Good afternoon, everybody. Welcome to the 42nd annual J.P. Morgan Healthcare Conference. My name is Dan Delfico, one of the associates on the healthcare banking team here. Today, it's my pleasure to introduce the Summit Therapeutics team. With us today, we have Dr. Maky Zanganeh, the CEO and President, Bob Duggan, Chairman and CEO, will be handling the presentation. At the end of the presentation, we'll be doing a Q&A, and we'll be passing around the mic. For the Q&A portion, we'll have a few other members of the team join us at the front, including Dave Gancarz, the Chief Business and Strategy Officer, Manmeet Soni, Chief Operating Officer, Dr. Allen Yang, Chief Medical Officer, and then Michelle Xia, CEO of Akeso, Inc., one of their collaboration partners. With that, I'll turn it over to Dr. Maky Zanganeh.
Thank you very much, Daniel. Thank you very much for the entire J.P. Morgan, and especially Mike Gaito, for having us today to present our company, Summit Therapeutics. Forward-looking statement, I'm sure all of you are very familiar with. I want to start first to talk about our company, Summit Therapeutics. We are a mission-focused company led by Bob Duggan, myself, co-CEO. As you know, Bob Duggan is the Chairman of the Board, as well as our lead investor in the company. We are supported by all of our leadership team with a proven track record, diverse background, and unmatched high-speed execution. We in-licensed our product, ivonescimab, recently last year from our partner, Akeso, which I'm going to discuss a little bit further.
Our lead compound, ivonescimab, is the only Phase III PD-1 VEGF bispecific antibody in our licensed territory, which is United States, Canada, Japan, and Europe. We have 100 employees, over 100 employees. We have 3 offices in Florida, California, and U.K. Our market cap as of today, I can say, is around $2 billion, and the cash position as of the end of the year, $186 million. We have kind of a very solid capital foundation to support all of our clinical development plan, as well as expand our company. Our focus in 2024 is to execute our 2 Phase II clinical trials and expand our clinical development plan. I would like to discuss about our partner.
Akeso is one of the leading pharma biopharma company in China, led by Dr. Michelle Xia, who is s he is here today, our co-founder, chairwoman, and president and CEO.
Akeso has over 3,000 employees, end-to-end in-house capability. They have a valuation of $5 billion. They have 30 compounds discovered in-house. Three of them, the main compound is already from this discovery to commercializations, and the one, obviously, a bispecific PD-1-based bispecific antibody is cadonilimab, and is already commercialized in China. And ivonescimab is one of the bispecific antibodies that we in-licensed in 2023. They have over 120 worldwide clinical trials, 19 clinical-stage candidates, and 6 of them are bispecific antibodies. They have impressive manufacturing capabilities with over 160,000 liters of current and short-term plant capacity for clinical and commercial antibody. We are planning to have multiple supply chains in our territory for ivonescimab as well.
As you see, they have more than 1,600 patients already treated with ivonescimab across 19 clinical trials, and that allow us to start right away our two phase III program this year, HARMONi and HARMONi-3. I would like to give you a little bit update what we have done in the past year, 2023. As mentioned, we got our product in early January 2023, and we started our development program. We started with our communications with the FDA for our ivonescimab IND proposed across multiple indications, and we started our two phase III program. One of them, HARMONi, we enrolled our first patients in early quarter two 2023. It was a record time in 4 months from the start of to getting the molecule till the first patient in. We raised $500 million.
1,500 individual investors participated, and I want to say I'm very proud to say that the company, the cost for raising this $500 million was just $500,000. We presented our clinical data Phase II from Akeso at ASCO, our mechanism of action in multiple conferences, ESMO or AACR. And we started our second phase III program in later in the quarter, I mean, early quarter four, and we enrolled the first patients. At the same time, we got different IC program proposal, and we are in the process to accepting some of them so that we can start it this year.
Let me discuss about the mechanism of action of ivonescimab, and later on during the Q&A, I would like that our Chief Medical Officer, Dr. Yang, Dr. Allen Yang presents a little bit more about the mechanism of action.
Ivonescimab is a first-in-class PD-1 VEGF bispecific antibody that was intentionally designed to improve upon the safety and efficacy standards of two established and approved target. Ivonescimab cooperative binding increases the binding strength of each target in the presence of the other target. In other words, cooperative binding allow for strong simultaneous blocking of both PD-1 and VEGF, which are present at their highest concentration in and around the tumor. Because ivonescimab binding strength or affinity to each other is highest in the presence of both target, and both PD-1 and VEGF are in their highest concentration in and around the tumor, it is believed that ivonescimab is effectively activated in the tumor microenvironment, where ivonescimab is designed to be and can drive its anti-tumor activity.
In addition, concentrating in the tumor microenvironment is believed to reduce certain adverse events, which may occur from binding to PD-1 or VEGF outside of the tumor microenvironment, including bleeding risk associated with some VEGF antibody. Ivonescimab goes where it is intended to go, optimizing anti-tumor activity and safety profile. And as you see, our ivonescimab is the most advanced PD-1 VEGF bispecific antibody and the only Phase III in our territory, which is again, Europe, Canada, Japan, and United States. But let me get a little bit more in details of this cooperative binding and the basis for the mechanism of ivonescimab. You can see from the image here, ivonescimab not only performs the function of both an anti-PD-1 agent and an anti-VEGF antibody, but it optimizes the activities of both in such a unique way.
It is effectively a unique mechanism of action from anything developed historically. It is greater than the sum of its individual parts. The presence of VEGF increases ivonescimab affinity to PD-1 by over 18-fold. The same is true of PD-1, increasing ivonescimab binding affinity to VEGF, in this case, by 4-fold. With PD-1 and VEGF highly concentrated in many tumor types, ivonescimab binding strength is then activated in tumor microenvironment. This is a critical component to explain the promising data we've seen in Phase II clinical trials to date. By concentrating in the tumor microenvironment, it enhances the activity of T cells. Both elements of ivonescimab work together to stimulate the immune system.
Because VEGF is often found as a dimer and ivonescimab has the ability to bind to multiple VEGF protein through its tetravalent structure, it can not only concentrate in the tumor microenvironment, but also cluster or daisy chain together, as illustrated here, further enhancing the PD-1 inhibition of the checkpoint on T cell and allowing the immune system to further destroy tumor cell. So this is a critical component of bispecific design. This is something that cannot be replicated, but co-administrating anti-PD-1 and anti-VEGF as separately. But let me discuss as well right now, the ivonescimab clinical data, which has been presented by Akeso at, ASCO 2023, and recently as well, they announced in their press release the updated data. And based on this, Phase II data that has been generated, we decided to start two Phase III program.
The study is AK112-201 study, and is, if you look at it, this is like a different cohort. The cohort 1 is a frontline advanced metastatic squamous non-small cell lung cancer. And you can see the water, waterfall plot that we have. Looking at the waterfall plot on the left, only 2 patients saw minimal increase in tumor burden. The remaining patients saw a reduction of the tumor burden, often significant, leading to a 95% disease control rate and a 67% response rate under RECIST 1.1 criteria. The progression-free survival in the 63 patients single-arm Phase II trial exceeded standard of care.
Showing you both the global trial that led the approval of combination of pembro and doublet chemotherapy and the Chinese extension of that trial, you can see that the data generated by our partner at Akeso in China is very promising, and this help us move directly into phase three program. The recent data of overall response rate is presented, two days ago by press release by Akeso, that announced both 12 months and 24 months overall survival rate of patient looking very promising in this setting. Over 85% of patients in this study were alive after one year, which would exceed what has been seen by the standard of care historically.
While median overall survival has not yet been reached after a median follow-up time of 21 months, you can start to see with the lower bound of the 95% confidence interval of 22.5 months, that we believe that there is a significant opportunity here. We're evaluating ivonescimab in frontline metastatic squamous non-small cell lung cancer in order to demonstrate its efficacy and safety profile. I would like to remind you that the overall survival is our primary endpoint in our HARMONi Phase III study. Importantly, from a safety perspective, ivonescimab plus doublet chemotherapy was generally well tolerated, highlighted by the fact that there were no treatment-related adverse event leading to death in the Phase II trial.
What makes this so critical is a certain prior anti-VEGF antibody, such as Avastin, were not able to be developed in squamous non-small cell lung cancer setting because of the risk of the severe bleeding. The fact that ivonescimab across 63 patients, specifically in the squamous cell carcinoma setting, has not seen the same issue previously observed, further amplifies the notion that ivonescimab mechanism is unique from previous compound or combinations. Taking a look at the Phase II trial data supporting those patients who have progressed after an EGFR tyrosine kinase inhibitor, such as osimertinib, we find that there is promise in space in which there is little effective therapy approved after the frontline TKI. This is data that support, in part, our HARMONi Phase III clinical trial.
We have included data related to ivonescimab in Phase II setting, as well as recently released data from trials that read out in 2023. In this setting, note that the chemotherapy arm of one of these trials shown in the final column on the right, is representation of the current second-line standard of care after progression from osimertinib or the third generation EGFR TKI. This regimen, placebo plus platinum -doublet chemotherapy, is the same regimen as our control arm in HARMONi study. The Phase II data for ivonescimab plus chemotherapy is very encouraging. Should the Phase II data translate into a Phase III trial in the way in which we believe it will, it will be another example of the differentiation of ivonescimab from the PD-1 inhibitor, an immunotherapy agent, or a combination of PD-1 and another agent.
Ivonescimab shows, again, based on its unique mechanism of action, has a tons of potential. Finally, presented here is updated data recently released by Akeso with respect to overall survival from the Phase II study in this setting. Again, the control arm of our HARMONi study is a placebo plus chemotherapy. We are highly encouraged by the potential for ivonescimab to help accomplish our mission, and we are testing ivonescimab plus chemo in this setting to demonstrate the efficacy and safety of combination for patients with a significant unmet medical need. From a safety perspective, ivonescimab plus chemotherapy was generally well tolerated in this setting. I want to talk a little bit about the safety. Ivonescimab has been generally well tolerated in chemotherapy across the two Phase II setting in which we spoke.
Treatment-related adverse event leading to the discontinuation of ivonescimab in was 11% and 0% in patients with front line squamous cell carcinoma and EGFR positive patients progressing after a TKI, respectively. Let's talk about the opportunity of ivonescimab. There are over 50+ approved indication in PD-1 and VEGF therapy. There are no PD-1 VEGF bispecific antibody approved in approved or in Phase III in Summit licensing territory. Per Cohen, TD Cowen, they estimated that, the worldwide PD-1 sales will exceed $64 billion by 2027, either in combinations or in the various tumor type. So it's a lot of great opportunity for ivonescimab.
Recently, we are all in the non-small cell lung cancer, and you see we have over 600,000 patients right now on the lung cancer, either in U.S., Europe, and Japan, and our two Phase III program, HARMONi or HARMONi-3, respectively, estimated 40,000 in HARMONi and 80,000 on the HARMONi-3 study. Actually, I like this slide a lot, is our clinical trials combinations, us and Akeso. Akeso, as mentioned, they enroll over 1,600 patients with ivonescimab. 19 clinical trials going on, 4 Phase III, 13 Phase II, and 2 phase I besides non-small cell lung cancer in seven other indications. You can look at it, if it's the gynecological cancer, breast cancer, colorectal cancer, several digestive cancer, as well as a head and neck squamous cell carcinoma.
Our two studies are HARMONi and HARMONi-3, both of them in the Phase III, as explained in the frontline metastatic squamous non-small cell lung cancer and EGFR resistance patient populations. We are a very, very... Actually, recently, we discussed, as I mentioned, with a different academic regarding IC program, and very soon we are going to start our I-IC program as well. Let's discuss the catalysts of the expected 2024. That's a very important year for us. In the next 6-12 months, we are going to discuss the result of AK112-301 study, and that is our partner Akeso. They will present it in China this study, the result, and they already submitted in the Chinese regulatory authority.
And we are going as well to present the interim analysis of the study 303 study, which is a monotherapy comparing ivonescimab to pembro in a lung cancer with the tumors with positive PD-L1 expression, which is an important study for us. As well as we are going to finishing our enrollment of the last patient in our HARMONi study by second half of this year. With that, I would like to just. That was, that was a summary of my talk in one minute, made by Michelle. I just want to thank all of my team that they are here, and I would like to open the floor for Q&A. And Dr. Michelle Xia, please, our CEO at Akeso, please. Allen, our Chief Medical Officer. Dave, our Chief Business Officer, and Manmeet, Chief Operating Officer.
Where is our J.P. Morgan person? Please go ahead.
We have the...
Any question?
Sorry.
Okay. Oh.
Thank you again for the great presentation. I know you had mentioned. Could you elaborate a little bit on the mechanism of action for ivonescimab, as well as what differentiates it from other compounds?
Allen?
Yeah, sure, David. I'll take that question. So, you know, as the video elegantly described and what Maky had described, you know, I think people don't appreciate the engineering that Akeso Bio put into this molecule, right? So it binds both PD-1 and VEGF, which are validated oncology targets, but the binding of VEGF increases the binding of PD-1 by 17-fold. The binding of PD-1 increases the binding of VEGF by 4-fold, right? And so you get an increase in affinity when both ligands are present, which we believe to be the tumor microenvironment. The thing that's a little bit harder to follow is beyond the affinity, is the avidity play. So what Maky described, as well as described in the literature for bevacizumab, because VEGF is a dimer, you can cross-link two bevacizumab molecules.
As a fact, as they are developing VEGF agents for eye disease, that's actually counterproductive, and that's why they developed the VEGF trap molecule that will just bind a single VEGF molecule. We believe in oncology, that actually plays a positive role 'cause you can cross-link multiple ivonescimab molecules and now present very high affinity PD-1 sites, multiple together, right? So that's an avidity compo play there. So there's an affinity cooperativity and an avidity cooperativity, which I think is very important for this molecule. Very elegantly designed bispecific. Spent a lot of time working on bispecifics. This is the only one I know that does this. Yeah.
And then maybe to take that a step further, you mentioned in the presentation that the bispecific makes the sum or the greater than the sum of the parts. Can you maybe touch on why you can't dose sequentially just an anti-PD-1 and then an anti-VEGF?
You want me to take that?
Sure. Thanks for the question, David. So you could, right? And so there is data that these are validated targets. You know, I think part of it was hampered by Roche having atezolizumab. So they did some bevacizumab, atezolizumab data. It does look to be additive there. There's data coming out from the ORIENT-31 that looked at PD-1 and a biosimilar bevacizumab. So we know that both targets are validated. They probably work together in an additive effect. The cooperativity, however, is the key here, and I think that's gonna help both, not only in PD-1 attacking VEGF, but improving the way that you address PD-1. And I think that's the sort of secret sauce and the elegance in the engineering that Akeso Bio has done. Yeah.
Then maybe one more from me for the team broadly: Could you touch on your primary plans for 2024, and will that be prioritizing additional NSCLC trials?
Thanks for the question. I think I'll take that. So from a 2024 perspective, and I think Maky spoke to this a little bit earlier, but one, executing on our current phase III clinical trials is paramount. But then two, expanding the opportunity. So there was, you know, Maky spoke to a multitude of opportunities that exist both in and outside of non-small cell lung cancer. Because of the data being generated by our partners at Akeso, we can rapidly move into phase III, both in additional non-small cell lung cancer settings, which we intend to do, but also we plan to go outside of non-small cell lung cancer as well to really emphasize the opportunity here, whether that's 2024 or shortly thereafter, but that really becomes our short to medium-term play in terms of really expanding what we have currently.
Anyone? Any other questions?
Maky, I have a question. I knew that. So from an investor point of view, how did a company move from less than $100 million market cap three or four years ago to today $2.3 billion market cap and an Olympian opportunity? Strike a partnership with the country of China, when the U.S. and China were politically and media-wise at loggerheads. Raised $500 million in 48 hours at a cost of less than $500,000, and attract leading attention from top executives, including our partners at Akeso, which, thank you. You're looking at the two women here, the two top leading biotech women on the planet. I thought that would bring a smile. It's a deserved smile. Just incredible.
And we have, probably most of you know, we have, I think, more women in our company. We do have more women than men, but it's not because we shoot for that. It's just because they're good at what they do, and we go after what's good and, you know, not, not, not anything else. So how did that happen? Is that anybody curious about what made that happen? I see Daniel nodding his head.
Yes, yes.
So I'll answer the question. We had to think big, and we had to come to a reality on existing circumstances. We took an all-in approach that if we brought together the top minds, that we would come up with a plan and an opportunity that honored their ability and their past experience. So we had done big things in the past. I think over the years, the core team here has created over $150 billion in market value, and we brought to the world of healthcare the concept of patient friendly.
And when we brought it, it was somewhat sneered at, like, "You've never been in an operating room," or, "You've never taken a drug." And, I've been in both plenty of times, heart bypass surgery and, you know, seen family and other friends, take drugs. But I knew that as an idealistic goal, that friendly, was the direction that we needed to head. If you look at the third definition in a good dictionary, friendly, it's an ally in support of a cause or struggle. And I would say those are your best friends. Those are friends that they help you that way once, you never forget them. So those were our targets. And when you set targets like that with men and women of top scientific background, science is a Latin word.
Scientia means knowledge as opposed to ignorance, that if they were, they were able to strive in their life to achieve the highest level of knowledge that they could attain through school, through experience in the real world, through reading and through asking people that know what they're doing. And so high level of curiosity is engaged and involved. When you bring a team that gets acknowledged for that and validated for that, and you leverage the ability of all human beings to imagine a better future. So we're always focused on a better future. We say, "Focus on your success and keep going." That's worth 10 books to describe the word drive. Focus on your success and keep going. Don't introvert on your losses. Don't get stalled out based on what other people say. If it's true for you, pursue what's true for you.
So having done that, and then, you know, Michelle had been a part of a company that finally had to give up on ibrutinib, and I think if not a tear in her eye, with a slight break in her heart, she, that drug went out the door because top management could not, with conviviality, get along with each other. So they lost a tremendous opportunity, and it was acquired by a company that Maky and I were stockholders in, and we were able to bring it to the market, just following instincts, one step after the next. Is it friendly? Is it caregiver friendly? Can it be well-priced? So I'd like to mention one other thing, too.
You hear the concept of we're going into an election period in a few months, and drugs and the pricing of drugs. If you look at drugs and their value over time, I'll just pull one out, Jonas Salk, the Salk vaccine. Any of you suffer from polio? Are you worried about polio for your kids, your relatives, your grandchildren? No, nobody is. Well, I was there when it was something you worried about, and you couldn't go to the local swimming pool because somebody was in it and they had a cough or a cold, and maybe that polio was floating on the top of the surface there. And it was insidious, pernicious, and a real bother to young kids like myself at the time.
If you have that problem now, $70 and it's taken care of in a vaccine. All drugs will go that way. There's a 20-year timeline. When you're covered, you get monopolistic prices, and you do just what we've done. I've got $750 million in Summit. Where'd I get it? Well, I made $3.5 billion with my previous company. That's where I got it. And the rest of the team, Maky and others, are doing the same thing. We put back into the same opportunities that gave us the right and the ability to invest in forward life for humankind. So that's the way we're thinking. Big picture. We love doing business with China. I was there in 1987. I saw the Chinese people.
It was kind of funny. They all wore the same blue, and none of them had a car, and none of them did wheelies in the street. But they walked to work, and they rode a bike. They were just coming up. But boy, did they ever appreciate seeing. I was, I was one of the first Caucasians some of them had ever seen. And they, they greeted me with not like, "Who is this guy? I should be scared of him." It was like, "Hey, I want to thank you. I have a cousin and relative in your country, and you're teaching them, and you're sending books over here. And, you know, our country wants to rise up too and show you guys what we're all about." And boy, did they ever do that.
Boy, have I ever received a lot of joy and compliments for helping them do that. These are my fellow human beings. They just, you know, a little, little, a little different nationality. But anybody who's got 1.3 billion people in their nationality has got to have done something right, or I'm making a mistake here. So yeah, I think that's the approach. Think big, work hard, be smart, validate others are doing the same thing, share profits, and go for the best. Go for making a significant difference for the better, and you'll wind up where you are now. I know many of you in the crowd, you're incredibly successful, but share that mantra with others. It's a very workable formula.
Then be lucky to find a Maky Zanganeh, or Michelle Xia and get them to partner with you, and you're looking pretty good.
Thank you.
In addition to men, me and everybody else here ... Everybody else here. People love being a winner, and they love to work hard. It's not the friendliest guy that gets you across the river, it's the guy that gets you across the river that becomes your friend. So get your people across the river. Obviously, you know, be their ally in support of that cause and struggle. But that's the soft sauce. But without that sauce, I don't care how many PhDs you have or who you are, we'll beat you to the finish line every time.
Can I-
Go, Bob.
Can I add some color? I was just gonna add some color to what Bob said. So you know, what he mentioned about the, the vaccinations and the cost of products here, so we realize that. So our clinical development program is very aggressive. We have four Phase III that are running right now. Three of them are against PD-1, and two of them are directly against Keytruda. So we understand that we have to demonstrate significant value, and we intend to do so because we believe we have the right molecule. And then Bob mentioned, you know, I think the key here of where the value was created was at a time when things were not good with China. He intentionally drove us to China to say that there's value, there's a diamond in the rough. And this Akeso Bio compound is that diamond in the rough, right?
It's this cooperative binding, validated targets. The value, you know, was probably there mostly in the sense that Akeso has invested incredibly into this molecule. They had almost 1,000 patients worth of Phase II and Phase III data at the time of the deal. They continue to invest in it. They have 19 clinical trials ongoing, which makes the development for us very easy, right? We know where to go with PD-1. We know where to go with VEGF. We're executing very quickly. Launched two global Phase III last year, right? Continue planning to do more Phase IIIs this year. But, you know, it, the decisions are easy given the work that Akeso does and continues to do for us-
In partnership.
Yeah.
Sorry, another question. Can you talk about the funding requirements to run clinical trials and also commercialization, once, once they're launched, and where you are, vis-à-vis funding?
Sure. Since I'm a physician, I'll just say it's expensive, and then pass it over to the business and operation guys.
Yeah, funding is... Yeah, I grew up in a low middle-class family, and I had—I needed a bike. I paid $3. I needed a dribble of basketball. I paid $2. I've never run out of money, never will run out of money. There's no scarcity of money. We raised $500 million in 48 hours, and we could raise that much or double it in 24 hours if we needed to. So you show me the opportunity, I'll show you the money.
Thank you.
It does take courage. It does take willingness to take chances because you learn from your mistakes. Work for people that will validate your courage and validate the fact that you will make mistakes, plural, mistakes, but you learn from your mistakes, and you'll stay right with them. No one will let you go because you make a mistake. They'll let you go if you can't admit it, if you won't learn from it. That's not. You're not gonna last long. But those are the step to success, the ladder to success in the top is comprised of successes and failures. And no one has achieved great success without some significant failures. It's what do they do when that happens? And money, we always talk about money being scarce. It's just, it's false data. It is not scarce. There's so damn much money.
It's all over the place. You just have to get in front of it. The bridge between money and an idea is confidence. Trust.
And-
When the money trusts the idea, it comes flowing.
Yeah. And I'll say from a development perspective, it's not money that's our rate limiting. I mean, we have the data from Akeso Bio that they've generated. We know the targets, and they're validated. We know disease to go after. It's really just operationally executing on that in a team that's rapidly growing. We're 111 people now, right? But we need to be significantly bigger to do the things that we think that this product deserves. Yeah.
I guess the question was more around what's the timeline to commercialization? How long do you expect your Phase III to run, and then what's the commercialization-
Yeah, I don't know how much we want to disclose about that.
I mean, we've not given any guidance on specific timing, on commercialization timing, but what we can assure you is, right, as Bob said, there is no scarcity of money to commercialize, and we have a lot of experience launching multiple drugs with the executive team.
Yeah, and so you can sort of guesstimate and triangulate that. This is what I would advise, since we're not disclosing it. You know, we said we're gonna finish our fast-to-market strategy, the HARMONi study, later this year, right? The PFS of that is well known in that disease population, so you can imagine when, when we'll need the events or get the events that we need to complete that study.
We have two more minutes to go. Any other questions?
All right. If no other questions, Maky, Bob, the entire Summit Therapeutics and Akeso team, thank you so much for all the work that you do and this great presentation.