Summit Therapeutics Inc. Price & Performance (SMMT)

Good morning and thank you for joining us. Two press releases were issued earlier this morning available the homepage of our website. Our Form 10 ks was also filed earlier this morning. Is available on our website. And an archived replay will also be made available later today on our website www.smmt.com. Joining me on the call today is Bob Duggan, our Chairman of the Board and Chief Executive Officer Doctor. McPhee Tonguey, our Chief Executive Officer and President Manmeet Soni, Chief Operating Officer and Chief Financial Officer and Doctor. Alan Yang, our Chief Medical Officer. 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 may 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 about these risks and uncertainties. Summit undertakes no obligation to update these forward looking statements. Except as required by law. Following comments from Bob McKee, and Amit, we will take questions.

With that, I will turn the call over to Bob. Thank you, Jay. Good morning, everyone, and thank you for joining us today. I am very pleased with recent accomplishments of Team Summit and the accelerating positive information and enthusiasm surrounding ivermectinib We our lead investigational asset In Q4 of last year and to date in 2025, we have reached several meaningful milestones around the development of ibenuzumab Importantly, with our partners in China, as well as here in The U. S. And Western markets, We continue to progress towards our mission of building an organization, making a significant positive difference in serious unmet medical needs. Specifically, earlier today, we announced a clinical trial collaboration with Pfizer which will evaluate ivermectinib in combination with multiple Pfizer antibody drug conjugates or ADCs. In unique solid tumor settings. Rapidly developing novel mechanisms that go beyond what is currently available to patients and physicians is what we believe will make the most significant impact for those facing the greatest challenges from cancer to date. We believe this collaboration with Pfizer will accelerate the advancement of potentially landscape changing therapeutic combinations which intend to improve the standards of care for patients facing serious unmet needs.

Clinical trials associated with this collaboration are expected to start by the middle of this year. In October of last year, completed enrollment in and received Fast Track designation for HARMONY, our global Phase three trial in patients with EGFR mutated advanced non small cell lung cancer who have progressed after treatment with a third generation EGFR tyrosine kinase inhibitor or TKI. Top line data from Ivantisumab's first global 2025. Additionally, on October of last year, we announced a steady amendment to the Harmony three protocol, expanding the study to include patients with both squamous and non squamous histologies. With this amendment, Harmony three is a multiregional registrational Phase three trial assessing avanosimab as first line treatment for patients with metastatic non small cell lung cancer with both squamous and non squamous histologies. Enrollment is ongoing globally for patients with tumors with squamous histology and we have begun enrollment in patients in United States with non squamous tumors. Harmony three now addresses a patient population two to three times larger than prior to the amendment significant prior to the amendment significantly expanding the numbers of patients with cancer that ibenasimab can potentially help. Towards the end of the year, we announced our third global Phase three trial, ARMY7, would be initiating early twenty twenty five.

Initial trial sites have begun activating in The United States and Harmony seven continues to progress as planned. As a reminder, Harmony seven is evaluating ivermectinib monotherapy against pembrolizumab monotherapy in first line metastatic non small cell lung cancer patients whose tumors have high PD-one LPD L1 expression without actionable genomic alterations. McKee will further discuss these accomplishments [indiscernible] additional strides taken to drive our continually and what could be accomplished by Team Summit as well as our conviction and the potential of vibranizumab in non small cell lung cancer and very importantly indications beyond lung cancer. We are a mission driven organization. We with an overriding patient goal to improve quality of life increase potential duration of life and resolve serious medical needs. We are the right team and we believe we have e molecule inibanisumab Summit to realize this goal. With that, I will turn the call over to Mackie for additional context and recent highlights for consideration. Mackie? Thank you, Bob, and good morning, everyone. As Bob said, I remain incredibly enthusiastic about the future of Summit and the possibilities of what can be accomplished with our lead candidate, Ibonizumab. Before providing some additional detail and reviewing the current pipeline, would like to touch on the clinical work that has been conducted with ivermectinib some of the interest and recognition received last year.

Since first entering the clinic with our partner Eclesobac in 2019, more than two thousand three hundred patients have been treated in clinical trials with Ibodizumab. In 2024, Elon, avanizumab was featured in 14 publications, across seven tumor types and selected for five oral presentations at major medical conferences. Currently, between our partners at EKESO and our team at Summit, four Phase three trials have been completed enrollment, two of which are waiting topline data readout including the Summit sponsored HARMONY trial. Five Phase three trials are currently ongoing. Two of these are Summit sponsored trials in first line non small cell lung cancer and three are AKISO sponsored trials studying abanizumab in head and neck biliary tract triple negative breast cancers. EKESO has also announced its intention to start a clinical study in pancreatic cancer later this year. A significant amount of additional data is being generated in additional indications including colorectal cancer, ovarian cancer, gastric cancer hepatocellular carcinoma. In addition to more data to support the lung cancer program. Turning specifically to the Summit sponsor's pipeline. As Bob mentioned, last quarter, Harmony completed enrollment in the fourth quarter with top line data expected in mid-twenty twenty five. This data is expected to contain data for both primary endpoint, progression free survival and overall survival.

Harmony three was amended by significantly expanding the addressable patient population to include all frontline metastatic non small cell lung cancer patients without driver mutations by including patients with non squamous tumors in addition to squamous tumors. Squamous tumors represent approximately twenty five percent to thirty percent of non small cell lung cancer in The United States non squamous tumors representing a large proportion of the rest. As a reminder, this trial includes patients with tumors that are PD L1 negative PD L1 low expressing and PDL-one high expressing. We announced our intention to initiate Harmony seven in early twenty twenty five for which we have begun to activate clinical trial sites The United States. Later this year, we expect to announce additional details around expanding our clinical development plan around ivermectinib specifically beyond lung cancer. After receiving interest for more than 75 investigator sponsored trials in the most recent open window, we have approved over 30 ISTs to date, which will either enhance our sponsor clinical development activities or can show signals in settings where EKESO has not yet had the opportunity to explore. In 2024, we started our collaboration with MD Anderson which now has studied that are activated and open for enrollment in Houston.

We have committed $15,000,000 to this collaboration to quickly discover additional opportunities for Imonetima including several tumor settings outside of its current development plan as well as the possibility of identifying biomarkers through additional research activities. Finally, as we announced this morning, our clinical trial collaboration with Pfizer will look at ivermectinib combination with several Pfizer, venetoclax ADCs in multiple tumor types. As we seek to accelerate the development of non small cell lung cancer and other solid tumor setting, This collaboration would allow us to quickly advance beyond our promising late stage development plan to evaluate avantizumab in combination with some of the most innovative ADCs from Pfizer. Clinical trials as part of this collaboration are expected to Pfizer will be responsible for the operations and costs associated with this trials. We will provide abonitimab and jointly oversee the study. As a reminder for those new to the Summit story, rivonizumab has significantly in the clinical development of this novel class of compound. Avanizumab brings two highly validated targets together into one novel bispecific antibody that targets both PD-one and BGF. Next, I would like to review upcoming catalysts for this year and beyond. As we touched on a moment ago, we are expecting Harmony top line in mid-twenty twenty five.

Which we expect will include both primary endpoints of progression free survival and overall survival. This will be the first global Phase three clinical trial readout for ivonizumab which provides a potential path to applying for marketing authorization in our territories including potentially The United States. Secondly, we intend to expand our sponsored clinical development plan to go beyond non sponsored lung cancer 2025 and 2026 in addition to continuing engagement with a rapidly increasing number of investigators, seeking to conduct investigator sponsored trial, at various institutions across a large number of different tumor types. And you will see continual activating of additional ISTs in variety of solid tumor settings.

This is in addition to AKASO including completing the enrollment of HARMONY-six in frontline squamous cell non small cell lung cancer with ivonizumab combined with chemo as well as continuing the enrollment of its Phase three biliary tract cancer triple negative breast cancer and head and neck cancer studies. Over the course of this year, we will continue to see clinical trial data readouts from AKHANZEON in variety of tumor types.

And finally, we expect to see more Phase three initiations from AKISO non small cell lung cancer and beyond Luckily, indications in which Phase two data has been generated which we touched on earlier. We are excited for the catalyst switch path ahead of us our conviction and belief in the potential for ivermectinib to improve patient lives for the better remains strong and consistent. Now I would like to take a moment to review study design for our two ongoing global Phase three trials Harmoniqile and Harmony seven. Here we have the study design for Harmony three. Harmony Tree is a randomized.

Double blind, global Phase III clinical trial evaluating avanosimab in combination with chemotherapy against pembro in combination with chemotherapy as first line treatment for patients with metastatic non small cell lung cancer. This trial includes patients with squamous or non squamous histologies with no activating genomic alterations regardless of PD L1 expression including high, low and negative PD L1 expressing tumors. Dual PARME endpoint for HARMONY-three include progression free survival and overall survival and results will be stratified by squamous and non squamous histology. We have the study design for Harmony seven.

PROMISE seven is randomized double blind global Phase three clinical trial evaluating avanizumab monotherapy against pembro monotherapy as first line treatment for the metastatic non small cell lung cancer patients with tumors with high PD L1 expression. Your primary endpoints for HARMONY7 include progression free survival, overall survival, results would be stratified by squamous and non squamous histologies. As a reminder, our HARMONY7 study shares similarity with AKSO sponsored HARMONY2 Phase three trials, which reported data last year. But specifically targeted PD L1 high expressing tumors consistent with the standard of care for monotherapy, immunotherapy in The U. S. And Europe. Turning to the market opportunity for ivermectinib. The value proposition here is clear. Avonizumab has the potential to be a platform blockbuster drug is well positioned to make a significant impact across the treatment landscape of non small cell lung cancer and beyond. Specifically in non small cell lung cancer, there are a combined six announced or ongoing Phase three studies conducted by either EKESO or Summit Summit. Non small cell lung cancer alone has an addressable market could ultimately approach $20,000,000,000 for checkpoint inhibitors according to the third research from the likes of TD Khan and others. But this is just the start.

There are more than 50 indications where PD-one, PD L1 or VGEL therapies have been approved. Ivermectinib will continue to be rapidly tested and developed beyond non small cell lung cancer. Across all checkpoint inhibitors indications the addressable market approached $90,000,000,000 globally in the next couple of years, according to IQVIA research. However, this still excludes the full impact that ivermectinib could have. Where it has shown promising data in multiple tumor types where checkpoint inhibitor have not been effective including microsatellite stable colorectal cancer PD L1 low negative triple negative breast cancer and EGFR mutant non small cell lung cancer after targeted therapy.

We are excited to continue to progress our development in non small cell lung cancer in 2025.

Additionally, data shared in 2024 showed that ibodizumab has a market potential much larger than non small cell lung cancer and our current ongoing global Phase three clinical studies that we are sponsoring at Summit.

There are multiple Phase two trials that have been conducted providing encouraging data to continue to explore ivermectinib and its opportunity to become a standard of care across several solid tumor settings which we intend to continue to explore with a goal to improve the lives of as many patients as possible facing high unmet medical needs.

I would also like to take the opportunity to thank most importantly the patients in our clinical studies as well as our investigators, hospitals, including our collaborators at MD Anderson, and our partner in China, Doctor. Michel Shaw and the entire EKSO team. As we continue to pave the way for rapid development of Avanisumab globally. And of course, the Summit team As Bob and I look back on all of the many achievements over just the past two years, Team Summit has done a tremendous job across every department in making our goals a reality and appropriately convincing time when and where possible. We continue to look at opportunities to accelerate our timeline in bringing additional therapeutic options to patients with Hi, Amit. Cancer needs. It's an honor and privilege to work with each member of Team Summit and I would like to express my heartfelt thanks to everyone of our team members. With that update, I will now ask Manmi to provide details on our financial position and operations update.

Thank you, Nikit, and good morning, everyone. This morning, we issued our earnings release for the fourth quarter and year ended 2024. Today, in addition to providing you with an update on our cash position, operating expenses, I will also be providing an update on our progress on clinical trial enrollment on Harmony three Harmony seven, an update on tech transfer for manufacturing in our licensed territories. On the financial front, let me start with the cash position. We ended the year 2024 with a strong cash position of approximately $412,000,000 Let me remind you that we have paid off our debt in entirety and now we are debt free. With a strong cash position, and zero debt, we are well positioned to continue to execute on our clinical trials. Turning to operating expenses, I will be providing details to both GAAP and non GAAP numbers. You can refer to our press release issued this morning for a reconciliation of GAAP non GAAP financial measures. Just to remind you, non GAAP expenses exclude stock based compensation expense. Our GAAP R and D expenses during the full year 2024 we're $150,800,000 compared to $59,400,000 for the previous year. And non GAAP R and D expenses were $134,800,000 during the full year 2024 compared to $55,000,000 for the previous year.

The increase in the R and D expenses reflect the expansion of our clinical clinical trials [indiscernible] Our acquired in process R and D expenses during the year 2024 were $15,000,000 compared to $520,900,000 for the previous year. To remind, acquired in process R and D expenses for the year 2023 which were $5.29 $520,900,000 were related to the upfront payments made to Queso for the licensing agreement. And $15,000,000 expense in the year 2024 is related to the amendment of the licensing agreement with the Queso to include Latin America, Middle East and Africa regions into our license territory.

Our GAAP G and A expenses during the full year 2024 were $60,500,000 compared to $30,300,000 for the previous year. And non GAAP G and A expenses $25,500,000 during the full year 2024 compared to $20,600,000 for the prior year.

Our GAAP G and A expenses primarily increased due to an increase in the stock based compensation charges related to achievement of certain market conditions on performance milestones, which vested during 2024. Overall, our non GAAP operating expenses during the full year 2024 were $175,300,000 compared to $596,500,000 for the previous year. The decrease in non GAAP operating expenses was primarily related to decrease in acquired in process R and D expenses as mentioned earlier, which were offset by the increase in R and D expenses due to the expansion of clinical studies development costs related to Avanosmab, To remind that last quarter we announced that we plan to expand Harmony three study to include non squamous patients in addition to the squamous patients. I'm very pleased that our Summit team was able to activate non premise ARM in a record time and we recently started enrolling patients for non squamous in The United States. We expect to start activating sites to enroll non SCRIMMs patients in other regions [indiscernible] continue to enroll SCRIMS patients in all the territories. Additionally, during last quarter, we had given guidance that we will initiate our newly announced COBRA trial, HARMONY-seven, in frontline non small cell lung cancer or PD-one high patients in early twenty twenty five.

Ahead of our schedule, TEAMS Summit has already begun to activate sites in The United States we expect to initiate activating sites in the other regions during the second quarter of twenty twenty five. Turning to Tech Transfer for Manufacturing, we continue to make progress in And with that, I will hand it back over to Dave.

Thank you, Bob, Nikky and Monique. We will now see if there are any questions that we can help our team can help answer. Kate, if you could please open up the line for questions. [indiscernible] Your first question comes from the line of Yigal Latromovitz with Citigroup. Please go ahead.

Hi, great. Thank you so much for taking the questions. Obviously, we're getting a lot of inbounds on Harmony, too. And Okeizo has provided some comments on the timing of the OS. If you could help us understand what you believe to be the timing for the Harmony two OS and given the fact that it may be approved in China as early as the third quarter of this year, for the second indication for FRONTLINE what is the potential or is there any expectation that we could see a glimpse of some early OS data in that China label? Thank you. Thanks, Higal. This is Dave. So appreciate the question. And I know there's a bit of commentary with respect to Harmony two. As our partners at Akesso have mentioned, they expect to reach the number of events required for their interim analysis. By the end of the year 2025. We ultimately don't have more information on that front, other than continuing partnership with our with Acesso. But at this point, there's been nothing New on that front with respect to any additional information, but appreciate the question.

Okay. No worries. And then on the second line EGFR, the HARMONY trial, I think, Markie mentioned you will have the OS data in the top line readout. What is your understanding as to whether you need that to be only a trend or actually hit onsets that sig in order to be in a good position for approval? In The U. S? Yes. Hi, Ygal. This is Alan Yang. Thanks for the question.

So I think there's two things. I think with would of course would want to hit OS and be statistically [indiscernible] in this space, they have not required OS for PFS has been adequate. Okay. And then I know and Amit just mentioned that you're starting to add the patients for non squamous in the second quarter for Harmony three. Is there any possibility you could provide even a rough guideline as to the timing for the top line readout for Harmony three? And if you can't do that, anything you can say around Harmony six given that's possibly helpful in terms of a read through to Harmony three? Thank you. Yes. Hi, Gal. This is Manmeet.

You heard it correct, right? We have just initiated our sites in U. S. And we have started enrolling for U. S. The non squamous arm. It's too early to give clarity on the completion of the enrollment until we complete all the sites in other territories, which is obviously in Europe and other regions. Which we plan to initiate. We would be able to provide once all those sites are activated. And we have a quarter or two of the run rate, then we will have clarity in our timelines over there.

Related to Harmony6, you're also correct, right, that trial has been completed enrollment, which was fully in China in the Spamous arm and what I believe as for the guidance from Akasil, that should lead out sometime in the middle to end of this year we don't have visibility into any more details further than that.

And then last quick one, I would be remiss if I didn't ask you about the news morning on the Pfizer collab. Anything you could say there in terms of additional details, which of the Vidotin ADC's, what tumor types, how big would these ROE studies be? And things of that nature? Thank you so much.

Yes. Thanks, Yigal. This is Dave. Really appreciate the interest there. I think so what we've said this morning multiple ADCs from Pfizer, We plan to go into multiple solid tumor settings and expanding that beyond just Summit cell lung cancer obviously. We haven't given specifics in terms of which ones just yet, but they are likely to be Phase 1b2 level trials at this point. We need these are the first combinations that we'll do with ivenessumab in these specific ADCs. So So normal Chorus operations there. But we'll give additional details as we get closer. But we are very excited to get moving here. And I think as we've mentioned before, this is one of the strategic advantages that we feel we have in terms of the opportunity to combine ibenestimab with a number of different products from another a number of different organizations of pharmas and biotechs. And so this is one of the first steps in terms of moving forward from that perspective, but we will be giving additional details as we continue to get closer [indiscernible] the beginnings of these trials, which are expected in the middle of this year, so short term from All right.

Thank you very, very much.

Thank you. Your next question comes from the line of Brad Canino with Stifel. Please go ahead.

Good morning. Thanks for the questions. In the Pfizer ADC collaboration, do you think about this more from the perspective of providing further therapeutic enhancement beyond the KEYNOTE-one hundred and eighty nine or more from the perspective of bringing ivenessumab outside of lung a better probability of success.

Hi, Brad. Thanks for the question.

Both, but probably the latter more. So clearly, ADCs are going to be important across solid tumor oncology.

I think the data in lung cancer is interesting.

But the data outside of lung cancer has been stronger. And I think the fact that there's multiple ADCs involved in this is important.

And maybe just a quick follow-up on that. In lung specifically, as I look at the Pfizer pipeline of ADCs, can I check your confidence level in integrin beta six for an ADC target over TROPE-two where obviously competitors have frontline Phase three is reading out this year? Yes. So appreciate the question, Brent. I think we'll be in a better position to give a little bit more details as we get closer to launching the Phase 1b2 clinical trials. But at this point, we're not really getting into the specifics just yet in terms of the design as we want to to allow for these trials to get up and the activation force and then ultimately get up and running. For what it's worth, it's an important question. Love to answer it, but we can't do it yet. All right. Maybe last for me. With the HARMONY eGFR data coming mid year, how do you plan to show the data to investors to demonstrate that there is comparable efficacy and safety and its effect in Western patients relative to KESSA's China patients? Thank you. Thanks, Brad. Yes, I mean, I think that is going to be a key component.

I think we and especially Alan have been talking about this for over the course of the past year or so. One of the key components will be showing the comparability of the data to your point, both efficacy and safety in the Eastern and Western population. So while we haven't explicitly described the ways in which we will show this, we'll obviously have presentations. It major medical conferences and this the granularity will be there so that that can be interpreted. Thanks, Brett.

Your next question comes from the line of Kelly Li with Jefferies. Please go ahead. Congrats on the progress. Thank you for taking my questions. Maybe a couple of questions on how many trial trial design? So regarding the following assumptions on both PFS and OS, should we assume it is designed based on the total four twenty patients?

But not a subgroup of ex China patients. Yes, Haley, this is Alan Yang.

Yes, it is a primary analysis of the total study population. Of course, as Brad alluded to, that there will be looks at the regional differences. We've had discussions on this from a regulatory standpoint about how the data should be analyzed and presented. But then, of course, during the analysis and then during the review process they could always ask for additional studies as well.

Okay. Thank you. And Okay, thanks. And you guided a midyear for data disclosure. I just want to confirm, this is referring to like June, July or actually could it be like the entire Q2, Q3 timeframe.

I appreciate the question, Kelly. I think we're probably a little bit broader on that more in the the Q2, Q3 timeline. But obviously, as we get closer to that, we'll be letting people know.

Okay, terrific. And then one more on Pfizer's color about collaboration. So regarding EV in bladder cancer, just [indiscernible] is there like a possibility to add some combo arm to the ongoing or the initiating Phase three trials running by Pfizer or should we expect more like early phase trials?

Yes. I don't think we've disclosed anything. We're exploring every opportunity to move as quickly as possible.

We haven't said anything about EV specifically, but we believe that EV is important in bladder cancer and [indiscernible] More to come.

Yes, we're excited to give you a little bit more details in in the upcoming couple of months.

Okay, great. Thank you for the color. Thanks, Kelly. Your next question comes from the line of Mohit Bansal with Wolfe Fargo. Please go ahead. Hi. This is Sadia Rahman on for Mohit. Thanks for taking the questions and congrats on all the progress. Over the year. So wanted to ask on the Pfizer collaboration. Curious how you're thinking about the overlapping toxicities with GADJF inhibition and vidotin based ADCs. And how could how this could differ from combinations of ABCs using topoisomerase payloads?

Yes, appreciate the question there. I think part of So if I take a step back, one of the things that we've expressed more broadly is that we want to be able to take iibonesumab in best available treatments on a tumor by tumor level, right? And so part of what we will be doing is doing safety run ins with any combination in which we combine with ivenessumab and that will be the same here. So I don't think we're in a position to commentate specifically on each of the different types of ADCs, whether it be MMAE based, whether it be to Hawaii, some areas based, We've seen data historically, whether it be in combination with immunotherapy like pembrolizumab in some of these ADCs, whether it be again MMAE based or Tuftsweissom areas based. But at this point, we're excited about the profile that's been shown to date for ibonessumab. We're very aware of the profile to date for many of the progressing ADCs. And I think that's where we're going to take the opportunity to do rational step by step combinations, and then we'll take that to the next step as we see the data. Yes. And I would just add that there's emerging data in combination with pembrolizumab that these types of ADC are feasible.

And we have good safety data comparing ipinestimab to pembrolizumab, so we don't expect any additions or surprises in the combinations.

Got it. Thank you. And then on the upcoming readout this year in mutant lung cancer, I think you said the majority of those patients are coming from the China Harmony study and the majority of those patients received a first or second gen TKI before getting a third gen TKI. Would all of the patients recruited into the HARMEE study receive only a third gen TKI in that first line setting? And can you talk about how about any differences in those populations that we could expect in terms of time from diagnosis or survival. After that third gen TKI and whether that could result in any differences in efficacy when looking at the next line of treatment?

A did receive a third generation TKI as part of the standard of care.

And those patients will be included whether they received a first or second generation before receiving a third generation, they would still be eligible. And in terms of differences in responses in those that got first or second versus third generation and where they got them, That's outlined in The Lancet publication by Zhang. At all and we don't expect any differences.

Okay. Thank you.

And then maybe one more on the HARMONY-two trial. And your global trial. So the time to separation on the PFS curve in HARMONY two, happened very early on. Can you talk about what you would expect for the global study since it adds on chemo combination, just trying to understand how much the curves could shift and how that could affect timing of when you hit on PFS relative to to one, Harmi, to head on PFS.

Yes. I think we've put out a decent amount of data with respect to AK-one 20 which was the Phase two which looked at ivermectinib plus chemotherapy. In multiple settings including squamous and non squamous in the frontline setting. That's probably the earliest best rather in terms of an early thought process with respect to what we would see from data with ivenessumab plus chemo and comparing that against the historical benchmarks that you would see from trials such as Kino-one hundred and eighty nine, Kino-four zero seven, etcetera. I think that's probably those are probably the landmarks that I would look at from an early read in terms of what's publicly available. And then obviously as we get continuing data, including Harmony six, from our partners at Acesso in the squamous frontline setting. Those will be additional [indiscernible] provide more color.

Okay, great. Thanks so much. Thank you.

Your next question comes from the line of Mitchell Kapoor with H. C. Wainwright.

Hey, everyone. Thanks for taking the questions and congrats on this deal. Can we just talk about kind of when you were searching for a PV transaction like this, could you just talk about what you were looking for before you came to this arrangement with Pfizer And now that this deal is on the table, do you foresee additional BD opportunities or does this kind of preclude those for a while? And could you just talk about if you expect future business development to be in the pursuit of combination similarly like this and if importantly, if there are any particular BD opportunities that you're not considering? Yes. Thanks for the question. Question, Mitchell. I think if I again take a step back here, I think one of the things that we have talked about is the strategic advantage for Summit and iibonesumab is that we don't have that pipeline internally that we're kind of almost committed to combining with and we'll almost force through combinations as much as possible to try to keep internal synergies. So in general, our approach will be to look out and say what are the best therapies, what are the standards of care across each of the different solid tumor settings and to the extent that ibanesumab plus one of those whether antibodies or small molecules make sense.

Then that will be an opportunity where ivenesumab can combine there. So I would say, as a whole, we don't believe that there's a single ADC platform that individually is the only way to move forward. But we do believe that multiple companies have multiple different types of ADCs, whether it be topoisomerase base, whether it be MMAE base, whether it's switching out the linkers of the antibodies in different settings. Obviously, there's a number of for example, Trope two ADCs with different antibodies. So what we can do is really explore different combinations of ivenessumab plus X, Y or Z ADC antibody, small molecule. So we're not really giving guidance in terms plan to do ex additional collaborations like this or whatnot. But in general, we've certainly feel well positioned for is that we will take ivernesumab and look to combine it with the best possible alternative, if you will, out there a standard of care perspective to bring the most potential value to ipinatumumab and ultimately help patients in any way that we can there.

Yes, Mitch, and this is Alan Yang. I would just add that we just want to pursue the best science to help patients, right? And so so I think there was a lot of interest in combining with pembro in terms of combination therapies with different other agents. And based on the HARMONY2 data, as we had suspected that now companies are interested in sort of pairing with ivermectinib Summit that's where the puck is going.

Okay, great. And just to clarify the last point, are there there anything any particular BD opportunities that you're not open to at this juncture?

No, I wouldn't say that there's specific things we're not open to. I think it's more about what is possible with Ivan Sinema. Yes. And I would just add, if there was some clear safety issue or something like that, but we have not seen that signal yet. So we're pretty excited that we have a lot of opportunity. Okay, great.

Sorry, Manmeet. Sorry, Manmeet. This is Manmeet. And I would just clarify, yes, to answer your question very specifically. This transaction with Pfizer doesn't preclude us to do any other regional or any partnerships or any other activities. Very helpful. And the last one for me, just on the first line trials. Can you talk about a little bit more about the HARMONY-three enrolled? And I know you briefly touched upon that, but does Harmony seven site activation compete for patients for the PD L1 high enrollment for Harmony three at all? Yes. Hey, Mitch, this is Manmeet again. Yes, obviously, there is a segment of patients for IPD1 high patients, which will be covered in our Harmony three also, right? So there is some sort of that. But as you know, we have much ahead in our schedule on Harmony three activations.

And there will be not a full overlap of the sites, right? As compared to how many seven. So we have just taken how many seven initiation in last few weeks and how many three is already enrolling, right? Patients that they would be. Obviously, there is an overlap, we don't expect there is a competition because of new sites which we are planning to add in Harmony seven.

Great. Thank you all very much for taking the questions and congrats again on this collaboration. Thanks, Mitchell.

Your next question comes from the line of [indiscernible] Securities. Please go ahead.

Hey, guys. Thanks for taking my question.

Wanted to dig into Harmony three a little bit please. Will this primary statistical analysis for that study are you doing the primary analysis on the combined non square minus plus squamous population or will you do it more in a stepwise manner kind of looking at the squamous and non squamous subgroups individually first and then look at the overall population.

I asked this because I believe the Biontech study is structured more like the latter I'm curious to know if you're taking a different approach and if so why you prefer your method?

Yes, Stikka. Thanks for the question. This is Alan.

Yes, so it is a our plan is to do a primary analysis of the combined population and we believe that that was the best way to bring this product to patients as fast as possible from an operational perspective Of course, there is always data and ongoing data coming out. The Harmony six will be informative as well. But our current plan is to do a combined analysis. Got it. Thanks, Alan.

Have you discussed with the FDA any way to accelerate a filing with Horme three? I'm wondering if you're seeing a strong PFS signal. Is there [indiscernible] talked to the FDA about maybe doing a sort of filing based on that?

Of course, we want to bring this to patients as fast as possible. We've had several discussions with them on this study, but I can't disclose our discussions at this time. Got it. Okay. And then on the Pfizer collaboration, do you feel ivermectinib would be could better leverage the immunogenic cell depth versus PD-one or is the rationale behind this deal mainly about layering on a class genogenic pressure addition to PD-one with AGC. [indiscernible] We could talk a lot about that. But with that said, part of it is empiric. We know that both of these drugs are a lot of these drugs are active in different tumor types and then then you clearly want to add those efficacies, whether there will be some synergistic profile it be different from pembro's sort of additive or synergistic effect We think all of those are actually possible and we're looking forward to these combinations. But yes, it's very interesting.

Great. Thanks for taking my questions guys.

Thanks very much. Next question comes from the line of Ran Benjamin with Citizens JMP.

Please go ahead.

Hey guys, thanks for taking the questions and congratulations on all the progress.

With Harmony three and seven kind of off to the races, can we talk a little bit about the next solid tumor indications you plan to invest in? And we've got some we had some ongoing study data reported last year Can you talk a little bit about when we might see some updated results from from those studies. And I guess just as a sticking with this theme, I guess broadly, do you kind of strategically follow at Kiso based on their data, their solid tumor data? And kind of do global studies based on what they've reported or do you kind of broaden exposure and go after indications that Sure, Ren. Thanks very much for In reality, everything that you mentioned resonates, right? And so if you think about the last part of your question, which is do you follow a Kessel or do you look to branch out? As Mickey talked about, part of our MD Anderson collaboration looks to accomplish parts of that as well as our IST program. If you look at some of the Phase two data generated by our partners at Acasto, which were released over the course of last year, whether it be B2B colorectal cancer, head and neck cancer, and triple negative breast cancer.

There are some promising signals that we see in that Phase two data. There are also additional indications have been explored in Phase II where data hasn't yet been fully disclosed from that perspective, which give us opportunities. And then obviously, we can run additional signal seeking or Phase two studies as well, whether on our own or through things like the collaboration the clinical trial collaboration with Pfizer here, which we'll look to do that as well. So as a whole, I think we've as Nikhil mentioned in her comments, earlier, we're very keen to in addition to the significant work being done in non small cell lung cancer look beyond lung cancer as well and that's part of our 25, 26 development plan. Got it.

Sorry, got No, Ren. I was just going to add. So We haven't disclosed it. We're in the midst of multiple regulatory discussions around that.

I would just say that we have been thinking about this for a long time. So we did this exercise even before the Harmony two data read out shortly after the deal was done. Looking at all the prior checkpoint inhibitor approvals, looking at all the angiogenic, anti angiogenic approvals, looking at what we think the population size would be, what the comparator arm would be, And then you layer on top of that the Phase two data coming out from a a Kessler that all goes into the calculus of how we make those decisions. And hopefully, we'll be able to disclose some exciting opportunities soon.

Outside of the opportunities, could we expect updated results from any of those studies or do you feel like they're largely largely concluded and it really it's about Phase three studies that are up and running.

Yes. Hi, Ran. This is Manmeet. Yes, you will continue to hear more updates as we progress on those all the studies which we had given Summit initial top line data earlier in the last year. But I would also mention that, right, colorectal cancer, right, where we are pretty excited and we have just recently partnered with Akaso also on the Phase two study which we have begun to activate. [indiscernible] on our side and that would be the first one which is which you would hear more details in next coming quarters.

Excellent. Okay. Thank you for that. And just one last one for us. I think ct.gov said that there are three active sites for Harmony seven. Can you talk a little bit about how many sites globally you expect to have on board by call it by the end of twenty twenty five and for both Harmony three and Harmony seven.

Hi, Ran. This is Manmeet again. I think we don't give specific number, but on the sites which we activate, because we go into multiple regions, right? This is a global multiregional study. But I would expect by end of twenty twenty five, almost most of the sites are looking 100 near to 100% of the sites should be activated.

Great.

Thanks for taking the questions guys and congrats.

Thanks, Chris. Thank you.

I will now turn the call back to Dave Gankorn for closing remarks.

Thanks very much. And I'd like to hand it over to Bob Duggan just for Yes. I just want to weigh in on the question of Biz Development.

Biz Development has a couple of armed One is optimize IVO, and make it the best product monotherapy, combination therapy that the world has can get from us and partner at Kessel.

And we're daily looking at that and evaluating that. There's plenty of room to go as you see with the trials that we're entering into. Second aspect of business development is what's the timing of gaining markets, additional market space, additional market opportunity and then how much share can you get and how do you go about doing that. And that's also a major part of this development. So we're very active on two footprints. Pfizer is footprint one, how do we optimize the product other other activities we're constantly working on those here Also, I just want to make clear that Pfizer is not the beginning and end of business development at Summit. Summit that it isn't for most of you, but even for some of you. So back over to Dave. Really appreciate it, Bob. Thanks very much. And I want to thank everyone for attending today's earnings call. An archived version of the webcast will be available later today on our website, www.smmttx.com. Thank you very much for your participation and we hope you enjoy the rest of your day. Thank you. [indiscernible]