Summit Therapeutics Inc. Common Stock Q2 2026 Earnings Call

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. 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 their 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 toward 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 three. Ivonescimab has read out four phase III clinical studies to date, all four with positive data. This has led to two approvals in China so far, with one 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 sync positive signals for patients facing high-end 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 four, we see a snapshot of the current ivonescimab development plans across Summit and Akeso, as well as a Phase III clinical trial sponsored by 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 a 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 their 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 result 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 continued positive regionally consistent data of this Phase III multi-regional 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 seven, we have four 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 first-line 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 first-line 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 a 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 first-line 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 first-line 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 head and neck cancer through a European cooperative group, GORTEC.

This is another multi-regional 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 U.S. based on continued progress. Additionally, we have over 65 ISTs that we intend to support in various stages of development. Of these, 24 are currently enrolling and more publication on being featured at each major medical conference, often in prominent session 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. I would like to take a minute to focus on some of the clinical trial collaboration 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 combinations, our collaboration with Revolution Medicines began enrolling in the first quarter of this year. This collaboration evaluates ivonescimab in combination with three 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-2α 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 optimists.

We have heard from many investigators as they consider the potential opportunity that ivonescimab presents across multiple tumor types and in multiple novel combinations regimens. Let's take a closer look at the clinical data we have seen from ivonescimab today, focusing on OS results. Of the four phase III studies that have read out to date, all four 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 replaced a PD-1 inhibitor in 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 0.6. 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 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 ivo, the potential next generation of cancer therapy. As we have said before, we feel the data speaks for themselves 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 nine 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 event 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 for 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, to our partnership with GORTEC 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 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 identify the more than 50 solid tumor settings where anti-PD-1, 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 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 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 indication, 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 a new tumor setting. Now I will turn the call over to Manmeet to provide a financial update. Manmeet? Thank you, Miky, 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.

$0.4 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. With that, I will turn the call back over to Dave. Dave? Thank you, Manmeet. We will now see if there are any questions.

Operator, if you could please open the line for those questions.

We will now begin the question and answer session. Please limit yourself to one question and one follow-up. If you would like to ask a question, please press star one to raise your hand. To withdraw your question, press star one again. We ask that you pick up your handset when asking a question to allow for optimum sound quality. If you are muted locally, please remember to unmute your device. Please stand by while we compile the Q&A roster. Your first question is from Yigal Nochomovitz with Citigroup. Go ahead. Hi. Great. Thank you very much for taking the questions.

Very interesting recent updated overall survival cut from the second-line EGFR study. I am 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? Thank you. Sure. Thanks, Yigal, and appreciate the question.

This is Dave. I think in terms of takeaways and learnings, maturity in 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 an overall survival median follow-up, or a median follow-up time rather of 21 months in its overall survival analysis.

The recent data that we published yesterday for HARMONi, the Western patients now have 23 months approximately of 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 both, so that 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, thanks. Just one quick follow-up, if I may, on HARMONi-3. Can you provide any more granularity on the timing within the second half of this year for the final PFS? With the early interim OS look, is this going to be 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.

Yeah, absolutely. I think with respect to timing, as we enter the second half of 2016, we have a little bit of a clearer view on event rates and are providing more precise language with respect to expectations here for disclosures. In general, event rates have slowed down a little bit. We still expect to reach the number of events needed for the PFS analysis in the second half of this year. That timing is not next month, and it is going to be likely towards the middle to back end of 2026, and that's why we're a little bit more precise within the press release itself. With respect to the actual disclosure itself, I don't know that we have a specific disclosure plan set, but I think what we would expect is a directional trend from that data.

Again, not necessarily a determined disclosure plan. What we do expect is an ability to meaningfully take away the opportunity of what overall survival will show in this study. Again, recall the fact that with 22, 23 months of overall survival or follow-up time in an overall survival analysis, we've shown meaningful data in HARMONi-6 in China, and then the global HARMONi data, the Western patients with meaningful follow-up time showed that benefit. The follow-up time will be important there to get a full clear picture. We do expect to see an overall survival trend that is meaningful to us when we look at it later on.

Great. Thank you. The next question comes from the line of Tyler Van Buren with TD Cowen.

Tyler, your line is open. Please go ahead. Great. Thanks very much.

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? 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? Thanks. That's a fair question, Nick, and appreciate it.

I think with respect to the additional overall survival interim analysis looked at in the first half of 2027, that gets closer to the median follow-up times that we saw with the HARMONi-6 OS analysis, as well as the western patients that we disclosed yesterday. I think that piece in particular, when we look at the first half 2027, that's really the first analysis that is independent of any pre-planned PFS analysis. That's why it was important, we felt, to call that out specifically in McKee's prepared remarks as well as our press release. That additional OS analysis, we used that first analysis that's not directly linked to a PFS analysis.

From a follow-up time perspective, we would expect that to be in the first half of 2027, the median follow to be consistent with what we saw for HARMONi-6 as well as for the HARMONi western data that we talked about yesterday.

Very good. Thanks. Your next question is from the line of Salveen Richter with Goldman Sachs.

Your line is open. Please go ahead.

Thank you. Good afternoon. Following up with the last questions, 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?

Yeah. Thanks, Salveen, for the question. I want to just clarify a couple of points. We'll hit the number of events, or we expect to hit the number of events for a PFS analysis sometime in the second half of this year. That will be accompanied by a supporting OS analysis, and that would be an interim. In the first half of 2027, that would also be an interim OS analysis. The final OS, as would be consistent with frontline studies, would be a ways out. What I would expect that we see when we look at the analysis in the second half of this year would be one that supports the curve splitting for survival.

A beginning look at overall survival that we would expect if we look and we compare when the curves split for HARMONi 6, that's a good indication in terms of what we would be looking to see. That'll be early, and that's really supportive of PFS. We look at many trials when they run a primary PFS analysis have a supporting OS look. We look in the first half of 2027, that now has median follow-up time consistent with what we saw, again, in the HARMONi analysis for Western patients that we talked about yesterday. When we look at HARMONi 3 squamous in the first half of 2027, that's really a powered look at OS from an interim analysis perspective.

We're not going to give specific thresholds per se, because I think that it's a totality of what the curve looks like, number of events, maturity, so on and so forth. That Q1 or first half rather, 2027 look, that really would be that independent of PFS, that powered interim look at OS.

Thank you. The next question is from the line of Brad Canino with Guggenheim.

Your line is open. Please go ahead.

Hi. Thanks for the updates. 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 happen in the HARMONi study. Thanks. Thanks for the question, Brad.

We've talked a little bit about the fact that the enrollment started together, generally speaking, but obviously enrollment in China is more rapid than it is in Western countries. There's certainly a little bit of data that you see that involves Chinese enrollment a little bit faster, which is typical of what you would see in many studies. I think when we look at the timing of the events, part of what we take away from the learnings from HARMONi and whatnot is to make sure we have sufficient events that have taken place across the globe. It's not sequential timing to the extent that HARMONi is by any stretch. Of course, it becomes important to have sufficient events across the study with respect to those events.

That's contemplated within our approach plan, and I'll let Alan add some comments as well.

Yeah, I'm going to add, Brad, to this. This is Alan. Brad, good question. Just commenting on some of the previous questions. I just want to remind everyone that HARMONi 3 was our global study, it was started globally at the same time. There are some differences. Certain regions open very quickly and enroll very quickly. Other areas, there's more administrative burden, like Europe, to get the ethics committee review to open. In the squamous study population, that is more prevalent in China, you'll see more aggressive enrollment. However, I think people are asking about the non-squamous cohorts, remember, we added that cohort after the study was ongoing. The sites were mostly open across the globe. In addition, 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 the squamous. Therefore, enrollment was actually very brisk in the West, we don't expect to see those differences.

All right. Thank you. Sure.

Our next question is from the line of Mohit Bansal with Wells Fargo. Your line is open. Please go ahead.

Hi, this is Will Vang on for Mohit Bansal. Thanks for taking our question. Just kind of following up on HARMONi-3, I know you guys previously expanded the enrollment for the trial to include both squam and non-squam, but also the total size of the trial to push up some of these PFS and OS analysis timelines. Just want to understand, how are you guys thinking about, one, the risk of a higher proportion of these PFS and OS events coming from early progressors or early OS event patients? Two, just how you're thinking about what the medium follow-up time will look like at the first half interim OS for squam.

Yeah. The last question, I think, is probably the easier of the two in the sense of when we get to the first half of 2027, we would expect median follow-up time, generally speaking, in the low 20s months. Right? As I was saying before, consistent generally with what we saw in the HARMONi-6 OS analysis, as well as what we saw in terms of the Western follow-up for patients in the HARMONi study. With respect to the first question on not being dominated by early progressors, part of that also includes the larger sample size takes that effect away. With the smaller sample size, you run more variability.

You could be more dominated with unexpected answers, if you will, with respect to if you have a few more patients who progress early or pass away early, with a smaller sample size, you have a little bit more variability in what you see there. With a larger sample size, with what we see in squamous, unfortunately, those patients pass on a little bit earlier, so that doesn't require quite as large of a sample size. For the squamous and non-squamous, we have what we believe is a sufficient sample size in order to be able to avoid any of that statistical noise and variability that you can see.

I would just add, unlike the KEYNOTE-024, 042 studies, which were monotherapy IO, this includes chemotherapy, it should prevent early progression. The chemo will control the disease early in both cohorts, and allow the IO to take it back.

Your next question is from the line of David Dai with UBS. Your line is open. Please go ahead.

Great. Thanks for taking my questions. For the updated HARMONi data that you were presenting 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 the investor should really focus on the incremental improvements for HR from 0.78 to 0.76, or the fact the OS benefit remains stable despite a substantially longer Western follow-up.

Yeah. David, the main takeaway from the analysis yesterday, right, is that with meaningful follow-up in both regions, Asian and Western, you have a similar magnitude of benefit, right? I think as everybody is well aware, the HARMONi study was effectively enrolled first in China, a pause, and then enrolled in the West. That was based on the timing of when we did the transaction to in-license ivonescimab with our partners at Akeso, right? That's a little bit driven based on the circumstances of timing of the transaction and what was already enrolled at the time. When we look at the study as a whole, EGFR mutation-positive lung cancer is a disease that is more prevalent in Asian patients.

We would expect a higher proportion of patients to be enrolled in Asia, as is typical and has been run with the osimertinib studies, some of the amivantamab studies, so on and so forth. Because of that, it's about 60% Asian and about 40% Western. Again, typical split with respect to that for EGFR mutation positive. When we look at the global survival analysis overall, we saw pretty consistent results with the HARMONi-A study that was China only, and the HARMONi study, which was important because there was no clear detriment that was being seen from Western patients with very early follow-up time at the beginning. As that follow-up time matured, what we saw is the Western patients really kind of merged in and saw the same magnitude of benefit with the Asian patients.

We saw across the whole study, we saw a consistent magnitude of benefit irrespective of when we looked at the data. We saw the 0.79, 0.78 in the follow-up shortly thereafter the primary, and then the 0.76 that was announced yesterday. We're seeing that consistent magnitude of benefit. What we see is when the Western subgroup has additional maturity and those patients progress along the Kaplan-Meier curve, if you will, they have the same magnitude of benefit. I think our real takeaway is the importance of follow-up time, the importance of the maturity of the data, and that ultimately the consistency by which we saw the Western patients perform when they had meaningful time on study, and I think that was important.

Got it. Thanks. Just want to follow up. You stated yesterday that the updated HARMONi data was provided to the FDA. 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?

Yeah. The data itself is a recently performed analysis. Even though the data cutoff is in June, it still takes a little bit of time to clean the data and finalize before performing. We've 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, and in particular including those patients in the U.S., given the specific health authority in which we're seeking approval in the U.S.

Got it. Thank you so much.

Your next question is from the line of Reni Benjamin with Citizens. Your line is open. Please go ahead.

Hey, thanks guys for taking the questions and 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? Do you think likely this is going to progress as scheduled? Do you think that an ODAC panel could potentially be convened for this application? Just as a follow-up, if we take a step back and just look at the landscape, I'm kind of curious as to how you guys are thinking about the competitive positioning given the amivantamab data, some emerging Trop2 ADC data. Do you guys kind of feel that ivonescimab will be in this sandbox and kind of playing with everyone else? Is there certain competitive edges that could squeeze other players out?

How are you thinking about it?

Thanks for the question, Renny. With respect to the PDUFA date, this is a new analysis, and again, we recently submitted this analysis to the agency. We don't have an expectation of the PDUFA date moving, but that's really a determination to be made by the agency, so we fully defer. That's ultimately their call should they decide that. The same holds true for any sort of advisory committee or ODAC as well. That's really exclusively an agency decision. With respect to where does ivonescimab fit in terms of competitive landscape and whatnot. As we look at these two agents right now that currently have some level of approval with the FDA.

There's a full approval for amivantamab in combination with chemotherapy, and then there's, as well as the datopotamab accelerated approval with respect to post-TKI and post-chemo, which is a little bit different than the indication that we're seeking, as well as the indication that amivantamab in combination with chemo has. Look, I think from an efficacy perspective, as McKee had mentioned, no compound at this point has shown a statistically significant overall survival benefit. If we look at the efficacy profile overall with respect to what we saw from the MARIPOSA-2 trial from the amivantamab plus chemotherapy, we see they're cross-trial comparisons, which is important, but generally consistent efficacy profile.

I think what we've shown with over 4,000 patients dosed across several different settings of clinical studies, we've shown a manageable safety profile that's consistent, generally speaking, irrespective of tumor type, irrespective of line of therapy, irrespective of histology. We've received a lot of KOL feedback with respect to the manageability and the tolerability of ivonescimab, and I think that's really important here. Obviously, datopotamab comes with a chemotherapy component, if you will, with a payload. All three regimens have a cytotoxic component. I think the other thing that's really important, there's also patients who will respond to different mechanisms. All three of these agents, the two that are approved, either accelerated or fully, and then the potential for the approval for ivonescimab would be three different components.

I think that provides physicians and patients with opportunities to mechanistically work differently from each other. A patient may respond to one and not the other. That choice is a good thing for physicians treating patients and for patients themselves, I think that's something that really differentiates this as opposed to maybe coming in with the same mechanism of action that we see in other spaces sometimes.

Great. Thanks for taking the questions.

Our next question is from Eric Schmidt from Cantor. Your line is open. Please go ahead.

Thank you for taking my question. Coming back to HARMONi-3, I think this is the first time we're hearing about two interim analyses. Want to confirm that that's always been the game plan, even if you haven't talked about it, that you're spending alpha on all three of these looks.

Eric, what I'd say is we've talked about OS analyses, plural, multiple times. I don't know if we've given the timing of the first half 2027 before. I think part of, as we look, we want to make sure we're transparent with respect to when the opportunities exist for results at different periods of time. Obviously we look at the OS analysis coming up. We look at follow-up time, what we've learned from HARMONi-6, and so on and so forth. With that follow-up time being important, we wanted to make sure that was highlighted for everyone.

There's alpha spent on all three days?

They're formal analyses. That's right.

One thing we didn't hear much about was your pre-commercial preparation in advance of the November 14th PDUFA date for HARMONi. Is that tracking as expected? Are you hiring field force or medical science liaisons? How's that going? Thank you.

Yeah, hey, Eric, this is Manmeet. As Micky mentioned in her prepared remarks, we are extensively preparing for our commercial launch with the anticipated PDUFA date of November 14th. We have already hired all the leadership team with extensive experience with both biotechs and pharma who have multiple launch experiences. We have market access team in place. We have marketing folks in place. Obviously, when you're talking about the field force, that generally comes a few weeks before the PDUFA date, but yes, we have all the planning and all the work under play.

I would just add on.

Thank you, Manmeet. Yeah, I'd agree with everything Manmeet said, and then I also, you asked specifically about MSLs as well, which we have ramped up in support of each of the things that Manmeet highlighted.

Thank you, Dave. Yeah, I totally agree. Yeah. We've already ramped up the MSLs.

Thanks, guys. Stifel. Your next question is from the line of Dara Azar from Stifel.

Your line is open. Please go ahead.

Hi. 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 the HARMONi-3 squamous next year as well? Would the alpha be passed to the next analysis if the first look is positive? A quick follow-up, is there any connection between tracking death events and the decision to add another look at the OS of squamous next year? Thanks so much. Yeah. A couple of points there, Dara.

I think on the last point, we've had this look in the first half of 2027. The timing, you don't necessarily always know the timing. It's event driven. The analysis has been there. The alpha spend with respect to the primary PFS look is pretty minimal, specifically because it's really intended to be supportive of the PFS analysis. In the events reached in the second half of this year is really intended to be the primary PFS look, and then there's a supportive look at OS. That alpha spend is minimal. There's not a lot of concern with respect to, if you will, quote unquote, "the amount spent" just based on maturity of OS at that time. It becomes pretty minimal. That gives an opportunity for two full looks, if you will, thereafter.

No real change in plan from that perspective. It's not like tracking death events, I think was the example that you gave. That's really been the plan throughout. As we look at the maturity timelines, the first half of 2027 is a key focal point with respect to reaching that median follow-up is a proxy that we've seen in both the HARMONi western patients where we showed that positive trending data yesterday and being more converged with the ITT in the Asian population, as well as the timing of the HARMONi-6 OS analysis as well.

Okay. Thank you. Your next question is from the line of Faisal Qureshi with Jefferies.

Your line is now open. Please go ahead. Hey, guys.

Thank you for taking the question. I wanted to actually 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 kind of interpreted missing that interim as suggesting that HARMONi-3 is tracking worse than HARMONi-6. Is that a correct take, and why or why not? Thank you. Thanks, Faisal. I think I'd probably say a couple of things to effectively answer the questions that you're asking, which is the threshold to achieve statistical significance at the interim was meaningfully higher than that of what is needed for the final analysis.

As well as we continue to see follow-up time is very important with IBRANCE and IMFINZI. That is certainly, I think as we talked about last time, the timing of that analysis was shortly after as we looked at the completion of enrollment. We effectively announced completion of enrollment and then right into that interim analysis. Not a lot of follow-up time for many patients on that study. Those are two reasons why I don't think it's necessarily the right way to look at it with respect to different from HARMONi-6 one way or the other.

It's important also, that analysis was performed by the independent data monitoring committee. We remain fully blinded to that data. That's not something that we have hazard ratios and additional data for. We're confidently going into the second half of this year, and we've continued to learn more each time we have conducted analyses with respect to ivonescimab and continued to increase that confidence.

Great. Thank you. Yeah, the only thing I'd add on top of that, Faisal, obviously, as you look at the Western subgroup that we published yesterday, with additional follow-up time, you see a pretty meaningful movement of the Western subgroups.

Is a proxy here for follow-up time. Let's talk about Western patients and more of a proxy for follow-up time, but with that additional follow-up time, you do see movement there, which is important.

Understood. Thank you. Your next question is from the line of Kristen Carter with Piper Sandler.

Your line is now open. Please go ahead. Hi, 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? Thank you. Yeah. I think the KOLs for HARMONi-6 were very positive on the data.

I think some of the feedback I've heard is that it's very encouraging. A 34% reduction in the risk of death is amazing over a PD-1. This is really phenomenal data. I think some of the feedback we got was that the discussant who wasn't very positive on the data sort of missed the point of the study, right? We understood fully, the ASCO committee understood fully that it was a regional study, right? Very exciting and intriguing data. There wasn't any discussion, the fact that we would have confirmatory or global data within the end of the year. We're less than six months away. The other thing is that there were other studies, three other studies supporting the observation that was seen there.

In addition, there was some discussion about age effect. In any of those other three studies, there was no difference by age group. In addition, the previous presentation of the HARMONi-6 data, which only had the PFS, there was an explanation of the age based on covariates. Finally, the most exciting thing about this agent is that it seems to be active in diseases that weren't traditionally active for PD-1s, like microsatellite stable colorectal cancer. None of these things were highlighted in this, but this was brought up a lot by a lot of the KOLs after the meeting.

Great. Thank you so much. Congratulations again. 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.

I think I will hand it over directly to Bob.

Hi. Thanks, Dave. It's good to hear from our shareholders and our fellow stakeholders. Over the years, from nothing, I've raised over $1 billion of after-tax money in support of healthcare 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. The question I leave you with is, what if ivonescimab works really well?