Good afternoon. Thank you for joining us today, and thank you to J.P. Morgan for having us today to present at this conference. I'm Dr. Maky Zanganeh, President and Co-CEO at Summit Therapeutics. Bob Duggan, Chairman and Co-CEO at Summit Therapeutics. I'm honored to go over the latest update for Summit, our lead asset, ivonescimab, as well as reviewing our upcoming catalysts for what we believe will be a positive, transformative year for Summit in 2026. Summit and our partner, Akeso, have now completed four positive phase III studies with ivonescimab, both in China with Akeso and globally with Summit, in settings either head-to-head against PD-1 inhibitors or in settings where PD-1 inhibitors have failed to show a benefit.
The potential first-mover status for ivonescimab in the frontline setting of multiple solid tumors and the positive result from the four phase III studies of ivonescimab give us a clear leadership position in the PD-1/VEGF space, a market we believe could be over $100 billion annually. I want to take this opportunity to thank our current long-term investors for their continued support and looking forward to what we believe will be a transformative year in 2026. That is our forward-looking statement. As guided during ESMO 2025 in October, we have submitted our BLA to FDA in Q4 2025. We did it based on the benefit-risk profile demonstrated by ivonescimab in the HARMONi study and considering the high unmet need and lack of options available for patients in the setting.
This is a historic moment for Summit, and I would like to take the moment to pause and thank FDA for their continuing collaboration in support of global innovation. At Summit, we are a highly focused, mission-driven, patient-first company. Our mission is to make a significant difference in improving the lives of patients suffering from cancer. I'm honored to lead the team at Summit alongside our Chairman and Co-CEO, Bob Duggan. Our team is currently over 275 employees, growing rapidly as we expand our clinical development plan and preparing for commercializations. At Summit, we are actively enrolling three phase III global trials: HARMONi-3 and HARMONi-7 , both in frontline non-small cell lung cancer. HARMONi-GI in frontline colorectal cancer.
Additionally, last year, we announced positive results of our phase III Harmony study in second-line EGFR mutant non-small cell lung cancer, which was the first global phase III trial completed for ivonescimab. Let's look at ivonescimab accomplishments today. There are many to list. We are just highlighting some of them. As I mentioned earlier, we have a significant multi-year head start over in-class followers. Ivonescimab has produced four positive phase III readouts today, leading to two approvals in China. At this time, 14 phase III trials have been announced, currently ongoing, or have readouts in multiple tumor types. 42 clinical trials have been initiated since 2019 between Summit and Akeso, evaluating ivonescimab in a number of solid tumors. When considering IST and other collaborative studies, a total of 116 clinical trials are now listed on ClinicalTrials.gov.
The enthusiasm demonstrated by investigators around the world to seek positive signals for patients facing high unmet medical needs really speaks to the opportunity and optimism surrounding ivonescimab. Together with our partner, Akeso, we have enrolled over 4,000 patients in clinical trials across the world. Commercially in China, over 60,000 patients have received ivonescimab based on two approved indications by the NMPA in non-small cell lung cancer, and the third indication based on the recently presented HARMONi-6 study is currently pending approval in China. I want to make sure this point is not missed. Four trials evaluating ivonescimab have readouts to date, and all four phase III data were positive. This represents the only phase III readouts that we have seen in PD-1/VEGF class to date. The positive trials are supported by ivonescimab's unique differentiated mechanism of action.
Ivonescimab is potentially first-in-class, and we believe the best-in-class PD-1/VEGF bispecific antibody. It was intentionally designed and specifically engineered to improve upon existing safety and efficacy standards of other drugs targeting these two established targets in several solid tumor settings. Ivonescimab's cooperative binding properties drive potential synergistic anti-tumor activity in the tumor microenvironment by simultaneously blocking both PD-1 and VEGF. In vitro, we have seen the several-fold increase in the binding strength to PD-1 in the presence of VEGF. In addition, since VEGF is often expressed as dimer, multiple Ivonescimab molecules may be able to link to VEGF, leading to a daisy-chaining of Ivonescimab molecules where PD-1 and VEGF are expressed the most in and around the tumor, avoiding healthy tissue and organs.
We believe this is why we have seen such a differentiated, promising efficacy result and a consistently well-tolerated, manageable safety profile in ivonescimab. Ivonescimab not only performs the function of both an anti-PD-1 agent and anti-VEGF antibody, but this actually optimizes the activities of both. It is effectively a unique mechanism of action from anything developed historically. We believe binding to PD-1 is biologically important compared to other molecules. The shortened half-life of ivonescimab, less than half of Avastin or Bev, is critical to the safety profile we have observed. Finally, we believe the structure, format, and placement of the binding domains of ivonescimab is an important factor in the human body biologically to allow for the cooperative binding properties to effectively take place. Here is the current ivonescimab development plan across Summit and Akeso.
In total, there are 14 randomized phase III trials, four of which are global Summit-sponsored studies in non-small cell lung cancer and colorectal cancer, and 10 of which are being enrolled by Akeso in a variety of tumor types, including lung, breast, head and neck, BTC, pancreatic, and colorectal cancers. Additionally, Akeso is also currently enrolling multiple phase II trials evaluating ivonescimab in other tumor types: ovarian, gastric, HCC, and others, including non-metastatic settings. This strong pipeline has led to a tremendous level of patient experience with over 4,000 patients who have been treated in clinical trial globally and over 60,000 patients dosed commercially in China to date. Through our highly collaborative partnership with Akeso, we are able to continuously compile a substantial amount of data, which allows us to make faster decisions and rapidly expand our global development plan.
This gives us a major competitive advantage, helping us to stay well ahead of others in this space. While many competitors are just entering late-stage trials or are still in a very early development, we are already leading in phase III across multiple tumor types. I would like to take a moment and thank our partner, Akeso, and Dr. Michelle Xia, their CEO and Chairwoman, for their collaboration and their efforts to bring ivonescimab to patients and physicians around the world. Thank you, Michelle. But this is just the beginning. Turning to our pipeline at Summit, we have four global phase III trials completed or ongoing: Harmony, which readout positively last year, Harmony III, Harmony VII, and Harmony GI III, all three of which are currently enrolling. Let's start with Harmony.
HARMONi evaluated ivonescimab plus chemo against chemo alone, a second-line treatment for EGFR mutant non-small cell lung cancer, a difficult-to-treat patient population with few available options. Positive results from this study were presented in the Presidential Symposium at the 2025 World Conference on Lung Cancer in Barcelona. HARMONi III is evaluating ivonescimab plus chemo against pembrolizumab plus chemo in frontline metastatic non-small cell lung cancer. This patient population represents a significant unmet medical need across over 100,000 patients in the United States alone, as this trial covers frontline non-small cell lung cancer patients without genomic mutation, irrespective of histology or PD-L1 status. Last quarter, we announced a strategic trial amendment for HARMONi III that resulted in two separate patient populations within the study, squamous and non-squamous. Both groups will be evaluated separately and have dual primary endpoints of progression-free survival and overall survival.
Effectively, Harmony III is now two global phase III trials in one protocol with a significantly expanded market opportunity. In the squamous arm of Harmony III, we have enrolled over 90% of patients and expect to complete enrollment in the first half of this year. Progression-free survival and interim overall survival data are expected in the second half of this year. In the non-squamous arm of Harmony III, enrollment is expected to complete in the second half of this year, and progression-free survival data is expected in the first half of 2027. The Harmony VII study is evaluating ivonescimab monotherapy against pembrolizumab monotherapy as frontline treatment for patients with non-small cell lung cancer that have high PD-L1 expression levels. Harmony VII continues to enroll well, and we look forward to providing updates as the trial progresses.
Finally, last quarter, we initiated and began enrolling patients in Harmony GI III, evaluating ivonescimab plus chemo compared to BEV plus chemo in first-line therapy in patients with unresectable metastatic colorectal cancer. Our decision to expand into colorectal cancer was driven in large part by encouraging phase II data published at ESMO 2024 and subsequent continuing enrollment in China and the United States with additional chemotherapy regimens. This data set allowed us to make an informed decision to move forward in CRC, specifically with the FOLFOX chemo combination. We look forward to providing further updates on Harmony GI III as the trial progresses. To demonstrate our lead, in-class competitors have announced studies in either first-line non-small cell lung cancer like Harmony III or first-line. Something going on. Okay, you go. Just bring it back. Thanks.
To demonstrate our lead, in-class competitors have announced studies in either first-line non-small cell lung cancer like Harmony III or first-line CRC like Harmony GI III. However, they either are still enrolling in the phase II portion of their phase II/III study or have otherwise not yet begun recruiting in their phase III study. As mentioned earlier, we have a significant lead in lung cancer and colorectal cancer, which are potentially the two largest indications by market across solid tumors. Looking beyond our own sponsored trials, we have an innovative way to expand our reach into additional settings with novel combinations. In June of last year, we announced our collaboration with Revolution Medicines to evaluate ivonescimab in combination with three novel RAS inhibitors across multiple solid tumors setting, prioritizing these three RAS mutant tumor types in non-small cell lung cancer, pancreatic cancer, and colorectal cancer.
We expect that study to begin dosing patients this quarter. Our second clinical collaboration was just announced this morning. In collaboration with GSK, we will be evaluating ivonescimab in multiple solid tumor settings in combination with their B7-H3 ADC. The study is expected to start mid-2026. Turning to investigator-sponsored trials, or ISTs, we have over 60 ISTs that we have agreed to support, 15 of which are currently enrolling. Of these 15, five are with our ongoing collaboration with MD Anderson. Collectively, these trials will enhance and inform our own sponsored clinical development activities and possibly show signals in settings where neither we nor Akeso have had the opportunity to explore. The large number of ISTs that are ongoing or are about to begin is a testament to the many investigators who are enthusiastic about the opportunity that ivonescimab presents across multiple tumor types.
We are also proud of the significant attention and praise that ivonescimab has received through top medical conferences and peer-reviewed medical journals around the world. Today, ivonescimab has been featured in 46 posters, publications, presentations, and that number only continues to grow. We look forward to seeing many of you at upcoming medical conferences in 2026 as additional ivonescimab data becomes available. Speaking of the trial result, the past 18 months have been transformative for ivonescimab as we saw four positive randomized phase III trials, a very promising indicator related to the opportunity ivonescimab presents. These include the first and only phase III trials to compare positively against anti-PD-1 therapies, including Keytruda. Again, these four trials readouts represent the only phase III trial readouts to date in the PD-1, PD-L1 VEGF class.
Starting with Akeso HARMONi-2 evaluating ivonescimab monotherapy compared to pembrolizumab monotherapy as a frontline treatment for patients with non-small cell lung cancer with positive PD-L1 expression. Results are announced at the WCLC 2024, showing ivonescimab monotherapy as superior to Keytruda as measured in PFS. The HARMONi-2 result represents the first time any therapy has received a clinically meaningful benefit over Keytruda in a randomized phase III clinical trial in non-small cell lung cancer. In April of 2025, Akeso announced that HARMONi-2 showed a clinically meaningful overall survival trend with an OS hazard ratio below 0.8 at this early look.
As a reminder, this study was not powered for overall survival, and this interim overall survival analysis was conducted at the request of the Chinese Health Authority, corresponding with Chinese approval by the NMPA for Ivonescimab use in frontline PD-L1 positive non-small cell lung cancer. Moving to Harmony VI, evaluating Ivonescimab plus chemo compared to anti-PD-1 plus chemo as a frontline treatment for patients with non-small cell lung cancer with squamous histology. Results were announced at ESMO 2025, demonstrating that Ivonescimab with chemo was superior to PD-1 plus chemo in PFS. The results from Harmony II and Harmony VI represent the first and only known regimens to achieve a clinically meaningful benefit over an anti-PD-1 or PD-L1 monotherapy, as we saw in Harmony II, or combined with chemotherapy, as we saw in Harmony VI in a phase III trial in frontline non-small cell lung cancer.
In EGFR mutant non-small cell lung cancer, both Akeso HARMONi- A trial and our own Global Harmony Phase III clinical trial achieved positive results. The Summit Sponsored Harmony trial results evaluating ivonescimab plus chemo compared to chemo alone as second-line treatment for patients with EGFR mutant non-small cell lung cancer that have progressed after receiving a third-generation EGFR TKI were presented at World Conference on Lung Cancer 2024 last September. Ivonescimab in combination with chemo, consistent with HARMONi- A from China, demonstrated a statistically significant and clinically meaningful benefit in PFS. A positive overall survival trend was observed with a hazard ratio of 0.79, barely missing statistically significant. In the subsequent analysis in September 2024, which included longer-term follow-up of Western patients and improving favorable trend in overall survival, was shown with a hazard ratio of 0.78 and a corresponding nominal p-value of 0.0332.
In both the May 2025 and September 2025 statistical analysis, consistent results were seen between Eastern and Western regions across safety and efficacy. In line with our prior guidance, we submitted our BLA filing to the FDA last quarter, seeking approval for ivonescimab based on the data for Harmony trial, and we expect a regulatory decision around the end of this year. In preparation for potential approval, we continue to build our commercial resources and capabilities in support of the successful launch of ivonescimab. We look forward to providing regulatory and commercial updates as they become available.
In addition, in November 2025 at SITC, it was announced that in the final overall survival analysis for the Akeso-sponsored Harmony A trial, ivonescimab plus chemo achieved a statistically significant hazard ratio of 0.74, supporting an efficacy profile where OS does not degrade, but rather improves over time in this setting. Across all four of these phase III positive readouts, ivonescimab was consistently well tolerated with a manageable safety profile. Ivonescimab has some immune-related and VEGF-related adverse events, as would be expected with ivonescimab's mechanism of action. However, the low frequency of AEs leading to discontinuation or death demonstrated a manageable safety profile. Here, we take another look at ivonescimab profile, specifically progression-free survival Kaplan-Meier curves for Harmony, Harmony II, and Harmony VI.
We see a visual representation of ivonescimab's potential superiority over the current standard of care in combination with chemo in second-line treatment for EGFR mutant non-small cell lung cancer, as monotherapy frontline treatment for PD-L1 positive non-small cell lung cancer, and in combination with chemotherapy in frontline treatment for squamous non-small cell lung cancer. Four phase III studies across three non-small cell lung cancer settings have produced statistically significant, clinically meaningful progression-free survival results for patients. Based on the results of Akeso Harmony A and Harmony II studies in China, ivonescimab has received NMPA approval in the second-line EGFR mutant non-small cell lung cancer setting, as well as for use as monotherapy in frontline PD-L1 positive non-small cell lung cancer.
Additionally, Akeso submitted an sNDA to the Chinese Health Authority last summer for potential approval in combination with chemo in frontline treatment for squamous non-small cell lung cancer, based on the result of Harmony VI, which is currently under review. This three phase III graph shows consistent, meaningful separation of progression-free survival curves, all favoring ivonescimab regimens over established standard of care. In particular, the graph on the left is in a setting whereby both Keytruda and Opdivo leading PD-1 inhibitors failed to show a benefit in PFS or OS. The graph in the middle and on the right are direct head-to-head results against PD-1 inhibitors. We appreciate the benefit these therapies were able to provide for patients in the past, but improvement is necessary, and we need to move forward.
The safety profile observed was consistent with the previously established safety profile from phase II studies, and low rates of treatment-related discontinuation and death were observed. Here are the milestones achieved with ivonescimab over the past 18 months. While much of this has been discussed already, I just want to highlight the continuous and growing flow of ivonescimab data readouts, approvals, and new trial indications that we have seen since we first enlicensed ivonescimab just three years ago. This visual excludes the phase III trials initiated by Akeso that you saw a few slides ago with the global pipeline. 2024 was a big year. 2025 was bigger. And with ivonescimab's first global phase III first-line non-small cell lung cancer trial readout expected in the second half of this year, among other meaningful updates and catalysts, 2026 will be a pivotal year for ivonescimab.
Here are three key questions that were asked at the beginning of 2025 that have been answered over the course of the last year. Number one, would Asian results from Akeso China only trials translate to results from Western patients in Summit's global trials? The answer is yes. Harmony results show clear consistency across regions in both safety and efficacy, and in both primary endpoints of PFS and OS. Number two, would progression-free survival result translate to overall survival? The answer is yes. In Harmony A, we have seen a statistically significant, clinically meaningful overall survival hazard ratio that improves with time, counter to the theory that therapeutics blocking VEGF would only worsen survival outcomes over time. In addition, Harmony II showed a strong early look at OS and Harmony, on a global study, had a nominal p-value that implied significance with more follow-up time.
Both Harmony and Harmony II had a hazard ratio under 0.8, and finally, number three, would ivonescimab's positive monotherapy result be sustained with the addition of chemotherapy? The answer is yes. Progression-free survival result generated for ivonescimab monotherapy from Harmony II and ivonescimab in combination with chemo for Harmony VI both demonstrated clinically meaningful improvement over current standard of care. Given the significance of the frontline non-small cell lung cancer study for PD-1 therapy plus chemo and the translation of PD-1 plus chemo as a backbone standard of care for many other solid tumor settings, this was a meaningful result not just in this study, but in the potential of ivonescimab in a more than $100 billion addressable market. Here are several upcoming meaningful inflection points for Summit. Our global clinical pipeline will continue to expand. We will provide further details in the next few months.
This will include additional novel combinations, like we announced this morning with GSK and our existing collaboration with RevMed, as well as new phase III studies that we intend to launch in 2026. We expect enrollment for the squamous cohort of Harmony III to complete in the first half of this year, with progression-free survival data and interim overall survival data coming in the second half of 2026. For the non-squamous arm of Harmony III, we anticipate enrollment completing in the second half of 2026, with progression-free survival data coming in the first half of 2027. With regard to the potential for ivonescimab's first U.S. approval, we expect the FDA to make a decision around our BLA submission in the second-line EGFR mutant non-small cell lung cancer setting before the end of this year.
Turning to our financials, last October, we raised $500 million over the course of about 48 hours, bringing our cash balance entering 2026 to about $710 million, and we remain debt-free. I would like to take this opportunity to thank our long-term investors for believing in us, as well as Bob Duggan and 10 other insiders who participated in the most recent round of investment. We remain well-positioned to develop ivonescimab broadly and deeply, supporting our clinical development plan with an impressive market opportunity. My last slide, the value proposition is clear. Ivonescimab on its own has the potential to be a platform blockbuster drug. Additionally, novel combinations with Ivo could bring potential improvements over current standard of care, which could expand market opportunity further. Ivonescimab is well-positioned to make a significant impact across the solid tumor treatment landscape.
Between checkpoint inhibitors and anti-VEGF therapies, TD Cowen and others estimate the total addressable market to be in excess than $100 billion globally. Just within the checkpoint inhibitor market for non-small cell lung cancer indication alone, the market estimate to top $20 billion by 2028. And yet, these estimates still exclude the full impact ivonescimab could have, as it has already shown promising data in multiple tumor types where checkpoint inhibitors have not been effective, including EGFR mutant non-small cell lung cancer and PD-L1 low triple-negative breast cancer. Ivonescimab differentiated profile from data generated to date supports its platform potential across multiple indications. Many of these settings individually may be blockbuster opportunities on their own. 2026 is a transformational year for ivonescimab and its potential to make a meaningful difference in the lives of patients with cancer.
In closing, and on behalf of the entire Summit team, I want to thank our incredible partners at Akeso, our clinical trial investigators, our collaboration partners, and especially the patients and patient families that have all played an instrumental role in getting ivonescimab to where it is today. Thank you for your time today, and I would like to open the question. Eight-minute record time. Any questions? Please. Dave, you want to answer? Can you repeat the question?
So thank you for the question. I think the question related to, with respect to Maky's comments regarding a platform, does that involve ivonescimab as a platform, or does that involve bringing in other molecules? And so I think, by and large, we think there's a significant opportunity that exists with ivonescimab.
In doing so, as we progress within the development plan for ivonescimab, novel combinations will be exceptionally important as well. And so while we're not excluding the possibility of bringing in another asset, what we think is very important is actually following the data, right? And so as opposed to locking down our pipeline with an additional asset that will effectively force pipeline optimization and additional combinations that favor those two assets together, we think it's important to follow the data with respect to ivonescimab. Look at, for example, what we did this morning with GSK, what will be started in a month or so with RevMed, and really develop the right opportunities for the right combinations in the right tumor settings, as opposed to trying to artificially expand those combinations into different settings where it may not be the best fit.
So we'll continue to follow the data. It was non-exclusive, as we announced this morning, so it doesn't force that to be the B7-H3, for example, that we will use going forward. But what we want to do is really leverage the data that's able to be generated to allow ivonescimab to have the most beneficial impact to patients with the right combination in different settings.
Any other questions? I love that. So everything is clear. That is cool. No questions.
If I may make a comment, thank you, Maky, for the presentation, and thank you, Michelle, for attending our presentation. We basically have the number one biotech company in Asia-China in joint relationship partnership with the number one biotech company based on historical experience of delivering what we promised in America and a $100 billion revenue opportunity, which is about a $400-$500 billion wealth-creating opportunity.
We're pleased with our shareholder base. Everyone else that has yet to make up their mind, you're always welcome. All these opportunities are something we focus our full attention on day in and day out. We're optimistic and pleased with everything we've seen. We've yet to see an indicator that this isn't anything other than an outstanding drug. One of the indicators is how many others have come along. I just remind you that the source of bispecific tetravalent for oncology and solid tumors is sitting in the front row with a group of people, numbering close to 3,000, that really engineered this specifically with all the white space in the world and no barriers to the freedom to operate back in 2013. Everyone that followed has to do something different than what this group decided to do.
And if you look at what the Akeso group has done away from this, it's all worked. So these are quintessential drug developers. Our relationship with Akeso goes all the way back to the Pharmacyclics days when Michelle was working at Celera, and we picked up Imbruvica. So she watched what we did then and somewhere in her mind thought, "I should have partnered with them at that time." And so this is her opportunity. She hasn't missed it. So with the complement of the people on the dais here, Dr. West here in the background, we're really pleased with what we see. It's great for patients. It's great for the industry. It's great for our two countries, by the way. We're bringing countries together, not separating them apart. And we think that's one of the real features of healthcare.
When a person is sick and they're in need of care, they don't ask, "What's the nationality of the inventor?" They go, "Give me that medicine. I need to be cured. I need to be mitigated." So it's been an honor. We thank you, and we thank J.P. Morgan for handling conferences like this. It'd be almost impossible otherwise to be in front of a group such as yourself.
Thank you so much.
And with that.