Cuộc họp báo cáo kết quả kinh doanh Quý 3/2026 của Nuvation Bio (NUVB): Doanh thu IBTROZI tăng 18%

Thông tin trọng tâm

• Nuvation Bio đã báo cáo tổng doanh thu quý 3/2026 là 45,0 triệu USD, bao gồm 27,5 triệu USD doanh thu sản phẩm ròng tại Mỹ từ IBTROZI và 17,5 triệu USD doanh thu hợp tác và nhượng quyền.
• Doanh thu IBTROZI tăng 18% so với quý trước. Khoảng 160 bệnh nhân mới đã bắt đầu điều trị trong quý, với khoảng 65% ở phác đồ điều trị bước 1.
• IBTROZI chiếm hơn 60% số bệnh nhân mới bắt đầu điều trị bước 1 vào cuối quý và trở thành thuốc ROS1 TKI dẫn đầu về tổng số bệnh nhân đang điều trị trên tất cả các bước điều trị, dựa trên dữ liệu yêu cầu bồi thường của IQVIA.
• Tổng số bệnh nhân mới bắt đầu điều trị bằng ROS1 TKI đã giảm khoảng 15% trong quý. Ban quản lý cho rằng sự sụt giảm này là do biến động bình thường giữa các quý trong một thị trường cực kỳ hiếm gặp, thay vì sự suy giảm vị thế cạnh tranh của IBTROZI.
• Nghiên cứu Giai đoạn II J201 của Safusidenib cho thấy tỷ lệ đáp ứng khách quan 52% ở 27 bệnh nhân mắc u tế bào thần kinh đệm đột biến IDH1 độ 2, tăng từ 44% ở đợt theo dõi trước đó. Thời gian sống thêm không tiến triển bệnh trung vị vẫn chưa đạt được, trong khi tỷ lệ PFS 36 tháng là 79%.
• Tiền, các khoản tương đương tiền và chứng khoán có thể bán đạt tổng cộng 663,4 triệu USD vào ngày 30 tháng 9 năm 2026. Dựa trên các dự báo doanh thu nội bộ và kế hoạch hoạt động hiện tại, ban quản lý tiếp tục tin tưởng rằng nguồn vốn hiện có đủ để đạt được lợi nhuận.

Dữ liệu tài chính chính

Trong 9 tháng đầu năm 2026, Nuvation Bio đã tạo ra 159,9 triệu USD tổng doanh thu. Số này bao gồm 69,2 triệu USD doanh thu sản phẩm ròng của IBTROZI tại Mỹ và 90,7 triệu USD doanh thu hợp tác và nhượng quyền. Chi phí R&D và SG&A trong 9 tháng lần lượt là 98,4 triệu USD và 123,5 triệu USD.

Kết quả hoạt động và kinh doanh

IBTROZI củng cố vị thế trên thị trường ROS1

Tập bệnh nhân đang điều trị bằng IBTROZI tiếp tục mở rộng mặc dù toàn bộ thị trường ROS1 TKI bị sụt giảm. Ban quản lý cho biết khoảng 160 bệnh nhân đã bắt đầu điều trị trong quý 3, trong đó sử dụng ở phác đồ bước 1 chiếm khoảng 65% số ca bắt đầu.

Công ty báo cáo rằng IBTROZI chiếm hơn 60% số bệnh nhân mới bắt đầu điều trị bước 1 vào cuối quý. Thuốc cũng trở thành ROS1 TKI dẫn đầu theo tổng số bệnh nhân đang điều trị trên tất cả các bước điều trị, bao gồm cả những bệnh nhân đã bắt đầu các liệu pháp cạnh tranh trong các giai đoạn trước.

Ban quản lý cho rằng vị thế này có được là nhờ hồ sơ lâm sàng của IBTROZI. Ở những bệnh nhân chưa từng điều trị bằng TKI trong nghiên cứu TRUST-I, liệu pháp này đã thể hiện tỷ lệ đáp ứng khách quan 90%, thời gian đáp ứng trung vị 50 tháng và thời gian sống thêm không tiến triển bệnh trung vị 50 tháng, được hỗ trợ bởi thời gian theo dõi trung vị là 51 tháng. Công ty cũng nhấn mạnh việc không có cảnh báo và thận trọng về hệ thần kinh trung ương (CNS) trên nhãn sản phẩm.

Theo ban quản lý, thời gian điều trị thực tế và việc ngừng điều trị do tác dụng phụ cho đến nay bám sát với các nghiên cứu lâm sàng. Tuy nhiên, trải nghiệm thương mại mới chỉ kéo dài 15 tháng, so với hơn 4 năm theo dõi trong thử nghiệm TRUST-I.

Nguồn bệnh nhân điều trị ở các bước sau có sẵn để chuyển từ các thuốc ức chế ROS1 cũ hơn đang trở nên nhỏ hơn. Do đó, Nuvation Bio kỳ vọng sự tăng trưởng trong tương lai sẽ phụ thuộc ngày càng nhiều vào các bệnh nhân mới được chẩn đoán, việc áp dụng ở phác đồ bước 1 và sự tích lũy bệnh nhân duy trì điều trị trong thời gian dài.

Khoảng trống trong xét nghiệm và điều trị vẫn là cơ hội mở rộng

Ban quản lý đã xác định hai rào cản đối với việc điều trị nhắm mục tiêu ROS1 rộng rãi hơn: xét nghiệm chỉ bằng DNA có thể bỏ sót một số hợp nhất ROS1 và quá trình điều trị có thể bắt đầu trước khi có kết quả xét nghiệm phân tử. Điều này có thể dẫn đến việc bệnh nhân phải điều trị bằng hóa trị hoặc liệu pháp miễn dịch thay vì liệu pháp nhắm mục tiêu.

Công ty đang đầu tư vào các sáng kiến xét nghiệm, cảnh báo phòng xét nghiệm, tiếp cận bác sĩ, hợp tác mạng lưới và tương tác với chuyên gia y tế được hỗ trợ bởi AI. Ban quản lý cho biết các cơ sở thực hành ung thư cộng đồng thường có tỷ lệ xét nghiệm thấp hơn và tỷ lệ sử dụng hóa trị hoặc liệu pháp miễn dịch cao hơn so với các trung tâm viện - trường.

Việc ra mắt IBTROZI tại Trung Quốc và Nhật Bản đang tiến triển vượt kỳ vọng của ban quản lý. Công ty cho rằng một phần của kết quả này là nhờ tỷ lệ xét nghiệm phân tử cao hơn ở các thị trường đó.

Mở rộng phát triển Safusidenib

FDA đã cấp chỉ định thủ tục nhanh (Fast Track) cho safusidenib trong điều trị u tế bào thần kinh đệm đột biến IDH1 vào tháng 8 năm 2026.

Trong nghiên cứu Giai đoạn II J201, 27 bệnh nhân mắc u tế bào thần kinh đệm đột biến IDH1 độ 2 chưa từng qua hóa trị và xạ trị đã đạt tỷ lệ ORR được đánh giá tập trung là 52% sau thời gian theo dõi trung vị 39 tháng. PFS trung vị vẫn chưa đạt được, tỷ lệ PFS 36 tháng là 79% và không có tín hiệu an toàn mới nào xuất hiện khi theo dõi dài hơn.

Kế hoạch phát triển mở rộng của Nuvation Bio bao gồm bốn nghiên cứu bao phủ các độ và nhóm nguy cơ khác nhau. Hai nghiên cứu—một nghiên cứu ở u tế bào thần kinh đệm ít nhánh độ 3 và một nghiên cứu khác ở bệnh nhân tiến triển sau khi dùng vorasidenib—sử dụng ORR làm tiêu chí đánh giá chính và có thể bắt đầu tạo ra dữ liệu đáp ứng vào năm 2027. Tốc độ phát triển khối u là tiêu chí đánh giá phụ trong cả hai nghiên cứu.

Hai nghiên cứu ngẫu nhiên chốt chặn khác, bao gồm SYGMA và một nghiên cứu về u tế bào thần kinh đệm đột biến IDH1 độ 2, sử dụng PFS làm tiêu chí đánh giá chính. Ban quản lý cho biết các nghiên cứu này dự kiến sẽ không đưa ra dữ liệu cho đến khoảng năm 2029 hoặc muộn hơn.

Cập nhật về nền tảng DDC vẫn đúng tiến độ

Nuvation Bio vẫn đúng tiến độ để cung cấp bản cập nhật về nền tảng phức hợp thuốc-thuốc (DDC) vào cuối năm 2026. Bản cập nhật dự kiến sẽ phác thảo kế hoạch phát triển của chương trình và lộ trình tiến vào thử nghiệm lâm sàng.

Triển vọng từ ban quản lý

Ban quản lý dự kiến sự tăng trưởng của IBTROZI sẽ tiếp tục, đồng thời cảnh báo rằng số bệnh nhân mới bắt đầu điều trị hàng quý có thể biến động trong thị trường ROS1 cực kỳ hiếm gặp.

Công ty không kỳ vọng có sự thay đổi đáng kể nào trong mô hình chi tiêu tổng thể trong phần còn lại của năm 2026. Chi phí R&D cao hơn cho safusidenib dự kiến sẽ được bù đắp theo thời gian bằng việc giảm dần chi tiêu cho chương trình TRUST.

Nuvation Bio kỳ vọng khả năng nhận được phê duyệt tại Châu Âu cho IBTROZI trong nửa đầu năm 2027. Nếu đạt được, phê duyệt này sẽ kích hoạt khoản thanh toán cột mốc khoảng 30 triệu USD từ đối tác của công ty.

Ban quản lý mô tả IBTROZI là một chương trình thương mại tự trang trải trên cơ sở tỷ lệ vận hành hàng quý độc lập, với doanh thu sản phẩm bù đắp cho các chi phí liên quan đến việc ra mắt. Trên quy mô toàn công ty, Nuvation Bio vẫn chưa đạt được lợi nhuận, nhưng ban quản lý tin rằng nguồn vốn hiện tại đủ để tài trợ cho kế hoạch hoạt động hiện tại cho đến thời điểm đó.

Rủi ro và các điểm cần theo dõi

• Thị trường ung thư phổi dương tính với ROS1 cực kỳ hiếm gặp, tạo ra sự biến động lớn giữa các quý trong việc chẩn đoán và bắt đầu điều trị.
• Tổng số bệnh nhân mới bắt đầu điều trị bằng ROS1 TKI đã giảm khoảng 15% trong quý 3, trong khi các cảnh báo xét nghiệm phòng thí nghiệm giảm khoảng 25%. Ban quản lý cho biết cần thêm vài quý nữa để xác định liệu quy mô thị trường có bình thường hóa hay không.
• Sự tăng trưởng của IBTROZI trong tương lai sẽ ngày càng phụ thuộc vào việc áp dụng ở phác đồ bước 1 khi nguồn bệnh nhân chuyển đổi ở các bước sau sụt giảm.
• Khoảng trống trong xét nghiệm phân tử và việc bắt đầu điều trị trước khi có kết quả xét nghiệm có thể hạn chế việc sử dụng các liệu pháp nhắm mục tiêu ROS1, đặc biệt là tại các cơ sở điều trị cộng đồng.
• Cạnh tranh trong liệu pháp nhắm mục tiêu ROS1 tiếp tục biến chuyển. Ban quản lý cho biết các đối thủ mới gia nhập gần đây chưa ảnh hưởng đáng kể đến thị phần bệnh nhân đang điều trị tổng thể của IBTROZI, nhưng cũng thừa nhận rằng không có vị thế thị phần nào được coi là vĩnh viễn.
• Tốc độ phát triển khối u hiện không phải là tiêu chí đăng ký được FDA chấp thuận. Do đó, Nuvation Bio tiếp tục xem tỷ lệ đáp ứng khách quan là tiêu chí chính trong các nghiên cứu safusidenib cho kết quả nhanh hơn.

Điểm nhấn phiên Hỏi & Đáp với các chuyên gia phân tích

Các chuyên gia phân tích tập trung vào tính bền vững trong tăng trưởng của IBTROZI, thị trường ROS1 suy yếu theo quý, sự biệt hóa cạnh tranh và thời điểm công bố dữ liệu safusidenib.

Ban quản lý cho biết sự sụt giảm số ca bắt đầu điều trị ROS1 tổng thể trong quý 3 có vẻ phù hợp với biến động bình thường thay vì sự thay đổi về tỷ lệ mắc bệnh hoặc vị thế cạnh tranh của IBTROZI. Công ty kỳ vọng thị trường sẽ bình thường hóa theo thời gian nhưng không đưa ra dự báo doanh thu hàng quý chính xác.

Về mặt cạnh tranh, ban quản lý nhấn mạnh ORR 90%, thời gian đáp ứng trung vị 50 tháng và hồ sơ khả năng dung nạp của IBTROZI. Công ty cũng cho biết việc đón nhận đối thủ cạnh tranh gần đây chủ yếu tập trung ở các bước điều trị sau, không ghi nhận trường hợp sử dụng ngoài nhãn (off-label) ở những bệnh nhân chưa từng điều trị bằng TKI.

Đối với safusidenib, ban quản lý kỳ vọng các nghiên cứu u tế bào thần kinh đệm ít nhánh độ 3 và sau điều trị bằng vorasidenib sẽ bắt đầu thu được các quan sát về mức độ đáp ứng trong năm 2027. Ít nhất 20 bệnh nhân dự kiến sẽ tham gia nghiên cứu độ 3 trong năm 2026, có khả năng cung cấp dữ liệu theo dõi từ 6 đến 9 tháng vào tháng 6 năm 2027. Ban quản lý lưu ý rằng sự đáp ứng thường xuất hiện sau 6 đến 12 tháng điều trị.

Công ty dự kiến việc ra mắt thuốc điều trị u tế bào thần kinh đệm trong tương lai sẽ chỉ đòi hỏi sự mở rộng hạn chế về bộ máy thương mại. Cơ sở hạ tầng thương mại, vận hành và tiếp cận thị trường hiện có có thể được tận dụng, mặc dù có thể cần thêm trình dược viên vì các trung tâm kê đơn khác với các trung tâm điều trị ung thư phổi dương tính với ROS1.

Toàn văn Biên bản cuộc họp Báo cáo kết quả kinh doanh

Toàn văn cuộc gọi công bố kết quả kinh doanh

Phần trình bày của ban lãnh đạo

Operator

Hello, and welcome to Nuvation Bio's Third Quarter 2026 Financial Results and Business Update Call. Today's call is being recorded, and a replay will be available on the company's website. [Operator Instructions]. Now I'd like to turn the call over to J. R. DeVita, Vice President of Corporate Development and Investor Relations at Nuvation Bio. Please go ahead.

Robert DeVita

Thank you, and good afternoon, everyone. Earlier today, we issued a press release summarizing our financial results for the quarter ending September 30, 2026, and provided a business update. The press release is available on the Investors section of our website at nuvationbio.com. Today's call includes forward-looking statements including statements about the therapeutic and commercial potential of [indiscernible] and savusitinib; our development plans for taletrectinib, satusitinib and our drug-drug conjugate platform, along with our plans for future updates from these programs. The components of our anticipated product revenue, our expected milestone payments and spending patterns and our cash runway and profitability potential. Because such statements deal with future events and are subject to many risks and uncertainties, actual results may differ materially from those in the forward-looking statements.

For a full discussion of these risks and uncertainties, please review our quarterly report on Form 10-Q, which we filed with the U.S. Securities and Exchange Commission today. Joining me on today's call are our Founder, President and Chief Executive Officer; Dr. David Hung, our Chief Commercial Officer, Colleen Sjogren, and our Chief Financial Officer, Philippe Sauvage. Now I'll turn the call over to Dr. David Hung. David, please go ahead.

David Hung

Thanks, J.R. Good afternoon, everyone, and thank you all for joining us. Today, I'm pleased to discuss the progress we made across our business in the third quarter. We generated $45 million in overall revenue driven by another quarter of strong pros growth. Net U.S. and IBTROZI product revenue was $27.5 million, which represented 18% growth from the last quarter. Approximately 160 new patients started treatment with IBTROZI, about 65% of which were in the first-line setting. The commercial signals that matter most to our long-term thesis remains encouraging. 15 months into our U.S. launch, we continue to both build a growing base of patients on therapy and strengthen our position in the Rosslyn market.

IBTROZI has reached an all-time high in its share of active patients receiving a ROS1 TKI and continues to lead in first-line new patient starts with greater than 60% market share as of the end of the quarter. Our revenue growth reflects an expanding active treatment base driven by an increasing proportion of first-line patients that we believe can stay on therapy for yearsas seen in our trust clinical speeds. IQVIA claims data for the third quarter demonstrated a 15% decline in total new patient starts across the ROS1 TKI market. This is further evidenced by a lower volume of ROS1 positive testing alerts from our laboratory data partners.

We believe these observations suggest that at least part of the softness in our first-line new patient starts is a reflection of the overall flow of newly identified and treated patients rather than a loss of gross competitive position. Despite the market dynamics described. As of the end of the quarter, we maintained our strong position as the leading ROS1 TKI in total active patients across all lines of therapy combined. ROS-positive lung cancer is an ultra-rare disease, and the number of new patients entering treatment can fluctuate from quarter-to-quarter.

We do not believe 1 quarter provides sufficient data to establish an identifiable demand trend nor draw clear conclusions. We are monitoring market activity and treatment patterns closely while maintaining our focus on the drivers we can influence identifying patients earlier, educating physicians about appropriate testing, supporting biomarker informed treatment decisions and an increasing appropriate use of targeted therapy. We also are encouraged by how IBTROZI's lodge compares with historical targeted lung cancer launches, particularly given the small ROS1 population and fragmented prescriber base. While we realize comparisons are nuanced due to differences in size of patient populations, cost of therapy and initially approved lines of therapy.

We believe this is helpful to put IBTROZI's launch in context. For example, [indiscernible] into the launches of Lebrina and Asensa for ALK-positive lung cancer. U.S. net revenues per SEC filings and financial reports were $25 million and $36 million, respectively. As you know, IBTROZI has already reached similar levels of sales in a more competitive market despite rosin incidents being approximately half that of ALK. It is key to remember that the ALK-positive lung cancer market was not developed overnight, it took time for testing patterns, positioning confidence durability on treatment and long-term data to align behind the agents that ultimately became market leaders today.

Most fundamentally, our confidence begins with the clinical profile. In TKI-naive patients in Trust 1, IBTROZI demonstrated a 90% objective response rate, or ORR, 50 months of median duration of response, or DOR, and 50 months of median progression-free survival, or PFS, is tolerability profile, including the unique absence of the CNS warning and precaution in the label, is another critical point of differentiation among brain-penetrant ROS1 PKIs. And remember, these metrics are supported by a median patient follow-up of 51 months in the TRUST 1 study. We believe these attributes can support physician confidence, sustained first-line adoption and meaningful time on therapy. This clinical profile is also one of the reasons we chose to develop a toy in the adjuvant setting. While we're encouraged that enrollment is fully on track in this first of its kind study for ROS1.

If approved, this indicates you could expand the patient population IBTROZI is able to address and the data from [indiscernible] study in RET-positive non-small cell lung cancer has given us even more confidence that we could reach a meaningful result in Ross on sooner than we initially thought. Taken together, the results reinforce our view that we are building a durable commercial franchise and that those has become the standard of care in ROS1-positive lung cancer. Quarterly new patient activity will not always move in a straight line, but our competitive positioning, growing active patient base and ability to reach more eligible patients provide a strong foundation for the years ahead. Moving to south lucitanib.

We remain very excited about this program and its potential to become a key value driver for innovation bile as we move to 2027 and beyond. In August, the FDA granted fast track designation to sacrusitinib for the treatment of IDH1 mutant glioma. We view this as supportive external validation of both the unmet need in this disease and the potential development path for sapucitinib. Fast Track designation is intended to facilitate development and expedite review of therapies that may address serious conditions with unmet medical need and we are pleased to have this designation as we continue to advance the program.

As a reminder, in July, we announced updated long-term results from the Phase II J201 study in 27 patients with chemotherapy and radiotherapy naive, grade 2 IDH1 mutant glioma. With a median follow-up of 39 months, the centrally assessed ORR increased to 52% from 44% at 28 months of median follow-up, median PFS had not yet been reached and the 36-month PFS rate was 79%. Responses in the study have continued to deepen and no new safety signals were observed with additional follow-up. We will present more detailed data beyond these top line results at the Society for Neuro-Oncology Annual Meeting next week. As a result of this encouraging data set, we recently announced an enhanced development plan that allows us to address two key goals.

First, our four studies together address all grades and risk groups within the broad IDH1 mutant glioma landscape. Second, two of these studies focus on patient groups with high unmet needs and no alternative treatment options and evaluate ORR as a primary endpoint, which will allow us to generate data quickly. In fact, these two studies in patients with Grade III oligodendroglioma and in patients who have progressed following treatment with vorasitinib also analyzed tumor growth rate or GR, as a secondary endpoint, which may provide an even earlier signal of efficacy. This is a key difference from our other two pivotal randomized studies, which evaluate PFS as a primary endpoint and will not generate data until 2029 or later.

As a reminder, these pivotal studies include SYGMA, which is evaluating [indiscernible] in patients with high-grade and high-risk astrocytoma and a separate study in patients with Grade 2 IDH1 mutant glioma. Enrollment in the SYGMA study, including the exploratory cohort is on track and we expect to be enrolling patients in all 4 studies in the coming months. We plan to provide more specific updates on enrollment and clarity around timing of data readouts next year. Finally, we also remain on track to provide an update on our drug conjugate, or DDC platform by the end of the year. This update will include additional detail on how we plan to move the program forward and into the clinic. We are excited by the progress of this program and look forward to sharing more information soon.

Overall, the third quarter reinforced the long-term opportunity in front of us. IMROZ is now a commercial leader with a growing active patient base that is driven by an increasing number of new first-line patients and their long duration of treatment. Saflucitinib continues to advance as a meaningful second franchise with potential data next year, and our DTC platform can contribute to future pipeline growth. With that, I'll turn the call over to Colleen to provide a more detailed update on IBTROZI commercial launch.

Colleen Sjogren

Thank you, David, and good afternoon, everyone. IBTROZI continues to strengthen its leadership in the ROS1 market with a launch trajectory that stands out against historical benchmarks. Just 5 months after launch, we have achieved approximately twice the cumulative patient starts of earlier generation ROS1 TKI launches at comparable points in their commercialization based on our internal data and adjusted claims estimates. This is particularly meaningful in an ultra-rare disease with a broad and fragmented prescriber base.

We believe this performance is a testament to both ptosis differentiated clinical profile and the strength of an experienced commercial team that knows how to successfully launch targeted oncology therapies. In the third quarter, U.S. net product revenue grew 18% sequentially to approximately $27.5 million despite an observed decline of about 15% in new patient starts across the overall ROS1 TKI market. This quarterly decline was observed in 2 distinct data sets. IQVIA data and the number of ROS1 NGS testing alerts from our contracted lab partners. This is the kind of fluctuation sometimes observed in ultrarare disease, and we do not believe is indicative of any trend.

In fact, it builds confidence that we continue to grow our active patient base and our sales in a down market. This growth was broad-based across treatment settings, reflecting deepening physician confidence, expanding adoption and sustained demand for those -- our commercial execution continues to translate into significant market leadership. And this quarter, we achieved an important milestone. If Toz is now the leading ROS1 TKI in total active patients across all lines of therapy combined, this based on IQVIA claims data. This is not simply a measure of new patient starts. It represents our share of all patients actively receiving a ROS1 TKI including those who have initiated therapy years ago on earlier generations of ROS1 TKIs.

Having achieved this leadership position just over a year post approval in a market with established therapies is particularly significant and reinforces both the strength of IBTROZI clinical profile and the success of our commercial execution. We are also continuing to strengthen our first-line position. We established IBTROZI as the market leader in total active first-line patients through the end of the quarter and today, our share of first-line new patient starts is more than 60%. As David discussed, IBTROZI's compelling efficacy, exceptional durability and generally favorable tolerability profile continue to differentiate it in the first-line setting.

Based on multiple advisory board meetings and one-on-one engagements, physicians continue to point to the strength of our clinical data supporting our belief that IBTROZI's durability is a benchmark against which other ROS1 therapies will be measured, especially given our mature patient follow-up. While our trust clinical studies were much longer than NETosis time in the market, to date, we have observed a clear similarity between duration of therapy in the real world and durability in our clinical trials. This is further evidence of why we believe IBTROZI can benefit patients for years. As the launch continues to mature, we are seeing a natural evolution in the ROS1 patient population. At launch, there was a pool of patients receiving earlier generation ROS1 inhibitors who were candidates to switch therapies due to disease progression or tolerability.

We have successfully captured many of these patients. As a result, the pool of patients immediately available to switch has become smaller and future growth will increasingly be driven by newly diagnosed patients. We believe this dynamic, combined with our entrenched commercial leadership provides a strong foundation for sustained long-term growth. And while new treatment options are entering the market, our leadership remains strong as intros continues to be the only brain-penetrant treatment option without a CNS warning and precaution in its label. To date, we have not observed a material impact on IBTROZI's overall active patient share with recent market entrants, and our data suggests that early uptake of a new competitor is largely concentrated in later lines of therapy with no off-label use in TKI-naive patients.

Beyond our growing market leadership, we are also encouraged by the opportunity to expand the overall ROS1 TKI market. Claims data show that the number of patients actively receiving a ROS1 TKI increased materially year-over-year following IBTROZI's launch, even with the market pullback this past quarter. We believe this growth demonstrates the potential to expand the population of receiving a ROS1/TKI. And we see an even more substantial opportunity ahead through earlier identification of ROS1 fusions and increased adoption of targeted therapies in place of chemotherapy with or without immunotherapy.

However, we see two key barriers remaining along the testing to treatment journey. First, limited awareness that DNA-based testing alone may miss ROS1 fusions. And second, the urgency to initiate treatment before molecular testing results are available. potentially leading patients to receive chemotherapy or immunotherapy instead of a targeted therapy. We have focused commercial initiatives underway to help drive the shift in testing and treatment decision behavior, which we believe are key sources of long-term growth for TRUs. For example, through our quality-based initiatives, we are addressing critical gaps in patient care from significantly improving NGS testing rates at key community oncology practices to ensuring patients receive optimal care with appropriate targeted therapies.

We are also assessing testing lab alert data to prioritize relevant physician outreach and advancing network collaborations to strengthen molecular testing and treatment decisions. Additionally, we are also investing in field training, coordinated omnichannel marketing and AI-enabled approaches to make HCP engagements more targeted and timely. We know this may take time, but patients deserve it. And our focus is always on increasing the rate of diagnosis and displacing inadequate treatment options. At the institutional level, we continue to strengthen access and pathway positioning. For example, one major community pathway recently reinforced the position of IBTROZI as its primary first and second-line ROS1 TKI treatment choice, along with focused contracting initiatives and tailored strategies across academic centers, IDNs and community practices, this reduces practical barriers to access.

These efforts require close appropriate coordination among sales, market access, marketing and medical and I'm incredibly proud of how our experienced teams are executing cross-functionally. What gives me confidence in the long-term success of IBTROZI is the combination of strong clinical differentiation, an established and growing market position and a commercial team that understands both the opportunities and the work required to capture them. We have built a strong foundation over the first 15 months and we remain focused on translating that leadership into sustainable long-term growth and bringing the potential benefits of Aptos to more appropriate patients.

With that, I'm going to turn the call over to Philippe.

Philippe Sauvage

Thanks, Colleen, and good afternoon, everyone. For detailed third quarter 2026 financial results, please refer to our earnings press release, which is available on our website. I will highlight a few key points from the quarter. For the third quarter of 2026, total revenue was $45 million, including $27.5 million in IPTV net U.S. product revenue and $17.5 million in collaboration and license revenue. For the first 9 months of 2026, we generated $159.9 million in total revenue. This included $69.2 million pros net U.S. product revenue and $90.7 million in collaboration and license revenue. The commercial dynamics David and Colleen discussed are consistent with our view of how this market would and will develop as behaviors change.

The later line pretreated ROS1 population represented an important but finite opportunity early in the launch. The long-term growth driver now becomes first-line adoption and the accumulation of patients who can remain on therapy for multiple years. David mentioned the trajectory of precedent launches in the ALK-positive lung cancer space. These precedents tell us a few things. First and foremost, that it throws these launches in line with prior rail lung oncology launches on a population-adjusted basis. but also that it takes time for the first-line patients on therapy to build a durable revenue base. This is why we continue to be excited by ptosis potential.

Our access strategy continues to be effective. Gross to net deductions were approximately 30% in the third quarter. We expect gross to net to remain generally stable as our payer mix and contracting mature. The remainder of our revenue was generated through collaboration and license agreements. We continue to receive royalty revenue from open biologics in China and [ Nippon Keeco ] in Japan. So China and Japan launches are progressing ahead of our expectations, and we continue to view our ex U.S. partnerships as a scoring component of the broader to the opportunity. In fact, $7.7 million of our total revenue for the quarter was driven by milestone and royalty payments from these partnerships. RECONNECT We are also working closely with ASI for Europe and other select territories. We expect potential approval in Europe in the first half of next year, which will trigger an approximately $30 million milestone payments to evasion buyer.

On the expense side, we continue to invest in the business and our programs, resulting in total operating expenses of $75.2 million for the quarter. R&D expenses were $32.7 million for the quarter and $98.4 million for the first 9 months of 2026, primarily reflecting investments in the trust and satellite clinical development programs as well as preparation for future development activities. SG&A expenses were $42.6 million for the quarter and $123.5 million for the first 9 months of 2026, primarily driven by support for the commercialization of IBTROZI. While we always expect small quarter-on-quarter fluctuations in our spend, we do not expect material changes to our general spending patterns for the remainder of the year as the rise of R&D spend on saprucidanib is compensated by gradual reduction of the [indiscernible] trust program over time.

It is also exciting to highlight that for the first time, Its is now in the quarterly revenue run rate related to launch-related expenses that represents a self-sustaining commercial program on a stand-alone basis. Our goal has always been for IBTROZI to be a driver of future profitability and we view this as a first step on the journey of IBTROZI being able to finance all of our spending activity.

Turning to the balance sheet. We had cash, cash equivalents and marketable securities of $663.4 million as of September 30, 2026, which now includes all proceeds from our convertible debt offering this summer. This solid cash position gives us the confidence to continue investing in our future, driven by our pipeline of exciting assets. Importantly, our approach to capital allocation has not changed. We remain disciplined, we will continue investing the IBTROZI, advancing [indiscernible] and progressing our DDC platform for a position of strength. We also continue to evaluate business development opportunities only where we see the potential to generate compelling returns and create long-term shareholder value. Based on our internal revenue projection and the current operating plan for all of our programs, we continue to believe we have solution capital to reach profitability. I'll now turn it back to David for closing remarks.

David Hung

Thanks, Philippe. This quarter really enforces what we are building at Innovation Bio, a commercial program with the potential to redefine the treatment of advanced ROS1-positive lung cancer A second program that continues to gain momentum in IDH1 and glioma and a pipeline platform that we believe can support future growth. We recognize that changing treatment behavior in target oncology takes time. But we are confident in the fundamentals. IBTROZI has a differentiated label, a growing active patient base and the durability and tolerability profile, we believe are necessary to support long-term adoption.

At the same time, safucitinib is advancing through a comprehensive development plan in an area of significant unmet need. I am proud of the progress our team continues to make and grateful to our employees, investigators, partners and shareholders and to the patients and families who place their trust in us. I'll now ask the operator to open the line for questions.

Operator

[Operator Instructions]. Your first question comes from the line of Farzin Haque with Jefferies. Please go ahead.

Phần hỏi đáp

Farzin Haque

First on Glioma, are you providing any color on the enrollment for the 2 cohorts, the [indiscernible] the post [indiscernible] patients? And when we could potentially get the ORR readout in 2027?

David Hung

We haven't yet provided color on that, but we will probably be doing that in the future time.

Farzin Haque

Got it. And then on IBTROZI, the October sales are looking in line with prior months. But with the new patient starts holding up and the first-line patient base is accumulating, how should we think about the 4Q revenues despite the broader ROS1 market decline that you're seeing? Is 108 million consensus the right area to think about for the year?

David Hung

Yes. I think there's lumpiness in this last quarter. So I think that we don't really look at that as a trend of any store. So we anticipate growth continuing around the same work as we've seen in the past.

Operator

Your next question comes from the line of Gregory Renza with Truist Securities. Please go ahead.

Unknown Analyst

It's Anish on for Greg. Congrats on the progress this quarter. We wanted to know within the first-line opportunity, how are you seeing IBTROZI compete with repotrectinib what is driving physician choice? And is the bigger remaining opportunity taking share from other TKIs or earlier ROS 1 testing and conversion from chemo/IO?

David Hung

Okay. Well, that's a lot of questions. But I think we're doing very well against repo. As you know, we are not only a market leader, but we are also -- in the first year of our loss, we've sold twice as much drug as all the ROS1 agents combined. So we've done extremely well against our competitors. We think the market is going to grow by a couple of ways. Number one, we do believe that we will take share from other TKIs given. If you look at our efficacy, which is not -- has not been matched our safety profile, has been mentioned, we are the only on TKI that penetrates the brain that does not have a CMS aware of precaution.

So that's unique. So we think we will continue to pick markets but from other TKIs, but we also do think that we will grow the market because good drugs grow markets. And we saw that happening with ALK. We saw that with GFR and we think that's going to happen in ROS1. We do anticipate increasing testing for ROS1, but we also anticipate other changes in practice that are now supported by NCCN guidelines, namely reduction of IO/chemo use and using a precision RAS1TKI for precision patient like RAS1. So we do think that, that will continue to grow the market. Colleen?

Colleen Sjogren

Yes. I want to add on to that, too. Thanks for the question. It's a good one. So when you look at IBTROZI right now, what is really remarkable looking at the team's achievement truly right now has the largest number of patients actively received in a ROS1 TKI. Now that's across all lines of therapy combined. And to your question, that's including patients who started in prior periods on therapies available for years. So this is distinct just from being #1 in new star. So reaching this position in just 15 months after launch, that reflects both new patient adoption and patients continue in treatment. So we think that's really important.

And I'd like to just address quickly what you said about testing. We see this as one of the most meaningful opportunities. So when we look at the two care gaps that matter most, we're looking at this idea that DNA-only testing can definitely miss some of these ROS1 fusions. And then the other part of it is these treatment decisions beginning sometimes before molecular testing results are even back and available. So we're hyper focused on improving comprehensive testing, and that's including appropriate RNA-based methods. We're also very focused on helping practices incorporate molecular results into their treatment decisions. So these changes do take time. We know that. This team has been an ultra-rare disease before but they definitely can improve care and expand the appropriate targeted treatment for these patients.

David Hung

And I want to add one more comment to Colleen's comments. So if you look at the duration of response in the [indiscernible], it's 50 months. That's like repo track them, their DOR around 36 months. So that's a pretty significant difference. And how long pages will be on therapy. That contributes to more patients being on therapy. But on top of that, I mentioned that we are the only as on TKM without a CNS warnings precautions. As you look at our median-time of follow-up with the cross data so far, it's 51 months. We're not talking about 14 months of follow we've had well over 4 years of follow-up, and you know that adverse events accumulate with time.

In spite of a 15 1-month follow-up, we have right now, no CDS works the cost in our label. We have a very, very low incidence of adverse events, we think that, that, combined with the efficacy leads to a growing pool of patients on therapy, which will contribute to the revenue stacking that we've talked about from day 1. So we do think that a number of patients [indiscernible] will continue to grow, especially because of our long duration of response and are really excellent tolerability.

Operator

Your next question comes from the line [indiscernible].

Unknown Analyst

Great. Congrats on the quarter I had a couple of questions. One for IBTROZI. Maybe it would be helpful to walk through in the U.S., the nuances between the community and the academic setting, other any differences there? And then as your partners prepare for a launch in China and in Japan, in that market, are there anything that then you would call out as differences that may help the launch and adoption? I'm just trying to think of the comparison to the U.S. And then I have a follow-up on [indiscernible].

David Hung

Sure. So in the community, we do see lower rates of testing than in many academic centers. So I think that will improve over time. But I would say that community is still not getting as much testing done as a emissions are. On top of that, we do think that there is probably more I/O chemo use in the community setting than there is in academia. So I think those are two of the most important differences. When we look at China and Japan, those launches have actually exceeded our expectations. And part of that's because testing is actually remarkably high in China and Japan. And in China, you get the trouble for not ordering NGS on lung cancer patient in 2026. I wish I could say that for the U.S., that's not the case. But I would say that the testing rates in China and Japan are excellent and probably contribute to the reason that those launch have actually exceeded our expectations.

Unknown Analyst

Okay. And then just on SAP with the expansion of the SYGMA study. Maybe just talk a little bit about what that means for the standard of care across the different European countries? I'm just trying to think of variations in the standard of care among the different new European countries and what that could do to some of your comps or maybe enrollment kind of time lines?

David Hung

Yes. I don't think it's going to really change in one of the countries. The things that all the patients have to have failed to get on to SYGMA study are all pretty standard I don't think that's going to continue to do any real variation. I think that this is a pretty uniform patient population we anticipated being pretty standard across all the countries. We are trying to find countries where there are different standards of care in which LoRa is not available to do a study against placebo because that's not possible in countries that do have more. But I would say for the sign signal countries, the standards of care are pretty standardized across all of them, and we don't anticipate any real problems from a clinical trial standpoint.

Operator

Your next question comes from the line of Li Watsek with Cantor Fitzgerald.

Li Wang Watsek

Maybe just on SAS readout, what should the endpoints could we potentially get in 2027? And what would be impressive outcomes either [indiscernible] for settings? And then on those just wondering what the reason might be behind the sequential decline of the new patient starts for the overall market?

David Hung

Okay. Let me answer your first question first. So with regard to [indiscernible] readout, we've previously said that we expect at least 20 patients to be enrolled this year in the grade 3 [indiscernible] on the study. So that means by June of 2027, we will have somewhere between 6- and 9-month follow-up on at least those 20 patients or more be enrolled more than that. So in general, if you look at how long it takes to get a response on saclasitinib, we would say those responses, we see are generally in the range of 6 -- between 6 months and 12 months. So we would expect a number of those patients to have objective responses. We are also initiating these postmorocitinib study.

This study is different because there are a lot of patients now who have been put on [indiscernible] in the thousands. And we know from the [indiscernible] that about 1/4 of them progress on [indiscernible] within about a year. So given the fact that [indiscernible] is now pushing almost 2 years since launch, we would expect there to be well over 1,000 patients that would be available that will be progressing on IBTROZI, and we believe that it will be very easy to identify patients progressing on [indiscernible] because or progressing clearly the opportunity to see responses there is even greater.

We believe that the [ BARDA beat ] is in the range of 20%. We know from Chimerix, as an example, their approval was based on 50 patients in their trial with 11 responses, about a 22% response rate. We know that other glioma trials have been in the range of about 70, 75 patients or so. So we think that's somewhere in the neighborhood of 50 patients at a 20% response rate gives you a data set that would be pretty compelling to FDA in an unmet need and certainly grade 3 [indiscernible] 2 indications where there is absolutely nothing available to these patients. So we think that's a wide-open opportunity.

Colleen Sjogren

You want me to take the -- Li, so your second question on Atos and the slowdown. So a couple of things. In my experience and the team's experience, this is really the volatility that you expect in an ultra-rare market, even when we look across the other TKIs in the lung space, you saw a sharp decline in EGFR and ALK Q1 and then it bounces back. We can never attribute sort of a slowdown to one single cause but the evidence that we do see here points in one direction. So the IQVIA data shows lower overall market status. We talked about that 15% pullback that we see -- and that aligns naturally with what we saw in our lab partner alerts move the same way. So approximately a 25% decline there.

So the good news in a market that's pulling back, it true you still maintain more than 60% share of first-line new patient starts. So while reaching, by the way, the leading position in total active ROS1 TKI patients, so this is very consistent with the smaller market flow than a broad deterioration in our competitive position. So additional quarters will show. And we expect that, that will show that the market volume will also normalize.

David Hung

And Li, just because we've heard some confusion over our clinical trials and what endpoints are being used and when the readouts. Well, let me just reiterate that for everyone. So there's core to -- the SYGMA study is a PFS readout. That's going to be long. That's going to read out in 2029 or so. And against vorisitinib, that's going to also be a PFS readout. However, two of our studies are response rate studies. The grade 3 [indiscernible] is a response rate study, which we believe we will have data on starting probably mid next year. and the post baricitinib study is a response-based study, which we will also start to have responses to 2027. So we would expect that.

So while we cannot tell you exactly when the response will occur we feel very confident given our data that we will see responses that we think that [indiscernible] selling will be the beginning of a number of response that will observe hopeful borrowing pacing for those indications.

Operator

Your next question comes from the line of Leon Timashev with RBC Capital Markets. Please go ahead.

Unknown Analyst

This is Vander on for Leo. So I know you touched on a little bit a bit of this already. But I guess when looking at the post more setting, are there any precedents or comps that you can point to that would be helpful when we think about reusing a mechanism while moving down in treatment line kind of how we can think about framing responses there. SP1 As the question why we believe that we will have responses in the [indiscernible]?

David Hung

Okay. I mean, first of all, if you look at our response rate, it's significantly higher than [indiscernible] more than double [indiscernible] response rate. So clearly, we are -- we have -- we just have low responses. But number two, if you look at the kinds of patients we're treating we have responses in sicker, more advanced types of glioma than [indiscernible]. And it's always hard to treat the more advanced, the harder ones than the easier one. So given the fact that we have high-grade responses when [indiscernible] and given the fact that we had more than double the low-grade response to [indiscernible] and given the fact that there's always some overlap in the spectrum that we almost have between low and high grade, we would certainly expect to have responses in those more failures.

I don't think our data are pretty compelling in that regard. On top of that, we've made the point previously that our adverse events are different. Our Vora's primary adopts liver [indiscernible]. Ours are immune type reactions, things that we believe indicate increased immune activity things like [indiscernible] our slightest rash paramos. These are things that we believe are consistent with an immune mechanism. And if you look at our responses that we've seen so far in all of our studies, as I mentioned, it can take 6 to 12 months of the response, that sounds an awful long like immuno-oncology. If you look at our response we get them, they're really durable.

If you look at our GVM, that patient's tumor has been gone for 3.5 years, high grade, [indiscernible] gone for 3.5 years. Those are immune type reactors that we think completely differentiate us more. So just given our efficacy at we see so far and the kinds of adverse event we've seen and the durability of our responses, we would certainly anticipate that we will see response [indiscernible].

Operator

Your next question comes from the line of Priyanka Grover with JPMorgan. Please go ahead.

Unknown Analyst

So on the persistence trends on the front line, second line, what have you seen throughout the quarter? Basically, are discontinuation rates still tracking with what was shown in the clinical trials?

Colleen Sjogren

Priyanka, so when we look -- yes, so when we look at treatment-related adverse events in the first-line and second-line TKI naive, we are tracking very closely. So when you look at launch through September, our TRAEs are tracking very closely to what we saw in our trust trials. So that's been consistent since launch.

David Hung

And generally speaking [indiscernible], we have not seen anything different from what we've seen in the clinical trial in terms of patients staying on therapy, to time with cell therapy and all of these things. Not anything different so far. Obviously, the clinical trial, we had more than 50 months integration. Here, we've launched only 15 months. So we cannot say for the future, but it's clear that so far, we've seen tracking it exactly to the clinical trial track. So really no difference there. It is very reassuring to the long-term potential of that market, of course.

Colleen Sjogren

And one thing maybe I'll add on to that, Priyanka. So keep in mind that many of the patients who started early in our [indiscernible], they had received prior ROS1 therapies. So in progression, that more heavily pretreated population has been an important driver of where we saw those discontinuations. But to Philippe's point, you monitor discontinuations by not only line of therapy, but cause, so not just in aggregate, and our adverse event-related discontinuations have, in fact, remained low and consistent with the trials.

Operator

Your next question comes from the line of Yaron Werber with Cowen.

Unknown Analyst

This is Steven on for Yaron. One from us on [indiscernible]. Are we inferring correctly that you might expect the grade 3 oligodendromo study to be the faster readout versus the [indiscernible] and then maybe a follow-up on the tumor growth rate, how would FDA acceptance of that endpoint change the timing on the path to market? And could we potentially hear an update around the growth rate before the ORR data come out?

David Hung

SP1 So I don't know which really faster. I think that we feel pretty confident that the all of the study will only be positive because we've seen great responses there. I think post [indiscernible], we also, as I mentioned, we have so much higher -- more than double the objective response rate in [indiscernible] the low-grade setting and have significant high-grade response for [indiscernible]. So I just think the spectrum of activity is so different between stat and right. I feel bullish on that study as well. I can't tell you which will read out faster. I think that the Voro study should accrue faster because there's more patients, but we started accruing the Grade 3 [indiscernible] study months ago.

So that, again, will they really be different, I don't know. Tumor growth rate, we think it's a really important endpoint. Now it's not accepted yet by FDA, but I think it makes the point that you can't have a response where that's growing, you can't shrink without paging is slow and that's just a no-brainer. So when we change the tumor growth rate from positive to negative, it's hard to ignore. And we're going to assemble data to show how well that correlates with ultimate response. But we do think that when you change the tumor that's growing with a positive flow to one that has a negative flow.

Certainly, the patient is going to feel a lot better about that as this is doctor, and I would imagine so with the FDA. Now whether or not they'll accept it at this point, we have no idea, we're not assuming that. We're still assuming they'll take response rate, but we will present those data with our objective responses to form a package. I think will be important in the future because I think that is where the CO had because I do think that you can't get a response without a change in the tumor growth. And maybe another point to keep in mind. We're not talking enters that often. We're not talking about the blind study. So you can see response rate over time. And doesn't necessarily mean you have to wait for a certain time to read out that we would do for PFS.

This is response rate that we are monitoring over time. So as we accumulate patients in both of those studies, we will have a better view of the response rate, and we will know where the slope is taking us to David's point about the tumor port, which will give a lot of confidence to us that if the tape of that curve is spending we will eventually get to the kind of response we are hoping for, and that's really important to you.

Operator

Your next question comes from the line of Michael Yee with UBS. Please go ahead.

Matthew Hagood

This is Matt on for Mike. Congrats on a nice quarter. Could you talk maybe for the Grade 2 low-grade low-risk study? Do you expect the control arm of that study to perform similarly to the original RORO study? Are there anything in the patient population to think about that might not be the same? Any thoughts there would be great.

David Hung

I do think there would be [indiscernible] so we're not inventing any new wheels here. We're just trying to do a better drug to get the same deal to get better results. We expect the trial to be very similar.

Operator

Your next question comes from the line of Mayank Mamtani with B. Riley. Please go ahead.

Unknown Analyst

[indiscernible] on for Mayank. Congrats on the share gain this quarter. So you had a slide show in comparing [indiscernible], both of which grew about fold from your third quarter as first frontline patients accumulated. What can you confident that IBTROZI closely follows that same curve? And also on [indiscernible], for next week, what should we focus on for the 4 SLO posters? n

David Hung

Yes. So as we had mentioned, if you look at the sales in the first 5 quarters of [indiscernible] they are in the range of $26 million to $30-something million. And we're smack that in that range despite the fact that loss incidence is half about. So in spite of big half the incidents, we're still generating about the same amount of sales. So we think that's pretty good. And they still grew that market fivefold more beyond that. And we think that given our trajectory we should, we're comparing quite favorably to the out launches. So we think that we're actually doing pretty well.

Philippe Sauvage

And the other thing which is very reassuring that Colleen was mentioning earlier, right, is that this has been, to your point, a very steady and important growth over time, but not necessarily like every quarter higher on new patient to. Colleen was mentioning that earlier. If you look at the new patients starting out, was down 19% versus Q1. So you do see in that gray space some fluctuation. But despite those fluctuations, the trend is clearly up in that space and has been up for a very long time. Because of the extremely long duration of our response and the very high celebrity of rosy, we believe we're going to see exactly the same thing, which is a general trend going up and going up for a very long time. Even if you could have the fluctuation of new patients to one part of the net, those things happen.

David Hung

Let me make another point. So if you look at the DOR of at least we elected it's much, much shorter than our 5-month DOR and [indiscernible] didn't at the time, did not even know that the Crown data will ultimately give them a 7-year PFS. But if you look at our duration, you're not going to even see that per year. So we're only 15 months -- 15 months out. you're not even going to see the stacking from its for another full stacking for another 3-plus years, right? So the fact that we're already matching the launches at half the epidemiology incidents and we haven't even gotten to the stacking suggest to us that we're going to do really well.

Unknown Analyst

Got it. And for next week for the SNO posters, what should we focus on?

David Hung

SP1 We haven't -- you're going to see more data on gaps and durability of responses. We can't give you a lot more color than that, but you're going to see more detail on the depth and durability of the responses that we've presented before.

Operator

Your next question comes from the line of Robert Burns with H.C. Wainwright. Please go ahead.

Unknown Analyst

Two questions for me, if I may. So obviously, we saw updated data for -- from the ARRIS 1 trial at ESMO this year, and GSK is planning to file an sNDA in the coming months. or is it same in the frontline setting. So considering that as well as the launch dynamics that you're announcing within the frontline setting for TROI, I wanted to get your thoughts on the potential impact of zidezamtinib's potential approval in the frontline setting on IBTROZI future revenue potential in the front line.

And then switching over to Vora. Obviously, considering that fact that we're going to see -- we're going to see data from the Phase II trials in 2027, which could potentially support an FDA approval. I want to get your thoughts as to how you're thinking about the build out -- whether you'll have to build out your commercial team further to launch it in the CNS indications that you're pursuing in 2028.

David Hung

Let me take the first question, and I'll turn it to Cole for a second. So the bottom line is we have a 5-month DOR in the first-line setting. We have not seen anything from the date on what their duration of response will be in the first-line setting. So I would just say that it's going to be pretty hard to beat a 90% response rate in the 5-month DOR. As we've mentioned, except for [indiscernible]. There are no drugs in the industry of oncology that have been able to better a 15-month DOR at those. So I would say that we don't know how their label will look. When their second line label came out, it there were some surprises. Zagato had CNS worries in Pecos, which no one had expected. If you look at their adverse events, even now, 42% peripheral edema, something that's very noticeable to patients.

CNS warning precautions, shortness of breath, 4% grade 3 shortness of breath. These are things that I think are going to make it more challenging to continue using drug in the first line setting where you're -- if you want to get to a 15-month DOR, you're going to have to have a pretty tolerable drug with 1 month of follow-up, we've shown extremely tolerable profile for IBTROZI. But after only 14 months of follow-on presidential, as I mentioned, they already are up to 42% [indiscernible] and toxicity plus all the other things I've mentioned. So I think the data will come out when the data come out. And right now, we think that we are at the bottom beat, and I think it's going to be hard to match. Colleen, I'll let you turn.

Colleen Sjogren

Yes, sure. I'll add a little bit on to that. I mean, first of all, we expect competition to evolve. And I just want to reemphasize, when you look at the accomplishments of what my team has done across cross-functional marketing, market access, sales, medical affairs, when you look what they have accomplished in 15 months as of fourth entry into the ROS1 market. It's just remarkable. And what brings us a lot of confidence in the future is that KOLs so are our top thought leaders consistently cite our durability and our data maturity as key differentiators.

So as David said, with many describing are approximately 50 months median duration of response, supported then by our 51 months [indiscernible] follow-up. It just has created a benchmark for them. So combined with our favorable tolerability profile, this just reinforces physician confidence, and I would say particularly in the first-line setting. So we will continue competing what I believe is most important is on the totality of evidence and on our execution rather than assuming any market share is permanent. We are ready for competition, and we feel well positioned.

Philippe Sauvage

And Robert, to your structure point about launching in glioma Obviously, there are lots of things that we will not have to do. Like we could leverage fully our commercial organization as it is. The only difference is different calling points. So we potentially need to add some reps. But when you think about day 1 at about 17 reps. So it's not -- we're not talking about a huge team. Glioma created a certain number of centers, which is rather limited because obviously, it's spring cancer you don't treat that everywhere. So we are thinking about relatively limited commercial team that will be able to fully exploit all of the synergy we've had by being already a fully commercial organization when you think about net OpEx management, all that we have to support Salesforce today, all market access, et cetera. All of this will be leveraged. So it's an addition because different calling points, but a relatively small addition.

Operator

Your next question comes from the line of Silvan Tuerakcn with Citizens JMP. Please go ahead.

Silvan Tuerkcan

SP-25 This is Josh Harman on for Silvan Perkin. Congrats on the update today. Maybe just on the variability in the ROS1 diagnosis how consistent has that, I guess, 3,000 annual diagnoses been year-over-year? And is the variability is it year-to-year? Or is it more quarter-to-quarter, I guess? And then additionally, maybe could you speak to some of the relevant updates in glioma at ESMO?

David Hung

Okay. So let me be clear, we were never talking about any data suggests that the epidemiology is on. There is a large amount of literature in the support roughly 2% incidence of non-small so long cash being going positive. What we were talking about just that where you have a rare indication like Glass quarter-to-quarter, there could be lumpiness. The thing is going to change. We've seen this -- if you look at Elk scripts, they varied as much in just recently, I believe that 1 of the quarters recently was showed a 15% reduction in outstrip in the quarter. We've seen that in other orphan indications. So we don't believe that the overall epidemiology [indiscernible]. We just believe that from quarter-to-quarter, when you have a rare indication, you may see some lumpiness and you may have quarters are down quarters that are out there.

But overall, it will equilibrate to roughly 2% of all lung cancer. New patients properly identify can situate from 1 quarter to the next. And that's what happened, as we said in our [indiscernible] everywhere really. But the trend in the epitogystands, which, to your point, means that it's a quarter-to-quarter fluctuation, another year of change.

Yes. I don't think there's anything in [indiscernible] really changed. In fact, it really further highlights how special [indiscernible] is because there were actually no data for any agent that had on results that are compelling, in our opinion, this happens. So nothing that we can identify in the landscape. We do think that [indiscernible] is the most polishing drug being decaled and so we are excited about the program.

Philippe Sauvage

To add to that, another point we made in the past is that because we are going to develop safe market for voice now available, it's going to be very, very hard for anyone in the future to develop anything in IDH1 written glioma without comparing to an active comparator, which will be either us or rating at that time. So not only we've not seen very much the development going on in that space. But any future development in that space will be much more difficult because we'll have to compare to an active comparator, and we know it's much harder to do and much longer.

Operator

Your last question comes from the line of Boris Peaker with Jones Research.

Boris Peaker

Just two questions. On IBTROZI, could you comment on the gross to net adjustments this quarter and how that is trending? And the second question on the SYGMA trial. I'm just curious in post-chemo radiation, sometimes you see pseudoprogression, which could complicate the modified no assessment. So I'm just curious what steps are you or the centralized blinded independent committee taken to adjudicate for progression versus maybe treatment-related inflammation or pseudoprogression.

Philippe Sauvage

I will start with the GTN. So pretty much stable this quarter like it has been in past quarter. As I mentioned in previous calls, so next time you're going to see [indiscernible] I'm sorry, can you hear me? Yes. So next time, we're going to see an evolution of our GTN will be at the time of our next price increase because of inflation impact and things of that nature. But it's been very stable throughout the year. And we think we really stabilized around this 30% gross to net. That's where we are, and that we believe we're going to spend through the end of the year. And I'll let David comment on the second question.

David Hung

This study is being compared against placebo with a blind independent committee review. So I don't I think that there will be significant differences between the two populations, but the comparator is placebo. So I think that's the control. And I don't know how the comment on that. It's a controlled study. We think that's...

Boris Peaker

I'm just worried that even on a placebo, but the radiation itself could cost due to progression?

David Hung

Well, but there's both -- there should be in both arms, right? The difference will be the drug. And just given the results we've seen so far in our SAP studies, we think the drug will be a significant difference.

Operator

There are no further questions at this time. I will now turn the call back to David for closing remarks.

David Hung

Well, we want to thank you all for your support, and we look forward to updating you on our next call. Thanks so much.

Operator

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