Okay, good afternoon, everyone. My name is Eric Schmidt. Welcome back to day two and our afternoon session at the Cantor Healthcare Conference. It's my pleasure to introduce our next presenting company. We've got with us the Crescent Biotech team for a fireside chat. We're thrilled to have with us Josh Brumm, the company's Chief Executive Officer, as well as Ellie Im, the company Chief Medical Officer. Josh, Ellie, thank you so much for being here. A relative newcomer to the public markets is Crescent Bio. Josh, why don't we start with kind of the high-level summary on what it is that you guys are doing and what you're up to? Yeah, great. Thanks, Eric. It's great to be here. We've been doing it a long time, so it's kind of fun to be back at the seat. I took a bit of a year off in between operating roles, and what I will say about Crescent is it was just something that kind of called your name. You know, kind of sit on the sidelines to investigate, and I had the opportunity to work with Peter, the parent of my team, bringing back a good portion of the team I worked with in my previous company. Really, the thing about the opportunity at Crescent is pretty special. We're really focused on our vision is to build a world's leading biotech oncology franchise, and we have a dual stride to do that. We have our sleeve, one of our businesses, I like to call the next generation bispecific, our CR-001, you know, VEGF/PD-1 bispecific antibody. We're super excited about that part of our business. We think that's a market that's ripe for cannibalization. We also have another important part of our business, which is the ADC sleeve of our business. While we'll bring those ADCs forward, we'll have our first ADC in the clinic that middle of next year. Our lead asset of the 01 and the IO part of our business will be in the clinic early next year. Really driving forward multiple strategies here to better patients' lives across solid tumor indications, and we're excited about that. Josh, one way that you're a little bit distinct already is you went public via the reverse merger process. Yeah. Sorry, just reverse merger, not as back, but yeah. Having gone through that process, how did it work out for you? I know you joined kind of midway through. Any reason that that was the right thing to do for Crescent Bio? I think it's a unique way to access capital and get broader access to capital, and it's been a pretty tough IPO market for biotech companies. It's also been a playbook of the paramount companies in some of Peter's strategy. I think where we sit today, this really affords us the ability to broaden our reach to shareholders, have broader capital, and to really build a syndicate of investors and then a group of investors that really support our vision. I think it's been pretty straightforward. We started trading mid-June, and it's nice to be a public company. I think there's just things about being public, visibility, branding awareness. I like that transparency and the dialogue with investors publicly, the way we've always done business. We define success at Crescent Biopharma by simply doing what we say we're going to do. Simply roll out what we're going to say, and we roll out our milestones. It's fun to achieve those publicly. It's tougher to manage, but seven companies in and having been a CEO of a couple of companies now, I really like that dialogue of give and take. It's kind of fun to be there, particularly with the team we have and our ability to run operations and their goals. Where are you with your cash and your cash runway? Cash runway gets us through 2027, and we've set that now for quite some time. We're in a strong position that's going to get us through our initial phase one data. I think where the company's headed over the next couple of quarters is, as I mentioned, our first asset for 001, which is the bispecific, will be in the clinic early Q1. We've said we'd have data coming out from that program as early as Q4 2026 or Q1 2027. We'll have the second program, our first ADC, which we've not disclosed the targets there yet, going to clinic in mid-2026. Being funded through that data generation is going to be pretty important. We're pretty excited about the strength of the position we sit in from a cash perspective, but more importantly, it's kind of a luxury of assets that we're working through. Great. Let's talk about CR-001. This is, as you mentioned, a VEGF/PD-1 bispecific. The class has gotten a ton of interest. Just your views on the class itself and why the interest is here. Thank you for the question. Earlier in my career, I was lucky to be leading two PD-1 inhibitors to that market. The first one is surufatinib in non-small cell lung and second. I haven't heard of that drug yet. Yes. The second drug is called the [GemFolly], currently owned by [GLK]. After that initial amazing data that we've seen from PD-1 and PD-L1 inhibitors, the entire world has been waiting for what's going to be the next IO drug. A lot of companies tried combination at best with Keytruda, and they've all failed at various stages. When we saw what has done so far in frontline non-small cell lung cancer patients, leading Keytruda head-to-head in randomized phase III setting, and also in EGFR-mutant non-small cell lung cancer patients where PD-1 inhibitors have not worked, and have shown that robust PFS data, while we are waiting for the mature OS data, all those things were so exciting. That's what we've been waiting for, for superior IO backbone, which can change the standard of care in multiple indications, just like what PD-1 did, what VEGF did. Now, in combining those two modalities together, we're seeing that we can go into the indications that those PD-1s and VEGFs have not worked. That whole opportunity is really exciting. The data that we've seen so far this year has been very validating in our view of PFS data. We know how highly statistically and clinically meaningful they are. Even the OS data that we are seeing, PGMs are seeing, that is so highly clinically meaningful. We are really looking forward to seeing additional information that will be released, I guess, this week at World Lung as well as at. As you all know, there's a number of different structures and frameworks for inhibiting PD-1 and VEGF in a bispecific format. You guys have chosen to mimic as closely as possible the i vonescimab structure. Why is that? What does that mean? Yeah. When we were developing this compound last summer, we were thinking about how can we be even better, like changing the structures. Now you're seeing some of them, different structures, binding domains, or PD-L1 instead of PD-1, or VEGF prep. All those different modalities have been using. Then FC, binding site, do we want to leave it as active or do we want to mute it? Looking back and studying what PD-1, PD-L1 inhibitors, the IO drugs have done so far, we understand that in the preclinical setting, changing the binding domain, the affinity, all those things might lead to have interesting preclinical data. We really need to see how that data will translate in the clinical benefit, especially PFS and ONC benefits. It takes a long time and many patients to get there. Instead of spending a lot more time in the laboratory setting and then developing a compound with the new structures and new entities, it's going to take a long time for us to get there. Understanding what ivonescimab has done so far and then the efficacy, robust efficacy, and clear safety signal that we are seeing, we thought that PD-1 inhibitor world is a good analog to this, Opdivo versus Keytruda. How different are they? The molecular perspective, right? Where it really differed and made Keytruda, the drug, the top drug it is, it's with their clinical development strategy. The timing of entry were not that different between Opdivo and Keytruda. We brought them back into the strategy that we can utilize here, right? Mimicking the functionality of ivonescimab that has already proven its track record with multiple randomized phase 3 trials. We also did a little bit of innovation by introducing new amino acid chains at the FDA's indole, which provided us excellent stability. We can achieve high concentrations. We think that should help us with manufacturing ability as well as how we can differentiate with the lifecycle management as well. Learning from PD-1 era and VEGF era and how ivonescimab data looked like, we thought that going into the clinic with a similar structure as ivonescimab and differentiating with our clinical strategy and expectation made a ton of sense. The timing of entry is also key, right? Because now, other than non-small cell lung and maybe small cell lung, a lot of indications are still new to the field. As Josh mentioned, we will do IND in Q4 this year, and then we will go into clinic generating global data early next year. We are literally lining up like a fine line with all the big players at the moment. How many others do you think are trying to be closer as opposed to further away from the construct that's ivonescimab? There are other players that say those are pretty similar to us or uniquely positioned as the closest potential to mimic oncology. I think we're the most similar to ivonescimab, clearly. I think that if you look at the strategy for where the dominant player in the market work is, they've also made the bet with the [Novas] that depicts something that's more similar to ivonescimab than, you know, some of the other apps that are out there. I think that also is validating for us in our approach on how we thought about potentially designing inhibitors that involve the oncology of CR-001. The one difference that you have, as you mentioned, is in the PD-1 binding SCFP domain. You know, that could be a feature or a bug. How should we think about that? Because there is some differentiation versus ivonescimab. How do you know or convince yourself that you're not giving up anything by introducing that potential change that helps on the manufacturing side? With that new amino acid chain, we are achieving higher stability, which is a really excellent point. We understand, as proving how CR-001 works, how that compares to ivonescimab or even any other drug that's in the play, we will prove it step by step. In our corporate deck, we have included in vitro data showing cell binding assay and then how that translates into the PD-1, PD-L1 signal blocking, which is a similar assay that ivonescimab has used to demonstrate proprio functionality. We are currently generating preclinical data to again show how we are working compared to ivonescimab. We will do that all enforced in clinic. That's where the point is. Our phase I study that we've designed will show exactly how this drug works and the clinical profile, BK profile, and our strategy and how the efficacy and safety data look like. All those things will really help us signify our strategy works and then how we can differentiate for it. Yeah, I'd say that the preclinical data we're generating today is showing that pharmacology is very similar. We'll share more of that in time. I think Ellie's made a good point about the phase one set design, getting that into different lines of patients quickly to show that we see similar responses as we see ivonescimab in the same safety profile. We're thinking about ways we can demonstrate in combination quickly as well. I think that will be incredibly validated. You can check the box on safety. Can you combine this drug? Those are all the things that I think we're focused on talking more about over the next couple of quarters as we get into the clinic, coming out, talking about what our phase one set design is, what data we're generating, what patient populations, what combination settings, when that data will be available. I think that will really start to block on, okay, these guys, they're serious about their strategy on building kind of two sleeves of business between the 01 asset and the IO sleeve and then the ADC sleeve as well, which, more to come on that when we start to be able to talk more about our targets and the indications we're going after. We're just not quite ready for that from a competitive standpoint, but it's coming soon. I think we're really looking forward to having that opportunity to share and discuss. Okay. Maybe before we get into your timelines and development strategies, just one more question on the overall landscape for VEGF/PD-1. What are you looking for out there from others in the space? You mentioned this weekend's update from ivonescimab in the EGFR-mutant setting, but are there trial readouts that you think you can learn from? What are you hoping to learn from the readouts of those coming before you? We are anticipating HARMONi data at World Lung and then HARMONi to the population data. Those data will be really valuable. Now we're learning more and more about it, and how Asian populations versus Western populations have done in terms of safety and efficacy. Also, how much of this, the subgroup, dividing them into looking at PFS and WASD benefits would help us going into that. HARMONi- 3 data, HARMONi- 6 data, we are anticipating it will be released at ESMO. That's the part of the chemo combo data in squamous cell carcinoma patients. We're also hoping to see more mature ONC data from HARMONi- 2 study, which is incredibly valuable. These are some of the phase 3 trials in non-small cell lung cancer. We are also seeing a lot more data coming from BioNTech and others in different indications. All those data we are studying carefully because understanding the trend, safety and efficacy, as well as what are the things that could have been determined to make the results even better. All these competitive intelligence points are something that we are keeping an eye on to make our development strategy even more efficient. I would just maybe add just quickly to think about where we're going to take monotherapy, 001, and our B10 indication. Monitoring, first and foremost, our own data will be critical, but also the clinic landscape. Outside of lung, it's pretty much open right now, first in class and all these other indications. We'll watch where other people are going, where our own data leads us, and that will help inform us where we think we want to make that B10 indication for our lead indication for 001. Also, where we take combination therapies and others outside and kind of build that portfolio approach along by 001. Should we think that lung is kind of closed, that ivonescimab is too far ahead to potentially broaden its development? I think you did a great job in your initial report on us of showing what being second, third, and fourth line of market mean. We have a very serious approach to how we think about developing our pipeline from a fast follower strategy, but also first in class. We'd like to have an indication at least one where we have first in class beachhead. Obviously, fast follower in lung makes a lot of sense. We're thinking about that as well. Where we see combination therapies where we could actually be first in class in lung. I think lung is wide open. Great. Just wanted to confirm. Yeah. All right. Let's get into CR-001 and development timelines. What's rate limiting to an IND? When can we expect that? Yeah, we're still on our track by year end to have the IND and that all filed away. There's nothing really rate limiting. Lots of medical writing, lots of just execution. That's what's ongoing now. I think we're in a great spot. Manufacturing, you know, wrapped up in a good spot. Same with our tox. It's just now put in the package and getting it all filed. Ellie, you talked about designing a phase one that was going to be informative in terms of the molecules' similarities to ivonescimab. What can we look forward to there? Yeah, so it's a first-in-human trial with solid tumor patients with the indications of our interest. There will be, of course, those escalation parts. We will enroll additional patients with these specific tumor types, which will help us generate safety and tolerability data, PK data, as well as pharmacodynamic data that ivonescimab used to demonstrate the receptor efficacy, as well as a VEGF serum VEGF level. We also understand the real value of oncology data is anti-tumor activity, right? Understanding how CR-001 works in helping patients shrink tumor or maintaining that tumor shrinkage is something that we will try to generate as efficiently as possible. We also understand the efficacy of PD-1 VEGF in the previously treated population versus in the earlier line patient population. Demonstrating all those things earlier and having robust data that can help us choose the indications that will go into the registration setting, as well as doing the thorough work on defining the recommended phase II dose, and obviously meeting the requirements from the FDA from the Project Optimus perspective. All those work will be done in the phase I study. Doing it well will help us accelerate our late-stage development going into the registration enabling studies as quickly as possible. Given the similarities of the molecule to ivonescimab, can you start at an efficacious dose? That's something that, of course, we have to carefully evaluate, our package that we are generating for the IND, and then have to discuss with the regulatory bodies to make sure that they feel comfortable. We plan to utilize available information as much as possible, given the safety data that we have now. We've seen that this class drug is actually quite safe. Probably utilizing those information will help us into the dose escalation more efficiently. It never hurts to ask regulators again. We'll ask to start where we take the can, shorten timelines from that perspective, and let them know what's good enough for us. As Ellie said, start to be fair with the regulators and we'll do that. Excuse me, where are you going to enroll this study? What sites? Which geographies? It will be a global study. The United States, as well as ex-U.S., including Europe and other major continents, will be included. We are doing this purposefully because one of the key questions that came from the investment community, as well as the investigators, was how would Asian data translate into the Western population data? Another thing is the Chinese NMPA regulatory endpoints sometimes can be different from the FDA's endpoint. What we are seeing from Summit and at CRISP, and what we are learning from them, is generating the global data from the beginning and showing how CR-001 works in all relevant populations would be very useful. Doing the dose finding work right on head so that we can develop this drug efficiently in the United States, which is the biggest market there is, is also important. This work will also plan out in terms of expediting our global registration study strategy as well. Yes, to answer your questions, we will go with the global sites. I would just maybe add to that that global sites not in China allow us to potentially get into earlier lines of therapy sooner and make some of those comparisons and validations earlier in the process that maybe you normally wouldn't get into. You have specific histologies already in mind that you're going to look at for dose expansion? Yes, we have our list of indicators. Which would those be? TBD on that.. We can tell you the three areas that we're kind of focused in, without being specific. Yeah, so our focus lies in thoracic, GI, and gynecology. Any rationale behind those choices? Thoracic being the obvious one, but the other two? GI indicates that gyne indications have had a lot of success with the PD-1 inhibitors as well as the VEGF inhibitors. There are some of the indications where we saw the marginal benefit from PD-1 inhibitors that we think we could do so much better with the PD-1 VEGF. There are some indications that PD-1 inhibitors did not work, and now seeing the possibility of going into those indications with the PD-1 VEGF and then really trying to understand that square will give us a pretty meaningful opportunity. I would say that what people still need to realize about us, it's very different than maybe some of the others, maybe more similar to what BioNTech is doing, is it's not just 001. When we build our portfolio, we're looking at where can we see 001 working with monotherapy, where do we see 001 working with monotherapy plus standard of care, and then where do we see our ADC portfolio also kick in. It's a little bit of a different matrix than what you might see from some. Okay, I get the hint you want to talk about ADC. I'm just saying. Just say that is part of the story. Before we get there, two more questions on just the bispecific. One, a lot of partnership interest in this class. Your thoughts on potentially forming a collaboration sooner rather than later or any value inflection points you see? Two, a lot of competition here. Can you do this by yourselves? Yeah. First of all, I love the competition or we wouldn't be here. I mean, I think that competition would drive the benefit to the patient. That's what this is all about. We welcome the competition. We join that with enthusiasm and alacrity. That's why we get juiced up in the morning and up to work. That being aside, can we compete on our own? The answer is we can because of our strategy between the two sleeves of business. We're also, you know, clearly deep conversations around partnering. There's a lot of activity, as we all know. The timing of a 001 specific partnership is really the question. If we want to do one, what do we want to do with? What do you have the most value for? What do we generate? There's a little bit of data to get more value for that. I think that while there's a lot of excitement about, you know, near term what's been going on, this is a nine-inning baseball game. I think we're at the top of the first inning. It's the long game ahead. We've got to realize that every indication requires, you know, the work, the studies, and see how the history taught us in the PD-1 initial market rollout. Joe Floyd's a great example. Some of the market, great outcome there. We're in the early stages of the game. There's no rush for us to do something there. I think what's equally as exciting to us is how do we reach that end? How do we think about leveraging 001 in combination therapy with others' portfolios around ADCs, et cetera? How can we generate data more quickly through partnerships, particularly maybe in China for even 001 or a combination? Or how we can accelerate the development of all the portfolio. Those conversations are also very real and quite exciting. I'd just say stay tuned on that. Okay. Let's talk about ADCs. What have you said? What do we know about ADCs? Yeah, we haven't said much. That's why I kind of chuckled when you said you want to talk about it. If you want to talk about it in the context of the strategy, we've not disclosed our targets yet. What we have said is that they're not novel targets. We're not going to start with novel targets. At some point in our history and what we built, we could see that happening, but that's not where we're going to start. We have our first one, 002, coming middle of the next year in patients. I think when we do disclose that, it'll make a lot of sense for people. We've been very nice to our portfolio. We're working on a three-asset at the time of that as well, which could be right behind 002 or maybe a similar timeline. I think that'll also show people that the strategy we're talking about is real. It's taking action on that, picking up for it, drive us to the clinics, generate data, and building, and we move out of the vision of the company that's much bigger than what basically it was today. With ivonescimab, you're unashamedly a me-too player at [Geneva], being one of the bispecifics. As close as you could be, sorry, with CR-001, you're as close as you could be to ivonescimab. With the ADCs, are you trying to do something differentiated or are you trying to do something quite similar? What's been successful? Yeah, there are ways to go after known targets that are clearly differentiated. I think you will see differentiation from us for sure. That is part of our types of features that you are trying to differentiate yourself. Could be payloads, could be combination payloads with known targets. Ellie? Yeah, and then, you know, of course, that it's antibody, linker, payload, right? All those aspects of it and then what's available and what's been developed and how we can fit in into that competitive landscape. We also have to remember ADC requires a lot of clinical development. Which indication are we going into? How are you defining biomarkers? How are you defining the dose? Ultimately, it comes down to, as a monograph, which indication can you go in and show that efficacy? Of course, we can combine with a CR-001 to demonstrate that as well. Yeah, we have a lot of experience with antibody conjugates, given our last company's experience, and very similar here. Taking the strategy of not taking risk on linkers when you don't need to, or thinking about things where you can take the appropriate risk in different parts of that conjugate, but not in certain areas where you've seen historical toxin issues. I think we're pretty well versed in that part of it. We know how to develop differentiation without taking a lot of risk. Next question, what is driving your disclosure of strategy on ADCs? What are you waiting for in order to say more? Yeah, I think there's no reason to rush out there in the competitive marketplace. I think I'd like to get out the update on 001 first, where we're going as far as clinical study design, timing of data, what data we'll see. At the right time, maybe it's through a BD partnership discussion, or maybe it's just a course of business. We'll talk more about the ADC targets and where we're at there. There's just no rush to do it, given the interest that we've had in the company's support from shareholders. We're well capitalized, and we are just marching on execution right now. I think that's what's kind of making our decisions for us. We are out of time. Thank you, Ellie, Josh, for a formative session. Appreciate it. Thank you. Thank you.