That was my pleasure.
I think we're all.
Ready to go?
Doing.
All right. Well, great. Good evening. My name's 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/researchdisclaimers. If any questions, feel free to ask your Morgan Stanley representative. Thrilled, like I said, to be joined by the Crescent team. I'll turn it maybe to Josh Brumm, CEO, to give a brief kind of introduction about the company and what you all have upcoming, and then we'll dive into some questions.
Great, and thank you for inviting us, Bob. It's great to be here. Our own disclaimer, so we have to start with the forward-looking statements. 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, really heading into a wealth of data coming starting in Q1 2027. For those of you who may not know, we started this company with the view that synergistic combinations in oncology is the way 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/VEGF bispecific CR-001 that's clinical-stage molecule. It's in development now, and we're very excited about that being a potential next backbone for IO therapy and oncology.
Then, the other sleeve of our business and that strategy is we have built our own portfolio of ADCs. The first one that we've in-licensed from Kelun-Biotech and a partnership that Jonathan can talk about here in a little bit, called CR-003. It's an integrin beta-6 topo ADC. We also have CR-002, which is a PD-L1 topoisomerase ADC, which will be in the clinic relatively soon. By the end of this year, we'll have three programs in the clinical stage, and we're driving towards significant data from the CR-001 program in Q1 2027, which we can talk about here in a little bit, as well as data from our partner Kelun-Biotech with CR-003 coming in Q1 2027.
Great. Well, Josh, I think it's really helpful to give kind of an overview, but maybe just to kind of dive in a little bit on CR-001. There's been a lot of interest in the PD-1/VEGF class, as you well noted, and kind of the evolution of external data. Could you just talk about maybe what you all have been encouraged by in terms of recent data sets from some of the other folks in the class, and then just a little bit around CR-001's kind of differentiation from your perspective?
Yeah, I think, really, to answer that question properly, we should just think about, again, the company was founded around specifically how we designed CR-001, our bispecific to replicate the cooperative pharmacology of ivonescimab, given some of the data they had shown at the time in October 2024. Since that time, we've had, I think with today's OS readout in HARMONi-2, four phase III studies that have read out successfully across multiple indications now, even outside of lung with the BTC Akeso data that came out a couple weeks ago. 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. I think we will leverage the way we designed our molecule to rapidly advance our clinical development strategy.
Yeah. 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 the existing data sets, and maybe more specifically, how that's informed a little bit of your initial development plans and how it might kind of going forward?
Yeah. What I'll do is maybe ask Ellie, our CMO, to talk a little bit about what data'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 CR-001 within the context as well.
Yeah, I think that's a really excellent question because the clinical development of most of all PD-1/VEGF inhibitors until we started global clinical development of CR-001 earlier this year, it all came from China, right? Even ivonescimab phase III 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. There are two sets of key data set that I would like to point to. The first one is more direct one. HARMONi study, which is ivonescimab's study in EGFR mutated non-small cell lung cancer patients. They've enrolled Chinese patients as well as Western population, North American, European population.
Once they have matched the follow-up period of the Chinese patients in 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 population looked pretty comparable. That's a direct data of ivonescimab PD-1/VEGF. Also, looking at the available phase III 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. 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.
Having said that, how we are going to make the transition of a clinical development from what originally ivonescimab studied targeting for NMPA, and then now they have to work with the FDA, EMA, and other health authority agencies, t hat execution can be challenging, and then we are seeing some of those challenges from some of its execution perspective. Then that applies to other agents as well, where their clinical development studied in China. Whereas in our case, our first in-human trial of CR-001, the ASCEND study, we started in United States, Europe, and South Korea. The data that we are generating will answer that question head-on, and o f course, we also have our partner, Kelun-Biotech, generating safety and efficacy data of monotherapy as well as combination data in China as well.
We are carefully studying what competitors are doing, and how they executed and how that affected their outcome of the studies. While we are generating a global data of CR-001, we'll take all those learning points and further optimize our development strategy and execution as well.
Yeah. I think you sort of closed with the point on the ASCEND study, w hich is ongoing. 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, b ut maybe just in terms of what you can say about what you expect to disclose as part of that data set, and 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 the ongoing development pathway, frankly.
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 McNeill, our President and COO, talk a little bit about the Kelun-Biotech partnership that we have. And then, Ellie can walk through those three different buckets and how we think about that data coming in 2027.
Yeah. Sure, yeah. The Kelun-Biotech partnership came together because they share our vision of synergistic combinations being the next wave of oncology therapies for many solid tumors. As many are well aware, Kelun-Biotech is a leading developer of ADCs globally. Their most advanced asset, sac-TMT, subject of a multi-billion-dollar collaboration with Merck, is currently in 17 registrational trials globally. But as Kelun-Biotech 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 Akeso, and was looking for a molecule that could replicate the cooperative pharmacology and safety profile of ivonescimab. 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 in-licensed the integrin beta-6 topo ADC, which we call CR-003, Kelun-Biotech calls SKB105, and we had rights to develop that both as monotherapy and in combination with CR-001 everywhere outside of China. Kelun-Biotech has the rights to develop our PD-1/VEGF, CR-001, in China, both as monotherapy and in combination with their full portfolio of ADCs. We get access to the data that Kelun-Biotech generates in any of those combo studies. You can imagine now that Kelun-Biotech has initiated their first of multiple ADC combo studies with sac-TMT and our PD-1/VEGF, CR-001, the value this provides to both of us as we learn the potential of CR-001 both as monotherapy and as a next-gen IO backbone with multiple ADC combinations.
Ellie, maybe you can touch on the data we're going to have with ASCEND and the Kelun-Biotech partnership as well.
Yeah. We have designed the compound intentionally to match the functionality of ivonescimab, and we try to match the structural aspect as well as the PK aspect of it. We have demonstrated it in preclinical setting and published that data at SITC last year. So now, we are going into clinical development. We will answer the questions on how the clinical profile of CR-001 then looks like in comparison to ivonescimab, as well as other leading PD-1/VEGF inhibitors. The global phase I/II 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 g yn-onc, ovarian, cervical, and endometrial. With these eight tumor types, we started dose escalation in February of this year.
While we are doing dose escalation, as we are clearing each dose level, we then open tumor type specific backfill cohorts at each dose levels. For example, after clearing 20 mg/ kg dose level, we can decide to open non-small cell lung cancer backfill, colorectal backfill, gastric backfill, or biliary backfill. This can happen at each dose level while we are doing dose escalation. 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, right? In terms of efficacy data up to date, PD-1 bispecific as a monotherapy in post PD-1 setting has been modest benefit, I would say.
It is difficult to interpret depending on how much of time between PD-1 treatment and then what was their first response to PD-1 inhibitors. We are including first-line non-small cell lung cancer patient cohort as part of this backfill, and that will be the patient population that will clearly answer the anti-tumor activity of CR-001. Be cause we know as a monotherapy in PD-1 bispecific inhibitors that we have seen so far, response rates have been somewhere around 50%-70%. If we can show that we match that is the clearest way for us to answer that question.
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 ivonescimab or any other leading PD-1 bispecific inhibitors that are out there. The second bucket of data, which is we are looking at middle of 2027, that will come from expansion cohort of the study. In that part, we are combining CR-001 with the standard of care chemotherapies of multiple different regimens in tumor types that we are studying in the study. 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 CR-001. Then, we have dose optimization cohort that is included in the ASCEND study as well. Once we have monotherapy safety efficacy profile, then in combination with standard of care chemotherapy and dose optimization speaking to recommended phase II dose, then this comprehensive data set will allow us to choose the indications for registration studies in the global setting in an efficient way. The third bucket of data is coming from ADC combination. So, initial data set, because Kelun-Biotech, and this is a great benefit that we are getting from Kelun-Biotech partnership, they have many clinical stage assets, including the assets that have approval, such as sac-TMT, and then have recommended phase II dose.
As Kelun-Biotech is combining CR-001 with their ADCs, that will be the first wave of ADC combination data that we will see starting from mid-2027. That data will answer a couple of key questions as a next wave of innovation, novel combination, how CR-001 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.
Yeah. So, clearly, a lot of data coming across these three buckets for CR-001. Ellie just walked through all of that data, and I think the objective for us is to generate meaningful clinical data in the CR-001 program by middle of next year, and then rapidly turn that into potential phase III study starts. In addition to that data that Ellie went through, we have the CR-003 data coming with the CR-003, integrin beta-6 topo ADC that Kelun-Biotech is running monotherapy study in China. That data will also be coming in Q1 2027. Then, early next year, we will see them start a CR-001/CR-003 combination study. Then, our second ADC program, CR-002, 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.
We have data coming across all the entire portfolio, both for monotherapy, combination standard care chemo, and combination with ADCs across a very robust portfolio.
Yeah. It's going to be a busy 2027. I guess just to maybe go back, Ellie, as you were describing the buckets, as you think about maybe 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, h ow do you think about, and appreciating, like, you sort of described it as triple digit number, initial data set, patients obviously divided into number of tumors, it can be smaller, h ow do you think about kind of what you might be looking for and how much detail you're going to get on a by tumor type basis to be able to make some of those decisions, Josh, you talked about in terms of the pivotal or registrational study starts?
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 currently used standard of care chemo combinations, we will make sure that there's a 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.
Right.
But also, sorry, w e can utilize the competitive intelligence.
Good.
Yeah, especially ivonescimab 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 is encouraging is that not just ivonescimab, other PD-1 x VEGF inhibitors are producing data in multiple indications, n ow we are seeing pretty much comparable efficacy data in the early phase I/II 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.
Yeah. 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 cohort of 12 patients, so a robust cohort at a dose that will be clinically meaningful. 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 20-3 0 patients per cohort.
Yeah.
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.
Yeah. No, I think that's really helpful to just kind of have the detail. As you, Jonathan, and you sort of touched on, right, the vision, and Josh, you as well, right, the vision of sort of combinations, right? And utilizing CR-001 as sort of this backbone therapy. Maybe just taking a step back, I think you well described all the data that will be coming, but just a little bit around both for kind of the two main ADCs that we're going to see data from. Just a little bit of what the kind of mechanistic rationale, some of the biologic rationale for exploring those combinations, because there is some data to date, I think from external parties that does kind of help back that up.
Speaking of our PD-L1 ADC as well as integrin beta-6 ADCs, so we chose those targets because the tumors that are expressing PD-L1 and integrin beta-6, the list of those tumors are fitting quite comprehensive way to the indications that we just described in the ASCEND study. Non-small cell lung cancer, GI indications, gyn-onc 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 integrin beta-6 ADC, as well as the PD-L1 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.
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 use 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. All these optimization that we've done should pay out for differentiated clinical safety and efficacy profile.
Yeah, and we've started to see that this has played out in some external data as well. For example, with sac-TMT and pembrolizumab, there was some very exciting and compelling data at ASCO this year, and given how good that data looked, then the question then becomes the natural question is what would sac-TMT and a PD-1 x VEGF look like given what we've seen relative to a PD-1 x VEGF versus a PD-1? So, we're very excited to work with Kelun-Biotech to be the first to generate that type of data. And then at World Lung just this week, BioNTech presented some interesting data with their own PD-1 x VEGF with a B7-H3 ADC with a topo payload as well. 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 of pursuing standard of care chemo combinations with CR-001.
Yeah.
And now we are seeing more promising data of ADCs that have potential to replace chemotherapies, right? One is B7-H3 ADC in small cell and then sac-TMT in non-small cell lung. For example, in non-small cell lung, why we are excited about ADC plus PD-1 x 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 bispec. 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 a PD-1 x 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.
Yeah. And I guess as you talk about the whole portfolio and the three buckets of data, the intention at the end of next year is to have a path forward from a plan, from a registrational perspective. I guess how should we think about how much information you might have to be able to determine if it's combinations, which combinations that might be? Maybe just talk us through when we might know more about that.
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. And I think what you'll see is us drive very quickly from kind of middle of next year on the readouts from the last of the data that we promised to phase III 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 is 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 III studies, where we're looking at the goal of getting the combination therapies, where we're looking at CR-002 and CR-003 plus CR-001. And we're also actively looking very carefully at other opportunities to add in combination with CR-001. So, we're very active on the BD side. I think we've done a very creative and unique deal thus far already with Kelun-Biotech for a biotech R stage.
Yeah.
I would say 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 leveraging the value of CR-001. Everyone's looking for that next generation IO backbone, and we're fortunate to own one in CR-001 that we think by middle of next year could be backed with data as a best-in-class partner of choice bispecific.
Yeah. No, Josh, was actually going to be my next question just around obviously the Kelun-Biotech partnership, super creative. Jonathan walked through the structure, right, both contributing assets from both sides. I guess as you all think about the BD landscape and the assets that you have today, just any additional thinking around those ongoing discussions?
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 CR-001, that's an active area of dialogue that we'll have on a continuous basis. As we generate more data with CR-001, those conversations become even more robust. So that's one bucket. In terms of a broader partnership, look, given that there's 40+ indications that we could pursue, we fully intend to fund some ourselves. But is there an opportunity for 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. Even Merck did a deal to fund their sac-TMT registrational study. So, there's various avenues open to us with the goal of reaching as many patients as possible with innovative therapies.
Yeah.
We've said this from the stage many times in late last year or middle of last year, but as a company, we are very much open for business and thinking about how to maximize the value of CR-001 and really benefiting patients and driving towards where the space is going, which is synergistic combinations. Those active discussions are ongoing.
Yeah. With some of your fundraising to date, maybe just remind us a little bit. Obviously, we talked through all the data upcoming, but just cash runway and what amount of all that is. How far are you funded?
Sure. 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. We're in a strong position to think about the first set of phase III studies that we'll run and the next stage of the company as we get past this initial phase I/ II ASCEND study, as well as all the data Kelun-Biotech will have on top of the numbers that we will generate from the U.S., Europe, and South Korea.
Yeah. I guess maybe just as we're getting close to time here, 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 think about the next 18 months, next two years, we talked through a lot of the data, but just in terms of what you're most excited about, maybe Josh, for you, just as you're thinking about the horizons.
Yeah. I mean, look, first and foremost, super excited to continue to work with the team. We worked together before at a couple of different places. We have been proven in our ability to stay the course in what we believed in. I think we saw a massive opportunity here to really usher in a next generation of IO therapy as backbone for oncology. I think that that was made by Peter and Fairmount early on. We just had continuous positive readouts and something that people have been trying to do for decades are trying to replace KEYTRUDA, beat KEYTRUDA in a phase III study. We have seen that now 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 III's you start, that makes this really fun.
But staying the course and driving behind the conviction we have for this space and where it is 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.
Great. Well, we appreciate you being here, and I think we will leave it at that. Thank you very much.
Thank you for having us.
Thank you.