Summit Therapeutics Inc. (SMMT) Earnings Call Transcript & Summary

Thank you for standing by, and welcome to the Summit Therapeutics ASCO update conference call. [Operator Instructions] I'd now like to turn the call over to Dave Gancarz, Chief Business and Strategy Officer. You may begin.

Good morning, and thank you for joining us. We have issued multiple press releases with one as recently as earlier this morning, and they are available via the Summit latest news button on the home page of our website. Our Forms 8-K were also reported earlier this morning and are 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, www.smmttx.com. Joining me on the call today is Bob Duggan, our Chairman and Chief Executive Officer; Dr. Maky Zanganeh, our Chief Executive Officer and President; Manmeet Soni, our Chief Operating Officer and Chief Financial Officer; Dr. Allen Yang, our Chief Medical Officer; and Dr. Howard Jack West, our VP of Clinical Development. 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 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 our team, we will take questions. And with that, I would like to turn the call over to Manmeet for some opening remarks.

Thanks, Dave, and good morning, everyone. This morning, we announced that the company received and accepted an unsolicited offer from an institutional investor to purchase $200 million worth of common stock at $9 per share, a premium to the closing price on Friday for aggregate gross and net proceeds to the company of approximately $200 million. This offer was accepted by the executives and approved by the Board. In addition, we also announced an expansion of our license territories for ivonescimab, via an amendment to our existing collaboration and in-license agreement with Akeso. Under the terms of this expanded agreement, now we will have Latin America, including Mexico and all countries in Central America and South America, in addition to Middle East and Africa. This expansion adds to the territories licensed by Summit earlier, which included United States, Canada, Japan and Europe. In exchange for these expanded territories, the total deal value is worth up to $70 million. Now I will hand it over the call to Dave.

Thanks, Manmeet. Before I hand the call over to Allen and Jack, I would like to take a moment to remind everyone of the 4 Phase III clinical trials to which we have recently spoken. On Slide 3 here, starting on the top right-hand corner of the slide and moving counterclockwise, HARMONi-A is a randomized single region multicenter clinical trial that was presented by Dr. Lee Zhang at ASCO last Friday. This is a clinical -- this is the clinical trial that was sponsored and conducted by our partners at Akeso that is the basis for the approval of ivonescimab plus chemotherapy in China. The study evaluated patients with advanced or metastatic non-small cell lung cancer, whose tumors were positive for an EGFR mutation and enrolled patients whose tumors had progressed after previously receiving an EGFR-TKI. The next trial to the left is our multiregional Phase III clinical trial, HARMONi in a similar setting. Our HARMONi trial is for patients who previously received a third-generation EGFR-TKI. It also have evaluated ivonescimab plus chemotherapy as compared to placebo plus chemotherapy. The analysis for HARMONi intends to include all patients from the HARMONi-A trial who previously received a third-generation TKI in addition to patients enrolled from the U.S., Canada and Europe. Claimed total enrollment for our Phase III multi-regional HARMONi trial is approximately 420 patients for which Summit intends to complete enrollment during the second half of 2024. Moving down, the HARMONi-2 clinical trial is a frontline non-small cell lung cancer trial is a randomized clinical trial evaluating monotherapy, ivonescimab as compared to monotherapy pembrolizumab in patients whose tumors had positive PD-L1 expression or a PD-L1 TPS score of 1% or greater. This is a single region multicenter Phase III clinical trial conducted and sponsored by Akeso for which high-level clinical trial results were announced last Thursday. And finally, moving to the bottom right of the screen is HARMONi-3, our multiregional randomized Phase III clinical trial evaluating ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy in frontline metastatic squamous non-small cell lung cancer. So with that, I would like to hand the call over to Jack to speak quickly to the HARMONi-A trial results that were discussed at ASCO last Friday.

Thank you, Dave. On Slide 4, we have the schema for the HARMONi-A trial. HARMONi-A is a Phase III trial of chemotherapy with either ivonescimab or placebo in Chinese patients with EGFR mutation-positive non-small cell lung cancer that has progressed on prior EGFR tyrosine kinase inhibitor or TKI therapy. Key eligibility criteria are shown here. Patients were randomized one-to-one and stratified by prior exposure to a third-generation EGFR-TKI and presence of brain metastases at baseline. Patients received either ivonescimab at 20 milligrams per kilogram plus pemetrexed carboplatin or placebo plus the same chemotherapy backbone then received either ivonescimab or placebo in combination with pemetrexed as maintenance for up to 24 months. Treatment was to be discontinued for intolerability, no clinical benefit or initiation of new antitumor therapy. The primary endpoint was progression-free survival by independent radiologic review committee, secondary endpoints for overall survival, response rate, duration of response and safety. Next slide. Here is the primary end point of progression-free survival by independent review, demonstrating a significant improvement for ivonescimab with a hazard ratio of 0.46, corresponding to a 54% improvement over the control arm and a median PFS of 7.1 versus 4.8 months favoring ivonescimab. Next, PFS benefit was observed in both patients with brain -- baseline brain metastases shown on the right and those without brain metastases on the left, CNS metastases are unfortunately not uncommon for patients with EGFR mutant non-small cell lung cancer, and they comprised about 22% to 23% of this study cohort. At the request of the Chinese regulatory authority, an early overall survival analysis was conducted approximately 2 months after the initial data cutoff and with 30% data maturity show an early separation of the curves, next slide, and that is maintained on a subsequent regulatory request with data maturity of 52%. Next slide. As would be expected, there were more grade 3 or higher and serious adverse events on the ivonescimab-containing arm, though the difference in discontinuation rates was only approximately 3% between the 2 arms, and there were no treatment-related deaths. Grade 3 or higher immune-related adverse events were slightly higher in the ivonescimab arm as expected, though there were no differences -- no clear differences in VEGF-related Grade 3 adverse events between the 2 arms. Next. Specifically, the most common adverse events were hematologic, with rates of non-hematologic grade 3 or higher adverse events, all 3% or less. Next. Immune-related events were as expected for an immune checkpoint inhibitor targeting PD-1, interstitial lung disease was very uncommon with rates comparable between the 2 arms. Next. While low-grade proteinuria and hypertension were more common in patients assigned to ivonescimab that's consistent with targeting VEGF, there was no increase in grade 3 or higher bleeding or thromboembolic complications.

Thank you very much, Jack. And I think the next slide now shows the pipeline for ivonescimab, which includes trials run by both Summit as well as those that have been previously or currently sponsored by our partners at Akeso. You see in addition to the Phase III clinical trials that are currently being conducted, there are several Phase II clinical trials also in progress, being currently conducted by our partners at Akeso in China. This gives us substantial opportunity in terms of our ability to move forward with our next Phase II and Phase III clinical trials that we'll choose to move forward with, and we're very excited to move forward in the short term. And finally, on the next slide, we see the headline with respect to the first trial that I earlier mentioned the HARMONi-2 study, which we are very excited to provide more details at a major medical conference upcoming likely in September. And with that, we'll now like to see if there are any questions that our team can help answer. And so I would turn to the operator to see if there are any open questions on the line.

[Operator Instructions] Your first question comes from the line of Yigal Nochomovitz from Citigroup.

Summit team, congratulations on the flurry of excellent data over the last several days. I think for those less familiar with the story, it would be great if you could frame and help people understand ivonescimab's mechanism action and why it's more than just the sum of the parts of a PD-1 and a VEGF discussing how it was rationally designed and in addition, the data on HARMONi-2 and HARMONi-3, how that potentially could translate to OS when say study IMpower150, there was bevacizumab, TECENTRIQ worked on PFS, but obviously didn't translate into OS.

So the first question is about the mechanism of action of ivonescimab. And I think the data -- clinical data is continuing to support the hypothesis that this is differentiated in terms of PD-1. As people know that ivonescimab targets both PD-1 and VEGF, but the secret for the sort of the strength of the molecule is really that there's cooperativity between the binding ligands of PD-1 and VEGF such that VEGF binding increases the binding of PD-1 by greater than 18-fold and the binding of PD-1 increases the binding of VEGF by greater than 4-fold. In addition, what's known because of the Morrison format and the fact that there are 2 VEGF binding sites, VEGF is a dimer, and then VEGF can cross link different ivonescimab molecules. So you can have a sort of daisy-chaining of ivonescimab and VEGF leading to multiple -- the presentation of multiple PD-1 site. In addition, there are some other properties that we think are important. The molecule has been engineered to be Fc-null, which we believe helps with immune-related adverse events, and it has a shorter half-life, which we believe helps with the VEGF associated adverse events. The second question around HARMONi-2 and HARMONi-3, remember, HARMONi-2 is a China-only study. And I think we want to be clear that it was never anticipated that we would be able to file on the HARMONi-2 data. However, given the strength of the data, we're going to sort of make every way possible to make this therapy available to patients as soon as possible. In addition, the question around PFS translating to OS, I would say that for HARMONi-2 and HARMONi-3, the earlier study usually occurs in other words, the earlier you make therapy available for patients, the more likely that you'll have a translation for PFS to OS. There's always the risk that PFS won't translate to OS. But again, given the strength of the data and the trends that we're observing gives us very good confidence that we'll hit those end points. Go ahead, Jack.

I would also just note that with some of these trials in the first-line setting, there can be sometimes differential crossover, and this is a setting where in our trials, the patients say, the HARMONi-2, there -- everyone has been exposed to a respected, a good immunotherapy checkpoint inhibitor. And so they're after [indiscernible] really would not be any expected big change from a crossover to any subsequently, really, you have things like docetaxel, that would be available to both arms at equal rates. So I don't think that there would be any reason to anticipate much movement from crossover effects.

Okay. And then obviously, with the very positive top line interim on HARMONi-2. Could you just broadly talk about some of the thoughts in terms of how you might develop ivonescimab in the non-squamous population in the United States. What sort of trials might you envision that would leverage that given as you point out, and we appreciate that you may not be able to directly use the HARMONi-2 for U.S. registration.

Yes, Yigal. Thanks for the question. We're not going to give details on that today. However, I will say that PD-1 and VEGF have been well described targets. You can sort of look at the precedent molecules and see where they have indications. And so we are looking at that. And again, what's very helpful is that [indiscernible] has been very proliferative in their clinical trial program. So we have a lot of upcoming Phase II data that we're reviewing to help inform those [indiscernible].

Your next question comes from the line of Brad Canino from Stifel.

I will echo my congratulations to the team on a successful ASCO. A few questions for me. First, I was wondering if you could just walk through the process of how HARMONi-A data you kind of incorporated into your registrational HARMONi-1 study? And when would it be reasonable for investors to expect the first BLA filing to the FDA?

Brad, thanks for the question. I think for those following the line, I think the easiest way in some ways is to walk through that is also from the press release that we issued last Friday in terms of how that data gets incorporated, but I'd be happy to walk through that right now. So the HARMONi-A trial incorporated 320 patients or a little over 320 patients who received the previous EGFR-TKI. What we did when we established the deal was create a multiregional Phase III study, the HARMONi study, and that will take all patients who previously received a third-generation EGFR-TKI from the HARMONi-A study. And that was about 85% of the patients. So the vast majority of the patients who were enrolled in the HARMONi-A trial will then become the Asia region for the HARMONi trial. So the HARMONi trial is a multiregional trial incorporating patients from China, from North America and from Europe. And so about 85% or 270, 276 patients from the HARMONi-A trial will be incorporated in the HARMONi study. And then we will, from there, enroll an additional 150 patients in the HARMONi trial to enroll a total of -- about 420 patients in total there. So we'll have multiregional input from Asia, North America and Europe. And that will be what is analyzed as part of our total study. I think, Brad, for the second question that you have in terms of what do we expect the BLA filing. What we have said at this point is for the patients from North America and Europe that we plan to -- that we're adding to enrollment, we plan to complete that enrollment in the second half of this year. And so based on some of the data that Jack walked through, while we haven't specifically said when that BLA filing will be, you can sort of back into when we would get to a data readout at that point and hopefully, that's at some point in 2025 and then the BLA filing process becomes thereafter.

Great. And then separately for HARMONi-2, how important was the consistent benefit for patients with PD-L1 high as you think about the potential for ivonescimab's development?

Yes. Thanks, Brad. I think what I heard from you there, sorry, was how important was the PD-L1 high expressers in terms of our overall evaluation. So I mean, I think that's very important, considering our mechanism of action. So I'm going to hand the answer over to Allen to really elaborate there.

Yes. So I don't think we've actually disclosed that data, Brad. So HARMONi-2 has always been an interesting experiment. And as we've discussed in the past, it would inform a lot of our development strategy. It included patients that had a CPS score of 1% or greater, which is not currently the standard of care in the U.S. Now ivonescimab targets both PD-1 and VEGF. And so the question we had always had scientifically is whether the benefit is predominantly seen in the patients that have lower PD-1 expression, suggesting that the targeting of VEGF is the true benefit or is the cooperativity helping both patients with the low PD-1 expression as well as those with high PD-L1 expression. So what I will say is that I will refer you to our press release, and we look forward to seeing you in September at that major medical meeting.

If I can add anything, this is Jack. For me, I think it was extremely important that the press release specifies that the PFS improvement was observed broadly across the different subgroups that included the low and the high as well as adeno and squamous. And we've seen extremely promising results in squamous and this really showed us it is not limited to any one group kind of pulling anybody else across the goal line, but rather that this is really seen everywhere. I'd also note that, of course, pembrolizumab was the first of these agents that was approved in first-line non-small cell lung cancer back in 2016 that changed everything and it has been the pacesetter with great results in high PD-L1. That was back in 2016. The first of them, that's been a high bar and showing that you can beat pembrolizumab in a setting where it has achieved very well is a very strong statement. So it's not just winning in the setting where there might be some relative weakness, but winning across the board and even in an area where pembrolizumab has been known to be an extremely strong treatment, and you can hope to do better than that is a real statement, I would say.

Okay. And then finally, last for me. Given that this weekend has served as a good introduction to ivonescimab. Could you just give us highlights from your meetings with the clinical investigator community as you discussed the drug? And should we expect investigator-sponsored trials to emerge in the near future?

Yes. It's the short answer. Fortunately, I have a history of decades as an academic or treating oncologist. And I've been a close part of this tight community. And so I was -- have always been able to reach and share plans and develop plans with my colleagues who are thoracic oncologists, but I'll tell you, as you might imagine that the news that had been anticipated at ASCO compounded by the press release about HARMONi-2 has only increased everyone's interest. And so that is the first question that I get in my meetings that have been up and down all throughout ASCO of how can I work on this, whether it is as an institutional IST or a cooperative group, et cetera. But we'll have many potential platforms and many eager partners for this. So for us, it is -- our big challenge will be to prioritize what should come first for us. But we have a lot of different people to work with and cooperative groups who will be eager to be partners with us.

Yes. And Brad, if I could just take a moment to thank our investigators and the patients involved in our studies. When we told our story, there were a handful of investigators that really sort of understood and took the time to understand the beauty of this molecule, and we wanted to thank them. You can only imagine now they feel sort of validated in that belief. There have been now new people approaching us. We had a very active IST program before in terms of patients approaching us given the unique mechanism of action and the known or familiarity with the target but that is only accelerated at this meeting.

[Operator Instructions] Your next question comes from the line of Carter Gould from Barclays.

Congrats on all the progress. I guess, one for Allen and Dr. West, I guess, particularly after sort of in ESMO last year in which there was a lot of discussion in terms of sequencing of EGFR agents and the various approaches there. Can you just speak as you think about now sort of ivonescimab positioning even as a second line versus some of the questions around how you position ivonescimab and sort of how you see that playing out? And then maybe just a more pointed question to Dave and the team around sort of the next steps for clinical development there. You talked about some of the -- working with Akeso and they clearly have a broad set of studies going on. But sort of the time frame for really kind of like teasing out that broader clinical development plan, is that something we should expect by the time we get to [indiscernible]?

Okay. This is Jack. I'm happy to fill things. I've had lots of conversations with my colleagues about their -- how they perceive the HARMONi-A data and how that may change the landscape. Obviously, at this time, it's not going to be commercially available to physicians and patients in the U.S. We have the ongoing HARMONi global trial. But I've also talked to them about the range of options. There's FLAURA2 and the potential integration of chemotherapy into the first-line setting and there's amivantamab and potentially lazertinib, but many, many of my colleagues, if not the majority, have a lot of patients who have been doing well on osimertinib for years, some for more than 5 years. And they are not eager to necessarily bring in chemotherapy and IV treatment in general into a setting where so many patients can do well on oral therapy for years at a time. In fact, one I spoke with yesterday shared that she has brought it up with several patients who have essentially categorically refused to consider it. So FLAURA2 and that concept of chemo and osimertinib is going to be a component for selected patients, but I don't think it is going to become the prevailing approach broadly. So I would say a lot of patients will have progression on osimertinib and still be chemotherapy naive or will not have received it for a long period of time and would be an appropriate candidate for the HARMONi or HARMONi-A approach. Of course, there is amavantimab, and we did see data from a few days ago that there's a subcutaneous administration that shortens the treatment time. But that has its own challenges that are largely related to toxicities not abrogated by the administration route and specifically the dermatologic ones that are a real challenge. So I would say it is somewhat influx, but just showing that you have a therapy that can be such a critical component to significantly improving outcomes is an important message, especially when that is not saddled with accompanying toxicity challenges like some of the other competing options.

What was the second part of the question?

The development program.

Okay. Yes. So I remember the question, it more based around EGFR or lung cancer, I'll try to answer both, right? So a couple of things. In the EGFR post space, it's pretty well defined what we need to do to add on given the changing landscape of different therapies, the FLAURA2 and Mariposa, and so we'll have a strategy around that. In terms of a broader development program, we're very excited that HARMONi-2 answers the questions we need to be answered, but we've only had the data for a couple of days. And so we're not going to sort of tell you all of our plans at this time.

And there are no further questions at this time. I will now turn the call back over to Dave Gancarz for some final closing remarks.

I really want to thank everyone for taking the time to attend our call this morning, and thank you very much for your continued and accelerated interest in Summit Therapeutics. An archived version of the webcast today will be available on our website, www.smmttx.com, and I really hope you appreciate the time we've taken this morning. Thank you for your time, and we hope you enjoy the rest of your day. Thank you.

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