Great. Good afternoon, everyone. Thank you so much for joining us. I'm Salveen Richter, a biotechnology analyst at Goldman Sachs, and we're really pleased to be joined by the Summit team, who's rather patriotic today. To start here, next to me, I have Maky Zanganeh, who's Co-CEO, Bob Duggan, Co-CEO, Manmeet Soni, COO and CFO, and Dave Gancarz, Chief Business Officer. With that, to start here, could you provide an overview of your lead molecule, Ivo, and where your programs stand, your strategy for your company, and the key events we should focus on in the second half and beyond? Dave?
I was going to give it to Maky. Maky is the cover girl of the upcoming Forbes magazine, and you'll hear plenty from her today. Dave, go ahead.
Sure. Thanks for the questions, Salveen. I think as we take a look back over 2025 thus far, we had announced at the beginning of the year that there would be three clinical catalyst events and one operational catalyst event. We began the year stating that we would focus on the ability to translate PFS into OS in the HARMONi study, monotherapy Ivonescimab and Pembrolizumab in the PD-L1 positive non-small cell lung cancer frontline setting. We would focus on the success that took place in HARMONi-2 in the monotherapy setting and seeing that benefit translate into the chemocombination setting. As we look at non-small cell lung cancer and solid tumors as a whole, the overwhelming standard of care in the frontline setting is often immunotherapy plus chemotherapy.
Third, we would look to show that the success in single region, albeit randomized phase III studies in China, would be comparable to the results in a multi-regional setting à la HARMONi-A to the HARMONi trial in second line eGFR mutant non-small cell lung cancer. All three of those data points read out earlier this year. We saw a strong positive trend in overall survival in a Health Authority-requested first look at overall survival in HARMONi-2 that showed a hazard ratio of 0.777 at a nominal alpha spend, given that that was requested by the Health Authority as opposed to a pre-planned analysis. That showed a strong favorable trend. We see oftentimes we look at clinically meaningful as being about 0.80. The first look at 39% data maturity showed positive and encouraging trends from there.
Also important to note that this trial at 398 patients was not intended to evaluate statistical significance of overall survival as this was a primary endpoint of PFS. That indication for ivonescimab has since been approved in China. The second aspect, chemocombination in HARMONi-6, looked at frontline squamous non-small cell lung cancer. That took a look at ivonescimab plus double chemotherapy against PD-1 plus double chemotherapy. In that trial, our partners at Akeso announced it was strongly positive on the first look at PFS. That was again a PFS primary endpoint. That data will read out in full at a major medical conference later this year. That data, it's a first interim look, so obviously it's a relatively high bar from a statistical plan perspective.
Therefore, it continues the favorable news and data with respect to Ivanacibab now in a chemocombination, which is important as we look at the opportunity in solid tumors as a whole and in particular in non-small cell lung cancer. Finally, with respect to the data comparability from single region China to a multi-regional setting, the HARMONi trial read out just before ASCO. That showed a statistically significant and clinically meaningful progression-free survival and a strong trend in overall survival, the two primary endpoints, which was consistent with what we saw in the HARMONi-A trial from the single region study in China, further validating that the randomized phase IIIs that we see in China continue to validate the opportunity as a whole for Ivonescimab in a global setting. The final operational catalyst that we discussed earlier was the expansion of our clinical development plan later this year.
We continue to effectively reaffirm our intentions from that perspective. Hopefully that gives decent color in terms of overall summary to date on where we are and what has taken place over the last few months.
I just want to add as well, for sure we have our partner Akeso, as you know, in multiple different meetings we announced as well that we have over 22, 23 different trials going on, all completed or going to start, but 11 of that is a phase III that China and us, we are combining, we are doing that. Over 3,000 patients is enrolled. We have a very good safety profile, efficacy profile in many different therapeutic areas, as well as from a commercialization point of view, we already in China, we got two FDA, two Chinese approval, which is significant from the progress that we are going to have here in America. The fact that right now they are selling the drug and it's more than 20,000-25,000 patients already enrolled with this product.
That is already talk a lot from, as I said, safety and efficacy point of view.
Maybe we can start here with the HARMONi study, just given we saw the data recently ahead of ASCO. Help us understand next steps from here for you in terms of providing data to us, but also in terms of what you might want to provide to the FDA down the road. Also just the meaningfulness of this indication in the context as a total opportunity that you're pursuing.
Sure. For the last question first, I think from an opportunity perspective, this was an important setting from a speed perspective as we looked to enter the market for Ivonescimab. From a total addressable market perspective, think of it as probably 1%-2% of the total addressable market within the possibility for Ivonescimab. When we look at the data itself, we were statistically significant and clinically meaningful in progression-free survival and a strong positive trend without hitting statistical significance in overall survival. When we look at this setting, you had a-sked, Salveen, with respect to filing and what-not, we noted in our release that we intend to file a BLA, but we want to make sure that we think through strategically the right next steps with respect to how to do that.
When we entered into the agreement with Akeso, this was a specific opportunity, as I mentioned a minute ago, to move quickly in this setting. This is a setting where PD-1 therapies have looked to become a part of, but both pembro and nivo had unsuccessful trials in this setting in both PFS and OS. This was a differentiation point for Ivonescimab against the existing PD-1s. We were very thankful in working with the agency from the beginning in 2023, and we appreciate the agency working with us in terms of moving forward here in this study immediately. We, at the agency's request, included overall survival as a primary endpoint along with progression-free survival. When the study read out, we were again statistically significant, meaningful in progression-free survival. The agency asked for statistical significance as well with overall survival.
When we look at the landscape for this particular patient setting, we see one approved regimen in this space that also showed a PFS statistical significance and an OS trend without hitting statistical significance. As we look at the overall package, we just want to work through strategically the right way to bring this forward as we work with the agency with respect to next steps. At ASCO, as Salveen mentioned, it was just ahead of the conference where we disclosed this data. We had a couple hundred interactions with either KOLs or other physicians who were attending the conference. It was overwhelmingly positive in terms of the opportunity that Ivanacibab plus double chemotherapy, the HARMOi regimen, if you will, what options that could provide in this particular setting.
We think it's a very good overall data package, and we're working internally to determine what are the right appropriate next steps, if you will, strategically. We had mentioned in our release the Friday before last that the patients from the Western countries, the median follow-up time was actually less than the median overall survival in this setting. We think there's value in continuing to follow all patients, but in particularly the patients from the Western countries in terms of adding to the overall package here.
Bob, do you want to add something?
No.
No? Good.
Maybe a twofold follow-up to that. One is, do you have an understanding of what's required from your clinical trial program in the context of ex-China data sets versus China data sets and how you think about that in the context of your overall program going forward? The bar for approvability at the FDA with these dual endpoints and the optimization that you have done to ensure you can hit on overall survival as well as PFS.
Sure. With respect to the first question, yes, each of our trials, we work with the agency in advance in terms of proportion of enrollment amongst other factors, design of the trial, et cetera. Going forward, you can expect much more of, for example, if there are three regions within the study, about a third in one region, a third in another region, and a third in the final region, more even split. As we mentioned with eGFR, it is a higher prevalence in patients of Asian descent. Typically, you see eGFR mutant trials have a higher proportion of enrollment from Asia. Going forward, in other indications, you would expect much more of an even enrollment across. That is effectively what we have planned for our two enrolling trials at this point.
With respect to the approvability, again, as we continue to have conversations with the agency, these details are worked out. I would say we started HARMONi-3 with an overall survival primary endpoint. Part of the reason for adding a dual primary endpoint when we added non-squamous on top of the squamous population was in response to the data that we saw in HARMONi-2 that had such a profound PFS benefit that we wanted to at least ensure the ability to have a conversation with the agency should PFS read out with such a significant difference in the HARMONi-3. However, we started with OS as the sole primary endpoint in that trial.
I think it's very clear that within the frontline non-small cell lung cancer setting, that will become extremely important in terms of showing an overall survival benefit over PD-1 plus chemotherapy in terms of realizing the potential of the market. As I mentioned in the opening, HARMONi-2 had early look, but had showed a very positive or favorable trend in terms of its first look. That continued to provide positive data that was encouraging. We have obviously a significant amount, Maky mentioned the number of trials, well over 20 trials that have been enrolled or enrolling. Those included a number of phase II trials as well in this particular setting where we can see the follow-up that's much longer now than what you see in the phase IIIs. We're very encouraged by what we see there.
You see the powering of our clinical trials that we run on a multi-regional basis, and those are intended to and are powered for statistical significance and overall survival.
Just one last question on HARMONi. What do you think played out here with regard to the trial that OS was not statistically significant? Was it powering or was it tumor type or other factors? Maybe help us understand what you think played out.
I can start and then after that. I mean, this study was a very interesting study. It was already enrolled in China. When we did the deal with Akeso, which was around February 2023, we started right away, we were in discussion with the FDA. For sure, the discussion was to add additional patients into the Chinese patient populations, which is 1/3. 38%-40% of these trials is ex-U.S. patients. We enrolled, we started the enrollment as soon as possible. For sure, at this moment of time as well, it was a time that we take a little bit to everybody questioning what is the bispecific, everybody questioning what is the China data. Everybody, it just was so much questions.
The first three months took us a little bit of time, and especially for a company like us that we didn't have phase I, phase II, we started right away on the phase III to bring awareness to the physicians, to the patients. Took a little bit longer time to take off on these specific trials. For sure, last ASCO and September when we announced our data, the enrollment went really, really fast in this regard. I know sometimes people say the study was not statistically significant, but if you really, really look at it, the P-value, I mean, the hazard ratio was 0.79, which is already unbelievable for this category of patient population. There is no other drug at this moment of time got the OS one.
Second, if you really look at the safety profile for these patient populations compared to existing drug, I mean, you cannot compare, which is a better safety profile. The efficacy was good. The only thing I can say, you say significant, and that is the difficulty when you look at the OS P-value of 0.057 instead of 0.05 is really you are playing with the penny numbers. It's not, you cannot say that the drug is not working. You cannot say the drug is not good for this patient population. If you take a little bit another look on it, at the end of the day, as a physician, as a human being, as a patient, you cannot just go and say because you did not hit 0.057, you cannot prescribe this drug into the patient.
A moment of time will come, either we will be on the NCCN guidelines, we are trying to go back to FDA to present our case, and it is a lot of other things. At the end of the day, we have to do everything possible to bring this drug in the hand of patients. That is bottom line. Therefore, yes, perhaps this number shows that, say, oh, we did not hit it, but in reality, I believe the study was very positive scientific point of view about it.
Yeah, I'd like to give Dr. Pazer a lot of credit. He could have easily agreed with the early take from the FDA was too much China data, and we just do not do that now. He stepped in and took a look at it, and he is familiar with Maky and myself from pharmaceutical studies and put a call and just said, I have a question. What is it? He said, why did you do this? He said, there is a major unmet need around the world. We think this molecule has some real life to it. And honestly, given what we have seen, we just felt we had an obligation to try to work this out. He paused. He said, it makes sense. He said, I'll let you do it, but the challenge is going to be OS. Now, that was like impossible.
We took it because what it could possibly show, even if we did not hit the OS at 0.05, is that the data is translatable. The progression-free survival was spectacular. OS is not even a question in eGFR, TKI, post-TKI. We thought all those would be wins. In fact, they were. That is why you can look at the trial and say it did succeed. I give him a lot of credit for, one, helping the two countries come together under something very substantial. We are exporting China technology. From China is exporting the technology, we are importing it. We exported money. It is exactly what the country wants. They want the money in and the tech out around the world. This is just one small step really for mankind and humankind. We are not in the war business. We are not in the IT business.
We're not in the AI business, although we use AI a lot. It just shows these two peoples, these two peoples can't get along. We do, and we did, and we'll continue. Our top partners from Akeso are, like many Chinese, educated in America. They're culturally Chinese. They speak both languages. They have American passports. We see every reason why we should get along, not why we shouldn't. We did this before Jamie Dimon and Henry Kissinger, rest his soul, went over to China to say these two countries really ought to be getting along. If you're going to get something going, this is the easiest patch in which to launch this. We're happy with our partner. There's no question about it. Ivo is a working drug.
We're pleased to find post the relationship that outside of NSCLC, there may be a bigger opportunity than insight. So that's what I can say about this.
The last thing for us was really important because instead to do a phase I, phase II, you go right away in the phase III and shows the Western patients versus Eastern, I mean, China versus ex-China, U.S. This consistency of the data, that was the biggest win that everybody wanted to see what's going to happen, what is the China data. If you look at it in a different angle, at the end was a lot of win-win position in this situation to do this study no matter the challenges. The rest of the study is different because, as you know, the global study mostly is one third China, two third ex-China is always now is one third Europe, one third US. It's a different dynamic. This one was very interesting, exceptional trials that we wanted to finish it.
I want to touch on one of the biggest opportunities you have in cancer and your frontline non-small cell lung cancer opportunity here with HARMONi-3. You have talked about how it is enrolling faster than expected. I do not believe you are going to give us timelines yet, but we will wait for them. In the interim, maybe walk us through the Akeso trial from HARMONi-6 that looked at their combination of Ivo with chemo in frontline squamous non-small cell lung, and just frame that result and the read-through to your study and also the differences that are playing out with your program versus the Akeso trial.
Yeah, I think you framed that well sounding in terms of frontline squamous non-small cell lung cancer, Ivo plus chemo versus tislelizumab, which is the PD-1 from Beijing, the PD-1 inhibitor plus chemotherapy. And tisle plus chemotherapy, for example, is approved in Europe as a standard of care for frontline non-small cell lung cancer. That study, PFS primary endpoint, squamous, but it is PD-L1 all comers, right? So negative, low, and high. Compare that against, excuse me, our HARMONi-3 study, which we are enrolling on a multi-regional basis, PFS, OS, dual primary endpoints. We talked about OS a minute ago. The PD-1 is pembrolizumab in that setting. It is squamous and non-squamous. Of course, multi-regional versus single region, right?
I think as we see now, as I talked about in the beginning, we saw the PFS to OS in HARMONi-2, we saw the top line data readout from HARMONi-6 in the squamous chemo combination setting. Now as we look at HARMONi-3, the read-through also is further backed up by the consistency of the results from HARMONi-A and HARMONi as well, right? More multi-regional studies will continue as we go into HARMONi-3 and 7. It is important that there have now been three successful phase III, randomized phase III trials against globally reputable standards of care, if you will, now run by our partners at Akeso. As we look at the data, there will be more data that is disclosed on that in the fall at a major medical conference. In the interim, it gives us, it further validates our confidence within the frontline setting.
It provides additional data points as we look at all of the major milestones that need to be accomplished in terms of the opportunity for Ivonescimab to eventually change standards of care on a multi-regional basis.
Can you touch on the strategy here for execution across this very broad space with this drug and how you intend to do that and move into various tumor types in a very quick fashion, recognizing that now you have all these followers with other large biopharmas that are doing partnerships with drugs in the same class?
I want to take it.
Yeah, Ivo is the best drug from everything we've seen and understand. The source of Ivo is Akeso, and they started in 2013 and brought the product out. As Maky said, there's over 20,000 patients dosed majorly successfully. They're dosing 200 patients a clip a day. Our trials are enrolling. They're enrolling fast. We are pleased with all that. It doesn't surprise us that there are a lot of followers who could be in this business and not see someone with a loss of entity value and approval going in 2028 off label and not one after it. It's a $30 billion business, plus there's easily another 20 off- target from NSCLC. When we did IMBRUVICA, we were the only ones until we showed that it worked. Within six months, there were 100 IMBRUVICA patents. It's not difficult to come up with a molecule.
No one has matched the molecule. Those that have graded it have looked at it and said, we are the best. If you're in a horse race, you want the fastest horse. If you're the fastest horse, you still need the best jockey. We think we're good jockeys, but we think partnering is going to be the way to go to really get it across the finish line. We're going to actively engage in that activity. We wanted to show what we could do, what we should do, and let the field settle down a little bit. We're going to be very active in that area. With the right partner, with the right drug, with the leadership from Akeso in terms of pushing outside the NSCLC arena, we think we're pretty pleased with where we stand here. We do appreciate competition.
It's basically a validation that what we have is right. The great thing about this business is the FDA gives you an AMA, work hard on it to make sure that this happens. You have a monopoly unless someone is better than you. It's not going to be easy to fund the other businesses that have to go head to head with pembro, much less ourselves, who then beat pembro. We need to establish that partnership and get rolling. We've let no grass grow under our feet. We've got over 50 ISTs. Six of them have already launched. We have a big partnership with MD Anderson. There's no one out there now, unlike the first four months when we took the drug over, no one knew of bispecifics, their activity.
No one knew that eGFR was not going to be a major bleeder in this space. No one wanted to partner with China, and no one really heard the name of Summit. That was a real stiff wall to climb, but that's been climbed now. This is our game to win.
How are you thinking about it from a combinatorial strategy standpoint across the cancer space?
All of the good different modalities or targets. The good news is, and I will let after that Dave answer more details, but the good news is that we have a very nice safety profile you can combine with any drug that you want to. I mean, if it's a combination with the ADC of the world or any other combinations, we are working on that. While we come up, we will announce it. You go like any other, at the end of the day, you are in solid tumors. At the end of the day, you have a patient's perspective. At the end of the day, every month counts, every day counts. At the end of the day, you want to give the best, safest product in the hand of patients, at the same time the most efficient drug in the hand of patients.
We will do everything possible to figure it out, what is the best combinations that they give this to safety and efficacy to the patients. You have to try it. On our side, we have one product that we can combine it with any other product that we want to, with any partners that we want to. There is no restriction. If we did a collaboration with Pfizer, it does not allow us to do with other people on the collaboration with the ADC.
Well said.
Thanks.
Manmeet, maybe you could touch on the balance sheet at this point and what it covers in terms of clinical development.
Sure. As you know, we finished our Q1 with over $360 million in the bank. We raised around $400+ million last year. We know that we need capital, right, to continue the development, but we have sufficient. Our run rate for Q1 was approximately $50 million, which will continue to increase, but we have sufficient capital to continue to execute on our current plans. As appropriate, Bob and I have always said that when appropriate, we will raise money.
Can you also speak to the manufacturing strategy here?
Sure. On the manufacturing front, as you all know, Akeso being the partner and developing Ivo, we have been relying on them for doing our clinical trials, and they have been producing. They have gone through their inspections, including FDA inspection for another product. They have passed through that. In the meantime, we have rights to develop in our territories. Our territories include U.S., Europe, Japan, Africa, and Middle East. We have full rights to develop and manufacture Ivonescimab We initiated tech transfer last year, and we are progressing pretty well on the tech transfer. We believe pretty soon we should have the ability to produce ourselves in our own territories, which will help us.
On the cash side, you all are investors, and you wouldn't be here if cash earned a super huge return annualized. It doesn't. You need to get into equities. You need to get into real- estate. You need to do something alternative to cash. As Buffett said, he's 94 years old. The dollar lost 92% of its value during that period of time. That's not going to change in anybody's lifetime. There is plenty of cash out there. The question is, does the owner of the cash have confidence in the business and the opportunity? When that answer is yes, the cash transfers, whether it's a recession, inflation, or a rapidly growing economy. We have not only the molecule, we have the source of the molecule and a relationship with them. We check all the boxes, and we are really set to go.
We did not want to compound a potential relationship in the making with raising cash. We do not need $2 billion on our balance sheet because we are talking about how we can put this company together and maximize the wealth opportunity for the stakeholders in the business, in addition to the opportunity for patients and society at large. When those chips fall, we can further entertain the question of cash, whether we need it or we do not. I do not think we will.
As a last question here, could you speak to the data sets that we're going to see over the next six to 12 months across both your portfolio and Akeso's portfolio? If there's anything that I didn't ask about that you want to highlight, I would do so as well.
Sure. Great set of questions. Thank you very much. Nothing too profound to highlight other than, data sets, we'll see HARMONi over the course of fall meetings or whatnot. We'll also see HARMONi-6. We'll see the multi-regional HARMONi, second line eGFR that we sponsored, HARMONi-6, frontline squamous combination with chemo sponsored by Akeso. I think we'll also, not a data set, but we'll also give further clarity with respect to the expansion of our clinical development plan. I think we'll also likely start to give a little bit more for timelines with respect to HARMONi-6, which we started a little while ago. In terms of that, we'll likely have additional other components, but there's no reason to give away the full story before. It's always good to have something else come into play.
Overall, we have a great product. We have a great team. We have the speed of light. I believe we show it with 185 people. We really did an outstanding job in the past two years. We showed to the world, and I believe you saw it with every bispecific, like a mushroom is coming up, that is kind of, we showed the molecule is a significant and important molecule to have. At the end of the day, again, people, they are afraid of competitions. Personally, I'm not because I believe every patient deserves the product that is working on you. Perhaps it's not going to work on me. At the end of the day, we'll do everybody possible to bring the best product in the hand of patients. We are in great shape. That's the only thing I can say.
The entire team is working very, very hard. We have great physicians, as Bob said. Our IST program is moving very, very nicely in the different indications. Our partner did an outstanding job as well. Bringing 11 phase III in such a short period of time is important and significant. We are very, I cannot say lucky, but I'm just saying we are pleased that they start the phase III and we can take it and bring the data and start our phase III. We do not need to go to the phase I, phase II process right now. We can catch the data from our partner Akeso and start right away another phase III. For sure, our regulatory group from China and U.S. is different. That is why we powered our trials. They have more patients because we powered for the OS and PFS.
That's where we are.
Before we end off, let me give a shout out to Salveen and her Goldman Sachs team. They do an unbelievable job of following this company in depth. It's not easy, but we're really appreciative of the work that Goldman does for all of us to bring liquidity to markets like we participate in. Thank you so much, Salveen.
Thank you.