Summit Therapeutics Inc.

Good afternoon and welcome to Summit Therapeutics Q4 and year-end 2025 earnings call. All participants will be in listen-only mode until the question and answer session portion of this call. We do not expect any technical difficulties today. However, in the event that we lose the webcast connection and 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. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press the star key followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one again. At this time, I would like to turn the call over to Dave Gancars at Summit Therapeutics, Chief Business and Strategy Officer. You may proceed.

Good afternoon, and thank you for joining us. On today's call, we will provide an update on our fourth quarter and year-end 2025 financial results and operational progress. This afternoon's press release is available on our website, www.smmtx.com. Our Form 10-K was also filed today and is 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. Joining me on the call today is Bob Duggan, our Chairman of the Board and Co-Chief Executive Officer. Dr. Matthew Zangane, our President and Co-Chief Executive Officer. Manmeet Soni, our Chief Operating Officer and Chief Financial Officer. And Dr. Alan Yang, Chief of R&D Strategy. I'm Dave Gancars, the Chief Business and Strategy Officer at Summit. 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 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, including the Form 10-K issued today, about these risks and uncertainties. Summit undertakes no obligation to update these forward-looking statements, except as required by law. One item to note, this presentation is being webcast with slides, so we'll be referring to the slides being displayed in the webcast link. I'd encourage you to use the webcast link to see the slides being presented this afternoon that will accompany our comments. Following comments from our team, we will take questions. And with that, I'd like to hand it over to Miki.

Thank you, Dave. Good afternoon, everyone, and thank you for joining us today. I'm very proud of Team Summit's ongoing accomplishments and the growing positive data sets and support around Ibonissimab, a PD-1 VEGF by specific or lead investigational asset. We are highly focused, mission-driven, patient-first company with a mission to make a significant difference in improving the lives of patients suffering from cancer. Our team is growing rapidly as we expand our clinical development plan and prepare for commercialization in anticipation of a decision from the FDA on our BLA near the end of this year. We have announced a few significant events today, starting with the updates related to our Harmony Tree study. Last quarter, we announced our Harmony III phase III trial evaluating Ibonissima plus chemo as first-line treatment for patients with squamous and non-squamous non-small cell lung cancer was amended to have separate analysis by squamous and non-squamous histologies for primary endpoints of PFS and OS for each cohort. The squamous cohort was planned to complete enrollment in the first half of 2026, followed by the non-squamous cohort in the second half of this year. As announced today, we have now completed screening patients for the squamous cohort of the Harmony Tree study, and the last patient will be randomized in the next couple of weeks. We have amended our statistical plan to now include an interim PFS analysis for our squamous cohort, and we are planning to conduct the interim PFS analysis during the second quarter of 2026. Overall survival will be immature at the time of this analysis. Therefore, we may not have overall survival results to communicate at that time. As you recall, We initially included PFS as a primary endpoint in this study, opened the readout of Harmony 2, comparing Ivonisimab to PEMBRO in PDL-positive frontline lung cancer patients, which showed a highly statistically significant and clinically meaningful benefit in PFS with a hazard ratio of 0.51 and a median improvement in PFS of over 5 months. This point was later validated with Harmony 6, showing that there was a substantial PFS benefit when comparing Ibanissima plus chemo versus a PD-1 inhibitor plus chemo with a hazard ratio of 0.60. Two Phase III studies conducted by ECASO in China in frontline non-small cell lung cancer demonstrated a 40% plus improvement in PFS for the IVANISIMAB-R. Both the HARMONY-2 and HARMONY-6 PFS results were based on the planned interim PFS analysis of each study. By adding an interim PFS analysis, we opened the door to an earlier discussion with the health authorities for our multi-regional phase III study. The final PFS analysis, if applicable, and an interim analysis for OS is planned to be conducted in the second half of this year consistent with previous guidance. For the non-squamish cohort of Harmony Tree, we continue to expect enrollment to complete in the second half of this year and to reach the pre-specified number of events for the final PFS analysis by the first half of 2027. There are several meaningful moments upcoming related to these two cohorts. each of which are independent from each other, like two separate studies in one protocol, where 2026 will be pivotal to providing additional clarity to expand the reach of Ivo to a broader population of lung cancer patients. Additionally, we announced today the first update to the Ivo Phase III clinical trial program, which will continue to expand throughout 2026. A new phase 3 study in PD-L1 positive front-line head and neck squamous cell carcinoma will be sponsored by GORTEC, a French cooperative group dedicated to head and neck oncology with initial enrollment expected to begin early next quarter. The study intends to evaluate both ivonisumab monotherapy and in combination with ligofalimab a case of proprietary anti-CD47 monoclonal antibody against monotherapy PEMBRO in this three-arm randomized study. Approximately 780 patients are intended to be enrolled across the three arms in multiple countries in Europe and in China. We may consider potentially expanding the study to include U.S. sites as well. Phase 2 data supporting the potential use of ivanesimab in this patient population was previously presented at ESMO 2024, where ivanesimab in combination with ligofalimab demonstrated an objective response rate of 60% in 20 patients with median PFS of 7.1 months after median follow-up of 4.1 months at the time of this analysis. no patient receiving avonisimab plus ligofalimab is continued treatment due to the treatment-related adverse events. The data generated in Phase II is encouraging in light of existing standards of care, and ECHESO is also running a single-region Phase III trial in this population in China. Turning to our clinical collaboration with Revolution Medicine, Today, we announced the first patient has been dosed in the collaboration's initial clinical trial. As a reminder, abonissimab is being evaluated in combination with three Ras-on inhibitors, including Laraxone Rasib, a multi-selective Ras inhibitor, Zoldan Rasib, a KRAS G12D selective inhibitor, and Eliron Rasib, a KRAS G12C selective inhibitor, across multiple solid tumor settings with RAS mutations, including pancreatic cancer, colorectal cancer, and non-small cell lung cancer. Finally, as we announced last month, we entered into a clinical collaboration with GSK to evaluate ibanesimab in combination with GSK novel B7H3 antibody drug conjugate in multiple solid tumors. The initial study under this collaboration is expected to begin dosing patients in mid-2026. Let's now take a step back and look at Ivonisimab accomplishments to date. There are many to list. We are just highlighting some of them. Ivonisimab has read out four Phase III clinical studies to date, all four of which have had positive data. leading to two approvals in China so far. At this time, a total of 15 phase 3 trials have been announced, currently ongoing, or have read out in multiple tumor types. 44 clinical trials have been initiated since 2019 between Summit and ECASO, evaluating Ivonecimab in a variety of solid tumors. When considering investigator-initiated and collaborative studies, a total of 142 clinical trials are now listed on clinicaltrials.gov. The enthusiasm demonstrated by investigators around the world to generate data and seek positive signals for patients facing high unmet medical needs really speaks to the opportunity and optimism surrounding Ibonissima. Together with our partner ECESO, We have enrolled over 4,000 patients in either Summit-sponsored or ECASO-sponsored clinical trials across the world. Commercially in China, over 60,000 patients have received IVANISIMA based on two approved indications by the NMPA in non-small cell lung cancer, according to our partners at ECASO. A third indication, based on the Positive Harmony 6 study in frontline squamous non-small cell lung cancer, is currently under review by the NMPA in China. I wanted to make sure this point is not missed. Four Phase III trials evaluating Abonissima have readout to date, and all four with positive data readouts. This represents the only Phase III readout that we have seen in the PD-1 VEGF bispecific class to date. These positive trials are supported by the by the differentiated mechanism of action of Ivonisimab. Here is the current Ivonisimab development plan across Summit and ECASO. In total, there are 15 randomized phase three trials, four of which are global Summit-sponsored studies in non-small cell lung cancer and colorectal cancer, one of which is a multi-regional cooperative group study announced today and 10 of which are being enrolled by ECASO in China in a variety of solid tumor types, including lung, breast, head and neck, BTC, pancreatic, and colorectal cancers. Additionally, ECASO is also currently enrolling multiple phase two trials, evaluating abonissimab in other tumor types, ovarian, gastric, HCC, and others, including non-metastatic settings. Through our partnership with ECESO, we continuously compile a substantial amount of data, allowing us to make faster, more informed decisions, fueling the rapid expansion of our global development plan. Focusing on our pipeline at Summit, we have four global phase three trials, completed or ongoing. Harmony, which read out positively last year, Harmony 3, Harmony 7, Harmony GI 3, all three of which are currently enrolling and progressing nicely. The Harmony trial evaluated Ibonissima plus chemo against chemo alone as treatment for EGFR mutant non-small cell lung cancer after TKI therapy, a population of significant unmet need with few available treatment options. We submitted a BLA filing last quarter, seeking approval in this proposed indication, and in January, we announced the US FDA's acceptance of the filing and a PDUFA target action date of November 14, 2026. As previously disclosed, the FDA noted that a statistically significant overall survival benefit is necessary to support marketing authorization in this setting. Considering safety and efficacy profile of the current FDA-approved options to patients in this setting, the positive regionally consistent results of this Phase III multiregional study As well as discussions with key opinion leaders and physicians who have administered Ibonissimab to patients, we believe that Ibonissimab is a potential treatment option with a favorable benefit-risk profile. In anticipation of potential approval in Q4 of this year, we continue to ramp up commercial capabilities in preparation for potential launch. Harmony 3 is evaluating IVANISIMA plus chemo against PEMBRO plus chemo in frontline metastatic non-small cell lung cancer. This patient population represents a significant unmet medical need with nearly 100,000 patients in the United States alone as this trial covers frontline non-small cell lung cancer patients without genomic mutations irrespective of histology or PD-L1 status. I spoke a minute ago about the recent changes to this pivotal study. For Harmony 7, this study is evaluating abonissima monotherapy against pembro monotherapy as frontline treatment for patients with non-small cell lung cancer that have high PD-L1 expression levels. Harmony 7 continues to enroll well, and we look forward to providing additional updates in the future. And finally, last quarter, We initiated and began enrolling patients in Harmony GI-3, evaluating Ibonissima plus chemo compared to Bev plus chemo in first-line therapy in patients with unresectable colorectal cancer. Our decision to expand into colorectal cancer was driven by encouraging Phase II data published at ESMO 2024 and subsequent continuing enrollment in this Phase II study in China and the United States with additional chemotherapy regimens. This dataset allowed us to make an informed decision to move forward in CRC, specifically with the fall fox chemo combination. We look forward to providing further updates on the phase two dataset later this year, as well as the Harmony GI tree study as the trial progresses. Looking beyond our own sponsored trials, we are expanding into additional settings with multiple collaborations and other groups. We have the Phase III Elamin study sponsored by Gortec, evaluating abonissimab in head and neck cancer that I spoke to earlier. With respect to novel-novel combination, we announced that the first patient was dosed this quarter in our collaboration with Revolution Medicine to evaluate abonissimab in combination with three novel RAS inhibitors across multiple solid tumor setting. We are excited to learn about the opportunity and potential to improve patient outcomes with Ivonisimab combined with these novel targeted therapies and promising molecules. This collaboration is intended to evaluate Ivonisimab in combination with one or more of RevMed's Ras-on inhibitors in pancreatic cancer, colorectal cancer, and non-small cell lung cancer. This collaboration has an opportunity to be mutually beneficial to both Summit and RevMed by leveraging a combination of potential next generation assets that individually have promise in each setting, and this may have high promise for patients with RAS mutant cancers. In our GSK collaboration evaluating avonisimab in multiple solid tumor settings in combination with their B7H3 ADC, we expect the trial to initiate in mid-2026. This is another example of promising targets seeking to significantly advance outcomes in settings where both IVO and B7H3 ADCs have shown promise. We have over 60 ISDs that we intend to support in various stages of development. Of these, 15 are currently enrolling, five of these in collaboration with MD Anderson, and Ivonisimab has now been featured in over 45 publications, presentations, and posters. Collectively, these trials enhance and inform our own clinical development activities as we learn more about new settings where neither we nor ECSO have had the opportunity to explore yet. Tremendous interest in ISTs is a testament to the enthusiasm we have heard from many investigators as they consider the potential opportunity that IVANISIMA presents across multiple tumor types. Over the past 18 months, we have seen four positive randomized phase III trials including the first and only phase three trials to compare positively against anti-PD-1 therapies. Each of these studies represent a benefit either over a PD-1 inhibitor or in setting where PD-1 inhibitors have failed to achieve a benefit in either PFS or OS. ECASOS Harmony II PFS results showed Ionissima monotherapy as superior to Keytruda in frontline non-small cell lung cancer. These results represent the first time any therapy has achieved a clinically meaningful benefit over Keytruda in randomized phase three trials. In April of 2025, AKSO announced that Harmony 2 achieved a clinically meaningful overall survival hazard ratio below 0.8 at this early look. Moving to ACASO's Harmony 6 frontline non-small cell lung cancer study in patients with squamous hostology, results were announced at ESMO 2025 demonstrating avonisimab with chemo was superior to PD-1 plus chemo in PFS. With this result, Harmony 2 and Harmony 6 represent the first and only known regimens to achieve a clinically meaningful benefit replacing an anti-PD-1 regimen. In EGFR mutant non-sponsored lung cancer, both AKSO's Harmony A trial and our own Global Harmony trial achieved positive, consistent results. In Harmony, a positive overall survival trend was observed with hazard ratio of 0.79, barely missing statistically significant. In a subsequent analysis in September 2025, with longer-term follow-up on Western patients, Ibonissima plus chemo showed a favorable trend in overall survival with a hazard ratio of 0.78 and a corresponding nominal p-value of 0.0332. In Harmony A, a KSO final overall survival analysis showed Ibonissima plus chemo achieved a statistically significant hazard ratio of 0.74 with a p-value of 0.019 supporting a treatment profile where OS does not degrade but rather improves over time in this setting. Turning to our market opportunity, the value proposition is clear. Ibanesimab on its own has the potential to be a platform blockbuster drug. Novel, novel combinations with Ivo could bring potential improvements over current standard of care, which could expand market opportunity further. Avonisimab is well positioned to make a significant impact across the solid tumor treatment landscape. Between checkpoint inhibitors and anti-VEGF therapies, TD Cohen and others estimate the total addressable market to be in excess of $100 billion globally. Looking only at the checkpoint inhibitor market for non-small cell lung cancer, market estimates for immunotherapy are expected to exceed 20 billion US dollars by 2028. And yet, these estimates still do not include the full impact Ivonisimab could have as it has already shown promising data in multiple tumor type where checkpoint inhibitors have not been effective, including EGFR mutant non-small cell lung cancer, and PD-L1 low triple negative breast cancer. Avonisimab differentiated profiles support its platform potential across multiple indications, many of which could be blockbuster opportunities on their own. We have a very exciting year ahead. Here are some of the upcoming milestones we expect to reach in 2026 and into the first half of 2027. Our global clinical studies pipeline will continue to expand. and we will provide further details in 2026 as we begin studies in new settings and indications. This will include additional novel novel combinations as well as the new phase three studies that we intend to launch in 2026. The first steps with respect to this expansion came today with the announcement of the cooperative group led illumine phase three clinical study in head and neck cancer. We will continue to expand upon the details of our clinical development plan throughout 2026, including sponsored studies. With today's Harmony 3 update, we anticipate an interim PFS analysis for the squamous cohort to occur next quarter. Final PFS and interim OS data are expected in the second half of this year. In the Harmony 3 non-squamous cohort, we expect to complete enrollment this year. we anticipate final progression-free survival data in the first half of 2027. And as already discussed, we are looking forward to a potential first approval for Ivonisimab in the U.S. around our November 14 PDUFA date based on our Harmony BLA filing. Now I will turn the call over to Manmeet to provide a financial and operational update for the quarter. Manmeet?