Summit Therapeutics Inc.

And thank you for joining us. Two press releases were issued earlier this morning and are available on the homepage of our website. Our Form 10-K was also filed earlier this morning and is 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.smmtx.com. Joining me on the call today is Bob Duggan, our Chairman of the Board and Chief Executive Officer, Dr. Mekshbi Zangade, our Chief Executive Officer and President, Manmeet Soni, our Chief Operating Officer and 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, Maki, and Manmeet, 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 Ivanisumab, our lead investigational asset. In Q4 of last year and to date in 2025, we have reached several meaningful milestones around the development of Ivanisumab, 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 ibanizumab 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 today. 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, we completed enrollment in and received fast-track designation for Harmony, our global phase 3 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 Ivanizumab's first global registrational phase 3 trial Harmony is expected in mid-2025. Additionally, in October of last year, we announced a study amendment to the HARMONY-3 protocol, expanding the study to include patients with both squamous and non-squamous histologies. With this amendment, HARMONY-3 is a multiregional, registrational Phase III trial assessing ivenizumab 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 the United States with non-squamous tumors. Harmony 3 now addresses a patient population two to three times larger than prior to the amendment significantly expanding the numbers of patients with cancer that Ibenizumab can potentially help. Towards the end of the year, we announced our third global phase 3 trial, Harmony 7, would be initiated in early 2025. Initial trial sites have begun activating in the United States, and Harmony 7 continues to progress as planned. As a reminder, Harmony 7 is evaluating ibenizumab monotherapy against pembrolizumab monotherapy in first-line metastatic non-small cell lung cancer patients whose tumors have high PD-1 LPD-L1 expression without actionable genomic alterations. McKee will further discuss these accomplishments, including additional strides taken to drive our continued belief in what could be accomplished by Team Summit, as well as our conviction in the potential of avanisimab in non-small cell lung cancer, and very importantly, indications beyond lung cancer. We are a mission-driven organization 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 the molecule in Ibonizumab 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, I would like to touch on the clinical work that has been conducted with Ivonecimab and some of the interest and recognition received last year. Since first entering the clinic with our partner Ecesobac in 2019, more than 2,300 patients have been treated in clinical trials with Ivonecimab. In 2024 alone, IVANISIMA was featured in 14 publications across seven tumor types and selected for five oral presentations at major medical conferences. Currently, between our partners at ECESO and our team at SUMMIT, four Phase III trials have been completed enrollment, two of which are awaiting top-line data readout, including the SUMMIT-sponsored HARMONY trial. Five phase III trials are currently ongoing. Two of these are summit-sponsored trials in first-line non-small cell lung cancer, and three are ECASO-sponsored trials studying abonissimab in head and neck, biliary tract, triple negative breast cancers. ECASO 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, and hepatocellular carcinoma, in addition to more data to support the lung cancer program. Turning specifically to the summit-sponsored pipeline, as Bob mentioned last quarter, Harmony completed enrollment in the fourth quarter with top-line data expected in mid-2025. This data is expected to contain data for both primary endpoint progression-free survival and overall survival. Harmony 3 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 25% to 30% of non-small cell lung cancer in the United States, with 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 PD-L1 high-expressing. We announced our intention to initiate Harmony 7 in early 2025, for which we have begun to activate clinical trial sites in the United States. Later this year, we expect to announce additional details around expanding our clinical development plan around ibanesimab, 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 IDCs to date, which will either enhance our sponsored clinical development activities or can show signals in settings where a case has not yet had the opportunity to explore. In 2024, we started our collaboration with MDN, which now has studies that are activated and open for enrollment in Houston. We have committed $15 million to this collaboration to quickly discover additional opportunities for Ibonizumab, 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 ibanesimab in combination with several Pfizer vedotin-based ADCs in multiple tumor types. As we seek to accelerate the development of ibanesimab across non-small cell lung cancer and other solid tumor setting, this collaboration will allow us to quickly advance beyond our promising late-stage development plan to evaluate ibanesimab in combination with some of the most innovative ADCs from Pfizer. Clinical trials as part of this collaboration are expected to start mid-2025. Pfizer will be responsible for the operations and costs associated with these trials. We will provide abonissimab and jointly oversee the study. As a reminder for those new to the summit story, abonissimab has significant lead in the clinical development of this novel class of compound. Abonissimab brings two highly validated targets together into one novel bispecific antibody that targets both PD-1 and VEGF. 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 data in mid-2025, 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 Ivonecimab, 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 in 2025 and 2026. In addition to continuing engagement with a rapidly increasing number of investigators, beginning to conduct investigator-sponsored trials at various institutions across a large number of different tumor types. And you will see continual activating of additional ICDs in a variety of solid tumor settings. This is in addition to ECHESO continuing its execution of its Phase III studies, including completing the involvement of Harmony6 in frontline squamous non-small cell lung cancer with ibanesimab combined from E-Queso in non-small cell lung cancer and beyond. Luckily, we have seen indications in which phase 2 data has been generated, which we touched on earlier. We are excited for the catalyst switch path ahead of us. Our conviction and believe in the potential for Ibanezumab to improve patient lives for the better, remain strong, and consistent. Now, I would like to take a moment to review study design for our two ongoing global phase three trials, Harmony T and Harmony Sub. Here we have the study design for Harmony Harmony 3 is a randomized, double-blind, global phase 3 clinical trial evaluating Ivanizumab in combination with chemotherapy against PEMBRO in combination with chemotherapy as a 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 primary endpoints for harmonic metastatic non-small cell lung cancer patients with tumors with high PD-L1 expression. Dual primary endpoints for harmonic metastatic include progression-free survival, overall survival, and result would be stratified by squamous and non-squamous histologies. As a reminder, our Harmony 7 study shares similarity with AKSO-sponsored Harmony 2 Phase 3 trials, which reported data last year. but specifically targeted at the PDR1 high-expressing tumors consistent with the standard of care for monotherapy, immunotherapy in the U.S. and Europe. Turning to the market opportunity for Ivonisimab, the value proposition here is clear. Ivonisimab has the potential to be a platform blockbuster drug and 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 ACASO or Summit. Non-small cell lung cancer alone has an addressable market that could ultimately approach 20 billion for checkpoint inhibitors, according to the third-party research from the likes of TD Khan and others. But this is just the start. There are more than 50 indications where PT1, PTL1, or VEGAS therapies have been approved. Ivonizumab will continue to be rapidly tested and developed beyond non-sponsored lung cancer. Across all checkpoint inhibitors indications, the addressable market approach $90 billion globally in the next couple of years, according to IQIO research. However, this still excludes the full impact that Ivonizumab could have where it has shown promising data in multiple tumor types where checkpoint inhibitor have not been effective, including microsatellite stable colorectal cancer, PDR1 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 Ibanissima has a market potential much larger than non-small cell lung cancer and our current ongoing global phase 3 clinical studies that we are sponsoring at Summit. There are multiple phase 2 trials that have been conducted providing encouraging data to continue to explore Ibanissima and its opportunity to become a standard of care. across several solid tumor settings, which we intend to continue to explore with the 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, Dr. Michelle Shaw, and the entire AKSO team, as we continue to pave the way for rapid development of Avonissima 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 condensing time when and where possible. We continue to look at opportunities to accelerate our timeline in bringing additional therapeutic options to patients with high cancer needs. It is an honor and privilege to work with each member of Team Summit, and I would like to express my heartfelt thanks to every one of our team members. With that update, I will now ask many to provide details