Good morning. And welcome to Summit Therapeutics' Q3 2024 Earnings and Update Call. All participants will be in a listen only mode until the question-and-answer portion of the call [Operator Instructions]. Please refer to the company's Web site for updates. Please note that today's call is being recorded. After the speakers' remarks, there will be a question-and-answer session. Thank you. At this time, I would like to turn the call over to Dave Gancarz, Summit Therapeutics' Chief Business and Strategy Officer. You may proceed.

Good morning, and thank you for joining us. Our press release was issued earlier this morning and is available on the homepage of our Web site. Our Form 10-Q was also filed earlier this morning and is available on our Web site. Today's call is being simultaneously webcast and an archived replay will also be made available later today on our Web site, www.smmttx.com. Joining me on the call today is Bob Duggan, our Chairman of the Board and Chief Executive Officer; Dr. Maky Zanganeh, our Chief Executive Officer and President; Manmeet Soni, our Chief Operating Officer and Chief Financial Officer; and Dr. Allen Yang, our Chief Medical Officer. Before we get started with the rest of the call, I would like to note that some of the statements made by our management team today and some responses to questions that we will make 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, Maky and Manmeet, we will take questions. And with that, I'd like to turn the call over to Bob.

Thank you, Dave. Good morning, everyone. Thank you for joining us today. I'm very proud of the recent accomplishment of Team Summit and the continuing positive information to be shared surrounding ivonescimab, our lead investigational asset. There have been several meaningful achievements around the progress of ivonescimab since our last earnings call, both with our partners in China as well as here in the US 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, we intend to amend the protocol for our multi-regional Phase 3 trial HARMONi-3 to now evaluate patients with first line treatment for metastatic non-small cell lung cancer with both squamous and non-squamous histologies. The prior trial design previously included only tumors of squamous histology. This is a significant immediate expansion of total addressable market of our current Phase 3 clinical trial portfolio. We will provide additional context in a few moments around HARMONi-3's expanded patient population. We have completed enrollment of our global Phase 3 HARMONi trial in patients with EGFR mutated advanced non-small cell lung cancer who have progressed after treatment with the third generation EGFR tyrosine kinase inhibitor or TKI. As previously announced, we expect HARMONi top line data in mid-2025. In addition, we received fast track designation from the FDA for this setting in the United States. Following the positive results of HARMONi-2, we announced our intentions for launching a third global Phase 3 trial, HARMONi-7, studying ivonescimab monotherapy in patients with first line metastatic non-small cell lung cancer whose tumors have high PD-L1 expression. Additionally, encouraging Phase 2 data featuring ivonescimab from China was featured at World Lung and the 2024 European Society for Medical Oncology or ESMO annual meeting in perioperative non-small cell lung cancer,…

Thank you, Bob. And good morning, everyone. As Bob said, I remain incredibly enthusiastic about the accomplishments of Team Summit and our partnership with Akeso. Before providing on some of the highlights, as Bob mentioned, I would like to discuss the clinical work that has been conducted with ivonescimab. There are more than 25 clinical trials around the globe evaluating ivonescimab across 17 tumor settings, including nine Phase 3 trials planned, ongoing or completed either in China or globally. While six of the Phase 3 programs across Summit and Akeso are currently focused in non-small cell lung cancer, three additional Phase 3 clinical trials have been announced by Akeso evaluating our lead candidate in solid tumor settings beyond non-small cell lung cancer. This include BTC, head and neck cancer and pancreatic cancer. At Summit, we are sponsoring two ongoing Phase 3 clinical trials, HARMONi and HARMONi-3. We are planning to initiate HARMONi-7 in early 2025. Based on the data Bob mentioned that was released at ESMO that I will speak more to it in a moment, we are excited to and are actively exploring expanding our Summit led clinical development plan beyond metastatic non-small cell lung cancer. As a reminder, ivonescimab is the only PD-1 VEGF bispecific antibody in Phase 3 in our licensed territories. Ivonescimab brings these two highly validated mechanism of action together into one novel molecule targeting simultaneously both PD-1 and VEGF. Next, I would like to review the many achievements completed as well as discuss some upcoming catalysts for the remainder of this year. The third quarter of 2024 was a landmark moment for ivonescimab and its development with significant catalyst events in the form of data related in September at the World Lung and ESMO conferences. Last month at the World Lung Conference, HARMONi-2 results…

Thank you, Maky. And good morning, everyone. We issued this morning our earnings release for the third quarter of 2024. Today, in addition to providing you with an update on our cash position, recent financing and third quarter operating expenses, I will also be providing an update on our clinical operations. On the clinical operations front, I'm really proud of the Team Summit for completing the enrollment ahead of schedule for our first registrational global trial HARMONi in patients with EGFR mutations post targeted therapy. We expect to have the top line data from our HARMONi trial, including patients from US and Europe in mid-2025. Also, since the release of ivonescimab data during September 2024 at World Conference on Lung Cancer and ESMO Annual Meeting, we have seen an increase in the screening and enrollment activity for the squamous patients at our existing sites in our HARMONi trial. Additionally, we have seen lots of excitement and outreach from both academic and community physicians to participate in the development of ivonescimab. We believe this interest will help us in accelerating activation of additional sites and ultimately enrolling patients faster for the two planned trials. HARMONi-3 for addition of non-squamous arm and also for recently announced HARMONi-7 trial, which we had in 2025. On the financials front, let me start with our cash position. We ended the third quarter of 2024 with a cash position of approximately $487 million. This cash position was strengthened at the end of third quarter with the closing of a $235 million private placement in September 2024 from multiple leading biotech institutional investors and insiders. Turning to operating expenses, I'll provide details to both GAAP and non-GAAP numbers. You can refer to our press release issued this morning for a reconciliation of GAAP to non-GAAP financial measures.…

Thank you, Bob, Maky and Manmeet. Now we'd like to see if there are any questions that our team can help answer. Operator, would you please open the line for questions?

[Operator Instructions] Our first question comes from the line of Mitchell Kapoor with H. C. Wainwright.

Just wanted to know on the expansion of the HARMONi-3 trial. Who are the likely first line non-squamous patients that you could likely enroll? And specifically, how do you think about recruiting patients who would otherwise be good candidates for KEYTRUDA? How do you think about getting those patients to participate in this study?

So the expansion is basically similar to the population that was treated in the KEYNOTE-189 study. So these are going to be non-squamous patients, probably [adeno] patients. And I think Maky reviewed the trial. I think the key here will be the chemo will be slightly different, it will be platinum pemetrexate for these patients. However, we have extensive experience with that from the HARMONi studies, HARMONi-A and HARMONi.

And do you have a target enrollment for the split between non-squamous and squamous for this trial?

We have not disclosed that.

We're just in the planning phase right now. As we said, we did the -- we gave the combined number, 1,080 patients, which we plan to enroll in both squamous and non-squamous, we have not given further splits yet.

And then the last one for me is just on HARMONi. Can you talk about the potential for accelerated approval? Could you file on PFS? And how does that differ in terms of the unmet need from the strategy with HARMONi-3 and HARMONi-7?

HARMONi has always been our path to market strategy. And as you know, we announced that we completed the enrollment earlier this month and now we expect the data in mid-2025. Obviously, based on the data we’re -- obviously we'll be assessing our regulatory strategy and then providing further updates.

And just to clarify, there's two parts to that question in terms of the PFS, right? So there's could you file only on PFS data and then the timing of which could you file with the PFS data before you have the OS readout. And so just for the precedent in this EGFR second line space, the approval has been on PFS, right? And unfortunately, it is second line. It's a large unmet need. So the time between PFS and OS readouts may not be significantly different, right?

The only thing I would add to that, Mitchell, just to round it out. I think you asked the question in terms of the difference between the HARMONi and the HARMONi-3 perspective. So just to reiterate. So HARMONi-3 is, when we -- with our intention to expand that population, that is patients already with squamous, so we'll keep that cohort. We'll add patients who are non-squamous but they'll be without actionable genomic alterations, right? So without driver mutations. Our HARMONi trial, will -- is focused on those with EGFR mutant driver -- the driver mutation of EGFR mutations, right? So that is they are separate, they're not overlapping populations, HARMONi and HARMONi-3. I just want to make sure that that's clear.

And just to further clarify, I just want to clarify for the HARMONi-3, as Maky mentioned, now the endpoint is PFS and OS and the question around PFS filing versus OS timing of the filing is relevant for that study.

Our next question comes from the line of Brad Canino with Stifel.

On the addition of PFS to the primary endpoint of HARMONi-3, can you talk about what types of regulatory feedback and clinical investigator feedback that went into that decision? And then related and sorry to push with a question like this, but we all know that investors are keenly aware and awaiting for an OS answer from your partner, Akeso. And a change like this before we get that naturally makes one wonder what the confidence of management is to achieve a clinically meaningful OS benefit in the frontline among setting. So can you talk about both of those elements?

So let me answer the last one first. There's no change in our confidence for the HARMONi-2 data around the OS, right? I think the opportunity was, and it was unrelated, but the magnitude of the PFS benefit in HARMONi-2 was so striking. You don't want to have a therapy that provides such a significant benefit and not make that benefit available to patients, right, just based on that number. Granted, there's a lot of issues that we won't get into about payer reimbursement and the value of OS versus PFS but we think that this is a positive thing in addition of the PFS endpoint as a primary endpoint for the HARMONi-3 study in both timing and availability and benefit to patients.

And just to answer the other part of your question that Brad you asked about regulatory feedback. So as we've promised from the beginning of this relationship with Akeso and our licensing of ivonescimab, we would be speaking, in particular with the FDA prior to these changes. So that we have had communications with the FDA here.

Especially for such an important change.

And now that HARMONi-3 does have both histologies. Do you plan to wait for them both to have data to do the top line or can they be reported separately? Right now, the NCT before you've updated says the primary completion estimate is September 27. Now that the trial has changed, how should we think about data flow, both histologies together et cetera?

So at the highest level what I would say there, Brad, is this is a single trial. So it's a single analysis set. So we wouldn't necessarily look to break out timing in there. Now we did say in the slides that we presented this morning that like -- and as would be expected from a stratification perspective, we would stratify it by histology, but it wouldn't be from a timing perspective broken out. I would say without going too far into the details, just given that we're intending to amend this shortly, there's a significantly broader population of non-squamous patients as well. And so from a timing perspective, there's more availability of those patients and there's a broader availability to enroll patients with non-squamous tumors.

And then last from me, I think as we see multiple PD-1 and L1 by VEGF bispecifics advance across multiple companies. I mean every day there seems to be a press release. It would be great to hear your thoughts on whether other designs and constructs, be they those that leverage PD-L1 or maybe broader VEGF isoform inhibition, are viewed internally as close replications of ivonescimab and its incredible profile to date or are viewed as potentially different?

So what I would say, when we enter into the deal with Akeso, we naturally expected to see a few more assets emerge with a similar construct in general as you mentioned, given the data that had been produced to date and our willingness to enter into a deal of that size and magnitude that we did. Of course, once the data from HARMONi-2 emerged, we expected to continue to see a rapid emergence of products looking to capitalize on the potential that ivonescimab had created at that point. And so most of these assets, I would point out are very early. A majority, a vast majority of preclinical with no in human data. However, we do review the construct of each of these compounds individually. And while we're not going to comment on any individual asset particularly, what I would say is that ivonescimab was specifically engineered to improve anti tumor activity and reduce toxicities associated with these two targets. And this specific engineering was not accidental, it was not serendipitous. And we're very happy with ivonescimab in its construct in particular and that ivonescimab is our asset and we have yet to find one that we would rather have versus ivonescimab. Two successful randomized Phase 3 clinical studies involving ivonescimab only kind of bolster that perspective.

Our next question comes from the line of Yigal Nochomovitz with Citi.

So just thinking a little bit more about the HARMONi-3 amendment which you announced. I'm just curious, did you consider just simply starting a new study in non-squamous so you could preserve the timelines for HARMONi-3 or is the argument that because you're amending to PFS, you're going to win back time on the time to primary endpoint since you're no longer looking at OS?

So we totally understand and we evaluate it. But as you know, right, in order to capitalize on our existing sites, which we already have on the squamous and this timeline to amend was much faster to add the non squamous arm, and as Dave just mentioned, right, non-squamous is almost double the population and it increases our total market size, right, and the potential and there are long lead times if we have to start another trial with new sites and new clinical trial agreements, the lead time is much longer. So this would allow us to enroll patients on both arms quicker and expand our market like almost like tripling our market opportunity. Yes, we had not provided you timelines because we were still enrolling and activating sites for squamous, so we had not provided you earlier. So we don't see this as a material change in delaying squamous but it adds non-squamous opportunity and get non-squamous much faster and earlier into the market.

If I can give some physician feedback that we've been receiving, they very excited about this change, they see the logic in this change. This is a type of patient that they see more commonly in their practices. So it just increased sort of participation and excitement around the study.

I mean, clearly, it makes sense given you fill the gap in terms of the spectrum of all the non-small cell patients that are addressable. The other question I had was regarding, we've gotten a lot of questions on HARMONi-2 hitting on OS. As you know, it's been a significant debate. I'm just wondering if you could kind of walk through the logic as far as the confidence you have that HARMONi-2 will eventually hit on OS? Obviously, people have been making comparisons, perhaps inappropriate comparisons to HARMONi-A and the strong PFS there and then the OS which is trending well, but obviously not hitting stats yet. So just wondering if you could frame that and talk about how you see the path to confidence on hitting OS in HARMONi-2, which would obviously be a very big win and translate positively to everything you're doing over in the United States?

Again, I think our confidence hasn't changed. I think if you look back at data from multiple frontline non-small cell lung cancer studies, remember the HARMONi-A study was a second line study in patients with refractory osimertinib or other TKIs. If the -- probably the classic study, if you look at the criticism around bevacizumab the ECOG study that led to the approval of bevacizumab had a strong hazard ratio, I think, but it was well above 0.6 and it still hit its OS endpoint, the atezo bev studies as well the EMPOWUR studies as well. And so with this strong of a hazard ratio in PFS, it's unlikely that the OS won't be there, the OS benefit won't be there. But I just want to remind everybody for HARMONi-2 the primary endpoint was PFS and this study was designed for PFS. And the question around statistical significance, that's a numeric value that the people are after. And the question is, how long will it take to show that given the sample size.

There are no further questions at this time. I would like to hand things back over to Dave Gancarz for some closing remarks.

Thank you, Ian. I just want to take the time to thank everybody for attending today's earnings call. An archived version of this webcast will be available on our Web site www.smmttx.com. Thank you for taking the time to join us and enjoy the rest of your day. Thank you.