Summit Therapeutics Inc.

Hello, everyone. First and foremost, we'd like to apologize for the delay of this event. Good morning and welcome to Summit fourth quarter and year end 2023 earnings call. All participants will be able to listen only until the question and answer portion of this call. We do not expect any technical difficulties today forward. However, in the event that we lose the webcast connection and we 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. If you'd like to ask a question during that time, please press the star button followed by the number one on your telephone keypad. If you'd like to withdraw your question, please press star and number one again. At this time, I would like to turn the call over to Dave Gunkars, Summit Therapeutics Chief Business and Strategy Officer. You may now proceed, please.

Good morning, and thank you for joining us. Our press release was issued earlier this morning and is available on the homepage of our website. Our Forms 10-K and S-3 were also filed earlier this morning and are available on our 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 of the Board and Chief Executive Officer, Dr. Mekhi Zangane, our Chief Executive Officer and President, Manmeet Soni, our Chief Operating Officer, Ankur Dhingra, our Chief Financial Officer, and Dr. Alan Yang, our Chief Medical Officer. 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 Bob, Mechie, and Ankur, we will take questions. With that, I will turn the call over to Bob.

Thank you, Dave. Good morning, everyone, and thank each of you for joining us today. I'd like to say a few words about our progress and what Team Summit has accomplished. Then I will hand it over to McKee to add more color, and then Ankur will provide financial updates. It has been just one year since we closed on our partnership with the KESO, and I'm very proud of the accomplishments and impressive progress Team Summit has made in this period of time. Avenisumab, our lead investigational compound and the only PD-1 VEGF bispecific antibody in Phase III in Summit's territories, continues to actively enroll two registrational base three trials in non-small cell lung cancer are Harmony and Harmony 3 trials. In Harmony, we are looking at avanisumab in combination with chemotherapy as a second line treatment for non-small cell lung cancer patients with EGFR mutations with disease progression after receiving a third generation TKI. In Harmony 3, We are studying avonisumab in combination with chemotherapy as first-line treatment for patients with squamous cell carcinoma of the lung in a head-to-head trial against the current standard of care. We treated our first patient in the Harmony 3 study, our second Phase 3 study in the fourth quarter of 2023. Combined, the two populations represented by these two clinical trials account for approximately 120,000 patients in our licensed territories for whom abonissimab could potentially offer a better treatment option. Team Summit's conviction and our belief in abonissimab continues to drive our progress forward in our efforts to collapse time and reach critical milestones faster. We approach these efforts with the intent of helping patients improve quality of life, increase the potential duration of life, and resolve serious medical needs in line with Summit's strongly held mission statement. McKee and I are appreciative and honored to be leading Team Summit, where our accomplished leaders and team members have unparalleled track records for high-speed execution that delivers intended results. This experience and our expertise are foundational to achieving our goals for 2024 and beyond, continuing to execute on our Phase III clinical trials while expanding our clinical development plan. With that, I would like to turn it over to McKee. to provide additional context for our accomplishments and next steps.

Thank you, Bob, and good morning, everyone. As Bob discussed, I remain incredibly enthusiastic about Ibonissimab and its potential, the strength of Team Summit, and the accomplishments we have made just one year into our partnership with ECASO. Across the globe, over 1,600 patients have now been treated with Ibonissimab. Currently, AKSO is conducting or participating in 19 clinical trials evaluating avonisimab, four of which are in Phase III, and seven trials are evaluating avonisimab in solid tumor settings beyond non-small cell lung cancer. We are fortunate to have such a strong partnership and ongoing collaboration with AKSO, including the ability to leverage data generated for avonisimab across multiple solid tumors studies in support of Summit's own clinical development in our licensed territories, the U.S., Canada, Europe, and Japan. Turning specifically to Summit's own Phase III trials, active enrollment continues in Harmony and Harmony III. As a reminder, Harmony, our fast-to-market approach, is in non-small cell lung cancer patients with EGFR mutations who have progressed following a third-generation TKI such as osimertinib. We intend to complete enrollment in this trial in the second half of 2024. Our Harmony 2 trial is seeking a frontline treatment indication for patients with squamous non-small cell lung cancer. This head-to-head trial is designed to compare Ibanissima plus chemotherapy against the current standard of care, pembrolizumab plus chemotherapy. We continue to progress as well as collapse time in order to achieve our aggressive but realistic goals for ivonizumab to ultimately improve existing treatment options to the many lung cancer patients with serious ongoing unmet needs. Our conviction and belief in the potential of ivonizumab and our decision to quickly pursue two registrational phase 3 trials has come in part from data generated from phase 2 clinical trials conducted by ECHESO. This data evaluating ibanesimab plus chemotherapy in multiple lung cancer settings AK112-201 was updated by ECHESO last month. Notably, in patients with first-line advanced or metastatic squamous non-small cell lung cancer without actionable genomic alterations in a Phase II population supporting our Harmony III trial, a 24-month overall survival rate of 64.8% was observed. Median overall survival has not yet been reached after a median follow-up time of 21 months. Furthermore, in patients with advanced or metastatic non-small cell lung cancer, with tumors positive for EGFR mutations and having progressed following an EGFR TKI, the Phase II trial cohort supporting our Harmony trial, a median overall survival of 22.5 months was observed. In both settings, Ivonisimab has had an acceptable safety profile in the Phase II clinical trial. We believe that this study data is very promising. Also, when considering the current standard of care in this patient population and the Phase II data supports our decision to directly move forward in both of our Phase III clinical trials. Slide 5, please. I would also like to spend a moment to remind everyone of the differentiated mechanism of action of IVANESIMA. To start, IVANESIMA brings two highly validated mechanisms in oncology together into one novel molecule targeting both PD-1 and VEGF. And as Bob mentioned earlier, we are the only Phase III PD-1 VEGF bispecific in our licensed territories, making it the most clinically advanced compound of its kind in the U.S., Canada, Europe, and Japan. What differentiates Ivanissimab in its intentional design is a concept known as cooperative binding. Specifically, in the presence of VEGF, the binding of Ivonecimab to PD-1 in vitro increases by 18-fold. In the presence of PD-1, VEGF affinity increases by over 4-fold. Ivonecimab's cooperative binding qualities lead to the potential to steer more drugs to the tumor and tumor microenvironment, the area around the tumor, where higher levels of PD-1 and VEGF are expressed and comparatively less drug, we believe, is steered toward normal, healthy tissues. On slide 6, you can see, in addition, because of the increased presence of PD-1 and VEGF in the tumor macroenvironment, there is not only increased affinity, but also increased avidity. Because VGEF is expressed as a dimer, there is an opportunity to bind multiple Ivonecimab compounds to these VGEF dimers in the tumor microenvironment as well. We believe Ivonecimab cooperative binding goes further than the sequential administration of an anti-PD-1 and anti-VGEF therapy. Our goal is to improve up and previously established efficacy standards in addition to side effects and safety profile associated with these two targets. We believe Ivonisimab has the potential to achieve this. Moving to slide 7. Looking at meaningful near-term catalysts for Ivonisimab, we are expecting multiple events to occur in 2024. Next quarter, there are two key milestones expected from randomized Phase III clinical trials in China from our partners at Ekeso. Data from the Chinese patients enrolled in AK112301 a large portion of which represent the Chinese patient included in the modified intent to treat population of our multi-regional study, also known as Harmony, was submitted to the Chinese regulatory authority, the CDE, last year, specifically seeking marketing approval in China. A decision is expected in the second quarter of this year from the CDE, We also expect that ECASO will provide a data readout of the top-line results of their Phase III trials at this time. Additionally, ECASO has an interim analysis planned for next quarter for its study comparing Ivonisumab to Pembrolizumab in a monotherapy setting for first-line advanced lung cancer patients harboring tumors with positive PD-L1 expression, referred to as AK112-303. This head-to-head trial against pembrolizumab is a major milestone for Ivanesimab, both in differentiating Ivanesimab from a PD-1 antibody as well as illustrating the potential of its novel mechanism of action that simply does not exist in oncology therapeutics today. Given the direct implications of the AK112301 results on our HARMONY study, as well as the potential ability to compare Ivonisumab-Pembrolizumab in AK112303, we believe these events will be pivotal moment drivers in Ivonisumab's development globally. As mentioned earlier, we also plan to complete enrollment in a Harmony study in the second half of this year, providing momentum towards a submission for Ivonisumab in our licensed territories. While non-small cell lung cancer indication represent our initial development plan for Ivonisumab, we will continue to expand our clinical program. Harmony and Harmony Tree represent the first step in our strategy, and we believe Ivonisimab has potential in both additional non-small cell lung cancer indications and in other solid tumors. In addition to progressing our internal development program, we appreciate a high level of enthusiasm we are hearing from key opinion leaders and and other physician leaders for what Ivonisimab can do to make significant positive difference in and outside of lung cancer. We continue to receive and are considering multiple inquiries for potential investigator-sponsored trials or ISD programs. We expect to share additional information later in 2024. Finally, to capitalize on and expand our reach with physicians, From KOLs and academic leaders to community physicians and local caregivers seeing so many cancer patients, we are participating in a few upcoming conferences. We will be at ISLAC targeted therapies for lung cancer or TTLC meeting later this week in Santa Monica, California. In addition, we plan to participate in ESMA European Lung Cancer Congress 2024 next month in Prague where we have submitted, along with our partners at ECASO, multiple abstracts for presentation on Ivonecimab. We intend to educate and activate as many physicians as possible regarding Ivonecimab and its potential as we ramp up phase three clinical trials in the United States, Europe, Canada, and Japan. With that update, I will now ask Ankur to provide details on our financial position and outflow.

Thank you, Mackie and Bob. and good morning, everyone. Echoing the sentiment, we're very pleased with the speed of execution of Team Summit and our partners at Tima Kessel in the development of Ivan SMR. Moving to slide eight, I'll give you an update on Summit's cash position, the extended cash runway guidance, and the P&L. We have a strong cash position with $186 million in cash and investments as of end of year 2023. This position provides us strong ability to continue our investments in the development of Ivan Asimov. In addition, we have taken steps to extend our cash runway going into the first quarter of 2025. As you may recall, our previous guidance for cash runway was going into September of 2024. As we announced earlier, we have amended the $100 million note to extend the maturity date to April 1st, 2025, and the future interest payments will also be paid at maturity. This extension, coupled with our strong cash position, provides funding to make significant progress in the development of ibanacimab, as well as covering some of the key milestones that Mackie spoke about. Going to the P&L, I will speak about non-GAAP OPEX, which excludes stock-based compensation, in-process R&D, and certain impairment charges. You can refer to our press release for reconciliation of GAAP to non-GAAP financial measures. During the fourth quarter of 2023, our non-GAAP operating expenses were $27.7 million. Aligned with the company's focus The majority of our spending is towards research and development, which is $22.4 million for the quarter on non-GAAP basis, and is focused towards clinical development of ibanesimab, including the clinical trials, the technology transfer, and people costs. And the GNA spend of $5.3 million for the quarter on non-GAAP basis represents all the functions that provide infrastructure and support for this development. So in summary, We're excited about the potential of Ivanacimab and have made a lot of progress in its development during 2023. We have a strong cash position, and we have extended our cash runway going into 2025. And with that, I will hand it back over to Dave.

Thank you, Bob, Maki, and Ankur. We can now transition to see if there are any questions that we can help answer. Operator, if you could please open the line for questions.

opening the floor for the Q&A question. If you'd like to ask a question, please press star number one on your telephone keypad. Our first question comes from Brad Canino from Stifle. Your line is now open.

Hi, good morning, and thank you for the updates and having me on your call. I just wanted to get your thoughts on how to best interpret the upcoming Chinese regulatory action on Ivanesimab for EGFR mutant lung, particularly in relation to your ongoing Harmony study. And I'm asking in light of some of the differences between the two studies, thinking about the third-generation TKI pretreatment requirements, and then your study also adding the co-primary of survival. Thank you.

Thank you, Brad. Alan, I'll hand that question to you.

Hi, Brad. Thanks for the question. This is Alan Yang, the Chief Medical Officer. So I think you should view it positively, you know, the fact that, as you know, The Chinese version of the Harmony study enrolled 320 patients, approximately 320 patients, of which about 50 of them received a first or second generation TKI, which is still considered standard care in China. We will be using 270 patients of that data, or approximately 270 patients of that data, which only received a third generation TKI, or received a third generation TKI, such as osomertinib, somewhere along the course of their treatment. And that represents about 85% of the data. So I think the data should correlate pretty well for the global study. Now, remember, we're adding 150 patients from North America and Europe to that. And, you know, I'm not aware of any treatment differences between Chinese and U.S. patients. In addition, I think the key question is, is there any difference in receiving a first or second generation TKI prior to receiving a third generation or receiving a third generation TKI on the impact of chemo and immunotherapy? And the answer is I'm not aware of any such data. I don't think that data exists. And then I think the last question you asked was around PFS and OS. And so, you know, PFS seems to track pretty well with OS. That's why it's used as a surrogate endpoint as often, especially in patients with sort of survival periods. So, you know, the short of survival periods, more likely that PFS will correlate with OS. But it is an unknown at this time. And so the fact that we have co-primary endpoint is a little bit different than the ACASO study. Thanks for the question, Brad.

Great. Thank you very much.

Our next question comes from Harthaj Singh from Oppenheimer. Your line is now open.

Great. Thank you. Thanks for the question. I just got a couple. One is your head-to-head study against PEMBRO and chemocombo against non-small cell lung cancer. Can you just talk a little bit about, you know, what's the differentiation for Ivanistamab and then maybe a little bit more into, I guess, what's the hurdle? You know, is it just the study on which PEMBRO chemo comma got approved? Just how to think about the hurdle that you're looking to either be equal to or surpass. And I just got a quick follow-up.

Thanks, Hartaj. So I think I heard two questions there. One, the differentiation between PEMBRO, the standard of care, and ibanesimab with respect to our Harmony 3 study. and then what other hurdle we may have in the Harmony 3 study, or what the standard of care, what we need to beat in that particular study is. So again, I'll hand that question to Alan.

Hi, Kosh, thanks for the question. So I'll answer the second part first. Well, let me just review the two studies. As McKee mentioned earlier, there's the Harmony study, which is our fast to market study, but that was Brad's question, in the second line, EGFR mutant population. The Harmony 3 study, which is sort of the first frontline study in squamous non-small cell lung cancer. So the second question about the benchmark is pretty easy. It's the Keynote 407 study, right? So this is where Merck got approval for pembrolizumab in the similar population. There are sort of expansion studies that look at the Chinese population. So you can look those studies up to get the proper benchmark. In terms of what distinguishes Ivanessimab, it's a very clean study. It's Ivanessimab chemotherapy and then PEMBRO using the same chemotherapy. And that PEMBRO chemotherapy was the 407 study, based on the 407 study. So I think there's a couple ways that are different, right? So Ivanessimab, from the simplest way to think about it, has a digest component to it. So if you think about the two targets independently, PEMBRO is PD1. And the second one is VEGF. And so we have that VEGF component. And so we think that that adds sort of value to patients and important for patients. And then there's the cooperativity that we think accentuates not only the VEGF, but also the PD-1. And so you can sort of distinguish that. And looking at that data, it'll be very interesting to look at the data both by PD-1, PD-L1 status. You know, how much are we beating in the high PD-L1 expressors, which is probably the PD-1 component. How much are we beating in the lower PD-L1 expression, which is the VADGF component? I would say some other bispecifics that target, let's say, PD-1 and CTLA-4 are concentrating on the non-expressing. We're going to go after all of those. So the last component to think about is that we know that Avastin was trying to be developed in this space, and then after phase two, they halted development. There was a concern about bleeding risks early on, and therefore, You know, I think lung cancer patients in the squamous setting never really realized the potential of anti-VEGF, and we believe that the safety profile demonstrated to date in the Phase 2, as well as our large database, is supportive of developing a VEGF that has been attached to PD-1 with cooperative binding in this space. So there's a number of different aspects where we think we can have an advantage. What's your follow-up question, Harthash?

Yeah, great. Thank you so much. That's really good detail. You know, if you can just kind of give us, you know, what is the next sort of clinical and regulatory steps for Harmony and Harmony 3? I know Harmony 3 might be a little bit into the future, but just not looking for guidance, but just kind of a rough change of events there. Thank you.

Around Harmony 3? I don't think we've disclosed this. I'll turn to Dave, but I'll just say that you can sort of calculate enrollment based on the Keynote 407. I think that's the key benchmark. And, you know, what's interesting, Hartaj, is the squamous non-small cell lung cancer population or that space has become a lot less crowded recently. So I think that will give us a lot of freedom to operate. I don't know, Dave, if you want to add anything to our disclosures.

Thanks, Alan. So at this point, what we have disclosed is that the Harmony studies, we plan to complete enrollment in the second half of 2024, the second half of this year. We haven't given further guidance with respect to the regulatory process there, except that we have our co-primary endpoints. From a Harmony 3 perspective, we just began enrollment in the fourth quarter of 2023, and we've yet to give the the guidance in terms of when that will complete, but we're currently enrolling and are excited about moving quickly in that setting as well.

Great. Thank you, everyone. Thanks for the updates.

Don't have any raised hands right now, so I'd now like to hand back over to Dave Genkars. Thank you.

I just want to thank everyone for attending our call and your continued interest in Summit. An archived version of this webcast will be available later today on our website, www.smmttx.com. I want to thank everyone again and enjoy the rest of your day. Thank you.

Thank you so much for attending today's session. Have a wonderful day.