管理層發言
Good afternoon, and welcome to Summit Therapeutics Q2 2026 Earnings Call. We do not expect any technical difficulties today. However, in the event that we lose the webcast connection and are unable to provide any updates, please wait up to 10 minutes for resolution. Please refer to the company's website for updates. Please note that today's call is being recorded. At this time, I would like to turn the call over to Dave Gancarz, Summit Therapeutics Chief Business and Strategy Officer. You may proceed.
Good afternoon, and thank you for joining us. On today's call, we will provide an update on our second quarter 2026 financial results and operational progress. This afternoon's press release is available on our website, www.smmttx.com. Our Form 10-Q was also filed today and is available on our website and via the SEC's website. Today's call is being simultaneously webcast, and an archived replay will also be made available later today on our website. Joining me on the call today is Bob Duggan, our Chairman of the Board and Co-Chief Executive Officer; Dr. Maky Zanganeh, our President and Co-Chief Executive Officer; Manmeet Soni, our Chief Operating Officer and Chief Financial Officer; and Dr. Allen Yang, Chief of R&D Strategy. I'm Dave Gancarz, the Chief Business and Strategy Officer here at Summit. Before we get started with the rest of the call, I would like to note that some statements made by our management team and some responses to questions that we make today may be considered forward-looking statements based on our current expectations. Summit cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Please refer to our SEC filings for information, including the Form 10-Q issued today about these risks and uncertainties. Summit undertakes no obligation to update these forward-looking statements, except as required by law. One item of note, this presentation is being webcast with slides, so we'll be referring to the slides being displayed in the web link. I'd encourage you to use the webcast link to see the slides being presented this afternoon that will accompany our comments. Following comments from our team, we will take questions. And with that, I'll hand it over to Bob.
Thank you, Dave. Good afternoon, everyone. Thank you for joining us today. I'm very proud of the highly focused, mission-driven patient-first team at Summit and the growing physician support around ivonescimab, our PD-1/VEGF bispecific and lead investigational asset. In addition, we continue to appreciate big pharma's high interest in ivonescimab as the backbone of combination therapy in many different solid tumor settings as we look to successfully combine ivonescimab with their innovative new targets. Our team continues to grow in number and ability as we expand our clinical development plan and prepare for commercialization in anticipation of a decision from the FDA on our BLA towards the end of this year. Before we start with key updates from the past couple of months, I'd like to take a moment to remind those of you who have been with us from the beginning and introduce to those of you who may be new to the story of what ivonescimab has accomplished to date. You can see this on Slide 3. Ivonescimab has read out 4 Phase III clinical studies to date, all 4 with positive data. This has led to 2 approvals in China so far, with 1 currently under review in addition to the pending BLA with the U.S. FDA. A total of 15 Phase III trials are currently ongoing or have read out in multiple tumor types. Between Summit and our partners at Akeso, 52 clinical trials have been initiated evaluating ivonescimab in a variety of solid tumors. When including investigator-initiated and collaborative studies, a total of 171 clinical trials are now listed on clinicaltrials.gov. The enthusiasm demonstrated by investigators around the world to generate data and seek positive signals for patients facing high unmet medical need really speaks to the opportunity and ever-present optimism surrounding ivonescimab. Together with Akeso, over 4,000 patients in either Summit-sponsored or Akeso-sponsored clinical trials across the world have been dosed with ivonescimab. Commercially, in China, over 70,000 patients have been administered ivonescimab. On Slide 4, we see a snapshot of the current ivonescimab development plans across Summit and Akeso, as well as a Phase III clinical trial sponsored by a prominent European cooperative group, GORTEC. Our collective pipelines cover not only multiple settings in lung and colorectal cancers, but also head and neck, breast, biliary, pancreatic, gynecological, gastric and hepatocellular cancer, including non-metastatic settings. Summit's announced Phase III studies focus on non-small cell lung cancer and colorectal cancer, and these studies represent only a subset of ivonescimab's potential future indications, as you can see here. Through our wonderful partnership with Akeso, data generated in our studies, as well as data generated through investigator-sponsored trials, we continuously consider evolving ivonescimab to drive more informed as well as faster decisions, all of which support efficient and timely expansion of our global ivonescimab development plan. I'll now turn it over to Maky to discuss some of the recent developments. Maky?
Thank you, Bob. Yesterday, we announced an updated OS analysis conducted for our global Phase III HARMONi trial. The HARMONi study evaluated ivonescimab plus chemo against chemo alone as a treatment for EGFR-mutated non-small cell lung cancer after TKI therapy, a patient population of significant unmet need with few available treatment options. In this most recent analysis with the data cutoff in June 2026, Western patients increased their time on study, reaching a median follow-up of over 23 months. Asian patients remained locked with a median follow-up time of 33 months. A hazard ratio of 0.76 was observed in both the total population as well as the regional Western data. The hazard ratio for Western patients has improved with more follow-up time. With longer follow-up, results of Western patients are now consistent in terms of the magnitude of OS benefit with those patients enrolled in Asia who had a longer follow-up at the time of the primary OS analysis. Ivonescimab continued to demonstrate an acceptable and manageable safety profile that was consistent with previous Phase III results of ivonescimab plus chemo. No additional safety signals were observed in this current HARMONi data cut compared to the previous data cuts. As a reminder, this setting is one in which multiple PD-1 inhibitors have failed previously to show a benefit in either PFS or OS. Prior Phase III studies were conducted in this setting individually with pembro or nivo, each in combination with chemo and were not successful. In addition, there are currently no approved agents in this setting, which have demonstrated an overall survival benefit compared to chemo alone. The encouraging results from this long-term overall survival analysis continue to support the ability to translate the therapeutic profile of ivonescimab across the globe, including the efficacy potential of ivonescimab in Western patients from North America and Europe. This data shows a consistent favorable OS trend across geographies, as Western patients were followed for additional time on study. With meaningful follow-up time in both regions, the magnitude of the OS benefit is consistent between patients enrolled in China and enrolled in Western countries, including the United States in the HARMONi study. We intend to provide exciting additional details from this new long-term analysis at a future medical meeting. We have also made these results available to the FDA. As previously disclosed, the FDA noted that a statistically significant overall survival benefit is necessary to support marketing authorization in this setting. Considering the safety and efficacy profile of the current FDA-approved options for patients in this setting, none of which have demonstrated a statistically significant OS benefit, as well as the continuing positive regionally consistent data of this Phase III multiregional study and discussions with key opinion leaders and physicians who have administered ivonescimab to patients, we believe that ivonescimab is a potential treatment option with favorable benefit-risk profile. Turning specifically to Summit's global ivonescimab pipeline, which is noted on Slide 7, we have 4 Phase III trials completed or ongoing. HARMONi, which we just covered, HARMONi-3, HARMONi-7 and HARMONi-GI3. HARMONi-3 is evaluating ivonescimab plus chemo against pembro plus chemo in frontline metastatic non-small cell lung cancer in both patients with squamous and non-squamous histologies, each of which will be analyzed separately. These patient populations represent a significant unmet medical need with the nearly 100,000 patients in the United States alone, as this trial covers frontline non-small cell lung cancer patients without genomic alterations. In line with prior guidance, we have completed enrollment in both the squamous and non-squamous cohorts. We expect to reach the number of events needed to conduct the PFS analysis for the squamous cohort in the second half of this year, which would also come with a corresponding early interim look at overall survival. We would expect to reach the number of events for the first look at OS that is independent of the PFS analysis in the first half of 2027. For the non-squamous cohort, we expect to reach the number of events needed to conduct a progression-free survival analysis in the first half of 2027. HARMONi-7 is evaluating ivonescimab monotherapy against pembro monotherapy as frontline treatment for patients with non-small cell lung cancer that has high PD-L1 expression levels. Enrollment continues to be strong, and we look forward to providing additional updates on this trial in the near future. HARMONi-GI3 evaluates ivonescimab plus chemo compared to beva plus chemo as frontline therapy in patients with unresectable colorectal cancer. Our decision to initiate this study was driven by encouraging Phase II data published at ESMO 2024 and supported by global Phase II data presented in Q2 of this year at ASCO 2026. We look forward to providing further updates as this global Phase III colorectal cancer trial progresses. In addition to our sponsored studies, the Phase III study, ILLUMINE, is currently enrolling in a head and neck cancer through a European cooperative group, GORTEC. This is another multiregional Phase III study that tests ivonescimab with and without an anti-CD47 agent head-to-head against pembro in an additional tumor setting from our historical work. The trial is enrolling in Europe, is intended to start in China later this year, and we will evaluate opening sites in the United States based on continued progress. Additionally, we have over 65 ISTs that we intend to support in various stages of development. Of this, 24 are currently enrolling and more publications are being featured at each major medical conference, often in prominent sessions at ASCO, ESMO and World Conference on Lung Cancer. Through this combined research, ivonescimab has now been featured in over 50 publications, presentations and posters. Now I would like to take a minute to focus on some of the clinical trial collaborations in which we have entered to evaluate ivonescimab with novel combinations. Clinical development of ivonescimab in additional tumor settings also continues to progress as planned via our collaborations with RevMed, GSK and now with Arcus. With respect to novel-novel combinations, our collaboration with Revolution Medicines began enrolling in the first quarter of this year. This collaboration evaluates ivonescimab in combination with 3 novel RAS inhibitors across multiple solid tumor settings, including pancreatic, colorectal and non-small cell lung cancers. We are enthusiastic about the opportunity of ivonescimab with multiple existing RAS inhibitors and what the combination has the potential to do for patients facing difficult-to-treat cancers. Our GSK collaboration evaluating ivonescimab in multiple solid tumor settings in combination with their B7-H3 ADC, is expected to enroll its first patient later this quarter. This is another example of promising targets seeking to significantly advance outcomes in settings such as multiple types of lung cancer and colorectal cancer, where both ivonescimab and B7-H3 ADCs have shown promise. We are also pleased to announce yesterday that we have established a collaboration with Arcus Biosciences to evaluate ivonescimab in combination with Arcus HIF-2 alpha inhibitor, casdatifan, in first-line metastatic clear cell renal cell carcinoma, the most common form of kidney cancer. This combination presents a compelling opportunity for a potentially well-tolerated TKI-sparing option to prolong survival in this setting. We expect initial data from this collaboration to be generated by mid next year. Collectively, these trials enhance and inform our own clinical development activities as we learn more about new settings where neither we nor Akeso have yet had the opportunity to explore. Additionally, the continued enthusiastic interest in ISTs is a testament for the optimism. We have heard from many investigators as they consider the potential opportunity that ivonescimab presents across multiple tumor types and in multiple novel-novel combination regimens. Now let's take a closer look at the clinical trial data we have seen from ivonescimab today, focusing on U.S. results. Of the 4 Phase III studies that have read out to date, all 4 studies had positive, statistically significant, clinically meaningful progression-free survival results. In each of these studies, ivonescimab has achieved overall survival hazard ratios less than the generally accepted clinical meaningfulness threshold of 0.80. We discussed the updated data from the global HARMONi study earlier. We look forward to presenting additional details such as Kaplan-Meier curves, medians and other important components of the analysis at an upcoming medical conference. While not achieving statistical significance at the primary OS analysis, the nominal p-value implies significance of the OS benefit for the global study, and this is further supported by the updated OS data announced yesterday. The HARMONi-A study in China in a similar setting to HARMONi, produced consistent results and demonstrated a statistically significant benefit in OS. HARMONi-2, conducted in China, which was the first time a Phase III clinical trial has shown a statistically significant improvement in progression-free survival directly replacing a PD-1 inhibitor in a head-to-head setting, reported an overall survival hazard ratio of 0.78 at just 39% data maturity. This study evaluated ivonescimab monotherapy against pembro monotherapy as frontline treatment for patients with non-small cell lung cancer, whose tumors have positive PD-L1 expression, a similar patient population to Summit global Phase III HARMONi-7 study, which focuses on tumors with high PD-L1 expression. Finally, the HARMONi-6 study conducted in China achieved an overall survival hazard ratio of 0.68 as announced at the plenary session of ASCO 2026. The magnitude of benefit measured by the hazard ratio for OS was consistent with the benefit for PFS, both with hazard ratios in the 0.6s. Again, this study compared ivonescimab with chemo against an anti-PD-1 plus chemo as frontline treatment for patients with non-small cell lung cancer of squamous histology. This is the first time a Phase III clinical trial in any tumor type, not just in non-small cell lung cancer, has shown a statistically significant improvement in overall survival compared to a PD-1 inhibitor in combination with chemo in a head-to-head setting. Four Phase III studies have been conducted in three different non-small cell lung cancer settings, all producing clinically meaningful overall survival hazard ratios under 0.80. Two of the four studies were conducted head-to-head against a PD-1 inhibitor with or without chemotherapy, and two were conducted in settings where PD-1 inhibitors are not approved because they failed in past Phase III clinical studies. These results speak to the opportunity to replace current immunotherapy options with ivonescimab, the potential next generation of cancer therapy. As we have said before, we feel the data speaks for itself and support immense potential for ivonescimab to help patients with lung cancer, and we believe in additional tumor settings as well as more data is generated and accumulates across Summit and Akeso trials, ISTs and collaborations. Turning to Slide 9, and looking to the existing next steps for ivonescimab, our global Phase III HARMONi-3 all-comers trial evaluating ivonescimab with chemo in frontline non-small cell lung cancer has completed enrollment in both the squamous and non-squamous cohorts. We expect to reach the number of events for the primary PFS analysis for the squamous cohort in the second half of this year, which would come with a corresponding interim look at overall survival. Importantly, we expect to have another interim look at OS in first half of 2027, which will have additional follow-up time, something we continue to note as an important factor in showing the value of ivonescimab in these clinical studies. For the non-squamous cohort, we expect to reach the number of events needed to conduct the PFS analysis in the first half of 2027. Turning to our BLA filing based on our Phase III HARMONi study seeking approval for ivonescimab plus chemo in the EGFR-mutated non-small cell lung cancer setting post-TKI therapy, the submission is currently under review with the U.S. FDA. The agency has provided a target PDUFA date of November 14 of this year. We continue to grow our commercial capabilities as we prepare in anticipation of ivonescimab's potential first U.S. approval and potential launch later this year. We will continue to provide further details on additional new global studies throughout the year, as they are ready to share. To date, we have initiated global Phase III studies in non-small cell lung cancer, colorectal cancer, through our partnership with GORTEC's head and neck squamous cell carcinoma. We look forward to continuing to grow our global pipeline, explore ivonescimab's potential to help additional patients in new tumor types and settings in the near future. On today's call, we have covered ivonescimab recent accomplishments in the clinic. But as a reminder, this is only the beginning of a vast potential market opportunity for ivonescimab across solid tumors. We have discussed this previously, but with each successful data set, it becomes closer to reality. Ivonescimab has the potential to be a platform blockbuster drug. Ivonescimab is well positioned to make a significant impact across the solid tumor treatment landscape between checkpoint inhibitors and anti-VEGF therapies. The estimated total addressable market is in excess of $100 billion globally. Looking only at the checkpoint inhibitor market for non-small cell lung cancer in which our first set of registrational Phase III studies are conducted, market estimates for immunotherapy itself are expected to exceed $20 billion per year by 2028. On Slide 10, we identified the more than 50 solid tumor settings where anti-PD-1 and anti-VEGF therapies are approved, established PD-1 and PD-L1 indications in green and anti-VEGF indication in purple. The settings highlighted in yellow represent the indications we are currently running global Phase III trials for ivonescimab, lung and colorectal cancers. Clearly, there are several additional opportunities for ivonescimab beyond today's PD-1 or VEGF landscape, including novel settings such as EGFR-mutant lung cancer. We intend to provide details regarding additional studies, including Phase III studies in the near term. Ivonescimab's differentiated profile as we saw with HARMONi-6 achieving a statistically significant, highly clinically meaningful progression-free survival and overall survival benefit, alongside the updated global HARMONi data support its platform potential across multiple indications, many of which could be blockbuster opportunities on their own. We have only just begun to see the potential of ivonescimab to help patients with solid tumors. These are exciting times at Summit, and we encourage you to follow our journey closely as we continue to expand the ivonescimab clinical development plan in new tumor settings. Now I will turn the call over to Manmeet to provide a financial update. Manmeet?
Thank you, Maky, and good afternoon, everyone. On the financials front, let me start with our cash position. We ended the second quarter of 2026 with a strong cash position of approximately $690.7 million as compared to $598.7 million at the end of first quarter of 2026. This increase of $92 million in cash position for the quarter is primarily due to the $231 million cash raised from our ATM facility, offset by the cash used in our operating activities of approximately $140 million for the second quarter of 2026. Consistent with our financing strategy in the past, earlier today, we also filed a prospectus supplement for a new ATM facility up to $380 million to provide us with additional flexibility for financing, both with respect to mechanism and timing. And finally, to remind everyone, currently, we have no debt on our balance sheet. Turning to operating expenses. I will provide details on both GAAP and non-GAAP numbers. You can refer to our press release issued earlier today for a reconciliation of GAAP to non-GAAP financial measures. As a reminder, non-GAAP expenses exclude stock-based compensation expense. Total GAAP operating expenses for the second quarter of 2026 were $220.5 million compared to $195.2 million for the first quarter of 2026. The increase in GAAP operating expense was primarily due to an increase in our R&D expenses related to clinical trial expenses for HARMONi-GI3, HARMONi-3 and HARMONi-7. Overall, our non-GAAP operating expenses during the second quarter of 2026 were $151.8 million compared to $122.4 million for the first quarter of 2026. This increase in non-GAAP operating expenses was primarily related to an increase in R&D expenses, as previously mentioned. And with that, I will turn the call back over to Dave.
Thank you, Manmeet. We will now see if there are any questions. Operator, if you could please open the line for those questions.
分析師問答
Your first question is from Yigal Nochomovitz with Citigroup.
So very interesting recent updated overall survival cut from the second-line EGFR study. I'm wondering if you could speak to the translatability of that conclusion in terms of equivalence on OS across geographies when thinking about some of the other larger markets, specifically, of course, frontline non-small cell lung cancer. Could you talk about how you think those OS results could translate to those other settings, please?
Sure. Thanks, Yigal, and appreciate the question. This is Dave. So I think in terms of takeaways and learnings, maturity and follow-up time is critical, in particular, for ivonescimab as a next-generation immunotherapy. As we think about the translatability, what we saw is with meaningful follow-up time, there was consistent magnitude of benefit of overall survival. That's particularly important when we think about the difference between what we saw at the primary analysis in HARMONi versus what we saw published yesterday. When we take that to the other frontline studies, we have an opportunity now to show a magnitude of benefit that is clinically meaningful in those studies as well with the appropriate follow-up time specifically for overall survival. If you recall, HARMONi-6 had a median follow-up time of 21 months in its overall survival analysis. In the recent data that we published yesterday for HARMONi, the Western patients now have approximately 23 months median follow-up time. As we look at what that means overall, it's important globally to have consistent follow-up time that's meaningful across regions. So not necessarily equal to each other, but meaningful for all regions. We expect the ability to translate clinically meaningful results in China to clinically meaningful results across the globe with meaningful follow-up time.
Okay. And just one quick follow-up, if I may, on HARMONi-3. So can you provide any more granularity on the timing within the second half of this year for the final PFS? And then with the early interim OS look, is this going to be like a qualitative comment? Or are you going to be able to perhaps give a very early hazard ratio? If you could speak to that, please?
Yes, absolutely. With respect to timing, as we enter the second half of 2026, we have a clearer view on event rates and are providing more precise language with respect to expectations for disclosures. Event rates have slowed down a little. We still expect to reach the number of events needed for the PFS analysis in the second half of this year, but that timing is not next month and is likely towards the middle to back end of 2026. That's why we're a little more precise within the press release itself. With respect to the disclosure itself, we don't have a specific disclosure plan set, but we would expect a directional trend from that data. We do expect an ability to meaningfully take away the likely direction of overall survival in this study. Recall that with 22 to 23 months of follow-up time in an overall survival analysis, we've shown meaningful data in HARMONi-6 in China and then the global HARMONi data with Western patient follow-up. Follow-up time will be important to get a full clear picture, but we do expect to see an overall survival trend that will be meaningful to us when we look at it later on.
The next question comes from the line of Tyler Van Buren with TD Cowen.
This is Nick on for Tyler. With the HARMONi-3 survival analysis, the interim survival analysis in the first half of next year, will we get an overall survival hazard ratio potentially at this point? And if so, what will be the median follow-up as we think about what the bar should be and how it could progress over time, just like we saw with the Western population in the HARMONi trial?
Yes. That's a fair question, Nick, and I appreciate it. The additional overall survival interim analysis looked at in the first half of 2027 gets closer to the median follow-up times that we saw with the HARMONi-6 OS analysis and the Western patients we disclosed yesterday. That first analysis is independent of any preplanned PFS analysis. That's why it was important to call that out specifically in Maky's prepared remarks and our press release. From a follow-up time perspective, we would expect that in the first half of 2027 the median follow-up to be consistent with what we saw for HARMONi-6 as well as for the HARMONi Western data.
Your next question is from the line of Salveen Richter with Goldman Sachs.
Just following up on the last question. But given the split of the study into separate squamous and non-squamous cohorts and that enrollment was overall back-end loaded, how do we think about the level of follow-up in the context of the interim OS readout? If statistical significance is not seen at the interim, in your view, what level of OS benefit would support or trend here would support a statistically significant final OS result?
Thanks, Salveen. I want to clarify a couple of points. We expect to hit the number of events for PFS analysis sometime in the second half of this year. That will be accompanied by a supporting OS analysis, an interim. Then in the first half of 2027 there will be another interim OS analysis. The final OS would be a ways out. For the second half this year, we would expect to see curve splitting for survival, a beginning look at overall survival that supports PFS. The first half of 2027 will have median follow-up time consistent with what we saw in the HARMONi analysis for Western patients. That first independent of PFS look will be a powered interim look at OS. We won't give specific thresholds, because it's a totality of what the curve looks like, number of events, maturity, and so on. But the first-half 2027 look is a key independent interim assessment.
The next question is from the line of Brad Canino with Guggenheim.
Question from me is around the regional enrollment in H3. I'm wondering if that was done in parallel or if that was staggered because I'm thinking about this from the perspective of making sure the subgroups at an early interim OS analysis aren't skewed by, say, the North American patients coming in later than the China patients and not having time to see the effect like actually happened in the HARMONi study.
Thanks for the question, Brad. The enrollment started globally at the same time generally speaking. Enrollment in China is more rapid than in Western countries, so you see Chinese enrollment happen a bit faster, which is typical. When we look at timing of events, we take lessons from HARMONi to ensure sufficient events have taken place across the globe. It's not sequential like HARMONi was. It's important to have sufficient events across the study. That's contemplated within our approach. I'll let Allen add some comments as well.
I'm going to add to this. Brad, HARMONi-3 was our global study, started globally at the same time. Certain regions open very quickly and enroll very quickly; other areas, like Europe, have more administrative burden for ethics committee review. In the squamous population, that's more prevalent in China, so you'll see more aggressive enrollment there. For the non-squamous cohort, remember we added that cohort after the study was ongoing. Sites were mostly open across the globe, and that disease is more prevalent in the West. It's probably two-thirds of non-small cell lung cancer outside of China, whereas in China it's the other way around with squamous. Therefore, enrollment was actually very brisk in the West. We don't expect to see those differences.
Our next question is from the line of Mohit Bansal with Wells Fargo.
This is Will Zhang on for Mohit Bansal. Following up on HARMONi-3. You previously expanded enrollment to include both squamous and non-squamous and the total size of the trial to push up some of these PFS and OS analysis timelines. How are you thinking about, one, the risk of a high proportion of these PFS and OS events coming from early progressors or early OS event patients? And two, how are you thinking about what the median follow-up time will look like at the first half interim OS for squamous?
The easier question is the median follow-up at the first half of 2027—generally speaking, we would expect median follow-up in the low 20s months, consistent with HARMONi-6 OS analysis and HARMONi Western data. Regarding domination by early progressors, a larger sample size reduces that effect. With a smaller sample size you'd see more variability. With larger sample sizes we avoid that statistical noise. Squamous patients unfortunately pass earlier so they need less sample size. For squamous and non-squamous we believe we have sufficient sample size to avoid statistical noise and variability.
I would add, unlike trials like KEYNOTE-024 or 042 which were monotherapy IO studies, HARMONi-3 includes chemotherapy, which should prevent early progression. Chemo will control disease early in both cohorts and allow the immunotherapy to take effect.
Your next question is from the line of David Dai with UBS.
For the updated HARMONi data that you presented yesterday, could you help us understand the maturity of the updated OS data set relative to the September 2025 analysis? And whether the incremental follow-up meaningfully increased the number of OS events observed? We just want to get a sense of whether investors should really focus on the incremental improvement from HR from 0.78 to 0.76 or the fact the OS benefit remains stable despite a substantially longer Western follow-up.
David, the main takeaway from yesterday's analysis is that with meaningful follow-up in both regions—Asian and Western—you have a similar magnitude of benefit. HARMONi effectively enrolled first in China and later in the West, based on timing of the transaction to in-license ivonescimab with Akeso. EGFR mutation-positive lung cancer is more prevalent in Asian patients, so a higher proportion of patients are enrolled in Asia—about 60% Asian and about 40% Western, typical for EGFR mutation-positive studies. When we look at the global survival analysis overall, we saw consistent magnitude of benefit with the HARMONi-A China-only study and the HARMONi study. There was no clear detriment from Western patients with early follow-up; as follow-up matured the Western patients showed the same magnitude of benefit. We saw a 0.79, 0.78 in earlier follow-up and 0.76 yesterday. We're seeing a consistent magnitude of benefit, and when the Western subgroup has additional maturity they show the same magnitude of benefit. The real takeaway is importance of follow-up time, maturity of data, and the consistency of Western patient performance when they have meaningful time on study.
Got it. And then just want to follow up. You stated yesterday that the updated HARMONi data was provided to the FDA. Maybe can you just discuss whether the agency specifically requested this data and whether you have received any feedback regarding how the FDA views the more mature survival data so far?
The data itself is a recently performed analysis; even though data cutoff is in June it takes time to clean the data and finalize before performing the analysis. We have recently performed this analysis and we have not received meaningful feedback in the short time since we made this data available to the FDA. Ultimately, we believe this data is important in the context of the full story regarding the HARMONi trial and the potential benefit of ivonescimab in the EGFR mutation-positive setting, including patients in the U.S., given the authority in which we're seeking approval.
Your next question is from the line of Reni Benjamin with Citizens.
Congratulations on the progress. Maybe just starting off with the upcoming PDUFA date. Do you think this filing with the updated OS could result in a major amendment and a potential pushing back of the PDUFA date? Or do you think likely this is going to progress as scheduled? And do you think that an ODAC panel could potentially be convened for this application? And then just as a follow-up, if we take a step back and just look at the landscape, I'm curious how you guys are thinking about the competitive positioning given the amivantamab data and some emerging TROP-2 ADC data. Do you feel that ivonescimab will be in this sandbox with everyone else? Is there a certain competitive edge that could squeeze other players out? How are you thinking about it?
Thanks, Reni. Regarding the PDUFA date, this is a new analysis and we recently submitted it to the agency. We don't have an expectation of the PDUFA date moving, but that's ultimately the agency's call. The same holds true for any advisory committee; that decision lies with the FDA. On where ivonescimab fits in the competitive landscape: two agents currently have some level of approval. Amivantamab has a full approval in combination with chemotherapy and datopotamab has an accelerated approval in a different post-TKI and post-chemo context than the indication we're seeking. From an efficacy perspective, no compound to date has shown a statistically significant overall survival benefit. Comparing across trials, the MARIPOSA-2 amivantamab plus chemo data is generally consistent in efficacy profile. We have dosed over 4,000 patients across several settings and shown a manageable safety and tolerability profile across tumor types, lines of therapy, and histologies. We've received a lot of KOL feedback about manageability and tolerability. All three regimens—amivantamab, datopotamab, and potentially ivonescimab—offer different mechanisms. That provides physicians and patients with options to use different mechanisms of action. Some patients may respond to one and not another; that choice is good for treatment. That mechanistic differentiation is an advantage.
Our next question is from Eric Schmidt from Cantor.
Just going back to HARMONi-3. I think this is the first time we're hearing about two interim analyses. Just want to confirm that that's always been the plan, even if you haven't talked about it, and that you're spending alpha on all three of these looks?
Eric, we've talked about OS analyses plural multiple times. We wanted to be transparent about when opportunities exist for results at different periods of time and provide clarity on timing. Follow-up time is important, so we highlighted the first half 2027 look specifically.
There's alpha spent on all three dates?
Yes, they're formal analyses.
Okay. And one thing we didn't hear much about was your pre-commercial preparation in advance of the November 14 PDUFA date for HARMONi. Is that tracking as expected? Are you hiring field force or medical science liaisons? How is that going?
Eric, as Maky mentioned in her prepared remarks, we are extensively preparing for a potential commercial launch with the anticipated PDUFA date of November 14. We have already hired all the leadership team with extensive experience in both biotechs and pharma who have multiple launch experiences. We have a market access team in place and marketing folks in place. Field force hiring generally comes a few weeks before the PDUFA date, but we have all the planning and work underway.
I would add that we have ramped up medical science liaisons in support of these preparations.
Your next question is from the line of Dara Azar from Stifel.
Congrats on all the progress. I have a question on alpha spending and its potential impact on HARMONi-3 squamous OS. I'm curious what gives you confidence that you can afford the alpha for another look at OS in HARMONi-3 squamous next year as well? And would the alpha be passed to the next analysis if the first look is positive? And a quick follow-up: Is there any connection between tracking death events and the decision to add another look at the OS squamous next year?
A couple of points. The alpha spend on the primary PFS look is minimal since it's intended to be supportive of the PFS analysis. The events reached in the second half of this year are intended to be the primary PFS look with a supportive OS look; that alpha spend is minimal. That provides the opportunity for two further looks thereafter. There's no change in plan; tracking death events wasn't the driver you asked about. The first half of 2027 remains a key focal point for reaching median follow-up and is consistent with the timing of HARMONi Western patient maturity and the HARMONi-6 OS analysis.
Your next question is from the line of Faisal Khurshid with Jefferies.
I wanted to go back to the HARMONi-3 interim PFS analysis that passed. Could you contextualize for us what was the alpha spend in that interim? Many investors have interpreted missing that interim as suggesting that HARMONi-3 is tracking worse than HARMONi-6. Is that a correct take? Why or why not?
Thanks, Faisal. A couple of points: the threshold to achieve statistical significance at that interim was meaningfully higher than for the final analysis. Follow-up time is very important for ivonescimab. The timing of that interim analysis was shortly after completion of enrollment, so there wasn't much follow-up time for many patients. Those factors explain why missing that interim doesn't mean HARMONi-3 is tracking worse than HARMONi-6. The analysis was performed by the independent data monitoring committee and we remain blinded to those data. We're confidently moving into the second half of this year and continue to learn as we conduct analyses, which increases our confidence. As I mentioned before, Western subgroup movement with additional follow-up is a proxy for follow-up time, and with more maturity you see movement.
Your next question is from Kristen Carter with Piper Sandler.
This is Kristen on for Kelsey. I believe you mentioned a little bit about what you've heard from KOLs. Could you expand on what they're saying post-ASCO for HARMONi-6, please?
KOLs were very positive on the HARMONi-6 data. Feedback has been that a 34% reduction in the risk of death is impressive over a PD-1—very encouraging. Some feedback was that a discussant who wasn't positive missed the point of the study. The ASCO committee understood it was a regional study, but the data is exciting. There were three other studies supporting the observation, and there was discussion about age effect; in those other studies there was no difference by age group. In the previous presentation of HARMONi-6, which only had the PFS, there was explanation of age based on covariates. The most exciting thing about this agent is that it seems active in diseases not traditionally active for PD-1s, like microsatellite-stable colorectal cancer. Those points were highlighted by many KOLs after the meeting.
We have reached the end of the question-and-answer session. I will now turn the call back to Dave for closing remarks. Please go ahead.
Thanks very much, and I think I will hand it over directly to Bob.
Thanks, Dave. It's good to hear from our shareholders and fellow stakeholders. Over the years, from nothing, I've raised over $1 billion of after-tax money in support of health care companies, whether they be drug or medical devices. It's been fun coming up with a vision and putting a team together for execution and watching the companies proceed. We know that ivonescimab works. So the question I'll leave you with is, what if ivonescimab works really well? Have a good day.
This concludes today's call. Thank you for attending. You may now disconnect.