Crescent Biopharma, Inc. (CBIO) June 2026 Conference Transcript

Well, good morning, and welcome to the next session. I am, it's my pleasure to host Crescent Biopharma. Here with me is Joshua Brum, an LEM, CEO and CMO of the company. Welcome to another year of Goldman Sachs conference. So 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.

Great, thanks. Thanks for the invitation to be here today. It's great to be here. Just a reminder, we'll be making a forelooking statement, so please refer to our filings in that regard. For Crescent, it's been a great year. Our aspirations to be a leading oncology budget company is really driven by our dual strategy around developing CR001, which in our view will be the next backbone therapy and I.O. for oncology. And 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 know, you can ultimately win with best-in-class therapies for patients and make the most impact. I think for us, you know, one thing I'll point out is there's a lot going on, and so walking through the pipeline is going to be helpful for people. So this year, in 2026, we'll start four or five clinical studies across three programs. First is CR001, which is our PD-1 by Jeff Bi-Specific. That went into the clinic in February of this year. We'll have our first data of three major buckets of data coming into that program in Q127 with our monotherapy frontline lung data coming. In mid-27, we'll have our multiple cohorts reading out with O1 combined with standard care chemo across the number of chemo agents. And then by the end of middle to the end of next year as well, we'll have CR001 combined with ADCs through our cooling partnership. And so that first ADC is going to be SAC-TMT. So we'll have the first bi-specific globally combined with SAC-TMT, and we'll see that data sometime next year as well. The second program is CR002, which is our PD-L1 topo ADC. We'll have an ID filed in that program mid-year this year, we'll be in the clinic this year, and so that program will start with data coming second half of 2027. And then CR003, which is our IB6 topo ADC that we license through our partnership with Colune, that is in the clinic in China through Colune, and that data and monotherapy data will be coming out in Q1 2027 as well. So there's quite a bit of data coming. There's additional combination therapies that will be working through our project with Colune and CR001 as well. And all of that data starts to come in Q127. So as you can tell, it's been a very busy year. There's a lot to keep track of, but we are truly driving data-driven decisions across our matrix portfolio.

Fantastic. And before we dive into 001, can you remind us of the current runway and what do you – and what does it include and not include?

Yeah, so all the milestones I just talked about started in Q127 through 01, 01-combo with standard care chemo, 01-combo with Colune ABCs, 02, 03, all of that data is in our current runway. Our current runway goes into 2028, and so we're well positioned there from the capital strategy.

Okay, got it. And also, what is that longer-term BDE sort of opportunity thinking here, either with Coloon or with other players in the ADC?

Yeah, so we really value our partnership with Coloon. It provides us to really generate data quickly in a meaningful way across their very robust ADC skills and the ADC global leader with the SAC TMT being at the forefront of that. So I think that it shows our creativity. You know, they were looking for a next-gen I.O. play, backbone therapy, and I.O., their CMO previously did Acaso and developed Avanesimab, and they chose us amongst all the biceps that we've seen in China, and so it was a very good marriage between our two companies. So 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 those three buckets of data to really validate that we have a best-in-class partner of choice by specific with CR001. And 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. And then also we'll continue to be creative thinking about other modalities, whether it's ADC, small molecule, et cetera, to combine with CR001 through partnerships as well. So we have lots of irons in the fire on the BD side. And you can imagine with the data out there from ASCO at Harmony 6 and what we're seeing in the bi-specific space and the way we've intentionally designed CR001, we have a lot of interest in what we're doing.

Fantastic. Okay, let's go into 001. So it's a very timely asset at this point. What is that overall vision for this asset that you think about a very crowded PD-1, PD-L1, VEGF by specific category? Is the goal to develop 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 that. I think our vision for CR001, right, is part of our broader vision with our CR001 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-27, as I mentioned, will let anybody come in and look at CR001 across monotherapy and lung, which is where all the data that'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? And do you have enough efficacy to truly be a backbone therapy? This is like building a Rituxan or building a Keytruda, right? And so the interesting thing here is that this is not like a very niche, you know, there's one market we're going after. This is replacing 40-plus labeled indications, $50 billion plus revenue from the current PD-1 class, plus the ADC revenue and VEGF revenue on top of that. And you're thinking about really a $100 billion market turnover. And so 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. And so that's another massive market for colorectal, where now you're thinking about, okay, so I'm going to build a layer, a base layer of foundation of revenue with my CR01 program, whether that's monotherapy, combination of standard care chemo, or combination with ADCs or other payloads that could then really drive the market. And 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 Kloon deal. And so there's lots of ways for us to win. But I think getting a base revenue, you say $1 to $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. And so I think that's overall the strategy that we're thinking about. I see. Got it.

And how do you believe the data that we saw from your competitor, Summits Ivo and Harmony 2, against Pembro, how do you think that provides that validation for 001 monotherapy and SCLC and other tumors? And also, where do you think 001 can do better?

Yeah, so I'm going to let Ellie answer that question, but I'll just start by saying, look, we think that this Harmony 6 data was landmark data. You know, it achieved what we've been trying to see with replacing the first-generation class of PD-1s for 15-plus years. I'd also say just overlooked often here is the safety piece of this. And I think that's where I've been asking Mavis data has been very, very strong. It allows for that backbone play, right? And so I think that's something that people probably just are overlooking a little bit, but it has a ton of value.

So your question was Harmony 2. Am I correct? So that probably was a landmark data that in non-small cell lung cancer where Keytruda became the biggest winner and then became the backbone therapy. Ibanez was able to reduce the risk of progression by 50%. So that's where actually we got the conviction that this is the right construct of the molecule, and we wanted to build the compound, the CR-001, to have the key features of Ibanez map. We thought that that data was meaningful in multiple ways. And then the first thing is reducing the risk of progression by 50 percent. But the second part is the safety profile, where there's a VEGF element to it, but we did not see a number of high-grade VEGF-related adverse events that are similar to Abastin. It was much less, and then the tolerability was there. And then another piece that was very encouraging was that regardless of a PD-L1 status, PD-L1 high patients and then PD-L1 low patients. There was a distribution of equal degree of benefit, whereas Keytruda, as we know, works so much better in PD-L1 high patients. So that gives us a chance to now think about how we can replace Keytruda in multiple indications as a better next-generation immunotherapy backbone. And as Josh mentioned, that also is possible because of the safety profile of Ibanez meth that showed immune-mediated adverse events perspective similar to Kichuda, but VEGF-mediated toxicity perspective a lot more tolerable than the vaccine.

Got it. And what do you think you can do better? What do you think O1 can do better?

So O1 can do better, and we've been saying this from the very beginning, that we are differentiating based on our clinical development strategy. But 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. And then at CFB, part of it, we implemented the proprietary engineering of amino acid chain to improve the stability. So Ibanez-MED is currently being manufactured and sold at 10 micromil, and we were able to push the initial concentration up to 150 micromil, so 15 times higher of stability. That could give us a lot of benefit with the bio side, as well as potentially looking into life cycle management with the sub-Q. And how we designed this compound of matching the key features of IVANetMAP, we were able to demonstrate that with the preclinical data in between in vivo data. And then now with our phase one trial, if we show similar and comparable safety tolerability, PK, BAMAC dynamics, and then the efficacy data, which the cleanest way to do that will be, to Josh's point, frontline non-small cell lung cancer data. We know Ibanez met the response rate of somewhere around 50% to 70%. So once we show that data, which will be released in Q1-2027, we will then have checked 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 3 trials to have that confidence because they haven't gotten to that point. Whereas Ibanez meth is the only compound that has multiple phase 3 trials for the PFS and OS benefits. And then the second part of our strategy comes with the clinical development part 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. And then our pipeline has ADCs, and we have also a really good relationship with Cologne. We're combining with the multiple ADCs that they have. So we're generating the data as a monotherapy in combination with the standard of chemo, also with multiple ADCs. and we're also looking for any other partners that have a good mechanism of action and clinical activity to really test the 001 in multiple different tumor types.

Okay, fantastic. So you guys have that, for 001, you guys have that Phase 1 to Ascend trial coming in the first quarter of 2027. And in that trial, there's three parts to it. There's that dose escalation, the backfill, and then the dose optimization. Can you go over, like, what's the significance of that trial design, and why do you guys do it that way? What's the backfill? What's the importance of the backfill portion of it? And what do you hope to learn from this trial relative to some of the IBO?

Yeah, I would just say, look, I covered the three buckets of data we're going to be generating from that study. It's a great study design. It leverages all of LA's background and experience developing to SARO and working on Keytruda. and really it allows us to combine, you know, data across standard care chemo combos, multiple chemo agents, ADCs through this, through a partnership of Colum, which is not part of the ASCEND study, but also would generate that data, but also the monotherapy data through the backfill cohorts. And it really does leverage the different cohorts to generate all of that data. And I think it just positions us to be in a really strong position as we head to mid-27 and really answer a lot of the questions that, you know, go to your previous question. And we're not trying to differentiate and be better than Ivinestimab. 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 LA's articulated, but also Kulin will be degenerating the data in China. So we'll have both sorts of data as a company. And then I think the real key with this SENS study is it puts us in a position to make our choices to where we go to build that foundational bucket of revenue and then where do we go put our best in class bets down, right? And I think we're in a very unique position to win because of our dual strategy between the ADC portfolio and owning O-1, the backbone therapy. The question for many other people in the oncology space is going to be, what is my play for a buy specific? How am I going to win with my ADC portfolio without being able to combine with the next-gen by specific standard of care here. So 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 combinations, the exciting combination therapies, is that can you talk about what's that forward path looking like after the Phase 1-2 data? Assuming this is possible, are you guys going to go straight into a phase three? Is it going to give you enough conviction to do that? And also, besides NSCLC, is there any other occasion that you would do that for?

Yeah, I mean, Ellen, this goes to your last question around what the value of the backfill and expansion codes are, but maybe Ellen, you can talk about what we'll do with that data and where we're going to go.

Yeah, so a SEND trial was specifically designed to answer a couple of key questions. First one is what is the recommended phase two dose of CR001 and also generating comprehensive data to really answer the question of how the clinical profile of CR001 looks like as monotherapy and in combination with the various standard of care therapy so that we can choose the indication for registration-enabling trials. So dose escalation and backfill will answer the question of how, as a monotherapy, how the safety and efficacy look like. And then in most of the indications currently, PD-1 plus chemotherapy is used as a center of care in frontline. And so our expansion cohorts will answer that part of the question. And then the dose optimization is to answer the recommended phase two-dose part, according to FDA's project optimist. 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.

Yeah, and just as a reminder, we've said it multiple times that, you know, kind of the areas that we're focused on is GI, thoracic, and reproductive. So 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. So in terms of the combination, we talked about the two different ADCs, the chemotherapies, what other combinations are you guys exploring beyond these three? What's that vision for these combinations, and how do you land on these three to begin?

So the combinations that we are exploring currently include CR001 and then the ADCs that we have, and then Kulun has 10 plus ADCs in their clinical pipeline. And so Cologne will generate their own data in combination with the various ADCs and we'll have access to that data. And then while we are generating our own combination data with our PD-L1 ADC, O2, and InnoGreen Beta 6 ADC, which is CR003, then that will help us choose the indications and how we want to execute the next registration trials. And these ADCs can be developed as a monotherapy as well as in combination with CR001. And as Josh mentioned, we are also looking at various opportunities to work with companies that have a promising asset. And regardless of mechanism action, that can be small molecules, radiopharmaceuticals, or any other large molecules that are out there. And the reason that we can do that is because PD-1 VEGF is a class, and especially Ibanez math, and 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 that. 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 1-2 study to really validate CR001 as a backbone therapy and best-in-class by specific. And 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 Colune deal. And I think people don't appreciate yet how much value and data we can generate through that partnership across combining CR001 across all of those ABCs. That is where the puck is moving. And so not only do we have a chance to build on a revenue base, I said earlier $1 to $5 billion, that could be $5, $10, $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? Then you start thinking about and imagining where you can get to in the combination strategy and then through a partnership like we have with Colune, it really comes down to data generation. The faster we can generate that data, right, the more we have confidence in where we want to go and can be, you know, winning best in class. So, you know, you said non-small seller 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, I think we think that, you know, winning with the best in class ADC combo well, it's something that we can do, and we can potentially be best in class in that market, let alone all the other opportunities behind lung. Lung's a big one, but colorectal, if diastasis work in colorectal, also a very big market. So that's how we're thinking about it. But for us, it comes down to generating the data quickly and making data-driven decisions. I see, got it.

Okay, and you guys have the chemo combination data coming out in mid-2027. And then at ASCO, we saw the, I think we talked about the phase three, Harmony 6, where they show a significant OS benefit. And what do you think about the bar now with Harmony 6 data out there for your combination in that 1L and a CLC?

So the bar for non-small cell lung cancer? So we thought that that data was really landmark data, practice-changing data, where this is the first time PD-1-VEGF as a class has shown OS benefits 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 multiple standard-of-care options and becoming a backbone. So we thought that that data was great, and finally answering some of the key questions of how PD-1-DGFS of CLEP can provide better PFS benefits and OS benefits. And this gives us now a chance to look at how the study should be designed, and we looked at the Kepler-Meyer curves where the curves are separating, and then the subgroup analysis and how the patients benefited depending on different stratifications. 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. And 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 Ivan SNS, so we can utilize all these things.

Yeah, I think it's worth reminding people that outside of China, there's no approvals for buy specifics to date, right? And so the door there is still wide open. I do think that there's going to be lessons learned from, you know, those that have come first on state 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 and long is a massive market opportunity from a revenue generation perspective. And the good news here is that's not the only indication. We have 40-plus where we can go be first in class. And so it just highlights how big the market opportunity is. And so I think that's really important. And I also think that from our perspective, until there's an approval, it really is a wide-open space. Okay. Makes sense.

So also at ASCO, I think the discussion was a very lively discussion. from the discussion, pointed out multiple caveats about the translatability of that patient population to the global population, lower efficacy in the elderly patients. And I think the other thing that they pointed out, I think year after year, is that what is the point of having a five-specific when you have a VEGF that's already available and is about similar, and then you also have PD-1 that's going to, the pattern's going to expire. So you always have that combination therapy at that place. So what's the point of doing that, having a biospecific? Maybe I'll pass it on to you guys to get your thoughts on what the discussion said about these points.

Yeah, I think, Ellie, you did a nice job talking about the three points that was brought up by the discussion and also maybe just touch on the reason why biospecifics are working where PD-1 and VEGF historically given severally is not.

Yeah, yeah. Thank you for giving us opportunity to talk about these points. I think Disgusten 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. So regarding the translatability of Chinese data to global data, we actually already have that data, that evidence coming from Harmony A study done in China versus Harmony study that was done in global settings. And Summit did a great job of showing the efficacy and safety profile in Harmony's study between Chinese patients and the Western patients, and they were comparable. So 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. And so we already have that data out there to answer that question. The second question about age, the older patients versus the younger patients. So this is the only study from the IVAN-SMAP trials so far that showed this trend that older patients didn't get as much of a benefit as younger patients. whereas Harmony A and Harmony 2 studies show that both younger and older patients have benefited from treatment. So it's not about PD-1 beta-based class or ibonasmap issue. It was specifically something that we saw from Harmony 6 study, and some it provided some information about what might have led to that, the imbalance of the two key risk factors that were seen in the older patient group that included the tumor size, the patients with the larger tumor size, and patients with the brain metastasis, the tumor that went to the brain, there were a higher proportion of those patients represented in the ibonizumab arm compared to tisolezumab arm. And so it's good that we are learning about this, and now we can stratify based on those risk factors to make sure that that doesn't become an issue for the next trials. So regarding the third question about we have a PD-1 and we have VEGF, why do we need a bispecific? And so that's the question that I think we have successfully answered with many studies by now. Now, we have an empowered study where Genentech-Bosch did with their artizolizumab plus bebasizumab in non-small cell lung cancer. That trial did not show superior PFS or OS compared to artizolizumab. And then Keytruda, as a monotherapy, could not work in EGFR-mutated patients, and Avastin also could not get that efficacy shown, whereas we saw what Ibonosimab was able to do in that EGFR-mutated patients. And colorectal is another example where Avastin is currently used in combination with chemotherapy. DTUDA did multiple trials to see if their drug can work in microsatellite-stable NSS cholera locations, which is like 97% of the population. None of those trials worked. So we have now data showing Ibonasmab as well as other PD-1 measures show standard of care chemo show response rate of 40% to 50%. Ibonasmap data showed a response rate of 70%. So these are some examples of how, as a PD-1 VEGF, it's not PD-1 plus VEGF, the way the built compound and how it works in the tumor microenvironment. It's all different. And then the last piece, which is also as important as efficacy, is safety. Avastin could not be approved or developed in squamous cell non-small cell lung cancer patients where Harmony 6 showed the positive data because of the bleeding issue. It created a lot of patients developing high-grade hemostasis, and due to that death risk, they had to stop the development. Whereas we saw that Harmony 6, that risk was relatively minimal, and then physicians thought that if this drug was approved today, they would definitely use it in the squamous patients. So in efficacy and safety perspective, I think there's a lot of data already validating that this is a different class of drugs than just giving PD-1 and VEGF-2 separate.

I see, okay. We have a couple more minutes left. I want to go into the ADC combination. So you guys have these two ADCs that you guys are developing in-house, the OO2 and then the OO3. along with 001. When you think about the structure of both of these ADCs, how do you think they lend well with 001, and where do you think are the greatest opportunities for each of these combinations?

Yeah, I mean, I think from our perspective is, you know, we worked with Paragon to develop O2 in-house, right? And also thinking about our criteria for targets for our shopping list for ADCs to bring in and thinking about IB6 being the top of that list. It really is looking at how we build that matrix portfolio across where we see OO1 opportunities combined with OO2 and OO3 and other modalities or other ADCs, as Ellie's mentioned. And so I think our view on that was to design best-in-class across the antibody linker and payload. And so we think we've optimized those three components for indications of what we're interested in. and there's lots of expression data out there where you can see either O2 or O3 being very efficacious and effective, but also thinking about how that ties back into the three TIs I talked about earlier, thoracic, GI, and reproductive.

I see, okay. And I also want to touch a little bit on the FAC-TMT. I think we talked a little bit about it before this session. What are your key takeaways there from that FAC-TMT data that was shared at ASCO that shows the PFS benefits and OR when you combine it with PAMBRO. Is that a good benchmark for your D-O-O-1 and some of the ADCs?

Maybe I'll just start by saying from a Colunic perspective, obviously a world-class ADC company. And the platform which SAC TMT was built on is the same platform we have with O-O-3. So there is some benefit there from that perspective, and why we're so excited to see CRZ1 combined with the broader portfolio of ADCs that Colun has. But in regards to the question, maybe, Elia, you could talk a little more about that.

So that was the first data set of ADC being combined with the IO agent in frontline non-small cell lung cancer. In that aspect, I think it's a really important study. And the benefit ratio of 3, which is really impressive, cutting the risk of disease progression more than 65%. It's 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. And from our perspective, why it was also important is because we have a topo payload ADC, in our pipeline, and this is a good study that demonstrated that TOPPO payload ADCs can be successfully combined with an IO agent. It was early, but we also saw robust OS trend showing that the benefit in the population as well. And overall, I think it is going into the direction of how we built the company. that, okay, now we are seeing that IO agent, Keytruda, being successfully combined with ADC. And then we are seeing the Harmony 6 data showing the PD-1 VEGES being combined with chemotherapy agent together in both the Informed-Line non-small cell lung cancer. What will be the next step? Naturally, it will be a PD-1 VEGES and combination with ADC and see if we can show even better efficacy and then tolerability compared to these two trials. So overall, we are very happy with the data that was presented at ASCO, and it really validates our strategy.

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. And I'll just turn it to Joshua for any final remarks.

Oh, 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. So thanks so much. Thank you.