Kick it off here for the first fireside of the day. My name is Brad Cannino. Thank you for joining us at the Guggenheim Second Annual Healthcare Innovation Conference. Happy to do the fireside today with Crescent Biopharma. We've got Josh Brumm, CEO, Ellie Im, CMO, on the stage with me. Josh, maybe if you'd like to kick it off to just introduce the company and talk a little bit about how you're positioning your PD1 VEGF CR001 relative to the other biospecifics in the space.
Great. Thanks, Brad. Thanks to Guggenheim for inviting us today. It's great to be here. First, to start off with, we'll be making some forward-looking statements, so please refer to our SEC filings as appropriate. Look, I think when it comes to Crescent, we're really working hard to embark on our vision to build the world's next leading biotech and oncology company. We have two very distinct focus strategies to do that. It starts with our 001 asset, our PD1 VEGF bispecific, next generation IO replacing KEYTRUDA out there as a backbone therapy for us. That asset's going to be in the clinic and dosing patients in early Q1 of next year. There is obviously a lot of excitement around Avanesta MAB. We've intentionally designed that molecule to replicate the cooperative pharmacology.
We've improved the CMC aspects of it, scalability, and the ability to dose subcutaneous in time, which I think is a real big advantage for us with that asset. I think there's obviously a crowded field, a lot of excitement there. We think we're one of a couple that really stand out in our ability to compete and win in this kind of redistribution of a $50 billion-plus market. That's one really important strategy that we have of our business. The other is our own internal ADC pipeline. We do believe strongly that the hockey puck, if you will, is moving quite rapidly towards synergistic combinations.
This dual approach strategy between our 001 backbone and asset with our ADCs gives us the ability to compete and develop best-in-class therapies across many, many different indications that are opened up by the, I guess, redistribution, if you will, of this next generation IO therapy. We feel really excited about that. That is Crescent in a nutshell. I think the ADC part of our business, our first ADC 002, will be in the clinic middle of next year. We are going to have two clinical stage assets here rapidly, end of 2026. 2027 is going to be a robust year of data flow for the company. I think that the other nice thing about this is it is not like you will hear Ellie's story here in a minute, but it is not like bringing the seventh or eighth KEYTRUDA to the market, if you will.
This is in the early innings of the game. We have a leadership position in this space, given the design of the molecule and also the dual strategy we have with the 001 asset and the ADCs. We feel like this is just in the very beginning of a long game to go out and decide where we want to win. There are many ways to win here for us. Choosing that strategy and the team we have behind us will really give us the ability to be differentiated. We are pretty excited about where we sit today.
Great. As an Avanesta MAB fast follower, can you just talk a little bit about your confidence around your IP and your freedom to operate in the space?
Yeah. We have total freedom to operate here. Obviously, having gone through an IPO process, all the diligence that's required, the investors that are behind us have really diligenced that as well. You get asked the question a lot. We have complete freedom to operate here, a really strong IP position. There is nothing there to really talk about.
Okay. Your decision process is you selected this specific construct to make. The choice between PD1 and PD-L1, which some other companies are pursuing, how did you think about that?
Yeah. So Ellie's our CMO. Maybe Ellie, you want to take this one?
Yeah, sure. That's a very interesting question, and it's a sort of decade-old question for people who have lived through the PD1, PD-L1 era. Of course, there has been a lot of discussion about which one is better. Looking at how the field evolved, we know that KEYTRUDA and OPDIVO, both PD1 inhibitors, are the two most revenue-generating compounds of checkpoint inhibitors. There are PD-L1 inhibitors that have had some success in other indications. Looking at the totality of data and the breadth of the indications that have had success, we thought that PD1 inhibitors have had more robust anti-tumor activity. That's one part. The second part is, as Josh mentioned, we looked at Avanesta data, Harmony A and Harmony 2 data from last year, and then we got Harmony 6 data this year.
Seeing that it works in indications where PD1s have not worked, and then it's also working better than KEYTRUDA, that gave us a lot of confidence about how the compound is built, and then the PD1 part and VEGF angle. We did not want to deviate too much from the great success that Avanesta MAB already has done. Of course, what Josh mentioned, we built a new molecular entity by introducing new amino acid chain in the scFv domain. We have full freedom to operate. In this way, we're actually taking a smart approach of utilizing the construct that worked, but we made it even better by increasing stability. With that data, we do not have to take a lot of clinical risks.
Once we generate the data from the phase I trial, then we can have a lot of confidence going into the later stage development, which might not be true for the compounds that have a different construct. In their cases, they have to go to the phase III trials and then demonstrate that they have a PFS and OS benefit.
Yeah. I would just add there's a really important point that I think hasn't sunk in yet with investors. The fact that we're going to be able to leverage the way we intentionally designed our 001 asset, it's not just thinking about where you go monotherapy or monotherapy standard of care. This also has a massive ability to accelerate combinations. We know, again, that's where that puck is moving. Thinking about, because of the data that's out there and the way we've replicated the cooperative pharmacology and the similarities to IVO, we're going to be able to move quite quickly into later stage studies in combination therapies as well. I think that's something that we're really excited about. We haven't talked a lot about our ADC strategy. We've not released our targets yet. There's multiple assets here that we'll be talking about soon.
We will also be talking soon about the phase I trial design for 001. All that stuff is coming. We are pretty excited about it, we have been here patiently waiting for over six months since we joined the company to talk about these things. We are getting pretty close to being able to do that.
Okay. Now, I'll ask a question that I got asked a lot with my coverage of Summit, which is, how do you think about the aspect of forming a company around a thesis where the majority of the data for the class were generated in a single region in China? How do you think about the risk of that or lack of risk?
Yeah. I mean, look, I think that was a big question when Peter and Fairmount thought about putting this company together. I think that there was just the PFS data from Harmony 2, I think, out when they kind of had this idea to put this company together and take it forward. I think as investors, you got to take early bets. If you were to ask the team now, "Hey, all of these data points came out the way they have since you started this thing, how would you feel about it?" I think we're jumping up and down. I think that's just part of making good investments, taking risks, calculated bets. I think the thing that will be remembered when this game gets at least halfway through it is the intentionality of how we design the molecule.
I think that's going to come back in spades to have such a big impact on our ability to move quickly, accelerate data, and get into combination therapies as well.
Got it. Okay. Let me ask a broader question on just the class. What extent of overall survival benefit do you think is needed for this class to become incorporated into standards of care? Is that going to be different across different cancer types as well?
Yeah. It is a really great question. When treating cancer patients, of course, the ultimate goal is to extend their survival benefit. Now we are getting a better understanding of what PD1 VEGF as a class can do in terms of providing OS benefit. We just saw Harmony A OS analysis at CITSI. It depends on the cancer types and what the comparator arm does, for sure. We are looking for treatments that can prolong survival, but also have a pretty good safety profile so overall patients can benefit from treatment. What has been very encouraging about Avanesta MAB data that we have seen so far, in all trials that we have seen, it has shown pretty clear separation of OS curves between the two arms. Sometimes it is chemo, and sometimes we are even comparing to PD1 inhibitor, which has been the biggest revolution of anti-cancer treatment.
We are hearing from the investigators and KOLs that the data has been very encouraging. Given favorable safety profile and overall PFS benefit, if this degree of OS benefit is maintained, they would prescribe it for the patients, which is a really encouraging thing. Of course, in different tumor types and different combinations, it is something that we should watch and see how that evolves. What we are seeing from available clinical data, to me, is very encouraging. It has definitely potential to transform standard of care.
Yeah. Maybe just a quick add there is that we can sense the enthusiasm from you as investigators because, as you mentioned in your previous question, much of this work has been done in China. We are the first global study where we are going to really generate that data ex-China with a biospecific. The investigators just cannot wait to get their hands on it. The interest that we have, the sites that want to work with us, all things we will be able to talk about soon. You can actually tangibly feel the interest here in the U.S.
Okay. Let's double-click on that a little bit because you mentioned this a little bit, Josh. When does CR001 enter the clinic? What can you say about how you're designing your first in-patient studies to really maximize speed and the value of the early data that you generate to get into the late stage studies and compete?
Yeah. I'll ask Ellie to talk about a little bit of the trial design, thinking about how we're putting that together. It's a very robust study, as you can imagine. It will allow us to quickly get into phase II, three studies as well. I think what's really important is that we're going to be dosing patients in early Q1. That's what we've said for a while now. We're well on track to do that. That's the next big jump for the company here.
Yeah. Regarding our first in-human trial, which will be a global trial, as Josh mentioned, we will be able to address the questions from the investors, like the Asian data versus Western data, how does that translate. We will be able to answer that question from the very beginning. The phase I trial, first in-human trial, will have a very comprehensive design of understanding safety, tolerability, PK, pharmacodynamics, as well as preliminary anti-tumor activity in the tumor types that we are interested in. What is the most important thing is about understanding how the exposure and the response for safety and efficacy works like for CR-001. Of course, that goes into which tumor types we should go into for the registration trials and what is the right dose and dosing regimen we should choose.
These are the two critical aspects of information that we should generate for us to move into the registration enabling trials in an efficient manner. The trial itself will have all those elements. From the speed perspective, we are in a great position because we can utilize data that is available out there, including Avanesta MAB and other PD1 VEGF inhibitors. As you know, we are biotech, and we have a very focused execution. We will maximize efficiency. We will also focus on maintaining the top quality of the data that we are generating. In terms of value-creating data, Josh and I, we have a pretty good understanding of what that would look like. We will start with the previously treated population, as all the first in-human trials would do.
As we are seeing with other companies' data, going into the earlier lines of setting and patients who have not received the treatment, that's where we are seeing most robust benefits. We will generate that data. From there on, we will quickly go into combination data, including standard of care, as well as ADCs or other novel mechanisms of actions.
Yeah. I would just say that there's no shortcuts in this business. Getting the phase I dose escalation work done right at a very robust, thorough level is really the quality we're looking for here. It will be robust. We will absolutely understand how to dose our drug and have that data behind us. Then, as I mentioned, because of how we design that drug, once we have the dose escalation and the dose work done, we can really, in a robust way, accelerate our path to clinic in monotherapy, but also in ADC combinations.
Okay. Now, what can you say about what cancer types you think Crescent will be best positioned to pursue? Is lung still on the table? Do you have a sense for where you fall within the competitive landscape of where all the other PD1 VEGFs are going in terms of additional cancer types?
Yeah. First of all, I love the competition. Been there, done that. I worked with Bob at Pharmacyclics. Learned a lot from Bob. He's a great leader. This is a massive space. There's lots of room for players here to build incredibly valuable companies. If it wasn't competitive, it's kind of like, why are we doing it? We led that collaboration there to a massive outcome. I saw how biotech, for the first time in my career, really can lead in innovation. 70% of all drugs come from biotech. We're excited about that. I love the question on lung. I think lung is wide open. Yes, we could be second, third to market in lung and monotherapy with 001. Again, I go back to leveraging our strategy between the 001 side of our business and the ADC part of our business.
This is where we will generate best-in-class opportunities. I look forward to talking more about how we think about lung specifically. There are many other indications where we can go out and create a nice little business for ourselves. I would say stay tuned on those indications. We will be talking about more of that soon.
Will you need to generate phase I/II data in all of those additional cancer types? Or from the phase I, which may be focused on lung or whatever other solid tumors, can you leverage that to then go at risk into phase III for other cancer types?
Yeah. No, I think it's a really great question. Our phase I trial will have a select number of indications that we are interested in. We will generate robust data. Of course, we will watch how the competitive landscape is moving. I think based on our data, as well as these competitors' data, we will have a pretty good understanding of how to pivot and what data for us to generate. If it's needed, I think we are not afraid of taking smart risks and trying to get to the right indication with the right combination and then see what is the right strategy to take there.
It's something that we want to keep an eye on while we are generating the data and then how we want to also design the registration enabling trial and see what types of efficiency we can utilize to get there. It's something for us to keep an eye on and then see how things go.
Okay. Josh, from a strategic standpoint, how have you thought about building an ADC portfolio around 001?
We've already been building that portfolio. As I mentioned, we have a couple of ADCs and targets internally already that we're building. Our first 002 asset will be in the clinic in the middle of next year. We've already thought about that matrix. It goes back to your last question. We have a pretty good idea of the range of indications where we'd like to focus. When you layer on the 001 asset with our 002, 003, and others that are in the portfolio, we really have a robust matrix pipeline that we're building. We'll talk more about that soon. I think that we're very intentional around the targets we're selecting for the ADCs and how we then would think about those as monotherapies, but also importantly in combination. That work has already been done.
We've mapped that out. There's always a balance between going down a path where the target's not novel, but you have activity or novel. I think earlier on, we're leaning towards non-novel ADC targets initially. And there's quite a bit of robust activity there, specifically in combination with 001.
Okay. Maybe to double-click on that, so leaning towards validated targets, what other aspects of ADCs were most important to you as you selected this pipeline of ADCs?
I mean, the target, but then there's also the linkers that you're looking at and how you differentiate there, internalization, all those good things. And then also the payloads. We had a lot of experience in my previous company thinking about the antibody, the linker, and the payload. It's not new to us thinking through all of the things that come along with that, affinity, DARs, all the things that you have to build in that conjugate. They all matter. Paragon's been a great partner to us initially as well in helping us get through a couple of those key decisions on how we construct the actual ADC. I think when we are able to talk about it, you'll see we believe we put together best-in-class ADC opportunities.
Okay. From a development standpoint, how do you best successfully approach that novel, novel clinical development with your pipeline combinations, especially as we think about what the FDA might be looking for in terms of novel, novel development strategies?
Ellie?
Yeah. So yeah, we understand how the FDA is now sort of doubling down on contribution of component and what they are asking for to demonstrate that and what types of data can be utilized to prove that there is a synergistic effect of the combination. Having said that, as Josh mentioned, we understand it is most important for us to see how the individual, so CR-001, PD1 VEGF, and then ADCs, finding the dose and finding the safety and efficacy profile of monotherapy first. Then we find the best way to combine those two at the right dose and then in the right indications. Of course, there are a number of different ways for us to go about it, generating robust data as monotherapy and then combine it in the later stage. We are doing adaptive design at the later stage and then having a three-arm study.
After intramural analysis, we can narrow it down to the two-arm study. We are well aware of how the FDA is focusing on this aspect of it. Based on the data that we are generating, we will then decide what is the best way to develop our novel, novel combination.
Yeah. It's also a strategic question too because, yeah, there's novel, novel. Yes, we're generating our own ADCs. But there's also, again, going back to how we design the molecule, once we lock in that phase I data and lock in our dose, then it's kind of like we also have a big shopping list for things that are already out there that may be approved or have robust clinical data past phase II where we can go out and combine those relatively quickly too. I'd say that just pay attention to the strategy as we get out there and generate this phase I data and lock in our dose because there's lots of ways to go to kind of win that synergistic combination game.
Got it. Okay. Maybe, Josh, another business development question for you. In terms of partnering 001, what type of deal could make sense for Crescent? How do you think about the timeline to when that deal would potentially best be maximized in terms of value?
Yeah. I would say that, first of all, we've seen the deals that have been done in the space already. We know the size of them. That just shows the interest in the space, which it's not lost on us. I think our view is, as I mentioned, let's get some phase I data. Let's just check off the box. I think it's also, again, stay tuned on the data we'll be generating. Is it just going to be dose escalation data? Or is there a potential to put in some frontline data in areas where we can most quickly check that box off that, yes, we've replicated what you've seen early on with Avanesta MAB and that cooperative pharmacology has been replicated, which we've seen preclinically now. You saw the CT poster last week. We want to prove that out quickly clinically.
Once we have that, I think it's about, OK, so we're a biotech. Capital will be constrained. I mean, these studies are so big that Pfizer can't run them all either. We have to pick and choose. We're going to pick our path where we want to own that indication and drive ourselves. Then thinking about where can we think about partnering and leveraging expertise and other indications or broadening the approach that we have with 001. Also thinking about then how do we leverage the ADC portfolio and others that may have ADCs in combination. I think the world's kind of open to us there. It's nice that we're still free and being able to think this through as we can watch this landscape evolve more with some of the data.
I think it makes the deals more rich, the more data that comes out. Let's execute on the phase I study. Let's get that right. I always talk to the team about getting that kind of ready from a partnering diligence perspective. When a big pharma comes in and looks at our work, have we done the right high-quality work for the phase I study? We get that right, I think that then it makes the deal we'll do and the value ascribed to it much, much more robust.
Makes sense. OK, maybe just in the last 10 seconds, balance sheet and runway through which particular catalysts?
Yeah. So we have $133 million in cash in the balance sheet in the last quarter. We just put that out. That gets us through 2027. That's going to get us through quite a bit of data readouts. That's late 2026, early 2027 phase I initial POC data. I think that's the big catalyst.
OK, great. Congratulations on the progress. Looking forward to next year and seeing the drug in the clinic.
Thank you.
Thank you.
Appreciate it for joining us. Thanks for listening on.