Cuộc họp công bố kết quả kinh doanh Q3 2026 của CytomX (CTMX): Nghiên cứu Varseta-M dự kiến vào H1 2027

Điểm nhấn chính

• CytomX kết thúc quý 3/2026 với 348 triệu USD tiền mặt, các khoản tương đương tiền và đầu tư, tăng từ mức 330 triệu USD tính đến ngày 30/6/2026. Số dư cuối quý bao gồm 37 triệu USD nhận từ Regeneron sau khi công ty này lựa chọn thêm hai mục tiêu hợp tác.
• Doanh thu quý 3 giảm xuống còn 1,7 triệu USD từ mức 6,0 triệu USD cùng kỳ năm trước, chủ yếu do thỏa thuận hợp tác với Astellas kết thúc vào quý 2/2026.
• Chi phí hoạt động tăng lên 25,2 triệu USD từ mức 21,7 triệu USD, phản ánh chi phí nhân sự và chi phí tư vấn gia tăng.
• Ban lãnh đạo dự phóng lượng tiền mặt hiện tại sẽ đủ tài trợ cho các hoạt động đến nửa cuối năm 2028, bao gồm cả kế hoạch thúc đẩy Varseta-M bước vào nghiên cứu đăng ký tiềm năng đầu tiên.
• CytomX dự kiến sẽ cung cấp bản cập nhật tổng hợp về Giai đoạn 1 của Varseta-M vào tháng 1/2027, bao gồm dữ liệu sống còn toàn bộ đầu tiên, thông tin lựa chọn liều lượng và chiến lược đăng ký tiềm năng.
• Công ty đặt mục tiêu khởi động nghiên cứu đăng ký tiềm năng đầu tiên của Varseta-M đối với bệnh ung thư đại trực tràng di căn vào nửa đầu năm 2027. Ban lãnh đạo kỳ vọng thời gian sống còn toàn bộ sẽ là tiêu chí đánh giá chính trong một nghiên cứu ngẫu nhiên.

Dữ liệu tài chính quan trọng

Kết quả kinh doanh và hoạt động

Đơn trị liệu Varseta-M

Varseta-M là một phức hợp kháng thể - thuốc (ADC) ức chế Topo1 nhắm vào EpCAM, được phát triển trên nền tảng ProBody của CytomX. Công ty bước đầu phát triển loại thuốc này cho bệnh ung thư đại trực tràng di căn và mô tả đây là ADC nhắm đích EpCAM duy nhất hiện đang trong giai đoạn phát triển lâm sàng.

Nghiên cứu đơn trị liệu Giai đoạn 1 đã tiếp nhận hơn 100 bệnh nhân trên khắp các nhóm thuần tập leo liều, mở rộng và tối ưu hóa liều. Phần lớn người tham gia đã trải qua ít nhất ba phương pháp điều trị bệnh di căn trước đó.

Quá trình tối ưu hóa liều đang đánh giá các mức 8,6 mg/kg và 10 mg/kg mỗi ba tuần, sử dụng phương pháp tính liều theo trọng lượng cơ thể lý tưởng đã hiệu chỉnh cùng điều trị dự phòng ban đầu để kiểm soát các biến cố bất lợi đường tiêu hóa. CytomX dự định sử dụng bản cập nhật tháng 1/2027 để trình bày các phát hiện tổng hợp về hiệu quả và tính an toàn, phân tích thời gian sống còn toàn bộ đầu tiên cũng như dữ liệu hỗ trợ lựa chọn liều.

Phát triển liệu pháp kết hợp trong điều trị ung thư đại trực tràng

Nghiên cứu Giai đoạn 1 về Varseta-M kết hợp với bevacizumab tiếp tục tuyển bệnh nhân ung thư đại trực tràng điều trị ở các bước muộn. Dữ liệu lâm sàng ban đầu dự kiến có vào nửa đầu năm 2027, tùy thuộc vào tiến độ nghiên cứu.

CytomX cũng duy trì đúng tiến độ để khởi động một thử nghiệm Giai đoạn 1/2 mới vào cuối năm 2026 nhằm đánh giá Varseta-M kết hợp với bevacizumab, 5-fluorouracil và leucovorin. Giai đoạn 1 dự kiến bắt đầu với các bệnh nhân giai đoạn muộn để tìm liều, tiếp theo là các bệnh nhân ung thư đại trực tràng bước hai ở Giai đoạn 2 nếu quá trình tìm liều thành công. Chiến lược này thay thế irinotecan bằng Varseta-M.

Mở rộng sang các khối u đặc khác

Công ty đã khởi động các nhóm thuần tập Giai đoạn 1 đối với ung thư dạ dày và ung thư chỗ nối dạ dày - thực quản không chọn lọc, cũng như ung thư biểu mô tuyến ống tụy và ung thư đường mật được chọn lọc theo EpCAM. CytomX ban đầu dự kiến tuyển khoảng 20 bệnh nhân cho mỗi loại khối u để đánh giá hoạt tính kháng u và tính an toàn trước khi xác định các phương án phát triển ở giai đoạn sau.

CX-801

Quá trình tuyển bệnh nhân vẫn tiếp tục trong nghiên cứu Giai đoạn 1 đối với ứng viên interferon alpha-2b dạng che chắn CX-801 dưới dạng đơn trị liệu và kết hợp với Keytruda cho bệnh u hắc tố kháng thuốc ức chế điểm kiểm soát. CytomX dự kiến sẽ báo cáo dữ liệu lâm sàng ban đầu về u hắc tố vào nửa đầu năm 2027.

Định hướng của ban lãnh đạo

Ban lãnh đạo dự phóng lượng tiền mặt đủ duy trì hoạt động đến nửa cuối năm 2028. Công ty cho biết nguồn lực này sẽ hỗ trợ các ưu tiên phát triển cốt lõi: thúc đẩy Varseta-M hướng tới một nghiên cứu đăng ký tiềm năng, đánh giá các liệu pháp kết hợp cho ung thư đại trực tràng ở các bước điều trị sớm hơn và mở rộng sang các khối u tiêu hóa khác có biểu hiện EpCAM.

CytomX đặt mục tiêu vào nửa đầu năm 2027 để bắt đầu nghiên cứu đăng ký tiềm năng đầu tiên đối với Varseta-M. Quần thể bệnh nhân cuối cùng, thuốc đối chứng và mức liều vẫn đang được đánh giá, cùng với các phản hồi từ cơ quan quản lý đóng góp vào kế hoạch phát triển.

Rủi ro và các điểm cần theo dõi

• Độc tính đường tiêu hóa: Tiêu chảy độ 3 vẫn là biến cố bất lợi chính đang được tích cực kiểm soát. CytomX trước đó đã ghi nhận tỷ lệ 10% sau hai tháng theo dõi tương ứng ở 20 bệnh nhân tối ưu hóa liều đầu tiên, so với hơn 30% ở các bệnh nhân thuộc nhóm leo liều và mở rộng trong khoảng thời gian theo dõi tương đương.
• Tối ưu hóa liều: Mục tiêu của ban lãnh đạo là kiểm soát tỷ lệ tiêu chảy độ 3 ở mức 20% trở xuống. Thời gian khởi phát trung vị được báo cáo là khoảng năm tuần và độc tính này dường như không mang tính tích lũy, theo thông tin từ công ty.
• Khả năng dung nạp của liệu pháp kết hợp: CytomX sẽ theo dõi chặt chẽ độc tính đường tiêu hóa khi Varseta-M được kết hợp với 5-fluorouracil. Ban lãnh đạo lưu ý rằng việc duy trì cường độ liều có thể đóng vai trò quan trọng đối với thời gian sống không tiến triển và sống còn toàn bộ.
• Thiết kế nghiên cứu đăng ký: Công ty vẫn đang đánh giá các quần thể bệnh nhân từ bước ba trở đi, thuốc đối chứng phù hợp và mức liều cuối cùng. Ban lãnh đạo đã viện dẫn thời gian sống còn toàn bộ khoảng chín tháng được báo cáo đối với Lonsurf kết hợp bevacizumab ở những bệnh nhân đã từng điều trị bằng bevacizumab như một thước đo quan trọng đang được cân nhắc.
• Cạnh tranh trong phát triển thuốc: Ban lãnh đạo chỉ ra các chương trình ADC nhắm vào Trop-2, M7088 và CDH17 là những hướng tiếp cận cạnh tranh trong điều trị ung thư đại trực tràng, qua đó củng cố thêm trọng tâm đẩy nhanh tiến độ phát triển Varseta-M của công ty.

Điểm nhấn phiên hỏi đáp với chuyên gia phân tích

• Thời điểm cập nhật vào tháng 1: Ban lãnh đạo cho biết việc dời lịch từ cuối năm 2026 tạo điều kiện để có thêm thời gian theo dõi tính an toàn và hiệu quả, thu thập dữ liệu sống không tiến triển và sống còn toàn bộ chín muồi hơn, cũng như trao đổi với các cơ quan quản lý.
• Thử nghiệm then chốt tiềm năng: CytomX dự kiến nghiên cứu đăng ký ban đầu sẽ là thử nghiệm ngẫu nhiên với tiêu chí đánh giá chính là sống còn toàn bộ. Chi tiết về bước điều trị, thuốc đối chứng và mức liều được chọn dự kiến sẽ được công bố cùng bản cập nhật tháng 1.
• Chiến lược cho các bước điều trị sớm hơn: Phần Giai đoạn 1 của nghiên cứu kết hợp bevacizumab và hóa trị nhiều khả năng sẽ bắt đầu trên bệnh nhân giai đoạn muộn. Phần Giai đoạn 2 dự kiến dành cho bệnh nhân ung thư đại trực tràng bước hai sau khi tìm liều thành công.
• Khác biệt về tính an toàn: Ban lãnh đạo nhấn mạnh tỷ lệ độc tính huyết học thấp được ghi nhận ở Varseta-M so với các thuốc ADC ức chế Topo1 khác, đồng thời thừa nhận độc tính đường tiêu hóa vẫn là khía cạnh chính cần theo dõi và giảm thiểu.
• Xác định liều theo trọng lượng cơ thể lý tưởng đã hiệu chỉnh: Mọi bệnh nhân trong nhóm tối ưu hóa đều được tính toán liều dùng bằng thuật toán trọng lượng cơ thể lý tưởng đã hiệu chỉnh. Công ty dự định phân tích liều tuyệt đối và cường độ liều theo thời gian trước khi lựa chọn phác đồ phục vụ đăng ký.

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

Toàn văn cuộc gọi công bố kết quả kinh doanh

Phần trình bày của ban lãnh đạo

Operator

CytomX's Chief Financial Officer. Please go ahead.

Chris Ogden

Thank you. Good afternoon and thank you for joining us. Before we begin, I would like to remind everyone that during this call, we'll be making forward-looking statements. Because forward-looking statements relate to the future, they're subject to inherent uncertainties and risks that are difficult to predict, and many of which are outside of our control. Important risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov. Except as required by law, we undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments, or otherwise. Earlier this afternoon, we filed our quarterly report on Form 10-Q for 3Q '26 and issued a press release with a summary of our third quarter 2026 financial results and business highlights.

We encourage everyone to read today's filing and press release. Additionally, the press release, recording of this call, and our SEC filings can be found under the Investors and News section of our website. With me on the call today is Dr. Sean McCarthy, CytomX's Chief Executive Officer and Chairman. Sean will provide an update on our pipeline and company progress before I cover the financials for the quarter. We'll then conclude with a Q&A session. With that, I'll turn the call over to Sean.

Sean McCarthy

Thanks, Chris, and good afternoon, everyone. We're very pleased to be here today to provide an update on our third quarter developments and what continues to be a highly productive year for CytomX as we advance our lead program, Varseta-M, towards its first potential registrational study in the first half of 2027. Varseta-M is an EpCAM-targeting Topo1 antibody-drug conjugate with strong potential in colorectal cancer and potentially other solid tumors. Importantly, to our knowledge, Varseta-M is first-in-class as the only EpCAM-directed ADC in clinical development. Varseta-M has been intentionally designed and uniquely enabled by our ProBody platform, creating a significant opportunity for differentiation and long-term value creation. Strategically, we are initially developing Varseta-M in metastatic colorectal cancer as the lead indication. Our sense of urgency for Varseta-M is driven by the significant unmet need in colorectal cancer, which is the second leading cause of cancer death in the United States and worldwide.

Varseta-M is on the leading edge of ADC innovation in CRC and has the potential to be 1 of the first monotherapy ADCs to market for the treatment of this very challenging cancer type. In terms of commercial potential, there are an estimated 35,000 addressable patients in the United States with third-line or later CRC. Given the anti-cancer activity we have reported previously across an unselected late-stage patient population and the limited clinical benefit of existing therapies for these patients, we see considerable opportunity for Varseta-M.

Based on Varseta-M's unique profile, we are actively advancing our development program across 3 strategic areas of priority. First, we aim to move our Varseta-M monotherapy into a registrational study in the first half of next year, enabling a potential first approval and meaningful market opportunity in metastatic CRC. Second, we continue our development of Varseta-M in combinations, including with Bevacizumab and with earlier line chemotherapy regimens with the goal of replacing current standard of care. And third, we have started to evaluate Varseta-M's pan-tumor potential across multiple EpCAM-expressing cancers, initially in additional gastrointestinal indications.

The monotherapy Varseta-M Phase 1 study has enrolled more than 100 patients across dose escalation, expansion, and optimization cohorts. As previously reported, patients enrolled in the Phase 1 study have been heavily pretreated, with most patients having received 3 or more prior treatments in the metastatic setting. In March, we reported encouraging progression-free survival at doses of 8.6 and 10 mg/kg that exceeded current standard of care. We also shared our increasing understanding of the safety profile of Varseta-M, particularly how to lower and manage rates of high-grade diarrhea. This initial experience with Varseta-M in very late-line patients will provide us with a highly relevant dataset to enable monotherapy dose selection and inform the potential first registrational study design.

Most recently, we have been highly focused on dose optimization, evaluating 2 doses, 8.6 and 10 mg/kg given every 3 weeks with adjusted ideal body weight dosing and upfront prophylaxis to manage gastrointestinal adverse events. We anticipate providing an integrated update in January across the Phase 1 study, including our potential registrational strategy and the data that underpin our plans. It's important to note here that we expect this next update to provide the first look at overall survival for Varseta-M, which we anticipate will be the primary endpoint in our initial registrational study. We look forward to providing this next update in the near term.

Now moving on to the Varseta-M combination development program. Our ongoing Phase 1 study evaluating Varseta-M in combination with Bevacizumab continues to enroll late-line CRC patients to assess dose and safety. We view this combination as a foundational first step in evaluating Varseta-M's potential in earlier line CRC. Subject to data from the ongoing Phase 1 study, we anticipate moving to earlier line CRC patients in the future evaluation of this combination, and we anticipate reporting initial clinical data from the Bevacizumab combination in the first half of 2027.

To also enable the use of Varseta-M in earlier lines of CRC therapy, we remain on track to initiate a study evaluating Varseta-M in combination with Bevacizumab, 5-fluorouracil, and Leucovorin by the end of the year. This study will be a new Phase 1/2 trial that would enroll second-line CRC patients once Phase 1 dose finding is successfully completed. We believe these Varseta-M combination studies have the potential to inform future development options and look forward to providing initial updates starting next year.

Now moving to the development of Varseta-M outside of CRC, our strategy is to develop and ultimately commercialize Varseta-M across multiple EpCAM-expressing solid tumors. And we have recently initiated Phase 1 cohorts in gastrointestinal indications with substantial unmet need and that we view as highly complementary to CRC from a commercial perspective. We have initiated cohorts in unselected gastric and gastroesophageal junction cancer as well as EpCAM-selected pancreatic ductal adenocarcinoma and EpCAM-selected biliary tract cancer. Each of these EpCAM-expressing tumor types currently have limited treatment options in later-line settings and may present expedited development pathways for Varseta-M upon clinical proof of concept. Our initial plan is to enroll approximately 20 patients per tumor type to evaluate Varseta-M's anti-tumor activity and safety before assessing later phase development options. Having focused Varseta-M exclusively in CRC for the first 2 years of development, we're very excited to now be evaluating Varseta-M's broader clinical potential.

Now turning to CX-801, our masked interferon alpha-2b program being evaluated in checkpoint refractory melanoma. We see CX-801 as an exciting and broad opportunity to reprogram the immune responsiveness of solid tumors. And we continue to enroll the ongoing Phase 1 study evaluating CX-801 as a monotherapy and in combination with Keytruda. Enrollment in the monotherapy cohort of our Phase 1 study continues, having exceeded dose levels of the approved dose of unmasked interferon alpha-2b. Initial biomarker data for CX-801 monotherapy presented previously have reinforced our mechanism of action hypothesis for CX-801 in combination with Keytruda. We continue to enroll in the combination cohort, and we look forward to sharing initial clinical data from the Phase 1 study in melanoma in the first half of 2027.

With those updates, let me now transition the call back to Chris.

Chris Ogden

Thank you, Sean. As Sean highlighted, we are making important progress across the Varseta-M program, including potentially moving towards later-stage development. As we progress the broadening Varseta-M development program, we have continued to maintain an efficient and flexible cost structure, enabling us to pursue the opportunities Sean described earlier. To that end, with our current balance sheet, we project cash runway into the second half of 2028. Importantly, our runway funds our key value creation priorities that Sean outlined, including advancing Varseta-M into its first potential registrational study, pursuing combination development to move Varseta-M into earlier lines of CRC, and then expanding into multiple other EpCAM-expressing gastrointestinal tumors.

With that, I'll now walk through our third quarter financial results. As of September 30, 2026, we ended the quarter with $348 million in cash, cash equivalents, and investments versus $330 million in cash as of June 30, 2026. The cash balance as of September 30, 2026 includes $37 million received from Regeneron following its selection of 2 additional targets under the recently expanded collaboration.

Looking at revenue and operating expenses for the quarter, total revenue was $1.7 million, compared to $6 million in the third quarter of 2025. The decrease in revenue was primarily attributed to the conclusion of the Astellas collaboration in the second quarter of 2026. Operating expenses for the third quarter were $25.2 million compared to $21.7 million in the third quarter of 2025. Research and development expenses were $16.5 million during the third quarter, representing an increase of $1.2 million versus the third quarter of 2025, primarily due to increased personnel-related costs and partially offset by lower Varseta-M spending due to the timing of manufacturing activities. General and administrative expenses increased by $2.3 million during the 3-month period ending September 30, 2026 to $8.7 million compared to $6.4 million for the corresponding period in 2025. Increased G&A expenses were primarily driven by personnel-related expenses and higher consulting spend.

As we move towards 2027, we will continue to be disciplined in capital allocation in order to progress the most compelling Varseta-M development priorities, and realize the broader value creation potential for CytomX stakeholders. With that, operator, let's go ahead and open up the call for Q&A.

Operator

[Operator Instructions]

Our first question comes from the line of Paul Jeng with Guggenheim.

Phần hỏi đáp

Paul Jeng

So I guess my first question is, can you expand a little bit about the Bev chemo combo study that's getting underway this quarter? Anything about the target enrollment number, and will this exclusively enroll second-line patients from the outset? And then, on the patients themselves, are you focusing more on patients coming off a FOLFOX-based frontline regimen, or do you otherwise plan to stratify by any key baseline characteristics? And then I have a follow-up.

Sean McCarthy

Great, thanks for the questions there, and we're really excited about the progress overall with the program and particularly moving further into the second line downstream with Varseta-M into the combination setting. And as we pointed out, the gaining of experience with Varseta-M in combination initially with Bev, which is ongoing, and soon to start with Bev plus chemotherapy, is a really important component of the program.

We do anticipate initially in the first part, the Phase 1 part of the study, that we'll enroll most likely late-stage patients as we dose range and gain initial experience of the combination strategy. And then as we open up further down the road, the Phase 2 part of the study, that would enroll second-line patients. And that's really all the detail that we're ready to give at this moment in time.

Paul Jeng

So then my second question is just would be great to get your current perspective on the broader landscape of ADCs in colorectal. Now there's a few competitors in Phase 3 as well as some recent data from emerging targets at ESMO. So how are you currently thinking about the positioning of Varseta-M given many of these are all using Topo1 payloads? Thank you.

Sean McCarthy

Yes, it's actually really exciting to see the field evolving in the way it is. I think we can say now quite clearly that antibody-drug conjugates are coming to colorectal cancer patients. It's been a long time coming, and this is just a really exciting development for the field overall, and of course, for the patients who are waiting and in desperate need for these innovative therapies. I want to really emphasize, in addition, of course, that our drug, Varseta-M, is the only EpCAM-targeting ADC. We are first-in-class on this target. We think that's a direct reflection of our proprietary masking technology. We've really been able to do something that no one else has been able to do.

We think that puts us in a strong position from a differentiation standpoint over time. And with regard to the other programs, yes, there are several to watch, and we're keeping a very close eye on them: the Trop-2 ADC, the Merck Serono program, M7088, and then more recently, I think as you're alluding to, including at ESMO, a number of CDH17 ADCs that have shown some encouraging, we think preliminary, data. We believe we've got to keep up a very competitive asset here, and it really underscores and fuels our urgency to move Varseta-M forward as rapidly as we can.

Operator

Our next question comes from the line of Etzer Darout with Barclays.

Etzer Darout

Just curious about the OS update in January for the first 73 or so patients. If you could maybe comment on when you think about third-line versus line setting versus pursuing a faster fourth-line setting. Is there a threshold relative to the roughly 9-month OS benchmark in Bev-experienced patients receiving Lonsurf plus Bev that you're looking at to decide whether you're going to go after maybe a third-line versus a fourth-line indication, knowing that the fourth line would probably get through the market faster? How are you thinking about that, and then I have a follow-up?

Sean McCarthy

Thanks, that's a great question, and you quite rightly point out the 9-month there or thereabouts OS that has been reported for Bev-Lonsurf in the post-Bev setting per the SUNLIGHT trial. That is an important number we are looking at relative to other components of standard of care in the third line, third line plus. And we continue to evaluate these options as we look towards potentially initiating this first registrational study in the first half of next year. We're continuing to look at these 2 options in terms of how we increasingly think about third line plus as the place to go.

And really the key questions for us are, what will be in this first pivotal study, what will the patient population be, what's the appropriate comparator in that patient population? Because I want to remind you that in the third line plus setting, although Bev-Lonsurf is, of course, thought of as the dominant therapy in the third line, treatment of third line patients and later is actually quite fragmented. And we see, as we really lock in on this study design, we think there's a number of ways to go to capture a significant portion of the third line plus market with a number of different designs. So more to come on that, and your question also does allow me to restate what I said in my prepared remarks, which is that we do anticipate that in this first registrational study, the OS will be our primary endpoint in a randomized study.

Etzer Darout

Great, thank you for that. And then for the January update now, is that primarily a planned conference timing and data maturation? Just wondered if you could comment on that in terms of now the data being in January of next year.

Sean McCarthy

We haven't specified the forum at this time. That will come in due course.

Operator

Our next question comes from the line of Edward Tenthoff with Piper Sandler.

Edward Tenthoff

I wanted to ask, with respect to the Avastin chemo arm study that you're going to start, in which it looks like you're replacing oxaliplatin, what safety endpoints are you going to be evaluating there to see whether or not the combination with Varseta-M is better tolerated? And maybe you can remind me how large that study would be. Thank you very much.

Sean McCarthy

Hi, Ted. Thanks for the questions. So the strategy in the Bev chemo combo will be to replace irinotecan with the ADC, so of course the Topo1 ADC really having been designed with that as 1 of the goals in mind. That's a very important part of the strategy. In terms of the safety profile, of course, this work is all about initially evaluating the combinability of Varseta-M with these other agents. And 1 of the things that we think could be very attractive about the Varseta-M safety profile that we've learned a lot about so far is the quite remarkably low rate of hematologic toxicity we see with Varseta-M relative to other Topo1 ADCs in development in CRC and elsewhere. So we think that certainly is an advantage.

I'd say the area that we'll be paying closest attention to would be the GI toxicity. We know that we have a certain rate of Grade 3 diarrhea with Varseta-M, something that we're continuing to learn a lot about and getting an increasing handle on, but that is something that we'll be watching very carefully in combination, particularly with 5-FU. But I would also say that, of course, irinotecan, since we're switching out irinotecan for Varseta-M, irinotecan itself has been known since the early days of its development to have its own rate of Grade 3 diarrhea. So we're switching Varseta-M for irinotecan, which I think could work in our favor. But we really need to do the work to evaluate the combinability.

Edward Tenthoff

Yes, makes sense. And would you be implementing the ideal body weight dosing and diarrhea mitigation in those studies, just as you have with monotherapy of Varseta-M?

Sean McCarthy

I think that's most likely, yes. Since we're still in the late stages, but we are coming to the later stages and I think soon a conclusion from our dose optimization work that we've been doing across the 8.6 and 10 mg/kg AIBW schedules, Q3 week schedules. So until we really pin that down, hard to say for sure, but I think it's not unlikely that we would be using AIBW moving forward in those additional combination studies.

Edward Tenthoff

Yes, makes sense. Thanks. Keep up the important work.

Sean McCarthy

Thanks, I appreciate the support.

Operator

Our next question comes from the line of Anupam Rama with J.P. Morgan.

Anupam Rama

This is Brooke on for Anupam. What drove the shift of the monotherapy update from year-end '26 to January? Is it more patient follow-up or waiting on FDA feedback? Thank you.

Sean McCarthy

Yes, as dose optimization has continued, we've really wanted to allow time for sufficient follow-up to assess safety and efficacy and also allow for the full engagement and feedback from regulatory authorities. We are looking forward to the update in January.

Operator

Our next question comes from the line of Roger Song with Jefferies.

Nabeel Nissar

This is Nabeel on for Roger. A couple from us. I guess regarding GI durability, it's encouraging to see the 10% Grade 3 in the 2 months as we get longer follow-up. I was just curious how you're thinking on time of onset, duration, and recurrence. And then as we go into second line, you mentioned earlier with 5-fluorouracil, we know that that may add some toxicity. We know that, as you mentioned, irinotecan is already used in second line. But what's the target for the GI toxicity that we're looking for?

Sean McCarthy

Yes, thanks, Nabeel. Great questions. And as I mentioned earlier, we're continuing to learn a lot about the safety profile of Varseta-M. And we did, as you also rightly point out, in March this year, report our initial experience in dose optimization, showing that after 2 months of matched follow-up with the patients in dose optimization cohorts, the first 20 patients in dose optimization cohorts across the 2 doses of 8.6 and 10 mg/kg, a rate of Grade 3 diarrhea of 10% relative to more than 30% in the time-matched patients from escalation and expansion. So an encouraging start.

I think we've been pretty consistent in talking about our goal for Grade 3 diarrhea based on work that we've done talking to oncologists and other market research that we've done, that we would like to manage the rate of Grade 3 diarrhea to 20% or below. We think that that is a more than acceptable rate in this disease. Obviously, we want to do the best we can in terms of leveraging the prophylaxis strategy, which in the March update was certainly showing a very good start.

Just a little bit more detail. Let me go into a bit more detail, since you mentioned time to onset, we've reported previously that time to onset for Grade 3 diarrhea with Varseta-M at these doses is about 5 weeks. And we've reported that it does not appear to be cumulative. We've also spent a lot of time over the last few months looking not just at the grade, but also digging deeper into the patient experience in terms of what is the amount of time that a patient spends in Grade 3 and what is the burden overall. And that's something that we'll have more to say about over time.

And the reason I point that out is that, of course, the goal of managing really this 1 significant AE that we have to think about with Varseta-M. The safety profile of Varseta-M overall we think is highly attractive, but our goal in managing the high-grade diarrhea is, of course, to maximize dose intensity. And we do anticipate that dose intensity will be an important determinant of efficacy, particularly in regards to PFS and OS over time. So ongoing work, and we continue to learn more all the time, and we'll look forward to providing the update in January. Thanks for the questions.

Nabeel Nissar

Yes, thank you, Sean. If I could ask a follow-up.

Sean McCarthy

Yes, go ahead, Nabeel, please.

Nabeel Nissar

So kind of taking a step back, we see the ESMO updates, encouraging to see more progress being done here. Curious if we take a step back and look at just the target itself, EpCAM, compared to targeting CEACAM5, both are glycoproteins. Can you comment on the rate of shedding compared to CEACAM5 for EpCAM? We know that CEACAM5 is more readily shed into the bloodstream. And do you think that in that regard, EpCAM has a more favorable target profile?

Sean McCarthy

Well, we do see EpCAM, I would say, compared to CEACAM5 being somewhat more highly and broadly expressed, although CEACAM5 is an abundant and broadly expressed target, which the data that I've seen is not so far from patients that have been selected for target expression, but we do continue to like EpCAM quite a bit as a target. In terms of shedding, I don't really have anything to say there in terms of comparison across the targets. And it's not, to be honest, something that we've spent a lot of time thinking about, but maybe we'll come back to you on that.

Operator

Our next question comes from the line of Olivia Brayer with Cantor Fitzgerald.

Olivia Brayer

I wanted to follow up on the January timeline or timing. Can you disclose what follow-up threshold you guys are looking to achieve, especially as you think about safety follow-up, but also thinking through survival and is this more about accruing events over time? I guess I'm trying to understand whether it's more about the dose expansion population or the 40-patient dose optimization cohort.

Sean McCarthy

Yes, hi, Olivia. So we've, I think, again, been pretty consistent here for a while now in terms of our goals and strategy for data disclosures. If we go back, I guess, a year or a year and a half, when we were approaching the data coming out from escalation and expansion, we communicated that we would share those updates, which we did in March this year, when we had an initial sense of progression-free survival on a dose-by-dose basis. With regard to the optimization data, similar guidance that we want to be able to share PFS from the optimization cohorts in the context of the first look at OS from escalation and expansion. So the January update, as I mentioned earlier on, is simply to allow sufficient time to give as robust an update as we think is appropriate.

Olivia Brayer

Helpful. And then, Sean, on the optimization cohort, how are you guys thinking about breaking out efficacy between patients who received an AIBW-adjusted dose and those who didn't? And I'm not sure if you can share this number, but any sense of what proportion of those 40 patients actually required a meaningful dose adjustment?

Sean McCarthy

Well, every patient's dose would have been calculated using the AIBW algorithm. I think it's a good question, but I would reframe it a little bit in terms of ultimately what's the dose, well, of course, what's the absolute dose that a patient receives and what's the dose intensity achieved over time? And that's the type of data that we're going to be analyzing and that we will be sharing in due course.

Olivia Brayer

Okay, understood. Looking forward to it. Thank you very much.

Sean McCarthy

You're welcome.

Operator

Our next question comes from the line of Kalpit Patel with Wolfe Research.

Unknown Speaker

This is Nikki on for Kalpit. I wanted to ask if, as you gain additional experience with the optimized dosing regimen, would you be able to give us any granularity on what that selected dose might be for the Phase 3 or what you're leaning towards? Thank you so much.

Sean McCarthy

Yes, thanks for the question. Can't provide any additional color at this moment in time, but that will be an important component of the update in January.

Operator

Thank you. I'm not showing any further questions in the queue. I would now like to turn it back over to Dr. Sean McCarthy, Chairman and CEO, for closing remarks.

Sean McCarthy

Thank you, and thanks, everyone, for listening in today. We continue to be highly encouraged by the progress we're making here at CytomX with Varseta-M, with CX-801, and more broadly with our ProBody therapeutic platform. We're excited about the breadth of opportunities in front of us as we drive toward the end of the year and rapidly, as it seems, into 2027. So thank you all for your time today.

Operator

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

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