Conference Transcript - CBIO 2026-09-14

Bob Klingenberger, Analyst — Morgan Stanley

Well, great. Good evening. My name is Bob Klingenberger. I'm an executive director with Morgan Stanley. Thrilled to be here with the Crescent team. For any information regarding research disclaimers, please go to www.morganstanley.com. And if any questions, feel free to ask your Morgan Stanley representative. And thrilled, like I said, to be joined by the Crescent team. and I'll turn it maybe to Josh Brum to give a brief kind of introduction about the company and what you all have upcoming, and then we'll dive into some questions.

Joshua Brumm, CEO

Great, and thank you for inviting us, Bob. It's great to be here. Our own disclaimers, we have to start with a forward-looking statement, so if you have any questions on that, please see our SEC filings. Again, great to be here. We've got a lot of exciting things coming up for Crescent in the second half of this year, We're really heading into a wealth of data coming, starting in Q127. For those of you who may not know, we started this company with the view that synergistic combinations and oncology is the wave of the future. That's where the space is moving. We have a two-pronged approach to deliver on that thesis. First is we have a PD-1-VF bispecific CR001. That's clinical stage molecules in development now. And we're very excited about that being a potential next backbone for iotherapy and oncology. And then the other sleeve of our business in that strategy is we have built our own portfolio of ADCs. And so the first one we've in-licensed from Column and a partnership that Jonathan can talk about here in a little bit called CR003. It's an integrated beta 6 topo ADC. And then we've also had CR002, which is a PDL1 topo ADC, which will be in the clinic relatively soon. So by the end of this year, we'll have three programs in the clinical stage. and we're driving towards significant data from the CR001 program in Q1 2027, which we can talk about here in a little bit, as well as data from our partner, Kloon, with CR003 coming in Q1 27.

Bob Klingenberger, Analyst — Morgan Stanley

Well, you know, and Josh, I think it's really helpful to give kind of an overview, but, you know, maybe just to kind of dive in a little bit on 001, you know, there's been a lot of interest in the PD-1 VEGFs class, as you well noted, and, you know, kind of the evolution of external data. You know, could you just talk about, you know, maybe what you all have been encouraged by in terms of recent data sets kind of from some of the other folks in the class, and then, you know, just a little bit around 001's kind of differentiation from your perspective?

Joshua Brumm, CEO

Yeah, I mean, I think really to answer that question properly, you should just think about, again, the company was founded around specifically how we designed CR001, our bispecific, to replicate the cooperative pharmacology of Ivanesimab, given some of the data that they had shown at the time in October 2024. And since that time, we've had, I think, with today's OS readout in Harmony 2, four phase three studies that I've read out successfully across multiple indications now, even outside along with the BTC KISO data that came out a couple weeks ago. And so it really has, I think, cemented that this is a new class of drugs, that it has a real impact and clinical benefit for patients' lives. And I think we will leverage the way we designed our molecule to rapidly advance our clinical development strategy.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah. And, you know, a big debate in the class has been around geographic differences, maybe in some of the data sets. Could you maybe just talk a little bit about how you're thinking about kind of your existing – the existing data sets and maybe more specifically how that's, you know, informed a little bit of your initial development plans and how it might kind of going forward?

Joshua Brumm, CEO

Yeah, maybe what I'd like to do is maybe ask Ellie and Marcemo to talk a little bit about what that's out there, what's been generated geographically, and how we can learn from and have some advantages in the way we're starting our studies for CR001 within the context as well.

Ellie Im

Yeah, I think that's a really excellent question because the clinical development of most of all PD-1 VGF inhibitors until we started global clinical development of CR001 earlier this year. It all came from China, right? So even IVANESMAP phase three studies have shown really successful data, superior OS and PFS compared to PD-1-containing regimens. But still people ask about would Chinese data translate to global population. So there are two sets of key data sets that I would like to point to. The first one is a more direct one. So HARMONY study, which is Ivanasmap's study in EGFR-mutated non-small cell lung cancer patients. They've enrolled Chinese patients as well as Western population, North American and European population. And once they have matched the follow-up period of the Chinese patients and Western population, we saw that the safety profile of PFS and OS benefit as well, I'm sorry, efficacy profile of PFS and OS, as well as the safety profile between the two populations looked pretty comparable. So that's a direct data of IVAN-SMAP, PD-1-DGF. And also looking at the available phase three studies, including immuno-oncology studies, Now we have a lot of data showing that PFS and OS data between Asian population or Chinese or non-Chinese population that are pretty matching well across multiple indications. So we have these two sets of data showing that likelihood of promising data we are seeing from Chinese population translating into the global population is pretty high. But having said that, how we are going to make the transition of a clinical development from what originally Ibanez has studied, targeting for NMPA, and then now they have to work with the FDA, EMA, and then other health authority agencies, that execution can be challenging. And then we are seeing some of those challenges from summit's execution perspective. And then that applies to other agents as well, where their clinical development started in China. Whereas in our case, our first in human trial of CR001, the ASCEND study, we started in United States, Europe, and South Korea. So the data that we are generating will answer that question head on. And, of course, we also have our partner, Kulun, generating safety and efficacy data of monotherapy as well as combination data in China as well. So we are carefully studying what competitors are doing and how they executed and how that affected the outcome of the studies. And while we are generating the global data of CR001, We'll take all those learning points and then further optimize our development strategy and then execution as well.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah, and I think you sort of closed with the point on the Ascend study, which is ongoing, and I know the initial data set is expected in the first quarter. Maybe just give us, to your point, it's going to answer a lot of these questions, But maybe just, you know, in terms of kind of what you can say about, you know, what you expect to disclose as part of that data set and, you know, maybe just give us a sense of where you all are focused, right, as you both compare to competitor data but also just to inform kind of the ongoing development pathway, frankly.

Joshua Brumm, CEO

Yeah, we have three what we call buckets of data coming in 2027. I think, to understand those three buckets, maybe I'll ask Jonathan McNeil, our president and COO, to talk a little bit about the Colun partnership that we have. And then Ali can walk through those three different buckets and how we think about that data coming in 2027.

Jonathan McNeill, COO

Sure, yeah. So the Colun partnership came together because they share our vision of synergistic combinations being the next wave of oncology therapies for many solid tumors. And as many are well aware, Colun is a leading developer of ADCs globally. Their most advanced asset, SAC-DMT, subject of a multibillion-dollar collaboration with Merck, is currently in 17 registrational trials globally. But as Glenn thought about the future, they were looking for a PD-1 VEGF to pair with their entire ADC portfolio, and they knew all the assets in China. But their chief medical officer is previously at Akiso and was looking for a molecule that could replicate the cooperative pharmacology and safety profile of Ivanesimab. And we at Crescent were looking for ADCs to add to our own portfolio, So there was an alignment of vision there, which led to our partnership. And it's structured as follows, which is that we enlicensed the Ingram Beta 6 Topo ADC, which we call CR003, Kloon calls SKB105, and we had rights to develop that both as monotherapy and in combination with CR001 everywhere outside of China. Kloon has the rights to develop our PD-1 VEGF, CR001, in China, both as monotherapy and in combination with their full portfolio of ADCs. we get access to the data that Colun generates in any of those combo studies. So you can imagine now that Colun has initiated their first of multiple ADC combo studies with SAC-TMT and our PD-1-Vegg F-CRO-01, the value this provides to both of us as we learn the potential of CRO-01 both as monotherapy and as a next-gen IO backbone with multiple ADC combinations. And so, Ellie, maybe you can touch on the data we're going to have with the SEND and the Colun partnership as well.

Ellie Im

Yeah, so we have designed the compound intentionally to match the functionality of ibanesimab, and we try to match the structural aspect as well as the PK aspect of it. And we have demonstrated it in preclinical setting and published that data at SITC last year. And so now we are going into clinical development. We will answer the questions on how the clinical profile of CR001 then looks like in comparison to ibanesimab as well as other leading PD-1-DGF inhibitors. So the global phase 1 to trial of ASCEND, which is the first in human study, we have eight different tumor types, non-small cell lung, and four indications in GI, including colorectal, gastric, hepatocellular carcinoma, biliary tract cancer, and three indications under Gynonc, ovarian, cervical, and endometrial. So with these eight tumor types, we studied dose escalation in February of this year. And while we are doing dose escalation, as we are clearing each dose level, we then can open tumor type-specific bacterial cohorts at each dose level. So for example, after clearing 20-week-per-kick dose level, we can decide to open non-small cell lung cancer backfill, colorectal backfill, gastric backfill, or biliary backfill. And this can happen at each dose level while we are doing dose escalation. So you can imagine that this is a very efficient way of generating PK data and pharmacodynamics data, namely receptor occupancy, VEGF neutralization, safety data at each dose level, and also talking about the tumor types, and then efficacy data. In terms of efficacy data up to date, PD-1 VEGF by specific as a monotherapy in post-PD-1 setting has been modest benefit, I would say. It's difficult to interpret depending on how much of time between PD-1 treatment and then what was their first response to PD-1 inhibitors. So we are including first-line non-small cell lung cancer patient cohort as part of this spec cell, and that will be the patient population that will clearly answer the anti-tumor activity of CR001 because we know as a monotherapy in PD-1 VEGF inhibitors that we've seen so far, response rates have been somewhere around 50% to 70%. So if we can show that we match that, that's the clearest way for us to answer that question. And so the initial data set that we will release in Q1 2027 will have a triple-digit number of patients in totality coming from dose escalation and backfill, really demonstrating the monotherapy safety, PK, pharmacodynamics, and efficacy data are comparable to Ibonasmab or any other leading PD-1-DGF inhibitors that are out there. And then the second bucket of data, which is we are looking at middle of 2027, that will come from expansion cohorts of the study. And in that part, we are combining CR001 with the standard of care chemotherapies of multiple different regimens and tumor types that we are studying in the study. And so that study with the efficacy and the safety data then will clearly answer the questions of more of as a potential to replace PD-1 inhibitors in these indications and being able to combine with the chemotherapy agents. Again, another way to clearly demonstrate safety as well as efficacy profile of CR001. And then we have dose optimization cohorts that's included in the ASCEND study as well. So once we have monotherapy safety efficacy profile and then in combination with standard chemotherapy and dose optimization speaking to recommended phase two dose, then this comprehensive data set will allow us to choose the indications for registration studies in the global setting in an efficient way. And the third bucket of data is coming from ADC combination. So initial data set, because Kulun, and this is a great benefit that we are getting from Kulun Partnership, they have many clinical stage assets, including the assets that have approval, such as a SEC-TMT, and then have recommended phase two dose. So, as Colun is combining CR001 with their ADCs, that will be the first wave of ADC combination data that we will see, starting from mid-2027. And so, that data will answer a couple of key questions. As a next wave of innovation, novel-novel combination, how CR001 plays the role of next-generation IO backbone? and that data will then help us inform our global development strategy of combination with our ADCs or other ADCs that are out there as well as molecules with a different MOA as well.

Joshua Brumm, CEO

So clearly a lot of data coming across these three buckets for O1 and I would just walk through all of that data. I think the objective for us is to generate meaningful clinical data in the O1 program by the middle of next year. and then rapidly turn that into potential Phase III study starts. In addition to that data that I only went through, we have the O3 data coming with the CR003, IV6, Topo, ADC, that Colun's running, myotherapy study in China. That data will also be coming to Q1-2027. And then early next year, we'll see them start a 001003 combination study. And then our own, our second ADC program, CR002, the PD-L1 Topo ADC, will be in the clinic this year, and that will have a data readout by end of 2027 as well. So we have data coming across all the entire portfolio, both from mild therapy, combination of standard care chemo, and combination with ADCs across a very robust portfolio.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah, it's going to be a busy 2027. I guess just to maybe go back, Ellie, as you were describing the buckets, right, as you think about maybe kind of the first two buckets of data, and I think you really nicely described the eight different tumor types, I think I counted correctly. You know, how do you think about, and appreciating, right, you sort of described it as triple-digit number, initial data set, patients obviously divided into number of tumors. It's going to be smaller. How do you think about kind of what you might be looking for and how much detail you're going to get sort of on a bi-tumor type basis to be able to kind of make some of those decisions? Josh, you talked about in terms of the kind of the pivotal or registrational study starts.

Ellie Im

So in each indication that we are looking into potential registration enabling studies from monotherapy data coming from dose escalation and backfill as well as expansion cohorts where we are combining with standard of care chemo combinations, we will make sure that there's comprehensive data being generated from the safety and efficacy perspective so that the data informs us which indications that we should choose for probability of success perspective. But also, we can utilize the competitive intelligence, especially IVANESMAP data. Because of the similarity of the compound, we can look at their data and see how we compare and then how much we can really delve into the population that they studied and then help us navigate into the indications. But also what's encouraging is that not just ibanesimab, other PD-1-DGF inhibitors that are producing data in multiple indications, now we are seeing pretty much comparable efficacy data in the early phase 1-2 study setting. So those data and then how the order of a potential registration studies that are being launched in the global setting, we are carefully looking at those as well.

Joshua Brumm, CEO

Maybe I'll just be specific about this, your question on number of patients. As it gets smaller, as you go to cohorts, what we said for the monotherapy non-small cell data would be a code of 12 patients, so a robust cohort at a dose that will be clinically meaningful. And that's where, for the Q1, we're looking at ORR is the readout for efficacy there. When we get to the standard care chemo combo cohorts, and we'll announce what those are later this year. There'll be multiple cohorts there. There'll be a minimum of 20 patients, so 20 to 30 patients per cohort, right? So you're going to get a robust read across multiple different indications and lines of therapy with standard care chemo combos and different chemo agents in combination. So you'll get to see a really good detailed view of safety and tolerability across multiple chemo agents as well as indications, lines of therapy. And that's where you start to get to hundreds of patients of data.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah. No, I think that's really helpful to just kind of have the detail. As you, John, and you sort of touched on, right, the vision, and Josh, you as well, right, the vision of sort of combinations, right, and utilizing 001 as sort of this backbone therapy, maybe just, you know, taking a step back, you know, I think you well described all the data that will be coming, but just a little bit around both for, you know, kind of the two main ADCs that we're going to see data from, just a little bit of what, you know, the kind of the mechanistic rationale, some of the biologic rationale for exploring those combinations. Because, I mean, there is some data to date, you know, that I think from external parties that does kind of help back that up.

Ellie Im

So speaking of our PD-L1 ADC as well as inner green beta-6 ADCs, so we chose those targets because the tumors that are expressing PD-L1 and inner green beta-6, the list of those tumors are fitting in a quite comprehensive way to the indications that we just described in the ASCEND study. So non-smobile cell lung cancer, GI indications, GYNNC indications, and one additional indication that we will also study with our ADCs is head and neck cancer. For us to build this matrix portfolio, we really like those targets. And there are a couple of assets for InnoGrim-Belastic ADC as well as PDR1 ADC that the clinical studies are ongoing. and we looked at the limitations, potential limitations to those assets and then try to optimize for safety and efficacy. So, for example, the PD-L1 ADC, we have used the antibody that is optimized for internalization instead of a binding affinity or signal blockade of PD-L1 and then used the FC-null antibody to potentially address the risk of pneumonitis and we are using stable and also clinically validated linker to reduce the risk of systemic toxicity. And this is a potent topo payload with the bystander effect. So all these optimizations that we've done should pay out for differentiated clinical safety and efficacy profile.

Jonathan McNeill, COO

And we've started to see that this has played out in some external data as well. For example, with SAC-TMT and PEMBRO, there was some very exciting and compelling data at ASCO this year. And given how good that data looked, then the question then becomes a natural question is, what would SAC-TMT and a PD-1 VEGF look like, given what we've seen relative to a PD-1 VEGF versus a PD-1? So we're very excited to work with Colune to be the first to generate that type of data. And then at WorldLong just this week, BioNTech presented some interesting data with their own PD-1-VEGF with a B7H3 ADC with a topo payload as well. So there's starting to be emerging data in this field. Of course, there's nuance around the differences of the assets, but the opportunity to combine a next-gen ADC with a next-gen IO agent across multiple solid tumor types is one that we're very excited to pursue, in addition to our strategy pursuing standard care chemo combinations with OO1.

Ellie Im

And now we are seeing more promising data of ADCs that have potential to replace chemotherapies. One is B7H3 ADC in small cell, and then SEC-TMT in non-small cell lung. For example, in non-small cell lung, why we are excited about ADC plus PD-1-VEGF is hazard ratio of ADCs appear to be lower in non-squamous patients. It works better in non-squamous patients compared to squamous patients so far, whereas it's the opposite when we look at the hazard ratio of PD-1 VEGF. So it showed better hazard ratio for squamous versus non-squamous patients. So once we combine, we can overcome the limitations of ADC as well as PD-1 VEGF that could potentially work in both histology well And then as long as there's no overlapping safety concerns, I think the combination can have potential to be the best-in-class profile in multiple indications.

Bob Klingenberger, Analyst — Morgan Stanley

And I guess as you sort of talk about the whole portfolio and the three buckets of data, I mean, the sort of intention, right, at the end of kind of next year, right, is to have a path forward from a, you know, kind of a plan from a registrational perspective, I guess. How should we think about, you know, how much information you might have to be able to determine if it's combinations, which combinations it might be? Maybe just talk us through kind of when we might know more about that.

Joshua Brumm, CEO

Yeah, so I think later this year we'll start to refine what next year looks like when we'll be making decisions on what indications we will turn into Phase III studies. We're going to have a wealth of data across all the data we just talked about to think about what decisions we will make and where we go. That's the first and foremost light that will guide our way. I think the other thing that we'll continue to monitor is the competitive landscape, right? And I think what you'll see is us drive very quickly from the kind of middle of next year on the readouts from the last of the data that we've promised to phase three study starts. And that's likely some mix of first-in-class opportunities as well as fast-follower opportunities. And that first foundational revenue piece where you're really starting to get the backbone of transitioning first-generation PD-1s to next-generation PD-1 bispecifics for the IO backbone, really that revenue is going to be foundational. And that will allow us then to transition from that revenue to phase three studies where we're looking at the goal of getting the combination therapies, where we're looking at O2 and O3 plus O1. And we're also actively looking very carefully at other opportunities to add in combination with O1. So we're very active on the BD side. I think we've done a very creative and unique deal thus far already with Colune for a biotech our stage. And I would say, you know, I'd expect more of those types of deals and collaborations to come. I think many people view this as a competitive space. I think it's a massive space that's just all about collaboration. And that's our view as a management team and how we think about, you know, leveraging the value of 001. And everyone's looking for that next generation IO backbone, and we're fortunate to own one in CR001. that we think by the middle of next year can be backed with data as a best-in-class partner of choice by specific.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah, and that, Josh, was actually kind of my next question just around, obviously, the Kloon partnership, super creative. I mean, Jonathan walked through kind of the structure, right? Both, you know, contributing assets from both sides, I guess. As you all think about kind of the BD landscape and the assets that you have today, I mean, just any additional kind of thinking around, those ongoing discussions?

Jonathan McNeill, COO

Yeah, I think there's a couple buckets of BD. The first is if there are late-stage or approved assets that we can combine with 001, that's an active area of dialogue that we'll have on a continuous basis, right? And as we generate more data with 001, those conversations become even more robust. So that's one bucket. And then in terms of a broader partnership, look, given that there's 40-plus indications that we could pursue, we fully intend to fund some ourselves, but is there an opportunity to do partnerships there? Yes, but they don't necessarily have to be strategic partnerships because we want to make sure that we generate sufficient clinical data to really maintain control and realize the full value of those. So there's other ways that we could expand the number of clinical trials that we could operate on. That could take the form of royalty deals and other things that you've seen in this space, and even Merck did a deal to fund their SAC-TNT registrational studies. So there's various avenues open to us with the goal of reaching as many patients as possible with innovative therapies.

Joshua Brumm, CEO

I think we've said this from the stage many, many times, and late last year, middle last year. But as a company, we are very much open for business and thinking about how to maximize the value of level one and really benefiting patients and driving towards where the space is going, which is synergistic combinations. And so those active discussions are ongoing.

Bob Klingenberger, Analyst — Morgan Stanley

And with, you know, some of your fundraising to date, I mean, maybe just kind of remind us a little bit. Obviously, we talked through all the data upcoming, but just kind of cash, runway, and, you know, kind of what amount of all that is, you know, kind of how far are you funded?

Joshua Brumm, CEO

So with the raise we completed in July, pro forma, we have about $305 million in cash. That gets us into the second half of 2028, so well past all of the data milestones that we just talked about today, which is, as we mentioned, a robust slew of data coming. And we're in a strong position to think about, you know, the first set of phase three studies that will run and the next stage of the company as we get past this initial phase one, two, ASCEND study, as well as all the data on top of the numbers that we will generate from the U.S., Europe, and South Korea.

Bob Klingenberger, Analyst — Morgan Stanley

Yeah. And I guess, you know, maybe just as we're sort of getting close to time here, you know, the company is, I think, as you well noted, still less than two years old, and I think you all have been public for still less than 18 months. A lot of progress in that time, I guess, as you sort of think about the next 18 months, next two years. You know, we talked through a lot of the data, but, you know, just in terms of kind of what you're, you know, most excited about, maybe, Josh, for you, just as you're thinking about the horizon.

Joshua Brumm, CEO

Yeah, first and foremost, super excited to continue to work with the team. You know, we worked together before a couple of different places. You know, we've been proven in our ability to stay the course and what we believed in. I think we saw a massive opportunity here to really usher in a next generation of iotherapy as backbone for oncology. I think that that was made by, you know, Peter and Fairmont early on. We just had continuous, you know, positive readouts and something that people have been trying to do for decades or, you know, trying to replace Keytruda, beat Keytruda in a phase-through study. We've seen that happen four times in this class of drugs. We love our asset. We love our assets across the portfolio. And I think the complexity of where you go, what studies you run, what phase threes you start, that makes this really, really fun. But staying the course and driving behind the conviction we have for the space and where it's going to go, I think, will prove valuable over time. And I think also just being a good partner and collaborative mentality that we have is also going to be a lot of fun, too, because you get to work with a lot of different companies, a lot of different management teams, and you get to spend more time together, which is always something we enjoy at Crescent.

Bob Klingenberger, Analyst — Morgan Stanley

Well, we appreciate you being here, and I think we'll leave it at that. Thank you very much.