Hi, good afternoon, everyone. Welcome to the 43rd Annual JPMorgan Healthcare Conference. My name is Denise Liu. I'm an associate here on the JPMorgan Healthcare Investment Banking team. Today, it's my pleasure to introduce the Summit Therapeutics team. We're excited to be here with Dr. Maky Zanganeh, CEO and President. We'll have time for Q&A at the end of the presentation, and we'll also be joined by Bob Duggan, CEO and Chairman, Manmeet Soni, COO and CFO, Dave Gancarz, Chief Business and Strategy Officer, and Dr. Allen Yang, Chief Medical Officer. So with that, I'll turn it over to Dr. Zanganeh.
Thank you so much. Good afternoon. Thank you very much for being here today. I would like to thank the JPMorgan team and especially Mike Gatto for inviting us today. I'm Maky Zanganeh, the Chief Executive Officer and President of Summit Therapeutics. Last year was an incredible year, and I'm proud for all of our achievements. When we presented last year at JPMorgan, our value was market cap $1.8 billion, and today the last that I saw was around $13 billion. We presented our excellent result of ivonescimab in multiple conferences, matching and in some cases exceeding our expectation. This molecule has shown the potential to become a game-changing treatment option for patients with solid tumors. We are just the beginning of this incredible journey. It's an honor and obligation to bring this product in the hands of many patients in need.
We have access to money, we have access to a lot of professional teams, and you can count on us. I believe by now all of you, you memorized the forward-looking statement. I don't need to go over that. We are a mission-focused company. I'm honored to lead alongside our Chairman and Co-CEO, Bob Duggan. Bob and I have worked together for over 25 years, and our track record clearly shows extraordinary results no matter how you measure it across multiple healthcare organizations. Our leadership team comes from a diverse background with a proven track record and known for their high-speed execution. We have approximately 175 employees. Our main purpose is to make a significant difference for patients diagnosed with cancer. We are focused on those whose lives have been interrupted by the uncertainty and torment of cancer and dream of returning to normal life one day.
Our goal through our development of our groundbreaking product candidate, ivonescimab, is to become an ally to patients and physicians to bring back the magic of normal to those who have lost it. Let's review our achievements in 2024. With our extraordinary Chinese-based partner, Akeso, we are rapidly developing ivonescimab in multiple therapeutic areas in solid tumors. As of today, we announced, initiated, or completed nine phase three trials between Summit and Akeso. Last June at Akeso 2024, the first randomized phase three study result, HARMONY-A, was presented in the second line plus EGFR mutated non-small cell lung cancer. This data supported the approval of ivonescimab in China. Last September, at the World Conference on Lung Cancer, our partner Akeso presented the result of the HARMONY-2 trial, which is a ivonescimab monotherapy versus pembrolizumab in frontline PD-L1 positive advanced non-small cell lung cancer.
This was, of course, the first randomized phase 3 study to go head-to-head against pembrolizumab, the world's best-selling oncology drug, and we showed a decisive, statistically significant benefit in the trial's primary endpoint. Last September at ESMO 2024, Akeso presented several phase 2 data updates, including five studies outside of advanced non-small cell lung cancer. Our broad phase 3 program reflects the strong phase 2 data that has been generated in both lung cancer and way beyond non-small cell lung cancer. Last October, Summit completed the enrollment of the first global phase 3 study evaluating ivonescimab, HARMONY. Top-line data from this study is expected in the middle of this year, and depending on the timing of the events and given that occurs, it would allow us to file by the end of this year. Let's talk about our financials.
Our stock performed particularly well in 2024, gaining more than 580% based on data and events we presented last year, and we believe this is just the beginning of the opportunity that we can deliver given our belief in the potential of ivonescimab. Last year, we raised $435 million. I would like to take this opportunity to thank our investors for believing in us, as well as our key insiders who participated in the most recent round of investment. As you can see, our confidence in ivonescimab remains strong, and we are doing everything possible to deliver this drug in the hands of patients in need. As of December 31st, our cash balance is in excess of $410 million. We have no debt. We remain well-positioned to take on these expanding large opportunities to develop ivonescimab broadly and deeply. Let's start to talk about ivonescimab, about the mechanism of action.
I believe by now all of you know about ivonescimab. It is a first-in-class PD-1 VEGF bispecific antibody that was intentionally designed and specifically engineered to improve upon the safety and efficacy standards of two established targets. The cooperative binding property of ivonescimab increases the binding strength of each target in the presence of the other target in vitro. In other words, cooperative binding allows for strong simultaneous blocking of both PD-1 and VEGF, which are present at their highest concentration in and around the tumor. ivonescimab not only performs the function of both an anti-PD-1 agent and anti-VEGF antibody, but it optimizes the activity of both in such a unique way. It is effectively a unique mechanism of action from anything developing historically. This specific engineering was not accidental, and this intentional design cannot be easily replicated.
Modifying this intentionally engineered property may change the dynamic value-add characteristic that we believe has led to the clinical trial result today with ivonescimab. To date, with over 2,300 patients treated with ivonescimab, let's review in more detail the current pipeline and where data has been and is being generated for ivonescimab. As mentioned in my previous slide, nine phase 3 studies which have been completed are enrolling or will begin the enrollment between Summit and Akeso team. Akeso has either launched or announced its intention for additional three phase 3 clinical studies outside of non-small cell lung cancer studied in head and neck cancer, biliary tract cancer, which are currently enrolling, and a study in pancreatic cancer, which will begin. A significant amount of additional data is being generated in other indications, including breast cancer, colorectal cancer, ovarian cancer, gastric cancer, and hepatocellular carcinoma.
As I said, excluding any commercial use, our partner Akeso, 2,300 patients have been treated. Nine phase 3 clinical trials are currently enrolling, starting enrollment or are fully enrolled. In addition, several phase 2 trials provide significant breadth and depth of data. In total, as of today, we have 31 sponsored studies combined across Summit and Akeso in non-small cell lung cancer and other solid tumors. We presented 14 publications in seven tumor types, as well as five oral presentations at major conferences in 2024. As you can see, in the coming year, we intend to rapidly develop ivonescimab along with our partner at Akeso across solid tumor indications. As I explained in my previous slide, it's all about the Akeso clinical trials. At Summit, beyond our three phase 3 programs in lung cancer, we intend to expand our clinical trials for ivonescimab outside non-small cell lung cancer.
Further, with more details to come later this year, we have approved over 30 investigator-sponsored trials which will either enhance our sponsored clinical development activities or can show signals in settings where Akeso has not yet had the opportunity to explore. In 2024, we have started our collaboration with The University of Texas MD Anderson Cancer Center, 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 ivonescimab, including several tumor settings outside of its current development plan, as well as the possibility of identifying biomarkers through additional research activities. Zooming in on the current non-small cell lung cancer phase three program for ivonescimab, we have initiated three global phase three clinical trials in multiple non-small cell lung cancer settings.
We have the approval of ivonescimab in China in 2024 based on the result of HARMONY-A study. This was followed by the landscape-shifting result of HARMONY-2, where ivonescimab became the first drug to show decisive superiority to pembrolizumab in a phase three trial. Akeso has submitted in China for approval in the PD-L1 positive first-line non-small cell lung cancer setting with monotherapy ivonescimab based on the HARMONY-2 trial result. Akeso also continued to enroll its HARMONY-6 study against another anti-PD-1 in combination with chemo in first-line lung cancer in China. At Summit, we have three phase three studies on the global scale. HARMONY is very similar to the HARMONY-A trial in second-plus line EGFR mutant non-small cell lung cancer, which we completed enrolling, and top-line data is expected in the middle of this year.
This is our fast-to-market strategy, which could allow for a BLA filing in the U.S. later this year, depending on the result of the data once available. HARMONY-6i was launched in front-line non-small cell lung cancer for patients with tumors with high PD-L1 expression based on the outstanding result from HARMONY II, and finally, we are enrolling in HARMONY III global studies in front-line non-small cell lung cancer in combination with chemotherapy compared to pembrolizumab plus chemo. This represents a significant unmet medical need across over 100,000 patients in the United States alone for undiscovered front-line non-small cell lung cancer patients without genomic mutation, irrespective of histology or PD-L1 results. Starting in front-line lung cancer, four of the six studies conducted by either Summit or Akeso are head-to-head against a checkpoint inhibitor, three of which are directly comparing ivonescimab with or without chemo to pembrolizumab with or without chemo.
Let's take a look at the data from Harmony II that was so groundbreaking from last September that informed our HARMONY-6i study, as well as the expansion of our Harmony III study, which now includes both squamous and non-squamous patients, significantly increasing the potential of addressable market. The design for Harmony II, Harmony II is a randomized double-blind clinical trial evaluating front-line monotherapy ivonescimab as compared to monotherapy pembrolizumab in patients with locally advanced or metastatic non-small cell lung cancer with positive PD-L1 expression. This is a single-region, multi-center phase three clinical trial conducted and sponsored by Akeso in China. Our partner at Akeso generated and analyzed the data.
The primary endpoint of progression-free survival by Blinded Independent Radiologic Review Committee for the entire study at the time of the first planned interim analysis, with a median follow-up of 8.67 months, demonstrated a significant improvement for ivonescimab with a hazard ratio of 0.51, corresponding to a 49% improvement over pembrolizumab. The median PFS was 11.1 months versus 5.8 months in the ivonescimab and pembrolizumab arm, respectively. You can see the median improvement is significant. The curve began to separate at the first point of radiographic assessment and maintained separation over the entire duration of the follow-up thus far, and the hazard ratio and the P-value leave no doubt as to the difference between these two therapy options for progression-free survival in this study. Now, let's focus for a minute on the patient with PD-L1 high-expressing tumors that is so important to the Western treatment paradigm.
While the analysis of subgroups revealed that the PFS benefit with ivonescimab was observed across nearly all subgroups, it actually showed a particularly strong signal as measured by stratified hazard ratios in the PD-L1 high-expressing subgroup. The curve again separated immediately and continued to widen as time progressed, which is an important characteristic as we evaluate this study. As monotherapy checkpoint inhibitor is a standard of care for patients with high PD-L1 expression in the Western markets, we have initiated our HARMONY-7 study in this population, in part based on the strong phase three data. As I mentioned, the result of HARMONY-2 also supported our decision and enthusiasm to expand our HARMONY-3 study to enroll patients of both histologies. You can see from the data on this slide that the benefit was similar for patients irrespective of histologies.
The result from patients with squamous non-small cell lung cancer showed a hazard ratio of 0.48 favoring ivonescimab, and those with non-squamous tumors showed a hazard ratio of 0.54. The current slide and previous slide represent a strong indicator that the benefit in HARMONY-2 was seen across clinical subgroups and underscores that the success of the trial overall was not driven by an especially strong performance of one subgroup. Let's talk about the safety. ivonescimab demonstrated its tolerability in the HARMONY-2 study. Most importantly, there were very few patients that experienced treatment discontinuation or treatment-related adverse events leading to death, and both values of which were numerically higher in the pembrolizumab arm. We see that there were somewhat comparable but numerically higher rates of serious treatment-related adverse events with ivonescimab, 20.8% compared to 16.1%.
Importantly, however, nearly all of the higher rates of treatment-related adverse events were lab-related abnormalities, such as hypertension and proteinuria, but generally did not lead to discontinuation of dosing. There are manageable conditions that are often seen by oncologists. As a result of the successful HARMONY-2 study and our analysis of their underlying data, here is the design of our HARMONY-7, a randomized global phase 3 study evaluating ivonescimab versus pembrolizumab, both monotherapy in front-line non-small cell lung cancer with tumors with high PD-L1 expression population. This study will begin enrolling in early 2025. HARMONY-7 has two primary endpoints: progression-free survival and overall survival. That is our HARMONY-3 trial that was initiated about a year ago in front-line squamous non-small cell lung cancer patients.
Starting with squamous patients because anti-PD-1 therapy was generally less effective in squamous lung cancer patients versus non-squamous, and because Avastin largely could not be used to treat patients with squamous lung cancer due to safety concerns, primarily serious bleeding risk, the phase two data produced by Akeso showed very promising efficacy data alongside what appeared to be an improved safety profile in the context of anti-VEGF therapies in this setting. The safety profile, which was revalidated in the HARMONY-2 trial, we felt that the data gave us a mandate to move very quickly in developing ivonescimab in squamous non-small cell lung cancer last year. The HARMONY-2 result made it clear that we needed to pursue the monotherapy setting, which is now the HARMONY-7 trial I just described, but the benefit seen was consistent across histology.
So ivonescimab also had transformational opportunity in non-squamous non-small cell lung cancer, which compelled us to move forward to benefit those patients in need. There are also significantly more patients with metastatic non-squamous non-small cell lung cancer as compared to squamous, nearly double in the U.S. alone, bringing the addressable patient population of HARMONY-3 to nearly 100,000 in the United States. Therefore, you can see the amended study designed for HARMONY-3 that now includes squamous and non-squamous patients. We will be testing for PFS and OS as primary endpoints and will stratify by histology as well. We completed the enrollment of our global HARMONY trial a couple of months ago, and we expect to read out the result of this trial in the middle of this year for those patients with non-small cell lung cancer with EGFR mutation having progress and standard of care targeted therapy.
Akeso has since received regulatory approval in China for HARMONY-A study. The primary differences are that we require patients to progress on a third-generation EGFR TKI in the global HARMONY study. Also, more than 85% of HARMONY-A patients receive a third-generation TKI, and secondly, the HARMONY-A study had a PFS primary endpoint, and our HARMONY study has a dual primary endpoint, which is PFS and OS. Importantly, as we have previously discussed, we pre-specified to include all of the patients from HARMONY-A who previously received a third-generation EGFR TKI, so a vast majority of the patients in our global HARMONY study. As we anticipate the result of our HARMONY study, let's quickly review the result for HARMONY-A, which was presented at Akeso last year and published at JAMA.
The study design of HARMONY-A, as you know, this compared ivonescimab plus chemo to chemo plus placebo for patients post-targeted therapy irrespective of PD-L1 expression. The PFS benefit was significant. The combination of ivonescimab plus chemo represented a 54% reduction in disease progression or death versus chemo alone. Median PFS was 7.1 months for ivonescimab plus chemo versus 4.8 months for placebo plus chemo. The overall response rate and disease control rate numerically favored ivonescimab plus chemo as well. As the study adds an anti-cancer therapy on top of another treatment, you would expect a numerically high rate of adverse events. However, the difference in discontinuation rate was approximately 3% between the two arms, and there were no treatment-related deaths, grade III or higher adverse events of special interest.
Immune-related adverse events showed the expected increase versus placebo and potentially VEGF-related adverse events were similar between the arms, and there were no grade III or higher bleeding events seen in either arms. We are excited to review the data, which is expected to be ready in the middle of this year for our HARMONY, the next significant catalyst for ivonescimab, representing the first global data readout for ivonescimab in a phase three registration enabling setting. As mentioned before, we are intent to go beyond advanced non-small cell lung cancer in the short term with our clinical development of ivonescimab. Let's review a snapshot of some of the data released in the last few months associated with ivonescimab in phase two study conducted by Akeso in China.
Perioperative or early-stage non-small cell lung cancer eligible for surgery plus systemic therapy with pathological responses and 12-month event-free survival metrics in this phase two study exceeding the established metrics from current standard of care. In microsatellite stable metastatic colorectal cancer, a place where anti-VEGF therapy dominates and PD-1 therapy is largely absent, ivonescimab plus chemo again exceeds the historical result seen from the standard of care of Avastin plus chemotherapy. The response rate seen by ivonescimab with chemotherapy, along with the early PFS benchmarks, exceeds the current standard of care metrics that include anti-VEGF therapy plus chemo. In PD-L1 positive recurrent metastatic head and neck cancer, a chemo-free option, the phase two data in China from Akeso combining ivonescimab with Akeso CD47 investigational compound exceeds the historical result seen by PD-1 therapy in this setting. In advanced triple-negative breast cancer, we see the trend from lung cancer continuing.
PD-1 therapy is only utilized in the PD-L1 high triple-negative breast cancer, represented by the gray bars, which ivonescimab phase 2 data exceeds historical benchmark for response rate and PFS. However, in PD-L1 low and negative triple-negative breast cancer, where PD-L1 therapy is not approved, ivonescimab shows very promising results as well, leading to another potential setting where ivonescimab may be effective where PD-1 therapy is not. In each of these settings, a manageable safety profile was observed, and you can see that discontinuation from treatment-related advanced events has not been observed as of the cut-off date. You can see a more complete presentation of this data on our website. As we look at catalyst events for ivonescimab, we can see three main concepts.
First, the first global phase three clinical study data is expected in mid-2025, which provides a potential path applying for marketing authorization in our territory, including potentially the United States. Secondly, we intend to expand our sponsored clinical development plan to go way beyond non-small cell lung cancer in 2025 and 2026, in addition to continuing engagement with a rapidly increasing number of investigators seeking to conduct IST programs at various institutions across a large number of different tumor types. This is in addition to Akeso continuing its execution of its phase three study, including completing the enrollment of HARMONY-6 in front-line non-small cell lung cancer with ivonescimab combined with chemo, as well as continuing the enrollment of its biliary tract cancer and head and neck phase three study. Akeso has announced its intent to explore additional phase three studies beyond lung cancer in 2025.
In addition, the readout from phase two and phase three studies will continue from studies sponsored by Akeso in China throughout 2025 and 2026, which will continue to inform our clinical development plan. The value proposition here is clear. Ivonescimab individually has the potential to be a platform blockbuster drug. Ivonescimab is well-positioned to make a significant impact across the treatment landscape of non-small cell lung cancer with a combined six phase three studies conducted by either Akeso or Summit. Non-small cell lung cancer has an addressable market in lung cancer that could ultimately approach $20 billion for checkpoint inhibitor alone, according to the third-party research from the likes of TD Cowen and others. But this is just the start, chapter one, if you will. The graphic here shows the 50-plus indications where PD-1, PD-L1, or VEGF therapy have been approved.
Ivonescimab will continue to be rapidly tested, and its development advanced way beyond non-small cell lung cancer. Just considering checkpoint inhibitor may lead to an addressable market approaching $90 billion globally in the next couple of years, according to the IQVIA Institute. But this includes the full impact that ivonescimab can have, where it has shown promising data in multiple tumor types where checkpoint inhibitors have not been effective, including microsatellite stable colorectal cancer, PD-L1 low and negative triple-negative breast cancer, and EGFR mutant non-small cell lung cancer after targeted therapy.
I would like to take this opportunity to thank mostly our patients in our clinical study, as well as our investigator, our collaborator at MD Anderson, our partner in China, Dr. Michelle Xia, our CEO and co-founder of Akeso. We will continue to pave the way for accelerated development of ivonescimab globally. With that, I will show you one minute of video, and I will let for Q&A. Shelly, the video is there.