẩy mạnh chiến lược TIL chính xác. Một phân nhóm có chọn lọc dấu ấn sinh học trong thử nghiệm Lung 202 đạt tỷ lệ đáp ứng 59,1%, bao gồm hai trường hợp đáp ứng hoàn toàn vẫn đang duy trì ở tháng thứ 21 và 49. Iovance dự kiến đánh giá nhóm này theo phương pháp tiền cứu trong nhóm thuần tập Positivity gồm 80 bệnh nhân và có kế hoạch nghiên cứu nhóm đối tượng này trong thử nghiệm điều trị bước một OPAL-1 vào năm 2027.

Đối với bệnh sarcoma đa hình không biệt hóa kháng trị và sarcoma mỡ khử biệt hóa, lifileucel đem lại đáp ứng được xác nhận ở 5 trong số 9 bệnh nhân, tương đương khoảng 56%. Hai trường hợp đáp ứng vẫn tiếp tục duy trì trên một năm. Thử nghiệm đăng ký lưu hành Saratoga đang tuyển 40 bệnh nhân cho mỗi nhóm thuần tập, với kế hoạch có thể nộp đơn sBLA vào năm 2028 hoặc 2029.

Đối với điều trị bước một bệnh u hắc tố tiến triển, phác đồ lifileucel kết hợp pembrolizumab mang lại tỷ lệ đáp ứng 62,5% và tỷ lệ đáp ứng hoàn toàn 29,2%. Thời gian sống thêm toàn bộ trung vị vẫn chưa đạt tới sau hơn bốn năm theo dõi. Thử nghiệm Giai đoạn III TILVANCE-301 đang tuyển bệnh nhân tại hơn 80 trung tâm nghiên cứu.

Các chương trình thế hệ tiếp theo bao gồm IOV-5001, liệu pháp TIL gắn IL-12; IOV-4001, liệu pháp TIL bất hoạt PD-1; và IOV-3001, một chất tương tự IL-2 biến đổi. Tất cả đều đang trong giai đoạn phát triển lâm sàng ban đầu.

Dự báo của ban lãnh đạo

Iovance tái khẳng định dự báo doanh thu cả năm 2026 trong khoảng từ 410 triệu đến 420 triệu USD. Ở mức trung vị, con số này tương đương mức tăng trưởng gần 60% so với năm trước. Ban lãnh đạo cho biết công ty đang bám sát phạm vi dự báo và đặt mục tiêu tăng trưởng so với quý trước trong quý 4.

Công ty kỳ vọng biên lợi nhuận gộp sẽ tiếp tục mở rộng theo thời gian nhờ hiệu quả hoạt động và kỷ luật đầu tư. Ban lãnh đạo không đưa ra thời điểm cụ thể để đạt điểm có lãi, nhưng cho biết công ty có thể có lãi trước các đợt ra mắt tiềm năng cho chỉ định ung thư phổi hoặc sarcoma nếu tăng trưởng doanh thu và kiểm soát chi tiêu kỷ luật tiếp tục được duy trì.

Dựa trên khoảng 382 triệu USD tiền mặt và các khoản đầu tư, cùng với tăng trưởng doanh thu và các kế hoạch phân bổ vốn, ban lãnh đạo kỳ vọng các nguồn lực hiện có sẽ đủ tài trợ cho các hoạt động tới tận năm 2029.

Rủi ro và các yếu tố cần theo dõi

• Độ bền vững đáp ứng trong thử nghiệm Lung 202 vẫn cần thêm thời gian theo dõi, và ban lãnh đạo cho biết thời gian đáp ứng trung vị có thể vẫn chưa đạt tới khi dữ liệu cập nhật được công bố vào năm 2027.
• Kế hoạch nộp đơn sBLA cho chỉ định ung thư phổi vẫn phụ thuộc vào việc hoàn tất tuyển bệnh nhân, các cuộc thảo luận với FDA, đánh giá độc lập và các hoạt động tiền đệ trình khác.
• Mức độ tiếp nhận trên thị trường quốc tế phụ thuộc một phần vào tiến độ thanh toán bảo hiểm, đặc biệt là bảo hiểm y tế công tại Canada và Úc.
• Iovance tiếp tục ghi nhận khoản lỗ hoạt động và ban lãnh đạo chưa đưa ra lộ trình cụ thể về thời điểm có lãi.
• Việc mở rộng danh mục sản phẩm phụ thuộc vào độ bền vững lâm sàng, quá trình xét duyệt của cơ quan quản lý và việc tuyển bệnh nhân thành công trên nhiều nghiên cứu đăng ký lưu hành.

Điểm nhấn phần hỏi đáp với chuyên gia phân tích

Ban lãnh đạo cho biết hoạt động bảo trì cơ sở định kỳ hàng năm dự kiến sẽ không còn ảnh hưởng đến sản xuất hoặc kết quả kinh doanh hàng quý. Công ty tiếp tục đặt mục tiêu tăng trưởng doanh thu so với quý trước, đồng thời duy trì dự báo cả năm đã công bố gần đây.

Hoạt động đặt hàng Proleukin đã được điều chỉnh phù hợp trở lại với nhu cầu của Amtagvi. Ban lãnh đạo cho biết Proleukin chiếm khoảng 16% nhu cầu liên quan trong quý, với các đơn đặt hàng từ nhà bán buôn được điều phối nhằm đáp ứng nhu cầu truyền thuốc của bệnh viện theo thời gian thực.

Về thử nghiệm Lung 202, ban lãnh đạo cho biết nghiên cứu dự kiến sẽ sớm đạt khoảng 80 bệnh nhân và dữ liệu cập nhật dự kiến sẽ có vào năm 2027. Các lãnh đạo đánh giá các cuộc thảo luận với FDA là hiệu quả và tái khẳng định niềm tin rằng bộ dữ liệu có thể hỗ trợ việc đăng ký lưu hành, đồng thời xác nhận kế hoạch nộp hồ sơ vào năm 2027.

Về việc mở rộng thương mại, ban lãnh đạo cho biết các trung tâm ATC cộng đồng đang tiếp nhận và bắt đầu điều trị bệnh nhân nhanh hơn. Các trung tâm học thuật hiện vẫn chiếm khoảng hai phần ba số ca truyền thuốc, nhưng công ty kỳ vọng các trung tâm cộng đồng sẽ trở thành nguồn đóng góp lớn hơn theo thời gian.

Toàn văn biên bản cuộc họp công bố kết quả kinh doanh

Toàn văn cuộc gọi công bố kết quả kinh doanh

Phần trình bày của ban lãnh đạo

Unknown Speaker

Thank you. Thank you, Daniel. Good morning, and welcome to the Iovance webcast to discuss our third quarter 2026 financial results, business achievements, and corporate updates. This morning, we issued a press release that is available on our corporate website at Iovance.com. This conference call will 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, submissions, feedback and guidance, plans and strategies, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, payer interactions, licenses and collaborations, cash flow, and more. in 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. I will now turn the call over to Dr.

Fred Boat, Interim CEO and President.

Unknown Speaker

Thank you, Jen. Good morning, everyone. Our third quarter delivered outstanding record setting results for EyePoint. Our highest ever revenue and margin and strong financial performance across the board. Total revenue of about $122 million surged 80% over the prior year. U.S. Empaveli revenue increased 77% over the prior year and crossed $100 million in a single quarter for the first time. We also passed an important landmark this quarter with more than 1,000 commercial Vyvgart patients now infused in the U.S. since launch. Based on this strong performance, we remain on track to achieve our full-year revenue guidance of $410 to $420 million.

Our authorized treatment center, or ATC network, continues to expand rapidly, and we fully expect to reach 110 or more authorized treatment centers by year end. Third quarter margin of about 60% also set a new all-time high for the second consecutive quarter, and we expect it to expand further over time. Our cash runway is now expected to fund operations well into 2029. The strong performance reflects the financial health of Iovance and the strong platform that we can build upon for upcoming launches. The third quarter and recent updates also reflect major progress across our TIL platform and pipeline programs. In metastatic non-small cell lung cancer, lifileucel continues to demonstrate a potentially best-in-class clinical profile. Earlier this year, the FDA granted fast track designation based on the strength of our data and the high unmet need.

Last week, we reported positive updated results from our registrational Lung 202 trial that included 69 patients with previously treated non-squamous metastatic non-small cell lung cancer. The objective response rate, or ORR, by RECIST 1.1 was 24.6%, consistent with our prior results in 39 patients. Durability, while still maturing, was also consistent with our prior results and has already greatly surpassed the current standard of care, docetaxel, which has a response rate of only 12.8%, short durability of 5.6 months, and median overall survival of just 12.3 months. Safety in Lung 202 is consistent with our lifileucel experience to date across our clinical trials of multiple solid tumors. Encouragingly, the safety profile on Lung 202 improved using the updated reduced dose lymphodepletion regimen. efficacy, including durability, remains comparable and consistent in Lung 202 before and after the change to reduced dose lymphodepletion. We will provide more details on Lung 202 as the study completes with potential presentations at medical meetings in 2027. Looking ahead, we are confident in our plans to submit a supplemental biologics license application, or S-B-L-A, in 2027.

We are completing enrollment in cohorts one and two with a target of approximately 80 patients for the SBLA. In parallel, we are advancing independent review committee assessments, FDA discussions, and other pre-submission activities, including preparation for a confirmatory trial. Alongside our latest Lung 202 update, we launched an innovative precision tilt strategy. We identified a biomarker-enriched subgroup of non-squamous, non-small cell lung cancer patients in Lung 202 that demonstrated a remarkable 59.1% response rate. Nearly six in 10 patients showed a deep, and durable response. These results are the foundation for POSITY, a first in class, prospectively defined, biomarker enriched cohort with registrational intent that we will pursue in addition to our initial sBLA in 2027 in non-squamous, non-small cell lung cancer. Positility is targeting 80 patients and will begin enrollment this month.

Utilizing the existing Lung 202 site footprint to speed enrollment is part of a planned transition. In 2027, we are also planning our OPAL-1 trial to investigate this population in the frontline setting. Together, these biomarkers selected front and second line settings representing U.S. opportunity about 10 times the size of advanced melanoma. At the ESMO Congress in late October, two oral presentations showcased the broader potential for Leifelusel to demonstrate deep, durable responses in soft tissue sarcomas and frontline advanced melanoma. Following one of the oral sessions at ESMO, this morning's press release included our most recent updates in soft tissue sarcoma. The confirmed ORR by RECIST 1.1 for lifileucel in refractory undifferentiated pleomorphic sarcoma, or UPS, and dedifferentiated liposarcoma, or DDLPS, has climbed to 55%. 25.6%, five of nine patients. Multiple durable responses have already been observed, including two ongoing more than a year from infusion.

Safety in the sarcoma trial is consistent with our lete-leucel experience to date across our clinical trials of multiple solid tumors. These powerful results in heavily pretreated patients are the basis for Saratoga, our registrational trial that is actively enrolling to support two more approvals for lete-lucel. After failing chemotherapy, second-line response rates are typically below 5%. Median survival is about 9 to 10 months, and there are no approved immunotherapies. In recognition of this unmet need, as well as our initial results, the FDA granted fast-track designation in both UPS and DDLPS. In addition, we have aligned with the agency on the design and a potential accelerated approval pathway based on the Saratoga trial with 40 patients expected in each cohort and sBLA submissions planned for 2028 or 2029. In our second oral session at ESMO, we focused on frontline advanced melanoma, where about half of patients do not achieve long-term benefit with today's standard combination checkpoint inhibitors.

In our phase two cohort, frontline advanced melanoma, 62.5% of patients responded, including complete responses in 29.2% of patients where tumors disappeared completely and did not Median overall survival was not reached after more than four years of follow-up. Safety was consistent with the known safety profiles of one-time lifileucel and pembrolizumab. These results reinforce Tilvance 301, our Phase III trial enrolling in more than 80 sites and expanding design to support both the frontline approval and serve as the confirmatory trial for full U.S. approval of Amtagvi. In summary, Iovance is focused on growing revenue, expanding into new indications and markets, and broadening TIL therapy into solid tumor indications, including biomarker-selective populations that collectively represent tens of thousands of cancer patients with poor prognosis and limited available options. I'm also thrilled to welcome our new Chief Medical Officer, Dr. Noah Berkowitz, to his first quarterly call at Iovance to discuss additional details about our pipeline. His valuable expertise in global drug development across cancer and blood disorders led to approvals for the CAR T-cell therapies Abecma and Breyanzi while at Bristol-Myers Squibb.

As the first and only company in the world to take TIL Therapy from concept to commercial treatment, we are forging ahead with tremendous momentum toward profitability and long-term value for patients and shareholders alike. Jean-Marc Roche, our Chief Financial Officer, will now highlight our financial results.

Unknown Speaker

Thanks, Fred, and good morning, everyone. The third quarter was another record quarter for Iovance, combining strong revenue, record margin, and disciplined spending.

Corleen Roche

Revenue is up 80% that's 80 year-over-year. Margin is at an all-time high of 60% 60 and operating expenses reflected discipline, intentional allocation of capital to our highest return priorities and now our cash run way expected to fund operations well into 2029. Total revenue once again achieved a new quarterly record of about $122 million, up 80% year-over-year as I mentioned and 22% sequentially. Amtagvi powered that revenue growth by reaching more patients than ever before. Amtagvi sales of around one hundred and and $2 million represent 77% increase year over year and a 12% increase sequentially, reflecting strong patient demand and broad adoption. Proleukin revenue contributed approximately $20 million in the third quarter, more than double the second quarter level as wholesaler ordering patterns are realigning with Amtagvi demand. As expected, the quality of our revenue remains high, with gross to net deductions around 1% consistent with prior quarters.

That high quality revenue is flowing through to margin, which reached an all time high for the second consecutive quarter of approximately 60%, up sequentially from our previous record of 56%. and that brings our year-to-date margin to 54%. Intacct growth, operational efficiencies, and investment discipline contributed to this margin gain and remain powerful levers for continued expansion as we drive further efficiencies across the company. Turning to operating expenses. Third quarter R&D expenses were down approximately 16% sequentially to about $49 million, marking the fifth consecutive quarter a reduced R&D expense. This trend reflects efficiency of our operations, including clinical and manufacturing, which allows us to advance multiple registrational programs at greater scale and much less cost than any TIL competitor. Total selling general and administrative expenses held flat at about $39 million sequentially, even as revenue grew about 22%. We continue to make targeted investments in revenue generating activities that drive the greatest commercial return. We are reaffirming our recently updated full year revenue guidance range of $410 to $420 million.

At the midpoint, that is nearly 60% growth over last year. Through the first three quarters of 2026, we have already delivered $292 million of revenue, expanded margin, and controlled operating expenses. We end the quarter in a strong financial position with approximately $382 million in cash, cash equivalents, short-term investments, and restricted cash on September 30th. Together with robust revenue and careful capital allocation, this cash position is now expected to fund operations well into 2029, giving us the runway to execute on our growth plan from a position of strength. In closing, we again delivered strong revenue, improved margin, and intentional capital allocation this quarter. With a strong balance sheet supporting us, we are well positioned as we build a valuable, self-sustaining business that delivers lasting value for patients and our shareholders. And behind these record results are the patients we serve.

For more on how we are reaching them, here's Dan Kirby, our Chief Commercial Officer, to review our commercial progress in more detail.

Unknown Speaker

Thank you, Corleen. Third quarter was the strongest quarter of the Amtagvi launch. Amtagvi revenue surpassed $100 million for the first time, and we treated more patients than in any prior quarter. Together with Filspari sales of approximately $20 million, we are confident in achieving our updated full year guidance of $410 to $420 million. We also achieved two milestones this quarter. We have now treated more than 1,000 commercial patients, and we have more than 100 ATCs. Access is expanding and more patients are able to receive a one-time cell therapy that can deliver long-term, durable responses. I'll cover how we got here through our three priorities, physician awareness, growing our ATC network, and clinical data.

First, physician awareness. Our latest market research shows durability of response is the leading reason physicians choose Amtagvi over other treatments. Durability was rated highly by more than 80% of our target physicians and was cited by nearly two-thirds as the key driver for the decision to treat. Durability with mTAGV is measured in years with over three years median duration while other options both on the market and in trials measure durability in weeks and months. Last week, Fox News covered a story about one of our patients, Patty Garcee, who is experiencing a long-term durable response to MTAG-D after a single infusion two years ago. Patient stories like Patty's are increasingly being featured across media outlets and continue to reinforce the promise of our TIL therapy. Also, our expanded sales force returned clear value on investment as they logged more customer interactions than in any quarter since launch, which translated into more patients treated than ever. Second, our ATC network. We now have more than 100 ATCs and are on track to reach at least 110 by the end of Most of the centers we onboarded in Q3 were community based and community ATCs represent over a third of our network.

New centers are also getting started faster as the time between authorization and first patient treatment continues to shorten. Behind these numbers is reliable delivery to patients. For the majority of lots, turnaround time is 30 days or less. only scaled centralized commercial manufacturing process approved by the FDA for TIL therapy. Iovance's manufacturing capabilities are faster and more reliable than any till therapy in development. Third, clinical data. Real-world studies show response rates of 50% or greater in second-line patients, supported by five-year durable responses after a one-time Amtagvi treatment. These results are the standard in second-line plus metastatic melanoma, where patients get better and more durable responses with mTAG-B than any other option. At ESMO, a new indirect comparison suggested that lifileucel may approximately double four-year overall survival compared with standard of care in anti-PD-1 resistant advanced melanoma.

Our teams also met with US and international thought leaders at ESMO who were excited about the data and what it means for their patients. Turning to Proleukin, third quarter sales were about $20 million, driven by Amtagvi demand. We expect that trend to continue in Q4. Now, international, Amtagvi is approved in Canada and Australia for previously treated melanoma, with our first ATCs ready in Canada and onboarding in Australia. We are progressing reimbursement discussions in both countries. These ATCs will initially treat private pay patients while we work towards public reimbursement, which is key to broad access. The UK application is under expedited review and the Swissmedic process is moving smoothly with potential approvals in both markets by the first quarter of 2027.

Also in 2027, we plan to submit an application in Brazil where expedited review is available and to resubmit our application in the European Union. Finally, looking beyond today's indication, in frontline advanced melanoma, the population is more than twice the size of the previously treated population we serve today. in metastatic non-small cell lung cancer with KRAS wild type, the first and second line addressable market is at least 10 times that of Amtagvi's current indication. In soft tissue sarcomas, the U.S. market opportunity in UPS and DDLPS is approximately the same as the current second-line metastatic melanoma opportunity for mTagV. Across indications, these patients are concentrated at centers of excellence that are already ATCs, which we believe positions us well to quickly reach and treat patients upon approval. To close, we had a record third quarter, approximately $122 million in total revenue, including more than $100 million in Amtagvi revenue. reaching more patients than ever. We are on track to reach at least 110 ATCs with community centers and faster onboarding driving growth. Finally, we are on track to achieve all of our commercial goals for 2026.

I'll now hand the call off to Noah, who will cover our pipeline in further detail. Thank you, Dan, and hello everyone. My name is Noah Berkowitz. Having joined the company a month ago, this is my first Iovance earnings call, and I am incredibly happy to be here. I joined Iovance because TIL is the first single administration cell therapy that achieves deep and lasting responses in a significant proportion of patients with advanced melanoma. This success is being replicated across our robust clinical pipeline with translational medicine and early development programs aimed at optimizing outcomes in patient populations that may derive the greatest benefit from TILT therapy. Today, I am pleased to talk more about our exciting pipeline. To begin, we are looking forward to our upcoming sBLA submission for lifileucel in previously treated non-squamous metastatic non-small cell lung cancer.

Our enthusiasm for this submission is driven by the strength of the response rates and the durability of responses in cohorts 1 and 2 in our Lung 202 trials. We believe the data compare quite favorably to docetaxel monotherapy, the disappointing standard of care in this treatment setting, with a published study in the National Institute response rate of under 13%. In our registrational patient population from cohorts 1 and 2, 17 out of 69 patients, or about 25%, experienced a PR or CR as well as durable responses, including many patients treated with reduced dose of lymphodepletion regimen. Impressively, about half of the responders remain ongoing in the study. As you may recall, to manage toxicity, the trial included a reduced lymphodepletion preconditioning dose that became a trial requirement for all patients after mid-2024. We have observed improved safety and are maintaining a similar ORR, including long, durable responses. In parallel, we are aggressively advancing our precision TIL strategy following our identification of a biomarker-enriched subgroup with a response rate of 59.1%, including two ongoing complete responses at 21 and 49 months.

This subgroup includes current or pre-pandemic responses. or former smokers without actionable driver mutations, patients with significant unmet medical need and no targeted therapy options available. This novel biomarker-enriched subgroup will be evaluated prospectively in cohort five for positivity in the LUN202 trial. This is a precision opportunity that we will advance alongside and not far behind our planned sBLA based on cohorts one and two. Our biomarker-enriched frontline strategy in metastatic non-small cell lung cancer is also moving forward. After six out of seven or nearly 86% of patients This subgroup responded. For patients with UPS and DDLPS, poor prognosis variants of soft tissue sarcoma, second-line response rates are typically below 5% after failing chemotherapy. Median survival is about 9 to 10 months, and there are no approved immunotherapies.

In oral session at ESMO Congress highlighted the pilot trial led by Memorial Sloan Kettering Investigator and included a 50% confirmed ORR among the first eight evaluable patients. As Fred mentioned, we included the recent results in today's press release with a 56% five of nine patients is being updated data. Multiple durable responses have already been observed, including two ongoing more than a year from infusion. The data are available in our corporate slide deck in the investor section of iovance.com. We are currently enrolling patients in the Saratoga registration at major US cancer centers. As you may recall, we reported positive initial data in the first quarter of 2026 in the endurance trial. Here we focused on previously treated metastatic serous endometrial cancer using a biomarker strategy based on histology.

Among the first five evaluable patients, we observed a 40% confirmed objective response rate and 100% disease control rate. We are planning discussions with the FDA on an expedited approval pathway and expect to increase enrollment based on this patient population. I'd like Let's shift gears for a moment and highlight our next generation approaches. Let's start with IOV 5001, our IL-12 tethered till therapy. We know that IL-12 engineered tills have previously demonstrated differentiated efficacy with a new mechanism of action. Based on that prior experience, we believe that IOV5001 is designed to remodel the suppressive tumor microenvironment and activate immunologically cold tumors, supporting TIL responses and boosting response rates. POTENTIL, a first in human trial of IOV5001, is currently enrolling patients with metastatic colorectal cancer, triple negative and estrogen receptor low breast cancer, and other solid tumors that represent more than 100,000 U.S. cancer deaths annually.

We're also investigating IOV4001, a PD-1 inactivated TIL therapy engineered to resist inhibitory signals in a first in human trial where we continue to enroll patients with previously treated metastatic non-small cell lung cancer. And finally, we have a phase one safety cohort investigating multiple dose levels of IOV 3001, a second generation modified IL-2 analog designed to selectively expand effector T cells while avoiding activation of regulatory T cells. IOV 3001 is a potential component of future TIL regimens with a lower dose IL-2 regimen and fewer adverse events. I'm energized by the work ahead at Iovance to develop the current and future TIL pipeline. My priority is rigorous execution, close collaboration with regulators, and letting the data speak for itself. I will now hand the call back to the operator to begin the Q&A session.

Daniel Kirby

To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. In the interest of time, we ask that you please limit yourself to one question. Please stand by while we compile the Q&A roster.

Phần hỏi đáp

Lin Tsai

Our first question comes from Andrew Tsai with Jefferies. Your line is open. Hi there. Good morning. Great execution. Thanks for the updates. My question is about the commercial franchise right now. So traditionally, you guys have seen some impacts due to maintenance of your facility around the December and January time frame, I think. This time around, is it fair to assume everything will be smooth and good to go because you switched to the modular manufacturing early in the year. And if that's the case, you know the guidance implies maybe a flattish to slightly up quarter-over-quarter growth for Q4.

Is that really going to be the case? Can you maybe then talk about any other potential headwinds we should think about for Q4 as it relates to your guidance? Thank you.

Unknown Speaker

Yes, thanks Andrew for the question. You're correct, the maintenance is no longer an issue. We don't, that will not affect our earnings going forward. That was primarily affecting us in Q1 in the first quarter of each year, and that effect has gone away. We just issued this guidance five weeks ago, and so yes, obviously, We would like to have growth quarter over quarter, and we expect that, and that's something we would aim to do. But just keep in mind that the guidance really just came out five weeks ago. Right now, we're tracking to achieve it.

And of course, of course, of course, if we can beat our guidance, we're very happy to do so. as we just did. Great, thank you.

Daniel Kirby

Thank you. Our next question comes from Edzer Darut with Barclays. Your line is open.

Etzer Darout

Great, thanks for taking a question. I guess you know with quarterly operating loss of about approximately 24 million I guess, is profitability achievable before launches in lung cancer or sarcoma? And I guess, what remaining revenue scale or gross margin improvements do you think are needed to reach operating cash flow break-even given the momentum we're seeing in second-line melanoma alone?.

Corleen Roche

Thank you. The answer is yes. So, I mean, if you look at the EPS, it's only 5 cents loss, and that's the best it's ever been. So we are on our way to profitability. I'm not guiding when, but if we continue on this path of revenue growth and disciplined investments, we'll get there.

Daniel Kirby

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

Yanan Zhu

Hi, thanks for taking our questions. This is Kuan-Nan for Yonan, and congrats on another strong quarter. For Perlucan, the sales increased from 9 million to 20 million, and you mentioned the ordering patterns are realigning with MTAGV demand. So can you share with us a little bit about the sales growth? How much does that reflect the expected use of mTAC-V? And is there an estimation on the average delay between Perlucan sales and the use for mTAC-V? Thank you.

Unknown Speaker

Thank you, Quan. Great question with it. ProLucan is in line with mTAC-V demand. So we had said before about 16% of the demand was represented by ProLucan. That is what this quarter represented. We're seeing the orders in line. One of the things that the teams are doing to ensure that their supply is a wholesaler is we're communicating planned orders. at the hospitals that pull from that wholesaler. So we are tracking in line with demand in real time with the wholesalers ensuring the hospitals have supply to support the mTAC-V infusions.

Yanan Zhu

Got it. And a quick question on Lung 002. When do you think we may see a mature median DOR data from this study? Thank you.

Unknown Speaker

Well, it's possible that when we complete this study, we may be not reached, so that we may have matured but not reached like we did with some other reports that we've done, so just bear that in mind. But as we mentioned a couple times now, we expect to finish the study imminently at 80 patients. We will report, as I mentioned in the prepared remarks, we'll report data on that at some point next year, and then at that point you should see what you might... I think what you mean by mature, median DOR, but just don't be surprised if it's not reached at that point with a lot of follow-up.

Daniel Kirby

Got it. Thank you for all the color. Thank you. Our next question comes from Nick LaRusso with TD Cowen. Your line is open.

Unknown Speaker

Hey guys, thanks for taking my question. You noted that community ATCs represent about a third of the current network, which is impressive. Can you discuss the current prescribing patterns and maybe the proportion of patients coming from the community versus academic centers and how we should think about this ramping over time?.

Unknown Speaker

Sure, great question Nick. So we are focused, we've been focused for over a year now on opening community hospitals and ATCs to serve What we're seeing is in general we've gotten better at opening accounts, so as I mentioned in the prepared comments, we're seeing a quicker activation of first patient treated, so we are seeing the ramps come up. Our business still is concentrated mostly in the academics, but the community ATCs are growing over time with this. of our ATC world but it's going to represent in the future probably more than half of our infusions right now it's still about two-thirds in the academic world a third in the community world but we do expect that to grow as we continue to open more community Thanks very much for the call.

Daniel Kirby

Thank you. And our final question comes from Joe Pantginis with HC Wainwright. Your line is open.

Unknown Speaker

Hi, this is Josh on for Joe. Thanks for taking our question. So, I just wanted to follow up on LUN202, if there's any additional color you can provide with your, with the discussions you've been having with the FDA about the sBLA submission.

Unknown Speaker

Yes, I'm happy to provide that. We're very focused right now on those discussions with the FDA, and we're having productive discussions right now. And we believe that this data set that we have right now should be registrational and should be approvable. I'll ask Raj Puri here, who's with me, to make some.

Raj Puri

comments on this as well. He's our head of Chief Regulatory Officer. Yes, I agree with Fred's comment that the FDA, we are on track to get BLA submission at the end of Q4 and based on our data, we are confident that FDA will consider for that is under prior approvals in this space with about 80 subjects trial.

Unknown Speaker

And just to clarify, we're planning to submit that BLA in 2027. Perfect. Thank you so much.

Daniel Kirby

Thank you. This concludes the question and answer session. I would now like to turn it back to Fred Vogt for closing remarks.

Unknown Speaker

Thank you for joining us. This is another record-breaking quarter, and our pipeline is advancing rapidly. We remain deeply grateful to the patients, partners, healthcare professionals, and advocacy communities we serve. Finally, I want to thank our exceptional Iovance team, our dedicated long-term shareholders, and our covering analysts for their continued support. We remain committed to our mission to innovate, develop, and deliver current and next-generation TIL cell therapies for patients with cancer.

Daniel Kirby

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

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