Good morning, and welcome to the next session. It's my pleasure to host Crescent Biopharma. Here with me is Joshua Brumm and Ellie Im, CEO and CMO of the company. Welcome to another year of Goldman Sachs conference. Before we go through the question, which I do have a lot, especially a lot on ASCO, what happened there and the redo from that, I'm going to pass it on to Joshua for opening remarks.
Thanks for the invitation to be here today. It's great to be here. Just a reminder, we'll be making some forward-looking statements, so please refer to our filings in that regard. For Crescent, it's been a great year. Our aspiration is to be a leading oncology biotech company. It's really driven by our dual strategy around developing CR-001, which is, in our view, will be the next backbone therapy in IO for oncology. We pair that with our second strategy around our ADC development and thinking about the power of synergistic combinations and thinking about that's really where the field is moving and where we think you can ultimately win with best-in-class therapies for patients and make the most impact.
There's a lot going on. Walking through the pipeline, this is going to be helpful for people. This year, in 2026, we'll start four or five clinical studies across three programs. First is CR-001, which is our PD-1 bispecific. That one entered the clinic in February this year. We'll have our first data of three major buckets of data coming in that program in Q1 2027 with our monotherapy frontline lung data coming. In mid 2027, we'll have our multiple cohorts reading out with CR-001 combined with standard care chemo across a number of chemo agents. By the middle to the end of next year as well, we'll have CR-001 combined with ADCs or through our Kelun partnership. That first ADC is going to be sacTMT. We'll have the first bispecific globally combined with sac-TMT, and we'll see that data sometime next year as well.
The second program is CR-002, which is our PDL-1 Topo ADC. We'll have an IND filed in that program mid-year this year, be in the clinic this year. That program will start with data coming second half of 2027. CR-003, which is our IB6 Topo ADC that we in-licensed through our partnership with Kelun. That is in the clinic in China through Kelun, and that data and monotherapy data will be coming out in Q1 2027 as well. There's quite a bit of data coming. There's additional combination therapies that'll be working through our partners with Kelun and CR-001 as well. All of that data starts to come in in Q1 2027. As you can tell, it's been a very busy year. There's a lot to keep track of, we are truly driving data-driven decisions across our matrix portfolio.
Fantastic. Before we dive into CR-001, can you remind us of the current runway and what does it include and not include?
Yeah. All the milestones I just talked about start in Q1 2027 through CR-001 combo standard care chemo, CR-001 combo with Kelun-Biotech ADCs, 002, 003. All of that data is in our current runway. Our current runway goes into 2028, and so we're well-positioned there from a capital strategy.
Okay. Got it. Also, what is that longer term BD sort of opportunity thinking here?
Yeah
Either with Kelun-Biotech or with other players in the ADCs space?
We really value our partnership with Kelun-Biotech. It provides us to really generate data quickly in a meaningful way across their very robust ADC skills and ADC global leader with the sacituzumab being at the forefront of that. I think that it shows our creativity. They were looking for a next-gen IO play, backbone therapy and IO. Their CMO previously was at Akeso and developed ivonescimab, and they chose us amongst all the bispecifics actually seen in China, it was a very good marriage between our two companies. I think that's the first kind of concept of how we think about BD. I think longer term, we'll have the opportunity through the data we're generating across these three buckets of data to really validate that we have a best-in-class partner of choice bispecific with CR-001.
That's going to allow us to sit back, generate that data because we're well-financed, and think about the maximum way to create optionality across building value in the portfolio. We'll continue to be creative thinking about other modalities, whether it's ADC, small molecule, et cetera, to combine with CR-001 through partnerships as well. We have lots of irons in the fire on the BD side, and you can imagine with the data out there from ASCO at HARMONi-6 and what we're seeing in the bispecific space and the way we've intentionally designed CR-001, we have a lot of interest in what we're doing.
Fantastic. Let's go into CR-001. It's a very timely asset at this point. What is that overall vision for this asset as you think about this very crowded PD-1, PDL-1 VEGF bispecific category? Is the goal to develop CR-001 to show best in class, or is it more or less just comparable drugs to kind of share a very large potential market?
Yeah, it's a great question. I don't get asked this question very often, so I'm glad you asked it. I think our vision for CR-001 is part of our broader vision with our CR-001 ADC pipeline and thinking about synergistic combinations. That's where the puck is moving. I think that the way we've set up these three buckets of data coming in mid 2027, as I mentioned, we'll let anybody come in and look at CR-001 across monotherapy and lung, which is where all the data's been generated, across multiple indications where we're using standard care chemo agents, multiple chemo agents, and with ADC combinations and say, "Look, across the board, are you safe enough?" Do you have enough efficacy to truly be a backbone therapy? This is like building a Rituxan or building a KEYTRUDA, right?
The interesting thing here is that this is not a very niche, there's one market we're going after. This is replacing 40 plus labeled indications, $50 billion+ revenue from the current PD-1 class, plus the ADC revenue and VEGF revenue on top of that. You're thinking about really a $100 billion market turnover. The 40 plus indications that are labeled doesn't include the opportunity like we saw some data at ASCO around CRC, where you're now expanding the labels of PD-1s, where PD-1s haven't been efficacious historically. That's another massive market for colorectal, where now you're thinking about, okay, so I'm going to build a base layer foundation of revenue with my CR-001 program, whether that's monotherapy, combination standard of care chemo, or combination with ADCs or other payloads that could then really drive the market.
There's so many ways for this to win that it'll be a combination thereof and really leveraging, and that's why we built the matrix portfolio we have with the ADCs we have. That's why we did the Kelun deal. There's lots of ways for us to win. I think getting a base revenue of, just say, $1 billion-$5 billion in revenue from the current market that's out there for PD-1s, and then allowing that to build on our aspirations to win best in class in combination therapy, where you're really going to drive the market. I think that's overall the strategy that we're thinking about.
I see. Got it. How do you believe the data that we saw from your competitor Summit's, Ivo and HARMONi-2 against pembro? How do you think that provides that validation for CR-001 monotherapy and SCLC and other tumors? Also, where do you think CR-001 can do better?
Yeah. I'm going to let Ellie answer that question, but I'll just start by saying, look, we think that this HARMONi-6 data was landmark data. It achieved what we've been trying to see with replacing the first generation class of PD-1s for 15+ years. I also say just overlooked often here is the safety piece of this. I think that's where ivonescimab and so much data has been very strong and allows for that backbone play, right? I think that's something that people probably just are overlooking a little bit, but has a ton of value. Ellie?
Your question was HARMONi-3, am I correct?
Yeah.
Yeah. That probably was a landmark data that more than a decade on. In non-small cell lung cancer, where KEYTRUDA became the biggest winner, became the backbone therapy, ivonescimab was able to reduce the risk of progression by 50%. That's where actually we got the conviction that this is the right construct of the molecule, and we wanted to build a compound with CR-001 to have the key features.
of ivonescimab. We thought that that data was meaningful in multiple ways. The first thing is reducing the risk of progression by 50%. The second part is the safety profile, where there's a VEGF element to it. We did not see a number of high-grade VEGF-related adverse events that are similar to Avastin. It was much less, and the tolerability was there. Another piece that was very encouraging was that regardless of a PD-L1 status, PD-L1 high patients, and PD-L1 low patients, there was a distribution of equal degree of benefit. KEYTRUDA, as we know, works so much better in PD-L1 high patients.
That gives us chance to now think about how we can replace KEYTRUDA in multiple indications as a better next generation immunotherapy backbone. As Josh mentioned, that also is possible because of the safety profile of ivonescimab that showed immune-mediated adverse events perspective similar to KEYTRUDA, but VEGF-mediated toxicity perspective, a lot more tolerable than Avastin.
Got it. What do you think you can do better? What do you think CR-001 can do better?
CR-001 can do better, we've been saying this from the very beginning, that we are differentiating based on our clinical development strategy. Even in the compound of how we built it, we had some different comes in the PD-1. Part of it, we matched that of pembrolizumab, VEGF part of it, we implemented the proprietary engineering of amino acid chain to improve the stability. ivonescimab is currently being manufactured and sold at 10 mg/mL, and we were able to push the initial concentration up to 150 mg/mL.
15 times higher stability that could give us a lot of benefit with the bio size, as well as potentially looking into life cycle management with the subcu. How we initially designed this compound of matching the key features of ivonescimab, we were able to demonstrate that with the preclinical data in between in vivo data. Now with our phase I trial, if we show similar and comparable safety tolerability, PK pharmacodynamics, the efficacy data, which the cleanest way to do that will be, to Josh's point, from my non-small cell lung cancer data, we know ivonescimab does response rates of somewhere around 50%-70%.
Once we show that data, which will be released in Q1 2027, we will then have Check the box and de-risked from the molecule perspective and going into the registration enabling phase with a higher confidence compared to other molecules that have different structure, potency, binding domain. They will have to run their own phase III trials to have that confidence because they haven't gotten to that point. Whereas ivonescimab is the only compound that has multiple phase III trials show the PFS and OS benefit. The second part of our strategy comes with the clinical development part, where we are starting with a global study, so we don't have to really think about how the Chinese data translating into the global data. Our pipeline has ADCs, and we have also a really good relationship with Kelun. We're combining with the multiple ADCs that they have.
We're generating the data as a monotherapy in combination with the standard of care chemo, also with multiple ADCs. We are also looking for any other partners that have a good mechanism of action and clinical activity to really test CR-001 in multiple different tumor types.
Okay, fantastic. For CR-001, you guys have that phase I/II ASCEND trial coming in the first quarter of 2027. In that trial, there's three parts to it. There's that dose escalation, the backfill, and the dose optimization. Can you go over what's the significance of that trial design, and why do you guys do it that way? What's a backfill? What's the importance of the backfill portion of it, and what do you hope to learn from this trial relative to some with Ivo?
I would just say, look, I covered the three buckets of data we're really generating from that study. It's a great study design. It leverages all of Ellie's background and experience developing Tesaro and working on KEYTRUDA. Really it allows us to combine data across standard of care chemo combos, multiple chemo agents, ADCs through our partnership with Kelun, which is not part of the ASCEND study, but also would generate that data. Also the monotherapy data through the backfill cohorts, and it really does leverage the different cohorts to generate all of that data. I think it just positions us to be in a really strong position as we head to mid 2027 and really answer a lot of the questions that go to your previous question. We're not trying to differentiate and be better than ivonescimab.
I think what we're trying to do is to learn from the lessons that have been out there. We'll start with global study and data as Ellie articulated, but also Kelun will be generating the data in China. We'll have both of the data as a company. Then I think the real key with this ASCEND study is it puts us in position to make our choices to where we go to build that foundational bucket of revenue, where do we go put our best in class bets down, right? I think we're in a very unique position to win because of our dual strategy between the ADC portfolio and owning CR-001, the backbone therapy. The question for many other people in the oncology space is going to be, what is my play for a bispecific?
How am I going to win with my ADC portfolio without being able to combine with the next gen bispecific standard of care here? I think as we start to replace first gen PD-1s, that's the question that other companies have to answer that we don't have to answer because we have that asset internally wholly owned.
I see. Okay. My last question before we go into some of the combination, the exciting combination therapies, is that can you talk about what's that forward path looking like after the phase I/II data? Assuming this is possible, are you guys going to go straight into the phase III? Is it going to give you enough conviction to do that? Besides NSCLC, is there any other indication that you would do that for?
Yeah. I mean, Ellie, this goes to your last question around what the value of the backfill and expansion cohorts are. Maybe, Ellie, you could talk about what we'll do with that data and where we're going to go.
Yeah. ASCEND trial was specifically designed to answer a couple of key questions. First one is, what is the recommended phase II dose of CR-001? Generating comprehensive data to really answer the question of how the clinical profile of CR-001 looks like as monotherapy and in combination with various standard of care therapy, so that we can choose the indications for registration enabling trials. Dose escalation and backfill will answer the question of how, as a monotherapy, how the safety and efficacy look like. In most of the indications currently, PD-1 plus chemotherapy is used as a standard of care in frontline, our expansion cohorts will answer that part of the question. The dose optimization is to answer the recommended phase II dose part according to FDA's Project Optimus.
We will utilize the data that we are generating, and we will also look at the competitive landscape and choose the indications for registration enabling trials based on probability of success, as well as the speed to market, then market size, and then how that fits to our matrix portfolio. For example, we can go and win with one indication in standard of care combination, and in other indications, we might be able to do that in combination with the promising ADCs.
Right. Just a reminder, we've said it multiple times that kind of the areas that we're focused on is GI, thoracic, and reproductive. Within those buckets, that's the best way for us to leverage our matrix portfolio across the current portfolio of assets we have.
I see. Okay. In terms of the combination, we talked about the two different ADCs, the chemotherapies. What other combination are you guys exploring beyond these three? What's that vision for these combinations, and how do you land on these three to begin with?
The combinations that we are exploring currently includes CR-001 and then the ADCs that we have. Kelun has 10+ ADCs in their clinical pipeline. Kelun will generate their own data in combination with various ADCs, and we'll have access to that data. While we are generating our own combination data with our PD-L1 ADC, 02, an integrin beta-6 ADC, which is CR-003, then that will help us choose the indications and how we want to execute the next registration trials. These ADCs can be developed as a monotherapy as well as in combination with the CR-001. As Josh mentioned, we are also looking at various opportunities to work with companies that have promising assets. Regardless of mechanism action, that can be small molecules, radiopharmaceuticals, or any other large molecules that are out there.
The reason that we can do that is because of PD-1 x VEGF bispecific, especially ivonescimab, then we build a compound to match the key features of that, has a really good safety profile that allows the combination strategy.
Yeah, I just highlight, I think we've said this for quite some time now. As we came in as a management team last March, the number one thing that we were focused on was to run a robust phase I/II study to really validate CR-001 as a backbone therapy, and best in class bispecific. The fact that we, again, have the rights to that drug gives us an incredible opportunity to leverage that in a number of ways. The first thing we did after we designed the study for ASCEND is we went out and did the Kelun deal. I think people don't appreciate yet how much value and data we can generate through that partnership across combining CR-001 across all of those ADCs. That is where the puck is moving.
Not only do we have a chance to build on a revenue base, I said earlier, $1 billion-$5 billion, that could be $5 billion, $10 billion, $20 billion of revenue, depending on how fast we can go, how broad we can go of just replacing the existing first generation PD-1s on label. Right? You start thinking about and imagining where you can get to in the combination strategy, then through a partnership like we have with Kelun, it really comes down to data generation. The faster we can generate that data, the more we have confidence in where we want to go and can be winning best in class. You said Non-Small Cell or lung. We get asked quite often, do we think, is it crowded? Is there room in there? We think lung is wide open, right?
I mean, we think that winning with a best in class ADC combo is something that we can do, and we could potentially be best in class in that market, let alone all the other opportunities behind lung. Lung's a big one, but Colorectal, if bispecific is working, Colorectal also a very big market. That's how we're thinking about it. For us, it comes down to generating the data quickly and making data driven decisions.
I see. Got it. Okay. You guys have the chemo combination data coming out in mid 2027. At ASCO, we saw the I think we talked about the phase III HARMONi-6 where they show a significant OS benefit. What do you think about the bar is now with HARMONi-6 data out there for your combination in that 1L NSCLC?
The bar for Non-Small Cell Lung Cancer?
Yeah.
Okay. We thought that that data was really landmark data. Practice-changing data where this is first time PD-1 x VEGF bispecific has shown OS benefit compared to PD-1 containing arm, and then it's a chemo combination for both arms in frontline squamous cell population. We've been waiting for this moment for 10 plus years. Since KEYTRUDA really revolutionized the multiple standard of care options becoming a backbone. We thought that that data was great, finally answering some of the key questions of how PD-1 x VEGF bispecific can provide better PFS benefit and OS benefit. This gives us now a chance to look at how the study should be designed.
We looked at the Kaplan-Meier curves of where the curves are separating, and then the subgroup analysis and how the patients benefited depending on different stratification. All those things are very helpful for us in terms of making a decision for our next registration enabling trials, and we can further improve the probability of success. This is possible because we are in a great position being a fast follower, and then we have a compound that matches the key features of ivonescimab. We can utilize all these things.
Yeah, I think it's worth reminding people that outside of China, there's no approvals for bispecifics to date. Right? The door there is still wide open. I do think that there's going to be lessons learned from those that have come first on study design, powering stats, et cetera. It puts us in a very strong position to be right on the heels of that. Particularly in such a large market opportunity, right? Even coming second or third in lung is a massive market opportunity. From a revenue generation perspective. The good news here is that's not the only indication. We have 40+ where we can go be first in class. It just highlights how big of a market opportunity is. I think that's really important. I also think that from our perspective, until there's an approval- it really is a wide open space.
Okay. Makes sense. Also at ASCO, I think the discussion was a very lively discussion from the discussant. Pointed out multiple caveats about the translatability of that patient population to the global population, lower efficacy in the elderly patients. I think the other thing that they pointed out, I think year after year, is that what is the point of having a bispecific when you have a bevacizumab that's already available- It's about similar. You also have PD-1. The patents will expire. You always have that combination t here at play. What's the point of doing that having a bispecific? Maybe I'll pass it on to you guys to get your thoughts on what the discussant said about these points.
Yeah, I think, Ellie, you did a nice job talking about the three points that was brought up by the discussant.
Oh, okay. Yeah.
Also maybe just touch on the reason why bispecifics are working where- PD-1 and bevacizumab historically g iven separately is not.
Yeah. Thank you for giving us opportunity to talk about these points. I think it's discussant brought out these points, and we heard a lot of people asking the same questions, but it's great that we can address it here, too. Regarding the translatability of Chinese data to global data, we actually already have that data, that evidence coming from HARMONi-A study done in China versus HARMONi study that was done in global setting. Summit did a great job of showing the efficacy and safety profile in HARMONi study between Chinese patients and the Western patients, and they were comparable. We already have this answer that it's not about Chinese versus Western population, it's more about how you're executing the trial.
Make sure that patients come in with the right stratification factor enrolled, and then when is the right time to do the analysis, and then do the statistical assumptions accordingly. We already have that data out there to answer that question. The second question about age, right? The older patients versus the younger patients. This is the only study from the ivonescimab trials thus far that show this trend, that older patients didn't get as much of benefit as younger patients. Whereas HARMONi-A and HARMONi-2 studies show that both younger and older patients have benefited from treatment. It's not about PD-1, bevacizumab class or ivonescimab issue. It was specifically that something that we saw from HARMONi- 6 study. Summit provided some information about that. What might have led to that.
The imbalance of the two key risk factors that were seen in the older patient group that included tumor size, the patients with the larger tumor size. Patients with brain metastasis, the tumor that went to the brain. There were a higher proportion of those patients represented in the ivonescimab arm compared to tislelizumab arm. It's good that we are learning about this.
Now we can stratify based on those risk factors to make sure that doesn't become an issue for the next trials. Regarding the third question about we have a PD-1 and we have bevacizumab, why do we need a bispecific? That's the question that I think we have successfully answered with many studies by now. We have IMpower study where Genentech did, Genentech Roche did with their atezolizumab plus bevacizumab in non-small cell lung cancer. That trial did not show superior PFS or OS compared to atezolizumab arm.
Right? KEYTRUDA as a monotherapy could not work in EGFR mutated patients. Avastin also could not get that efficacy shown. Whereas we saw what ivonescimab was able to do in that EGFR mutated patients. Colorectal is another example where Avastin is currently used in combination with chemotherapy. KEYTRUDA did multiple trials to see if their drug can work in microsatellite stable MSS colorectal patients, which is like 97% of the population. None of those trials worked, right? We have now data showing ivonescimab as well as other PD-1, bevacizumab show standard of care chemo show response rate of 40%-50%. Ivonescimab data showed a response rate of 70%.
Right? These are some examples of how as a PD-1, bevacizumab. It's not PD-1 plus bevacizumab. The way they built the compound and how it works in the tumor microenvironment, it's all different. Then the last piece, which is also as important as efficacy, is safety.n Avastin could not be approved or developed in squamous cell non-small cell lung cancer patients where HARMONi-6 showed the positive data because of the bleeding issue. It created a lot of patients developing high-grade hemoptysis. Due to that risk, they had to stop the development, whereas we saw that with HARMONi-6, that risk was relatively minimal.
Physicians thought that if this drug was approved today, they would definitely use it in the squamous patients. In efficacy and safety perspective, I think there's a lot of data already validating that this is a different class of drug than just giving PD-1 and VEGF together.
Hmm. I see. Okay. We have a couple more minutes left. I want to go into the ADC combination. You guys have these two ADCs that you guys are developing in-house, the 002 and then the 003, along with CR-001. When you think about the structure of both of these ADCs, how do you think they lend well with CR-001, and what do you think are the greatest opportunities for each of these combinations?
Yeah. I think from our perspective is we worked with Paragon to develop 002 in-house, right? Also thinking about our criteria for targets for our shopping list for ADCs. Thinking about IB6 being the top of that list. It really is looking at how we build that matrix portfolio across where we see CR-001 opportunities combined with 002 and 003 and other modalities or other ADCs as Ellie's mentioned. I think our view on that was to design best in class across the antibody linker and payload. We think we've optimized those three components. For indications, what we're interested in. There's lots of expression data out there where you can see either 002 or 003 being very efficacious and effective. Also thinking about how that ties back into the three TIs I talked about earlier. Thoracic, GI, and reproductive.
I see. Okay. I also want to touch a little bit on the sac-TMT. I think we talked a little bit about it before the session. What are your key takeaways there from that sac-TMT data that was shared at ASCO that shows the PFS benefits and OR, and then when you combine it with pembro? Is that a good benchmark for your CR-001 and some of the ADCs? Yeah.
Well, maybe I'll just start by saying from a Kelun-Biotech perspective. Obviously, a world-class ADC company. The platform which sacituzumab was built on is the same platform we have with 003. There is some benefit there from that perspective and why we're so excited to see CR-001 combined with the broader portfolio of ADCs that Kelun-Biotech has. In regards to your question, maybe, Ellie, you could talk a little more about that.
That was the first data set of ADC being combined with the IO agent in frontline Non-Small Cell Lung Cancer. From that aspect, I think it's a really important study, the benefit with a PFS ratio of 1.3, which is really impressive, cutting the risk of previous progression more than 65%, is something that provides us a really good opportunity to utilize that ADC and then see how we can further improve the frontline Non-Small Cell Lung Cancer treatment options. From our perspective, why it was also important is because we have a Topo payload ADCs in our pipeline, this is a good study that demonstrated that Topo payload ADCs can be successfully combined with the IO agent. It was early, but we also saw robust OS trend showing that the benefit in the population as well.
Overall, I think this is really going into the direction of how we build the company. That okay, now we are seeing that the IO agent, KEYTRUDA, being successfully combined with ADC. We are seeing the HARMONi-6 data showing the PD-1 VEGF being combined with chemotherapy agent together both in frontline non-small cell lung cancer. What will be the next step? Naturally, it will be a PD-1 VEGF in combination with ADC and see if we can show even better efficacy and then tolerability compared to these two trials. Overall, we are very happy with the data that was presented at ASCO, and it really validates our strategy.
Fantastic. Well, we're out of time. Thank you so much. This has been a very exciting session and a very exciting time for these bispecifics. I'll just turn it to Joshua for any final remarks.
Just thanks for the invite today. It's great to be here. It's always fun to talk about our vision and our company and making the world a better place with patients. Thanks so much.
Great. Thank you.
Thank you.