Summit Therapeutics Inc. Q4 FY2025 Earnings Call

Good afternoon, and welcome to Summit Therapeutics Q4 and Year-End 2025 Earnings Call. We do not expect any technical difficulties today. However, if we lose the webcast connection and cannot provide 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 at 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 fourth quarter and year-end 2025 financial results and operational progress. This afternoon's press release is available on our website, www.smmttx.com. Our Form 10-K 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 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-K issued today about these risks and uncertainties. Summit undertakes no obligation to update these forward-looking statements, except as required by law. One item to note, this presentation is being webcast with slides, so we'll be referring to the slides being displayed in the webcast 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'd like to hand it over to Maky.

Thank you, Dave. Good afternoon, everyone, and thank you for joining us today. I'm very proud of Team Summit's ongoing accomplishments and the growing positive data sets and support around ivonescimab, a PD-1 VEGF bispecific or lead investigational asset. We are a highly focused, mission-driven patient-first company with a mission to make a significant difference in improving the lives of patients suffering from cancer. Our team is growing rapidly as we expand our clinical development plan and prepare for commercialization in anticipation of a decision from the FDA on our BLA near the end of this year. We have announced a few significant events today, starting with the update related to our HARMONi-3 study. Last quarter, we announced our HARMONi-3 Phase III trial evaluating ivonescimab plus chemo as first-line treatment for patients with squamous and non-squamous non-small cell lung cancer, was amended to have separate analysis by squamous and non-squamous histologies for primary endpoints of PFS and OS for each cohort. The squamous cohort was planned to complete enrollment in the first half of 2026, followed by the non-squamous cohort in the second half of this year. As announced today, we have now completed screening patients for the squamous cohort of the HARMONi-3 study, and the last patient will be randomized in the next couple of weeks. We have amended our statistical plan to now include an interim PFS analysis for our squamous cohort, and we are planning to conduct the interim PFS analysis during the second quarter of 2026. Overall survival will be immature at the time of this analysis. Therefore, we may not have overall survival results to communicate at that time. As you recall, we initially included PFS as a primary endpoint in the study upon the readout of HARMONi-2 comparing ivonescimab to pembro in PD-L positive frontline lung cancer patients, which showed a highly statistical significant and clinically meaningful benefit in PFS with a hazard ratio of 0.51 and a median improvement in PFS of over 5 months. This point was later validated with HARMONi-6, showing that there was a substantial PFS benefit when comparing ivonescimab plus chemo versus a PD-1 inhibitor plus chemo with a hazard ratio of 0.60. Two Phase III studies conducted by Akeso in China in frontline non-small cell lung cancer demonstrated a 40% plus improvement in PFS for the ivonescimab arm, both the HARMONi-2 and HARMONi-6 PFS results were based on the planned interim PFS analysis of each study. By adding an interim PFS analysis, we opened the door to an earlier discussion with the health authorities for our multiregional Phase III study. The final PFS analysis, if applicable, and an interim analysis for OS is planned to be conducted in the second half of this year, consistent with previous guidance. For the non-squamous cohort of HARMONi-3, we continue to expect enrollment to complete in the second half of this year and to reach the prespecified number of events for the final PFS analysis by the first half 2027. There are several meaningful moments upcoming related to these two cohorts, each of which are independent from each other, like two separate studies in one protocol, where 2026 will be pivotal to providing additional clarity to expand the reach of ivonescimab to a broader population of lung cancer patients. Additionally, we announced today the first update to the ivonescimab Phase III clinical trial program, which will continue to expand throughout 2026. ILLUMINE, a new Phase III study in PD-L1 positive frontline head and neck squamous cell carcinoma, will be sponsored by GORTEC, a French cooperative group dedicated to head and neck oncology, with initial enrollment expected to begin early next quarter. The study intends to evaluate both ivonescimab monotherapy and in combination with ligufalimab, Akeso's proprietary anti-CD47 monoclonal antibody, against monotherapy pembro in this three-arm randomized study. Approximately 780 patients are intended to be enrolled across the three arms in multiple countries in Europe and in China. We may consider potentially expanding the study to include U.S. sites as well. Phase II data supporting the potential use of ivonescimab in this patient population was previously presented at ESMO 2024, where ivonescimab in combination with ligufalimab demonstrated an objective response rate of 60% in 20 patients with a median PFS of 7.1 months after median follow-up of 4.1 months. At the time of this analysis, no patients receiving ivonescimab plus ligufalimab discontinued treatment due to treatment-related adverse events. The data generated in Phase II is encouraging in light of existing standard of care, and Akeso is also running a single-region Phase III trial in this population in China. Turning to our clinical collaboration with Revolution Medicines. Today, we announced the first patient has been dosed in the collaboration's initial clinical trial. As a reminder, ivonescimab is being evaluated in combination with three RAS(ON) inhibitors, including daraxonrasib, a multi-selective RAS inhibitor, zoldonrasib, a KRAS G12D selective inhibitor, and elironrasib, a KRAS G12C selective inhibitor across multiple solid tumor settings with RAS mutations, including pancreatic cancer, colorectal cancer, and non-small cell lung cancer. Finally, as we announced last month, we entered into a clinical collaboration with GSK to evaluate ivonescimab in combination with GSK's novel B7-H3 antibody drug conjugate in multiple solid tumors. The initial study under this collaboration is expected to begin dosing patients in mid-2026. Let's take a step back and look at ivonescimab accomplishments to date. There are many to highlight. Ivonescimab has read out four Phase III clinical studies to date, all four of which have had positive data, leading to two approvals in China so far. At this time, a total of 15 Phase III trials have been announced, currently ongoing, or have read out in multiple tumor types. 44 clinical trials have been initiated since 2019 between Summit and Akeso evaluating ivonescimab in a variety of solid tumors. Considering investigator-initiated and collaborative studies, a total of 142 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 needs really speaks to the opportunity and optimism surrounding ivonescimab. Together with our partner, Akeso, we have enrolled over 4,000 patients in either Summit-sponsored or Akeso-sponsored clinical trials across the world. Commercially in China, over 60,000 patients have received ivonescimab based on two approved indications by the NMPA in non-small cell lung cancer according to our partners at Akeso. A third indication based on the positive HARMONi-3 study in frontline squamous non-small cell lung cancer is currently under review by the NMPA in China. I wanted to make sure this point is not missed: four Phase III trials evaluating ivonescimab have read out to date, and all four with positive data readouts. This represents the only Phase III readout that we have seen in the PD-1 VEGF bispecific class to date. These positive trials are supported by the differentiated mechanism of action of ivonescimab. Here is the current ivonescimab development plan across Summit and Akeso. In total, there are 15 randomized Phase III trials, four of which are global Summit-sponsored studies in non-small cell lung cancer and colorectal cancer; one of which is a multiregional cooperative group study announced today; and 10 of which are being enrolled by Akeso in China in a variety of solid tumor types, including lung, breast, head and neck, BTC, pancreatic, and colorectal cancers. Additionally, Akeso is also currently enrolling multiple Phase II trials evaluating ivonescimab in other tumor types, ovarian, gastric, HCC, and others, including non-metastatic settings. Through our partnership with Akeso, we continuously compile a substantial amount of data, allowing us to make faster, more informed decisions, fueling the rapid expansion of our global development plan. Focusing on our pipeline at Summit, we have four global Phase III trials completed or ongoing, HARMONi, which read out positively last year, HARMONi-3, HARMONi-7, and HARMONi-GI3, all three of which are currently enrolling and progressing nicely. The HARMONi trial evaluated ivonescimab plus chemo against chemo alone as treatment for EGFR mutant non-small cell lung cancer after TKI therapy, a population of significant unmet need with few available treatment options. We submitted a BLA filing last quarter, seeking approval in this proposed indication. In January, we announced the U.S. FDA's acceptance of the filing and a PDUFA target action date of November 14, 2026. 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 to patients in this setting, the positive regionally consistent results of this Phase III multiregional study as well as discussions with key opinion leaders and physicians who have administered ivonescimab to patients, we believe that ivonescimab is a potential treatment option with a favorable benefit-risk profile. In anticipation of potential approval in Q4 of this year, we continue to ramp up commercial capabilities in preparation for potential launch. HARMONi-3 is evaluating ivonescimab plus chemo against pembro plus chemo in frontline metastatic non-small cell lung cancer. This patient population represents a significant unmet medical need with nearly 100,000 patients in the United States alone as this trial covers frontline non-small cell lung cancer patients without genomic mutations irrespective of histology or PD-L1 status. I spoke a minute ago about the recent changes to this pivotal study. For HARMONi-7, this study is evaluating ivonescimab monotherapy against pembro monotherapy as frontline treatment for patients with non-small cell lung cancer that have high PD-L1 expression levels. HARMONi-7 continues to enroll well, and we look forward to providing additional updates in the future. Finally, last quarter, we initiated and began enrolling patients in HARMONi-GI3 evaluating ivonescimab plus chemo compared to bev plus chemo in first-line therapy in patients with unresectable colorectal cancer. Our decision to expand into colorectal cancer was driven by encouraging Phase II data published at ESMO 2024 and subsequent continuing enrollment in this Phase II study in China and the United States with additional chemotherapy regimen. This data set allowed us to make an informed decision to move forward in CRC, specifically with the FOLFOX chemo combination. We look forward to providing further updates on the Phase II data set later this year as well as the HARMONi-GI3 study as the trial progresses. Looking beyond our own sponsored trials, we are expanding into additional settings with multiple collaborations and other groups. We have the Phase III ILLUMINE study sponsored by GORTEC evaluating ivonescimab in head and neck cancer that I spoke to earlier. With respect to novel combinations, we announced that the first patient was dosed this quarter in our collaboration with Revolution Medicines to evaluate ivonescimab in combination with three novel RAS inhibitors across multiple solid tumor settings. We are excited to learn about the opportunity and potential to improve patient outcomes with ivonescimab combined with the novel-targeted therapies and promising molecules. This collaboration is intended to evaluate ivonescimab in combination with one or more of RevMed RAS(ON) inhibitors in pancreatic cancer, colorectal cancer, and non-small cell lung cancer. This collaboration has an opportunity to be mutually beneficial to both Summit and RevMed by leveraging a combination of potential next-generation assets that individually have promise in each setting, and this may have high promise for patients with RAS-mutant cancers. In our GSK collaboration evaluating ivonescimab in multiple solid tumor settings in combination with their B7-H3 ADC, we expect the trial to initiate in mid-2026. This is another example of promising targets seeking to significantly advance outcomes in settings where both ivonescimab and B7-H3 ADCs have shown promise. We have over 60 ISTs that we intend to support in various stages of development. Of these, 15 are currently enrolling, five of these in collaboration with M.D. Anderson, and ivonescimab has now been featured in over 45 publications, presentations, and posters. Collectively, these trials enhance and inform our own clinical development activities as we learn more about new settings where neither we nor Akeso have had the opportunity to explore yet. Tremendous interest in ISTs is a testament to the enthusiasm we have heard from many investigators as they consider the potential opportunity that ivonescimab presents across multiple tumor types. Over the past 18 months, we have seen four positive randomized Phase III trials, including the first and only Phase III trials to compare positively against anti-PD-1 therapy. Each of these studies represent a benefit either over a PD-1 inhibitor or in a setting where PD-1 inhibitors have failed to achieve a benefit in either PFS or OS. Akeso's HARMONi-2 PFS results showed ivonescimab monotherapy as superior to KEYTRUDA in frontline non-small cell lung cancer. These results represent the first time any therapy has achieved a clinically meaningful benefit over KEYTRUDA in a randomized Phase III trial. In April of 2025, Akeso announced that HARMONi-2 achieved a clinically meaningful overall survival hazard ratio below 0.8 at this early look. Moving to Akeso's HARMONi-6 frontline non-small cell lung cancer study in patients with squamous histology, results were announced at ESMO 2025, demonstrating ivonescimab with chemo was superior to PD-1 plus chemo in PFS. With this result, HARMONi-2 and HARMONi-6 represent the first and only known regimens to achieve a clinically meaningful benefit replacing an anti-PD-1 regimen. In EGFR mutant non-small cell lung cancer, both Akeso's HARMONi-A trial and our own global HARMONi trial achieved positive consistent results. In HARMONi, a positive overall survival trend was observed with a hazard ratio of 0.79, barely missing statistical significance. In a subsequent analysis in September 2025 with longer-term follow-up on Western patients, ivonescimab plus chemo showed a favorable trend in overall survival with a hazard ratio of 0.78 and a corresponding nominal p-value of 0.0332. In HARMONi-A, Akeso's final overall survival analysis showed ivonescimab plus chemo achieved a statistically significant hazard ratio of 0.74 with a p-value of 0.019, supporting a treatment profile where overall survival does not degrade, but rather improves over time in this setting. Turning to our market opportunity. The value proposition is clear: ivonescimab on its own has the potential to be a platform blockbuster drug. Additionally, novel combinations with ivonescimab could bring potential improvements over current standard of care, which could expand market opportunity further. Ivonescimab is well positioned to make a significant impact across the solid tumor treatment landscape. Between checkpoint inhibitors and anti-VEGF therapies, TD Cowen and others estimate the total addressable market to be in excess of USD 100 billion globally. Looking only at the checkpoint inhibitor market for non-small cell lung cancer, market estimates for immunotherapy are expected to exceed USD 20 billion by 2028. And yet, these estimates still do not include the full impact ivonescimab could have as it has already shown promising data in multiple tumor types where checkpoint inhibitors have not been effective, including EGFR mutant non-small cell lung cancer and PD-L1 low triple-negative breast cancer. Ivonescimab's differentiated profile supports its platform potential across multiple indications, many of which could be blockbuster opportunities on their own. We have a very exciting year ahead. Here are some of the upcoming milestones we expect to reach in 2026 and into the first half of 2027. Our global clinical studies pipeline will continue to expand, and we will provide further details in 2026 as we begin studies in new settings and indications. This will include additional novel combinations as well as the new Phase III studies that we intend to launch in 2026. The first steps with respect to this expansion came today with the announcement of the cooperative group-led ILLUMINE Phase III clinical study in head and neck cancer. We will continue to expand upon the details of our clinical development plan throughout 2026, including sponsored studies. With today's HARMONi-3 update, we anticipate an interim PFS analysis for the squamous cohort to occur next quarter. Final PFS and interim OS data are expected in the second half of this year. In the HARMONi-3 non-squamous cohort, we expect to complete enrollment this year. We anticipate final progression-free survival data in the first half of 2027. And as already discussed, we are looking forward to a potential first approval for ivonescimab in the U.S. around our November 14 PDUFA date based on our HARMONi BLA filing. Now I will turn the call over to Manmeet to provide a financial and operational update for the quarter.

Thank you, Maky, and good afternoon, everyone. On the financials front, let me start with our cash position. We ended the year 2025 with a strong cash position of approximately $713.4 million. And to remind everyone, currently, we have no debt. Turning to operating expenses. I will provide details on both GAAP and non-GAAP numbers. You can refer to our press release issued this afternoon for a reconciliation of GAAP to non-GAAP financial measures. As a reminder, non-GAAP expenses exclude stock-based compensation expenses. Total GAAP operating expenses for the fourth quarter of 2025 were $225 million compared to $234.2 million for the third quarter of 2025. This decrease in GAAP operating expenses was primarily due to the lower stock-based compensation expense of $19.1 million, and this was offset by an increase in our clinical trial-related spend of $8.8 million. Overall, our non-GAAP operating expenses during the fourth quarter of 2025 were $113.3 million compared to $103.4 million for the third quarter of 2025. This increase in non-GAAP operating expenses was primarily related to an increase in R&D expenses related to HARMONi-3 and HARMONi-7 trials. As you will note, we have been very efficient and disciplined in controlling our G&A spend. Our total G&A spend, excluding stock-based compensation expense, has been approximately $43 million for the full year 2025 with a run rate of approximately $10 million to $11 million per quarter in 2025. On the operations front, I'm extremely proud that Team Summit has been able to accelerate the enrollment of 600 squamous patients ahead of our planned timelines, which will allow us to have interim readout by the second quarter of 2026. With the acceptance of our BLA with the FDA, we have accelerated our commercial readiness activities to prepare for our potential commercial launch of EGFR mutant non-small cell lung cancer post TKI therapy. With respect to manufacturing and drug supply readiness, we have successfully transferred and validated the production process of ivonescimab to a U.S.-based manufacturer. And with that, I will hand it back over to Dave.

Thank you, team. And we will now see if there are any questions that our team can help answer. Operator, if you could please open the line for questions.

We'll take our first question from Salveen Richter at Goldman Sachs.

This is Mark on for Salveen. Congrats on the quarter. Can you talk about what drove the decision to include the interim PFS analysis for HARMONi-3 for the squamous cohort and also frame expectations for both the initial data in the second quarter and also the potential final PFS analysis in interim OS in the second half? Will we see curves in addition to the top line data? And now given the split, do you expect that OS could reach that statistical significance by that final PFS analysis time?

Thanks, Mark. Appreciate the question. This is Dave. So we decided to amend the protocol for the HARMONi-3 study by including an interim analysis for the PFS primary endpoint. If you recall, we previously amended the HARMONi-3 study in order to add PFS as a primary endpoint in addition to overall survival. The reason for the addition of PFS as a primary endpoint was based on the results of HARMONi-2, which showed the large PFS delta that Maky spoke to, a hazard ratio of 0.51, comparing ivonescimab to monotherapy in a number of lung cancer patients. And then this would allow for an earlier discussion with the agency based on the PFS primary endpoint and now an interim PFS. So it's really about accelerating the timelines with respect to the data based on two interim readouts from our partners at Akeso in studies in lung cancer. And so with both studies reading out positively, the overlap in the indication with respect to HARMONi-6 gives a strong indication in terms of the opportunity that exists here with ivonescimab plus chemo versus a PD-1 plus chemo here. What I would say with respect to your question on survival, and I think Maky emphasized this point a minute ago as well, overall survival will be immature at the time of the interim PFS analysis. In terms of disclosure with respect to when that will take place, we plan to run the analysis in the second quarter. Ultimately, what gets disclosed will be determined based on output results as well as traditional major medical conference guidance depending on how results are read out one way or the other. And we do not guide, nor do we comment historically on our expectations with respect to results, though we are encouraged by ivonescimab's Phase II data and the Phase III data that took place in HARMONi-6. We are really looking to continue to follow those trends.

Thanks for the comprehensive update, Maky and team. So just to press further on this question around the interim PFS in the second quarter now. So it sounds like what you're saying is that this is based on the optimism from HARMONi-2 and HARMONi-6. But I just want to check, was there anything specific that you saw in HARMONi-3 with respect to an event rate that's faster or any new piece of information that increased your confidence in doing this interim analysis now in the second quarter? Or is it really just a question of providing this update sooner to accelerate development based on, as you pointed out, what you saw with HARMONi-2 and HARMONi-6?

Yes. Thanks, Yigal, for the question. It's really a data-backed decision, as we mentioned, with respect to interim readouts for HARMONi-2 and HARMONi-6. And then obviously, the significant overlap in a setting with HARMONi-6. I would also reemphasize we are not changing the timing in terms of guiding towards final PFS expectations and then the interim OS. So no change there from event count. I'll let Allen provide more commentary as well.

Yes, Yigal, I think what you said, it's the latter. Remember, this study was designed way back in '23, right? And since then, we've had the HARMONi-2 and the HARMONi-6 readout. Our mission is always to bring this very important medicine, which we think is a game changer, to patients as soon as possible, right? And I think the HARMONi-2 and now the HARMONi-6 data gives us growing confidence, granted both of those studies read out on an interim PFS, which was very dramatic. PFS is a surrogate endpoint. So there'll have to be some regulatory discussion, but we'll need to look at that data before we can make those decisions. Again, I think this is an opportunity to bring patients faster.

Okay. And at this point, are you providing any other details with respect to the alpha spend or the number of events that are triggering this interim in the second quarter?

No, nothing in terms of a statistical plan at this point has been provided, neither for the interim PFS nor the final. But we have provided approximate sample sizes for both cohorts and then obviously, the primary endpoints of both PFS and OS.

Okay. And then a totally separate question. I just want to comment or ask about ILLUMINE. So is there... you had the data in ESMO in 2024. What do you know about the contribution of components with respect to ivonescimab and ligufalimab? Is there evidence to suggest synergy or not? Or is this just an additive effect? If you could just spend a little bit more time explaining the thinking scientifically to put those two together? I know the ESMO data was a little bit of time ago back in 2024.

Sure, Yigal. Thanks for the question. So if you recall from ESMO 2024, we showed data that was generated from our partners at Akeso, both in monotherapy ivonescimab as well as ivonescimab in combination with ligufalimab that as Maky explained, was Akeso's proprietary CD47 antibody. That data was encouraging in both cohorts, but it did show an additional uplift that was seen with ivonescimab plus ligufalimab. Our partners at Akeso launched a Phase III study with the combination in PD-L1 positive head and neck cancer. We've explored and have been encouraged by this data as it continues to mature. The Phase II data continues to be maintained well. The study being a three-arm study, with ivo in one arm, ivo plus ligufalimab in the second arm and then the control arm being monotherapy pembro, that will help answer definitively that question regarding the contribution of components. The data from ESMO showed that the combination of ligufalimab and ivonescimab had a higher overall response rate than ivonescimab alone. We have a stringent clinically sound, scientifically robust study designed to demonstrate that.

Next, we'll move to Brad Canino at Guggenheim.

Congrats on the screening completion. For me, it's not quite clear yet why adding the interim provides a benefit with regulatory discussions because it seems like you'll reach final PFS before any OS data, interim or final. And can you help square that for me? And sorry to beat the horse on this one.

No, great. Thanks for the question, Brad. I think there are a few key points to consider regarding your comments. First, it's essential to have data when discussing matters with regulatory agencies. The interim analysis enables the generation of primary endpoint-based data. As we further develop that data, there will be no change in our guidance concerning final PFS and interim OS timing in the second half of the year. By combining these two points, we can advance the conversation without significant delays, despite the several months between the second quarter and the second half of the year. This approach allows us to engage with the agency effectively, armed with data to facilitate the next steps.

And I guess when I hear this and along with the regulatory strategy in EGFR mutant, should we read this as like a company's evolving view that frontline lung could see approvals with just PFS benefits and only OS trends?

Yes. I think it depends on – it's a combination, right? It depends on the timing and magnitude of the benefit is important. There'll be some contribution in terms of overall survival trends. And across solid tumors, you see that in several places as well. The studies, to be clear, are certainly powered for both primary endpoints, which is an important point as well.

So Brad, this is Manmeet. I think in other words, right, depending upon this earlier interim PFS data and the magnitude of the PFS, that will allow us a potential discussion with the FDA to accelerate our submission as we submit. OS may come and mature, and that is the path forward to accelerate providing this drug to patients much earlier.

Our question is on the head and neck Phase III. Why opt to go through a co-op group here? And what signal will you want to see before committing to expanding into the U.S. here? And could it be used to leverage for a U.S. approval?

Yes. Josh, thanks for the question. A couple of points: We've talked a few times now in terms of expanding our Phase III program more broadly. So in some ways, there's an opportunity to work with some of the premier cooperative groups in terms of adding additional indications that we see promise in as well. We think there are multiple opportunities for patients in this setting. Working with cooperative groups also expands the number of trials that can be performed ultimately. It's important that we are taking on as many opportunities as we can with respect to bringing ivonescimab to as broad a set of patients impacted by cancer as we can. That is a strong approach overall.

I would just add that, as Dave said, they approached us. Head and neck is an unmet need. It's not the largest unmet need in the PD-1 VEGF space. We're going to focus our resources on the largest unmet needs, and this one was convenient because they came to us wanting to do a study.

Yes, I don't think we want to start disclosing specific details at this time. We will gain enthusiasm regarding enrollment and feedback from GORTEC as they implement the study. Additional data is being generated by our partners at Akeso in Phase III in China. There are many potential paths, but I have nothing more specific to share at this moment.

Congrats on the squamous enrollment completion and the progress. Should we expect the HARMONi-6 OS data later this year? And how about HARMONi-2 OS data as well? Given the upcoming HARMONi-3 OS data over the next year, can you reiterate what gives you the most confidence that all the positive PFS data we've seen from the frontline lung cancer trials will ultimately translate to OS benefits in the frontline Western population or global studies?

Appreciate the question, Tyler. The HARMONi-2 and the HARMONi-6 studies are sponsored by our partners in China at Akeso. They have not guided looks on overall survival readouts at this point. It's important to note HARMONi-2 was not powered for overall survival and was not powered for overall survival at all. HARMONi-6 was powered for PFS, but has a larger sample size. Assurance on translation into HARMONi-3 is the key focus here, evidenced by a 40% improvement in PFS reduction of risk and/or death. OS trends are noted positively in previous studies.

From a clinical perspective, the mechanics of the study are not crossover designs. The standard of care for both arms is the same. Patients are blinded. If standard of care begins much later due to PFS benefits, we can expect OS benefits.

So I've got a more commercial question here. How much of the commercial footprint you’re building out for EGFR mutant non-small cell lung would be usable for the broader squamous population? I'm assuming all of that. But then how much more would you add on top of that to address the broader squamous population? And then I have a follow-up.

Asthika, this is Manmeet, and I can take that question on commercial readiness. There are a lot of synergies. If you see our EGFR and squamous and non-squamous, all are coming from non-small cell lung cancer. Most of them are treated by similar physicians. Our footprint and synergies will align well. The EGFR population is much smaller, squamous is approximately 2.5 to 3 times bigger than EGFR, and non-squamous is nearly double that of squamous. We’ll have to do a lot of education, and learning from our existing setting, with the basic infrastructure in the coming quarters.

So Manmeet, how should we think about the ramp-up in your expenditure for the SG&A line item?

Yes, we have been pretty efficient over there. The most expenditure will come as we hire our sales teams. We've been doing a lot of activities on the medical affairs front. There will be expense, but that will come a quarter before the PDUFA as we ramp up sales and marketing for potential commercial launch.

Got it. I like that you're offsetting some of the development to these cooperative groups, like GORTEC. But of course, these groups are going off the data that's generated in China, also with novel agents that are not yet approved in the U.S. and Europe. So how are you thinking about these data, converting them for U.S. submissions, and how are you getting these cooperative groups to ensure that the data generated is going to be applicable for a U.S. submission too?

That's a great question, Asthika. Our partners at Akeso have initiated a Phase III in China. Importantly, the cooperative groups are very familiar with the thought processes of health authorities, which has not been of high concern with respect to pushback. That is well understood.

We've used Chinese data clearly to satisfy Project Optimus before. So that shouldn't be an issue.

Just on the HARMONi-A trial in second-line EGFR non-small cell lung cancer. Can you provide additional color on the FDA interactions leading to the BLA submission? Any insights on the FDA stance on OS?

We've been very transparent that the study is positive with a PFS endpoint. We missed OS due to pandemic-related enrollment delays. The FDA was clear that they wanted to see OS to make this a fileable package. We've submitted it, and they've accepted that filing, and they're reviewing the data now.

Yes, we've had interactions with the agency. We don’t disclose meeting-by-meeting discussions. Those discussions are intended to be confidential, which is important for the totality of what we’re looking to accomplish with ivonescimab.

With HARMONi under consideration from the FDA, could you walk through your high-level thoughts on pricing strategy given the competitive landscape in EGFR non-small cell lung cancer?

It's very early to start talking about pricing. Pricing is dependent on the final label and the indication for the launch. While we have the potential to price it well considering the benefit, multiple indications are forthcoming.

Our strategy is not dependent on partnerships. We will have sponsored studies based on Akeso data and moving forward. Expect more of those studies to come.

I wanted to go back to HARMONi-3. I'm wondering if you've had discussions with the FDA around what you think would be the maximum disclosable set of information while maintaining the integrity of the trial. Do you think you might be able to provide curves along with the top line data?

We have several opportunities regarding data and the analysis, and we’ll provide clarity on that. What is important is that we want to provide this agent to patients as soon as possible. The regulatory interaction requires patience, given how the studies are being progressed.

We're managing expectations here. We're looking to ensure the data is analyzed properly before making further disclosures.

I wanted to ask on the FDA review for HARMONi. Have you had any interaction with the FDA since having the BLA submitted? Is there anything in the FDA's stance changing on acceptability of PFS?

Yes, we've had interactions with the agency, but we respect their confidentiality regarding our step-by-step updates.

Not only is David correct in saying that we have a tremendous respect for the FDA, it is probably America's most respected agency around the world for its integrity, the due diligence of its work, putting patients first, and we're really honored to be reporting into them. Lastly, we're also very impressed with our partner, Akeso. Akeso has almost a few hundred million dollars of investment value in their ownership, along with you all that are owners of Summit, and we're happy that they chose to do that. We're also quite pleased to see that time after time when they introduce new drugs, they get through their own agency, they get clearances, they're doing quite well. If there's any China look-alike Regeneron, it's Akeso, just a fabulous company with great engineers, great scientists, and we're pleased that they are the source of the bispecific tetravalent back in 2013. And yes, we're proud to have that in-licensed, and we're making great progress with that. So thank you all, and we look forward to updating you on our next call unless there's great late-breaking news in between.

Thank you, everyone.

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