Summit Therapeutics Inc (SMMT) 2025 Q4 法說會逐字稿

(Operator Instructions)

Good afternoon and welcome to Summit Therapeutics Q4 and year in 2025 earnings call. All participants will be in listen-only mode until the question-and-answer session portion of this call. We do not expect any technical difficulties today. However, if 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.

After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press the star key followed by the number one on your telephone keypad. If you would like to withdraw your question, press one again.

At this time I'd 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.smmtx.com.

Our Form 10k 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 Yancars, 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 10k 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 ibanisimab, a PD-1 VEev by specific 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 an updates related to our Harmony Tree study.

Last quarter, we announced our Harmony Tree Phase three trial evaluating bonesimab 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 histologist 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 Harmony Tree 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, opened the readout of harmony two, comparing vanisimab to Pembroke in PDL positive frontline lung cancer patients, which showed a highly statistically significant and clinically meaningful benefit in PFS with a hazard ratio of 0.51 and a median improvement in PFS of over five months.

This point was later validated with harmony six, showing that there was a substantial PFS benefit when comparing avanisimab plus chemo versus a PD1 inhibitor plus chemo with a hazard ratio of 0.60.

Two phase studies conducted by EASO in China in frontline non-small cell lung cancer demonstrated a 40% plus improvement in PFS for the vanisimab or both the harmony 2 and harmony ix 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 multi-regional phase three studies.

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 Harmony Tree, we continue to expect enrolment to complete in the second half of this year and to reach the pre-specified number of events for the final PFS analysis by the first half of 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 IO to a broader population of lung cancer patients.

Additionally, we announced today the first update to the IO Phase three clinical trial program, which will continue to expand throughout 2026.

Ilumin, a new phase three study in PDL1 positive frontline head and neck squamous cell carcinoma, will be sponsored by Gore tech, a French cooperative group dedicated to head and neck oncology, with initial enrolment expected to begin early next quarter.

The study intends to evaluate both ivvanisimab monotherapy and in combination with ligoalimab, Eso proprietary anti-CD47 monoclonal antibody against monotherapy Pembroke 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 US sites as well.

Phase two data supporting the potential use of Ivanisimab in this patient population was previously presented at ESO 2024, where Ivanisimab in combination with lecothalimab demonstrated an objective response rate of 60% in 20 patients with median PFS of 7.1 months after median follow-up of 4.1 months.

At the time of this analysis, no patients receiving avanezumab plus legoalimab discontinued treatment due to the treatment-related adverse events.

The data generated in phase two is encouraging in light of existing standards of care, and EESO is also running a single region phase three 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, abonizimab is being evaluated in combination with three RAS-1 inhibitors, including kaxone, RIP, a multi-selective RAS inhibitor, Zolan RIP, EKAS G12D selective. Inhibitor and aron RIP, a KRS G12C selective inhibitor, across multiple solid tumour 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 ibanisimab in combination with GSK novel B7H3 antibody drug conjugate in multiple solid tumours. The initial study under this collaboration is expected to begin dosing patients in mid-2026.

Let's now take a step back and look at Ivanissima's accomplishments to date. There are many to list. We are just highlighting some of them.

Avonisimab has read out four phase three 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 three trials have been announced, currently ongoing, or have read out in multiple tumour types.

44 clinical trials have been initiated since 2019 between Summit and EESO evaluating bonesimab in a variety of solid tumours.

When 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 surroundingvoissima.

Together with our partner ECESO, we have enrolled over 4,000 patients in either summit sponsored or EESO 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 EESO.

A third indication based on the positives Harmonyix 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 three trials evaluating ivonescimab have readout to date, and ALL four with positive data readouts. This represents the only phase 3 readout that we have seen in the PD1 VEF bispecific class today. These positive trials are supported by the differentiated mechanism of action of ivonescimab.

Here is the current ivonescimab development plan across Summit and EASO.

In total, there are 15 randomized phase three trials, four of which are global summit sponsored studies in non-small cell lung cancer and colorectal cancer, one of which is a multi-regional regional cooperative group study announced today. And 10 of which are being enrolled by EASO in China in a variety of solid tumour types, including lung, breast, head and neck, BTC, pancreatic and colorectal cancers.

Additionally, EESO is also currently enrolling multiple phase two trials evaluating ivonescimab in other tumour types, ovarian, gastric, HCC, and others, including non-metastatic settings.

Through our partnership with EASO, we continuously compile a substantial amount of data, allowing us to make faster, more informed decisions, fuelling the rapid expansion of our global development plan.

Focusing on our pipeline at summit, we have four global phase three trials, completed or ongoing. Harmony, which read out positively last year, Harmony 3, Harmony 7, Harmony GI 3, All three of which are currently enrolling and progressing nicely.

The harmony 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, and in January we announced the US FDA's acceptance of the filing and a PEUA 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 safety and efficacy profile of the current FDA approved options to patients in this setting, the positive regionally consistent results of this phase three multi-regional 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 favourable 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.

Harmony Three 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 PDL-1 status.

I spoke a minute ago about the recent changes to this pivotal study.

For Harmony seven, the study is evaluating abonisimab monotherapy against Pembro monotherapy as frontline treatment for patients with non-small cell lung cancer that have high PDL1 expression levels. Harmony seven continues to enroll well, and we look forward to providing additional updates in the future.

And finally, last quarter, we initiated and began enrolling patients in Harmony GI three, 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 two data published at ESO 2024 and subsequent continuing enrolment in this phase two study in China and the United States with additional chemotherapy regimen.

This data set this data set allowed us to make an informed decision to move forward in CRC specifically with the FFO chemo combination. We look forward to providing further updates on the phase two data set later this year, as well as the harmony GI three 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 three ilin study sponsored by Gore Tech evaluating ivonescimab in head and neck cancer that I spoke to earlier.

With respect to novel combination, we announced that the first patient was dosed this quarter in our collaboration with Revolution Medicine to evaluate. ivonescimabin combination with three novel RAS inhibitors across multiple solid tumour settings. We are excited to learn about the opportunity and potential to improve patient outcomes with ivonescimab combined with these novel targeted therapies and promising molecule. This collaboration is intended to evaluate ivonescimab in combination with one or more of RevMed's RAS1 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 avonisimab in multiple solid tumour settings in combination with their B7H3 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 IO and B7H3 ADCs have shown promise.

We have over 60 ISDs that we intend to support in various stages of development. Of these, 15 are currently enrolling, five of these in collaboration with MD 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 EASO have had the opportunity to explore yet. Tremendous interest in ISDs is a testament to the enthusiasts we have heard from many investigators as they consider the potential opportunity that ivvanisimab presents across multiple tumour types.

Over the past 18 months, we have seen four positive randomized phase three trials, including the first and only phase three trials to compare positively against anti-PD1 therapies. Each of these studies represent a benefit either over a PD1 inhibitor or in setting where PD1 inhibitors have failed to achieve a benefit in either PFS or OS.

ESO's harmony two 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 randomized phase three trial. In April 2025, EKO announced that Harmony Two achieved a clinically meaningful overall survival hazard ratio below 0.8 at this early look.

Moving to EESO's harmony six frontline non-small cell lung cancer study in patients with squamous histology, results were announced at ESO 2025 demonstrating avonisimab with chemo was superior to PD1 plus chemo in PFS. With this result, harmony two and harmony six represent the first and only known regimens to achieve a clinically meaningful benefit replacing an anti-PD1 regimen.

In EGFR mutant non-small cell lung cancer, both ESO's Harmony A trial and our own Global harmony trial achieved positive, consistent results.

In harmony, a positive overall survival trend was observed with hazard ratio of 0.79, barely missing statistically significance.

In a subsequent analysis in September 2025, with longer-term follow-up on Western patients, ivonescimab plus chemo showed a favourable trend in the overall survival with a hazard ratio of 0.78 and a corresponding nominal p value of 0.0332.

In Harmony A, ESO's final overall survival analysis showed avanisimab plus chemo achieved a statistically significant hazard ratio of 0.74 with AP value of 0.019, supporting a treatment profile where OS does not degrade but rather improves over time in this setting.

Turning to our market opportunity, the value proposition is clear. Avanisumab on its own has the potential to be a platform blockbuster drug. Additionally, novel combinations with IO 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 tumour treatment landscape.

And yet these estimates still do not include the full impact ivonescimab could have, as it has already shown promising data in multiple tumour types where checkpoint inhibitors have not been effective, including EGFR mutant non-small cell lung cancer and PDL1 low triple negative breast cancer.

ivonescimab differentiated profile support its platform potential across multiple indication, 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 3 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 Illumin phase three clinical study in head and neck cancer. We will continue to expand the details of our clinical development plan throughout 2026, including sponsored studies. With today's Harmony Tree 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 Harmony Tree non-squamous cohort, we expect to complete enrolment 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 US around our November 14th PEUA date based on our harmony BLA filing. Now I will turn the call over to Manmeet to provide a financial and operational update for the quarter. Manmeet.

Thank you, Maky, and good afternoon, everyone.

On the financial front, let me start with our cash position. We ended the year 2025 with a strong cash position of approximately 713 and $13.4 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 spent 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 Harmony three and Harmony seven 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 $10million to $11 million per quarter in 2025.

On the operations front, I'm extremely proud that Team Summit has been able to accelerate the enrolment of 600 squamous patients ahead of our planned timelines, which will allow us to have interim readout by second quarter of 2026.

With the acceptance of our BLA with 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 awareness map to a US 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.

(Operator Instructions)

Thank you. We will now begin the question-and-answer session. If you have dialled in and would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your questions, simply press one again.

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

Hey, this is Mark on for Saldean.

Thank you so much for taking our question and congrats on the quarter. Can you talk about what drove the decision to include the interim PFS analysis for Harmony three, for the squamous cohort, and frame expectations for both the initial data in the second quarter and the potential final PFS analysis and in 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 physical significance by that final PFS analysis time?

Thanks, Mark. Appreciate the question. This is Dave. So, we decided to amend the protocol for the Harmony Three study by including an interim analysis for the PFS primary endpoint. If you recall, we previously amended the Harmony re study 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 Harmony two, which showed the large PFS delta that McKee spoke to a hazard ratio of 0.51, comparing IO to monotherapy Pembroke.

Of lung cancer patients and then this would allow for an, so this was then seen again in the Harmony Six data so this would allow for an earlier discussion with the agency based on the PFS, primary endpoint and now an interim PFS. So, it's about accelerating the timelines with respect to the data based on two interim readouts from our partners at ACESO in studies in lung cancer. And so, with both studies remaining or reading out positively the overlap and the indication with respect to harmony three, that gives a strong indication in terms of the opportunity that exists here with IO plus chemo versus a PD1 plus chemo here.

What I would say with respect to your question on survival, and I think McKee, 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, on.

With respect to when that will take place, that'll, so we plan to run the analysis in the second quarter, and then ultimately from there 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 then with respect to your final question on final PFS interim OS, so that remains, no real change in timing. That's the second half of this year again, we're not really guiding, and we don't really comment historically on our expectations with respect to results. We don't, we obviously are encouraged by. Ivonescimab phase two data, the phase three data that took place in Harmony six, and so we really, are looking to continue to, following those trends but don't necessarily guide specifically with respect to our expectations numerically, if you will.

Excellent thank you.

(Operator Instructions)

We'll go next to Yigal Nochomovitz at City.

Okay, great, thank you very much for taking the questions and for the comprehensive, updates, Makyand team. So just to kind of press further on this question around this interim PFS in the second quarter now, so it sounds like what you're saying is that this is based on the optimism from Harmony two and Harmony six, but I just want to check, was there anything specific that you saw? In harmony three, with respect to an event rate that's faster or other new piece of information that increased your confidence in doing this interim 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 Harmony two and Harmony six thank you.

Yeah, thanks Yigal for the question. It's really a data backed decision, as we mentioned with respect to interim readouts for Harmony two and six, and then obviously the significant overlap in setting with Harmony six.

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 events. I'll let Alan provide more commentary as well.

Yeah, you go, I think it, what you said, it's the latter. Remember, this study was designed way back in 23, right? And since then, we've had the harmony two and the harmony six 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 Harmony two and now the Harmony six data give us growing confidence. Now granted, both of those studies read out on an interim PFS.

Which was very dramatic, and 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, but 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, not nothing in terms of a statistical plan at this point's 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 totally separate question. I just want to, come in or ask about alum alumine. So, is there, you had the data in EMO in 2024, is what do you know about contribution of components with respect to IO and legithalimab? Is there evidence to suggest synergy, or or not or is this just an additive effect if you just spend a little bit more time explaining, the thinking scientifically to put those two together I know the ESO data was a little bit of time ago back in 2024.

Sure, I got, thanks for the question. So, if you recall from ESO 2024, we showed, data that was generated, from our partners at ACESO, both in monotherapy, Ivanesimab, as well as ivanesimab in combination with ligoalimab that as Macky explained, was, Akiso's proprietary CD47. Antibody and that data was encouraging in in both cohorts, but it did show an additional uplift that was seen with ivanesimab plus ligothallimab and so we've seen our partners at ACESO launch a phase 3 study in with the combination in PDL1 positive head and neck cancer. And so we've explored and have been encouraged by this data as it continues to the phase two data continues to mature, and part of the study being a three arm study, with IVO in one arm, IO plus ligothalimab in the second arm, and then the control arm being monotherapy Pembro, that will help answer.

Definitively that question with respect to contribution of components, but the two cohorts within the phase two each were encouraging, and there was encouragement from the cooperative group in Gore-tech, and I'd like to obviously, thank Gore-tech for, their enthusiasm, in terms of the study, and that's, what's led to the progression here.

Yeah, I would just add that, as they've said, Yigal, that the data from EMO showed that the combination of ligofthalimab and ivanesimab was had no higher overall response rate than ivanesimab alone. We're excited to. Work with Gore-tech, which is a premier cooperative group in head and neck cancers, and they've designed a very rigid, clinically sound, scientifically robust study to demonstrate that, and I think McKee's comments, in the script, showed that there are going to be ivanesimab as one group and Ivanesimab plus ligothalumab, so you can demonstrate the contribution components against. The standard of care pembrolizumab, so I think that's going to be very important.

Thank you. Thank you.

(Operator Instructions)

You.

Next we'll move to Bradley Canino at Guggenheim.

Hey, afternoon, 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 TFS before any OS data, interim or final, and presumably you would need the OS to file anyway. So can you help square that for me and you, sorry to beat the horse on this one.

Oh, no, great, thanks for the question, Brad. And so, I think there's a couple things in terms of what you said. So first, you can't really have a discussion with respect to data with the regulatory, agencies without data, right? And so, part of the interim analysis allows for the generation of primary endpoint-based data. And then, as we continue to mature, that data you'll see also, no change in our guidance with respect to, final PFS as well as in OS timing in the second half of the year as well and so when you kind of combine those two points it allows for the acceleration of the conversation. Without much delay with respect to, there's several months in between, obviously second quarter versus the second half of the year, but it allows for progressing that conversation, with the agency with data in hand to allow for 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?

Thank you.

Yeah, I mean, I think they're, depending on the it's a combination, right? It depends on the timing, right? The magnitude of the benefit is important, and then obviously there'll be some contribution, in terms of, overall survival trends, and I think that's where we see, dual primary endpoints, in this study and then across solid tumours 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 my meat. 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, right? OS may come and mature, and that is the path forward to accelerate providing this drug to patients much earlier.

(Operator Instructions)

Okay, thank you.

We'll go next to Corey Kasimov at Evercore ISI.

Hi, this is Josh on Cory Kasimov. Thanks for taking our question. Our question is on the head and neck phase three. Why I opt to go through a co-op group here and what signal will you want to see before committing to expanding into the US here and could it be used to leverage for a US approval?

Yeah, hey Josh, thanks for the question. So, a couple of points there, I think one, we've talked a few times now in terms of, expanding our phase three program more broadly. So, I think 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 promises in as well, and this is one of those indications. There's a highly competitive space. In head and neck cancer, and we think there are multiple opportunities for patients in this setting, and we think Ivonescimab presents a strong opportunity in particular Ivonescimab and then potentially Ivonescimab in combination with leofaliab, right? And so working with cooperative groups also expands the number of trials that can be.

Performed ultimately and so it's important that we are taking on as much opportunities as we can with respect to bringing Ivanesimab to as broad of a set of patients who are impacted by cancer as we can. So, so we think that that is a strong approach overall. It's a strong cooperative group who's run multiple studies as well, and they were highly enthusiastic based on the data that's been presented and obviously working with them. Since and so as McKeey emphasized earlier as well, it's important to note that we do plan to continue to expand that phase three program in 2026 and I think we've been clear that as we plan to. Launch additional studies, we would wait until we get to the readiness to launch and we we'd have FBI in sight. And so part of this will be over the course of 26, but this was an important concept that we had with respect to working with a highly enthusiastic cooperative group in a setting which they specialize and it was an opportunity to really explore on a multi-regional setting, this, these two regimens, really the monotherapy as well as the combination regimen.

Audit and anything, yeah, go ahead.

Sorry, I was just going to add they approached us, right, so they came to us, head and neck is an unmet need, it's not the largest unmet need in the PD1 VEGF space and so I think we're going to, as Dave said, focus our resources on the largest unmet needs, and this one was convenient because they came to us, wanting to do a study.

Yeah, sorry, Josh, I interrupted you.

No, thanks Allen. I was going to ask if there was anything specific you could give us on what may, trigger like a US expansion here.

Yeah, not, I don't know that this time we want to start disclosing specific details, but obviously we'll get enthusiasm with respect to enrolment. There are several countries in Europe who are enrolling in the study. Feedback from Gore tech as they operationalize the study. There's also additional data being generated by our partners at ACESO in phase three in China with respect to the setting. So, I think there's a multitude of different. And it is continuing maturity of the phase two, obviously as well, so there's multiple paths, with respect to that, but nothing more specific there just at this point.

Got it.

Thank you.

(Operator Instructions)

We'll take our next question.

From Tyler Van Buren at TD Cowan.

Hey guys, congrats on the squamous enrolment completion and progress. So, should we expect the Harmony 6OS data later this year? And how about Harmony 2 OS data as well? And in general, given the upcoming Harmony three OS data over the next year, can you just reiterate what gives you the most confidence that all the positive PFS data we have 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. I think, as we have said a few times, so the Harmony two and the Harmony six studies are, studies that are, conducted by and sponsored by our partners, in China and at ACESO, and so they have not necessarily guided in terms of looks on overall survival. A readout at this point, it's important to note again Harmony two is not necessarily powered for overall survival and what was not powered for overall survival at all. That was a PFS primary endpoint exclusively. Harmony six was also a PFS primary endpoint, but obviously a little bit larger in the sample size, over 500 patients. And so, I think the protocol for Harmony six was published and so that would appear at some point, to look like 2026 is an event, but they have not guided more specifically to that. I think the second half of your question with respect to, translation into harmony three and then obviously the confidence that we have, with the PFS data translating to OS, so I'd make a couple of points.

I don't think there's a better analogy in terms of opportunity with respect to a randomized phase three study, and in this case, in squamous, non-small cell lung cancer, IO plus chemo versus PD1 plus chemo, then a randomized phase three, that was nearly identical just run in China, right? And so that was strongly positive. The PFS has a ratio, indicated a 40% improvement, in terms of PFS, reduction of risk and or death. And so, when we look at the translation from, China to the global setting, we're obviously very confident in in harmony helped enforce that with, very consistent results with respect to OS both from a media perspective as well as hazard ratio. I think the other thing is we step back, we often talk about the question with respect to PFS and hey, what's the confidence level translating that into OS. And so, at this 0.4 randomized phase 3s have read out, right? Harmony A was the first, and that was, in China, the EGFR mutant non-small cell lung cancer after TKI and that, final PFF final OS analysis was statistically significant, and that was, displayed at SSI.

The second was the Harmony study, and we've talked, at length there with. A very strong showing with respect to overall survival. The final analysis was not statistically significant, but with longer follow-up time, given the delays in initial enrolment in the follow-up time differences between China and the US, we saw a nominal P value that was below any threshold with respect to, what would be required for significance. We saw AP value of 0.03.

When we look at Harmony Two, the only readout we've seen thus far was the NMPA, the Chinese Health Authority requested, look, and that showed a, an OS hazard ratio of 0.777 comparing IO to Pembroke.

So, at this point, Harmony 6 has not even hit that point and it's still that that application's in review as our partners at ACESO have announced, and so there hasn't been a look yet at overall survival. But of the four that have read out three of those studies have shown some data towards OS.

All of them have shown a hazard ratio less than 0.8, which when we speak to KOLs, we speak to. Physicians globally, that's kind of the, generally agreed upon threshold for clinical meaning, clinical meaningfulness, if you will. And so, the amount of encouragement that we've seen with respect to OS is about as high as you can get with respect to the time that we're at. I appreciate everyone's, focus on overall survival, but overall survival takes time. In terms of the readout and all the readouts that we've seen to date have pointed it in one direction, which has been highly encouraging. So, hopefully, Tyler, a comprehensive answer to your question, but one that answers.

It. And Tyler, this is Alan. I would just add from a clinical perspective, from the mechanics of the study, they're not a crossover design. The standard of care for both arms is the same, right? And the patients are blinded, so they don't even know whether which arm they were on, so they should get balanced standard of care. Now, if you start that standard of care in the second line or later line, five months later because of the PFS benefit seen on that should translate to a benefit in OS, right? It, it's just such a large magnitude in delaying that next line of therapy.

That's great, thanks.

(Operator Instructions)

And as they go, your line is open. Please go ahead.

Oh, hi guys, thanks for taking my questions. So, I've got a question, more of a commercial question here. So, as you're thinking about the commercial footprint you're going to need for EGFR mutant on small cell lung that you're plan that you're building up right now, how much of footprint could you, would be, usable for the broader, for the broader, squamous population? I'm assuming all of that, but then how much more would you have to add on top of that to address the broader squamous population and then have a follow-up.

Hey Asthika, this is Manmeet, and I can take that question on commercial readiness, right? There are a lot of synergies, right? If you see our EGFR and squamous and non-squamous all are coming from the non-small cell lung cancer, right? And as you would know it, right, most of them are treated by similar physicians over there. So, our footprint and synergies will come, right, pretty much. EGFR is a much smaller population base. Squamous gets over like. 2.5 to three times bigger than EGFR and then non-squamous comes, which is almost double of squamous, right? So, it keeps expanding, but it gets our foot into the door. We will have to do a lot of education, a lot of, learning from our setting, our, basic infrastructure in next coming quarters, and that will, be the backbone of as we expand into squamous and non-squamous because these are all similar, physicians.

Institutions.

So that is how should we think about, I guess the ramp up in your expenditure, for the DFTM airline and.

Yeah, we have been like pretty efficient over there, as I said. EGFR is the smallest one right to initiate. We don't have to put a lot of expenditure and most of the expenditure will come right when we hire our sales teams over there. We have been already doing a lot of activities on the medical affairs front. Which we initiated right last quarter and those all are happening, so I would say there will be expense, but that will come, a quarter before the podufa right as you get into that you hire more sales people and other things, but other than that we are already, doing, much of the activities and, managing that right now very well.

Got it. Thanks for that. And then as we're, I like that you guys are offsetting some of the development to these cooperative groups like Vortech. But of course, these groups are going off data that's generated in China, also with novel agents, that are not yet approved in the US and Europe. So, I guess how you think about, when you think about these data, converting them for US submissions. How do you think about, some of the regulatory requirements like Project optimist that might be required, perhaps to be done before a phase three is started, and how are you getting these, cooperative groups to kind of play ball with that and make sure that that the data that they're generating is going to be applicable for a US submission too.

Yeah, it's a great question, Asthika. And so importantly, our partners at AESO here have started a phase three in in China in this setting, and so that also speaks to the additional data that exists with respect to, some of the work that's been done in this setting. And also, there's optimist, there's contribution of components which we spoke to, earlier as well, and obviously with the novel opportunity here with IO and LIU, it's important to show IO is a monotherapy as well as IO and LIU combined. And so, I think. A lot of the concepts that you're speaking to are something that's permeating both in the US as well as Europe. The cooperative groups are very familiar with those thought processes of the of the health authorities and so in general that's not something that.

It is of high concern in terms of pushback or anything like that with the with the cooperative groups. That's something that's well understood at this point.

Yeah, hi Ashtika, this is Allen. I just add to what Dave said is that we've used Chinese data clearly to satisfy project optimists before, so that shouldn't be an issue.

Got it thanks guys.

(Operator Instructions)

We'll take our next question from David Dai at UBS.

Great, thanks for taking my questions. Just on the Harmony I trial in second-line GFR and also cell lung cancer, I mean just, could you provide some additional colour on the FDA interactions leading to the BLA submission, and then more importantly, anything you can share on the FDA stance on the OS, how has that changed over time?

Yeah, this is Alan Ying. So again, I think we've been very transparent that, the study is positive with the PFS endpoint. We just missed OS because of delays to enrolment, due to sort of, post effects from the pandemic.

The FDA was clear that they wanted to see OS to make this afiable package. And we said, look, we think the data are important when we look at our data compared to other agents approved in the space, we think that this satisfies an important unmet need for patients and so we wanted them to review the full package of the data, we submitted it and they've accepted that filing and they're reviewing the data now.

Got it. Okay, that's helpful. And then just on the most recent, collaboration with GSK of the B7H3 ADC in combination with IO and so help us understand a little bit more on the initial indication you're exploring. We know that the GSK is currently exploring BMH3, for, small cell lung cancer. Is that an indication you think it would make sense for you to explore it in combination with IVO?

Yeah, we, we've specifically talked about in our press release announcing the collaboration small cell lung cancer, right? And so that is a place we've also been clear also that there's multiple solid tumour settings where we believe both B7H3 as well as IO have shown promise.

And so, but there's obviously a place where with the evolving landscape of small cell lung cancer. That that's an important place for us to explore, and we think the B7H3, ADC, the GSK has, is a, is, very much showing a lot of the, we're not going to go into details with respect to the comparisons we've done against the B7H3s across multiple companies. But it's important that we did look at that asset and feel that that was a very appropriate partner for IO with respect to collaborating in small cell as well as, a couple other solid tumour settings.

Thank you so much.

(Operator Instructions)

And we'll move next to Mitchell Kapoor at H.C. Wainwright.

Hey everyone, thanks for taking the questions. With harmony 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, but also the benefit of Ivonescimab, what it could provide in future expansion indications.

Hey Mitchell, this is Manmeet, and it's very early to start talking about pricing. Pricing, is, dependent on, it's finally decided, right, based on the final label you have and the indication which we are launching it, and obviously EGFR, is our first one, but, you will not be commenting on the price, obviously, as you see the other benchmarks, right, and, you can easily look at, right, how other second line EJFR drugs are priced, you could see that there is a big range. And we have the potential based on the benefit of having a snap to price it very well, but as you also stated right in the long run, we have multiple more indications to come, so we'll have to price it appropriately, but more to come. I think there is no decision or nothing to add over here right now.

Okay, fair enough. And then on those potential expansion opportunities, obviously Ivonescimab is kind of this pipeline and a drug opportunity which is rare these days, but what kind of gating items, would be there to determine how fast you could initiate more trials? Is it additional partnerships or anything that can determine, the next steps you take? Are you watching a Tesso's next moves or, what, what's helping you decide how fast to initiate additional studies?

Yeah, it's a great question, Mitchell. I think so. I want to emphasize one of the points that McKee spoke to because I think sometimes it, there's a lot of really positive events that take place with IO and sometimes it's important to slow down on a couple and so over 4,000 patients have been treated with ivanesumab just in clinical trial, clinical trials sponsored by either Summit or Kuso, right? So, this doesn't include. The over 140 total clinical trials listed on clintrials.gov at this point. This doesn't, such as ISTs and whatnot, but so when we look at the amount of data generated, by Ivanesimab, there's a significant amount of information that can be, well understood in several different settings. We've also, it's important. That our partners at ACESO have initiated 10 phase three clinical studies and so underneath that you can see the amount of data that has been generated in terms of really understanding where Ivanesimab can be successful and then obviously there's also significant.

Place where we can continue to explore where maybe the prevalence of a particular disease in China is not necessarily as high as it may be in the US and vice versa, right? But there's a lot of overlaps with respect to the characteristics of those diseases. It's important for us to be able to kind of translate that information across, but because there's so much patient data.

With respect to how patients have performed on ivanneumab that really allows us to, triangulate, if you will, the information, so we're not running, hey, we've been able to dose 30, 40, 50 patients with IVO, and now it's very encouraging. So, we are trying to figure out how to move forward. There's a plethora of information and data, so much of it truly highly encouraging in terms of what that. Can be and that really gives us the opportunity to really think through the different places, the different standards of care. It's important to also consider what the standard of care is in some of these settings. How is that evolving? How is that evolving in the short-term? How is that evolving by the end of what would be a phase three clinical study? And so, we can really look at the information we have internally, what's happening in the in the market, to really, at the end of the day, what we're trying to do is provide a medicine.

That improves outcomes for patients, right? But that takes an ecosystem to do. Physicians need to be able to, access, understand, and have clear op, answers from that data. Patients need to be able to see what opportunities exist based on data and outcomes from trials. And so when we look at the totality of the landscape across, many of the tumour types that, are sensitive either to immunotherapy, antiangiogenic therapy, places where neither have been successful, but there's an opportunity with ivanesumab, we can look at the totality of the landscape, the data generated, what physicians will need to see in a couple of years to really come up with the right answer. And that's why some of these even collaborative studies or collaboration opportunities rather with RevMed, with GSK, that's important. We'll have more of those coming as well. But when we look at the totality of what's out there, it's important to consider, each of those points. And so that's why we really look to expand much further in 2026 as well. Yeah, Mitch.

And I want to just address. A couple of your comments, so, at JPM McKee announced that we're going to be doing multiple new phase three programs. We will, of course, continue to explore cooperative groups, studies, and collaborations with external partners, and you should expect more of those to come, but our strategy is not dependent on that. We will have sponsored studies based on the ACESO data and, moving forward, and so you should expect more of those studies to come as well.

Wonderful, thank you Guys.

(Operator Instructions)

Next, we'll go to Eric Schmidt at Cantor.

Well, thanks for taking my question. I wanted to go back to Harmony three and beat the horse a little bit more.

I'm wondering if you've had discussion with the FDA around what you think would be the maximum disclosable set of information given you need to maintain the integrity of the trial.

Do you think, for example, you might be able to give us hazard ratios or any other meaningful data at that time?

Thank you.

And Eric, you're just to be clear, Eric, you're speaking about the interim BFF.

I am, thank you, Dave.

Yes, yeah, no, I appreciate it, Eric. So I mean, look, I think, and I think we kind of mutually addressed this across comments from Amit Makki and myself a little bit earlier, but it's important that the analysis is run and then we see the analysis in terms of outcomes, in terms of what the next, logical steps are in that respect. And so, and then obviously.

Positive data, requires, contemplation with respect to major medical conferences as well. And so, it's, we have, several, we're, opportunities if you will, in terms of the data and what that readout will look like. And as we get a little bit closer, we'll be providing. A little bit more clarity on what that looks like, but obviously we thought it was very important now to provide, it effectively an immediate answer with respect to the analysis being, run in the second quarter, and then the amount of that disclosure in some ways depends on, what both the data shows and what the next steps are.

Yeah.

And I just want to manage expectations here. Once we get the data, the most important thing is trying to provide this agent to patients as soon as possible. That requires a regulatory interaction, right? And as a courtesy to them, we need to demonstrate to them first, right? Then, in collaboration with our investigators, we want to present this at a major medical meeting. So, unfortunately, sort of. A press release with Kes for you guys as investors and analysts are not going to be a high priority for us.

Well, I guess my question was even just very specific to maintaining integrity of the final PFS readout from a regulatory standpoint and whether even if you were able to give an interim PFS readout, that would be too great a disclosure, making regulators too uncomfortable, but do you have a view on that?

Sorry Eric, I'm not sure we followed exactly what you're.

I think what he's saying is, Eric, correct me if I'm wrong, but what you're saying is if we were to release top-line interim PFS, would that impact the study scientifically in terms of unblinding it for the final PFS, right? Exactly, thank you. Yeah, I understand what you're saying, and I guess I just don't want to disclose too much about what we're doing currently. I understand your question. We're of course going to take that into consideration, but I just don't want to disclose how we're going to do this right now.

Yeah, I would say a couple of key principles, right? We're never going to do anything that puts at risk the final analysis if you will, and I think it part of this becomes, an outcomes driven, response as well in terms of what that data shows to be able to, provide the clarity and transparency, but also be able to. Maintain the integrity of the study itself as well as the interactions with the health authorities.

Okay, thanks guys. Appreciate all the Updates.

(Operator Instructions)

And we have time for one more question, and we'll take that question from Faisal Khurshid at Jefferies.

Hi, thank you guys for bringing the question. I wanted to ask on the FDA review for Harmony; have you guys had any interaction with the FDA since having the BLA submitted? And is there anything in the FDA's stance changing on acceptability of PFS and read through of that to Harmony three.

Yeah, thanks. I think we addressed most of this, a little bit earlier, but yes, we have interactions with the agency. We don't necessarily disclose, meeting by meeting discussions and whatnot, and so what we don't want to do is we're not looking to leverage external sources in terms of, pressuring the agency or anything like that. We have confident those discussions are intended to be confidential, so we're not necessarily giving step by step updates with respect to that, but we have. We do have interactions with the agency, both for this study as well as, other current studies and then, potential future studies, and so it's important in terms of the totality, of what we're looking to accomplish with Ivanesimab that we have a, we have the utmost respect for the FDA. I think that's a just a level setting point that becomes very important in terms of, with the platform. Opportunity if you will, for IO.

There's a lot of studies with a lot of potential settings where Ivanesimab may bring benefit to patients, and we want to make sure that we have a strong relationship with the agency in order to do what our mission is really to bring ivanesimab to be to as many patients facing an unmet need as possible in doing what's right for ultimately patients, facing cancer diagnosis.

(Operator Instructions)

Understood, thank you.

And that concludes our Q&A session. I will now turn the conference back over to Dave Gancars for closing remarks.

Hi, this is Bob Duggan.

Not only is Dave correct in saying that we have 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 honoured to be reporting into them.

Lastly, we're Also very impressed with our partner Kessel. Kessel has almost a few $100 million 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 that that that time after time when they introduce new drugs, they get through their own agency, they get clearances, they're doing quite well. It, if there's any China lookalike Regeneron, it's a Keso, just a fabulous company with great engineers, great scientists, and we're pleased that they are the source of the bi-specific tetravalent back in 2013, and yeah, we're proud to have that in licensed and, we're making great progress with that. So, thank you all. We look forward to updating you on our next call unless there's great late breaking news in between.

(Operator Instructions)

Thank you everyone.

This concludes today's conference call.

Thank you for your participation. You may now just.