All right. Good afternoon, everyone. I'm Steve Willey, one of the senior biotech analysts here at Stifel. Glad to have with us in the next session, Crescent Biopharma. We have Jonathan McNeill, who is the Chief Operating Officer, Joshua Brumm, Chief Executive Officer, Ellie Im, who's the Chief Medical Officer. Thank you all for the time today. Always appreciated. Any opening statements or just kind of quick overview you want to provide before we jump right into Q&A? Yeah. Thanks, Steve. I think we just always want to make sure before we begin that we've been making some forward-looking statements, so please refer to our SEC filings. For more info on that, I would say it's great timing on the day here, just given what's come up at ASCO, the excitement that we see coming at the conference next week. Again, a reminder that at Crescent, we're really focused on delivering the next generation oncology company, with a couple of key strategies and two pillars that we're focused on. One is advancing our PD-1 VEGF bispecific antibody, CR-001, which has the potential to be best-in-class therapy for IO and IO backbone, kind of replacing the first generation PD-1s. The other is our ADC pipeline and portfolio, which currently includes CR-002, our PD-L1 TOPO ADC, and CR-003, our integrin beta-6 (ITGB6) TOPO ADC that we in-licensed from Kelun. We've got the opportunity to be best in class and first in class across a number of indications with this strategy. We're excited to talk more about that today with you. All right. Definitely want to touch on all of those things, including ASCO, but maybe just kind of bigger picture for us, right? It kind of feels like the story, and maybe this is just my naive perception, but it feels like it's evolved a little bit over the last 12 months, right? Where I think initially the narrative was kind of more of a bit of a fast follower approach to ivonescimab, but now you've kind of taken this direction that allows you to both competitively benchmark yourselves to Ivo, but then also position yourself to generate a lot of this kind of first proof of concept data in combination with ADCs. Was this always the plan from the outset, or were there some external, internal learnings along the way that kind of crystallized the development strategy that you're pursuing now? Yeah. Jonathan. Yeah. It's always been part of our strategy to pursue a matrix portfolio across two key areas of our business, next-gen IO agents, ADCs, and synergistic combinations of both. You can see this from our development of CR-001, our internally developed PD-1/VEGF, CR-002, our PD-L1 TOPO ADC that we internally developed, but then also a partnership with Kelun that was announced last December. Kelun, as you know, is a leader in ADC development commercialization, and this really accelerated and expanded our efforts to develop synergistic combinations of CR-001 and ADCs. It is truly a transformational partnership. Kelun's an ideal partner. They are a commercial leader in ADCs, and we are so fortunate to be partnering with them because they share our vision of developing synergistic combination next-gen IO and ADCs. As you know, Kelun developed Sac-TMT, partnered with Merck, running currently 17 global registrational trials. Kelun also has 10+ other clinical stage ADC assets. As part of our collaboration, Kelun will be developing CR-001 in China, both as monotherapy and in combination with their full portfolio of ADCs. This includes Sac-TMT, they also have several HER2 ADCs, Claudin ADCs, Nectin ADCs, and we have access to all of that data to inform our own portfolio and future partnerships we could pursue in pursuit of these synergistic combinations. This has always been part of our strategy. The Kelun partnership accelerated and expanded that, and we're very excited to continue to advance that, both as monotherapy and in combinations as we drive toward multiple clinical data sets in 2027. You know, I would just say that we've always planned to be a leader in this space. I think we took last year when we joined the company about 12, 15 months ago, to really kind of quietly and humbly build our portfolio, build our pipeline, and execute on our strategy that we saw around synergistic combinations between building the next gen best-in-class IO bispecific, as well as the ADC portfolio. I think we really are serious about being a leader in this space. I think over the past 12, 15 months, we're now cementing that position as we go forward. Okay. You're currently pursuing 001 in dose escalation through the global phase I ASCEND trial, phase I/II ASCEND trial. We've seen other companies take a very similar approach to kind of running global studies earlier in the clinical development process. How do you think this approach impacts the breadth of your early data generation and kind of the operational speed at which you can advance into registrational studies? Yeah. Thank you for that question, Steve. ASCEND is a global phase I/II trial of CR-001. This study is designed to generate comprehensive data and also is clinically meaningful. By the end of this trial, we'll have comprehensive set of data to determine recommended phase II dose, as well as data that can help us determine the registration enabling study indications. When we are running this global trial, we were met with very thrilled enthusiasm from multiple sites and investigators from global locations such as U.S., Europe, as well as Asia-Pac. While running this trial, we have a great advantage of utilizing preclinical data that we've generated from CR-001, and we intentionally designed to match this compound to have key features of ivonescimab, and then our preclinical data that suggested that investigators really appreciate our strategy and how we are generating the data in the dose escalation, as well as backfill to bring this point to the meaningful strategy. Our advantage of a global clinical strategy is coming to working directly with the Western sites as well as the Asia sites, and working with the registrational body such as the FDA and EMA from the beginning, and understanding what they need in terms of getting the drug approved and designing the study to meet their endpoints, and eventually improving the probability of success for registration-enabling studies. Okay. I know you're guiding to an initial data disclosure in the first quarter of next year. How should we think about what that looks like? What are you hoping to provide in terms of patient numbers, duration of follow-up? If there's a take-home message that you want investors to have after this disclosure, what would that be? Yeah, this is a really important question. I think one that we want to just pause on for a second and talk about the totality of what's coming in 2027. The intentionality of how we designed the ASCEND study, Ellie's done a phenomenal job with the team, thinking through the strategy on different buckets of data coming from this study. As you mentioned, the first will be Q1 2027. Also validating our strategy with the Kelun partnership and what data's coming next year in conjunction with the work that they're doing. This really does put us into a very strong position as we get into middle of next year. Let's talk about those three buckets. The first bucket of data will be coming out of the ASCEND study. That's going to be the Q1 2027 data that we promised around first-line non-small cell lung cancer and monotherapy, saying that's going to come from our backfill cohorts in the ASCEND study. Honestly, our view on that is that just checks the box on how we intentionally designed CR-001 to be replicating the cooperative pharmacology of ivonescimab. We wanted to get something out that could give people confidence that we saw clinically what we saw pre-clinically with our intentional design of CR-001. Check the box that we see efficacy and safety similar to what we see in ivonescimab's data, and that will be in a cohort of 12+ patients in Q1 2027. That's the first bucket of data. The second bucket of data comes from our ASCEND study and the expansion cohorts, and that'll be across various tumor types, combining CR-001 with standard of care chemo. Multiple different chemo agents across different tumor types, some that are currently on PD-1 label, and maybe some where we're looking for expansion. Like in colorectal, for example, where we can see the benefit of a bispecific in combination with standard of care chemo in those settings. I think that's going to be very important data for us to think about, okay, between the first two buckets of data, where do we want to take our registrational studies? What indications? How do we want to think about being a leader and owning part of this turning over of the original PD-1 first gen opportunity? I think the third bucket of data is going to be where you see the Kelun relationship come into play, where you see the CR-001 combo with ADC and the Kelun portfolio. As Jonathan mentioned, that can include something like sacituzumab or any of the other late stage ADCs in Kelun's portfolio. Across all three buckets of data coming around mid 2027, also circling around our recommended phase II dose at that point in time, we have all the data we need to think through not just our clinical development strategy, but also how we want to build this company, where we want to take this as far as first in class or best in class opportunities, and leverage the matrix portfolio that we've built here as a company. Okay. Maybe just on the future indication selection front for future registrational studies, obviously ASCEND will give you some ability to make a data-driven decision, but then there's also obviously a lot of stuff happening competitively in the background. How do you strike a balance between those two things as you choose which indications to move forward in? Ellie? Yeah, Steve, that's a really great question, and this is a really exciting field, and we are seeing data from multiple agents almost coming out every week. So far, what we are gaining is that it's seen as a real class of drug with a full potential to replace PD-1 inhibitor in multiple indications. Having said that, we have designed or sent a study to study eight indications of our interest as a monotherapy, and as Josh mentioned, we will also study in combination with the standard of care. Data that's coming from our study will be the critical information for us because we want to follow the data. We are closely looking at competitive landscape and data that is emerging from our competitors. We will look at all this data very carefully and then choose the indications that provide us a high probability of success, but also giving us chance to secure the attractive market size. Also looking at our matrix portfolio and thinking about what is the indication that we can go in as a first-in-class. Also, with our combination strategy with our ADCs or other mechanisms of action, we can also have a shot at best-in-class opportunities across these multiple indications. Maybe just to break this down a little bit further, because we all often get asked this question, and I think there's so many ways for us to win for patients and win for our shareholders here, given how big this space is. Just to drill down a little bit more, first-in-class opportunities where PD-1s have worked historically, where there's not work ongoing in the field. There's 40 + indications. There's still very large markets where outside of lung and some really early initiations in colorectal and a few other indications, it's wide open from a first-in-class opportunity. That would make a lot of sense for us. You could look at that from a monotherapy, probably more likely from a combination standard care chemo perspective for first-in-class. You look at areas like lung, where we get asked this question quite often, "Is lung still open?" We think it's wide open because with our portfolio, you think about the opportunity to combine with ADCs or other agents of activity, we think that you can go in and win in frontline in that setting. CR-001 plus CR-003 is an example where potentially in lung, you could be very competitive, and even though it's a competitive field, there's ways to win in frontline setting in big indications like lung. I'm not saying that's where we're going, but that's the way we're thinking about the various opportunities. That applies to any other indications or tumor types that we like. Once we have our established dose for CR-0 01, you can imagine various pharma and biotech companies thinking about how we can combine CR-001 to deliver efficacy and for patients in those indications. I just highlight that because there's so many ways for us to win. I think we're going to be guided by the data we generate across these three buckets. We'll somewhat look at the competitive landscape, and then we'll think about how we best attack and finance the company to drive as many shots on goal as we can to be a leader in this field. Okay. You talked about the timing of this being very prescient, given the proximity to ASCO. Maybe we can talk about ASCO a little bit. Akeso is presenting interim OS data from HARMONi-6 and [squamous] that's getting most of the attention. We're also going to see some updated phase II data from BioNTech's ROSETTA Lung trial and Pfizer and 3SBio's phase II monotherapy effort in frontline lung as well. What are you going to be the most interested in, and how do you think about the read-through of these data, specifically HARMONi-6, just because that seems to be getting the most investor attention? How do you think this reads through, if at all, to what you're doing internally? Yeah. I think that there's going to be a lot of lessons here that we can sit back and learn. I think given what we've seen transpire in the field, particularly again over the last 12 months, that we've been here as a management team executing on our strategy. I think there's very little that's going to change our direction. I think it's going to be validating to where we're going. Maybe I'll ask Ellie to talk a little more about that in detail. Yeah. Regarding upcoming ASCO, there are a lot of important data that's coming from our key competitors of PD-1 and [bispecific]. I think we are anticipating exciting data, HARMONi-6 OS data being one of the key ones because, I guess from investor perspective and from people who are working on this field, the two questions, right? One is OS benefit, the second was how we are successfully developing this drug class in global setting. Regarding OS data benefit that we are anticipating with the HARMONi-6, if this data shows clinically meaningful benefit in first-line non-small cell lung cancer patients compared to PD-1 inhibitor, I think this will be highly validating and really answering one of the key questions that PFS benefit, robust PFS benefit that we saw from ivonescimab, if that translates to OS, then what else can we do with this class of drug? As Josh mentioned, PD-1 inhibitors have been approved in 40 + indications, and we are seeing a lot of encouraging data in multiple tumor types. We are also anticipating exciting data coming from Pfizer, as well as BioNTech. All this information, we will take a look at it and then learn from how they executed the trial and how the results look like. It will be a great opportunity for us to have a great information. From our strategy perspective, we feel pretty good about how we create this compound, matching the key features of ivonescimab. We think that ivonescimab is one of the PD-1 bispecific that has a structure that is unique to optimize efficacy and safety profile. It's the only PD-1 bispecific that has a multiple phase III trials that demonstrated that. Of course, we optimize further with our improved stability. That opportunity gives us to generate comprehensive data from phase I study and then have an early de-risking event, and then we'll have an expedited process going into the registration enabling trials. Overall, we think it's a really exciting event, and we'll learn a lot from it. Based on this data, we see that people will have more conviction that PD-1 VEGF as a class is a real next-generation IO backbone. Okay. Yeah, no, I know we hear it from investors. I'm sure you do as well. Right? This notion that at least over the near term, you guys are kind of tethered to whatever happens at Akeso, S ummit, whether that be good or bad. I think that perspective seems to not take into account this notion that your position here allows you to benefit from these successes and failures and to pivot accordingly over the longer term. I think that's a really important part of the story that we find ourselves explaining sometimes. I guess, Ellie, it sounds like you're optimistic going into. into the HARMONi-6 OS update. I know there's a lot of investor and KOL discussion around what constitutes a good hazard ratio and a good absolute OS benefit. Would you care to opine on what you think would be a fundamentally positive update? Fundamentally positive update to me is OS benefit that is clinically meaningful and in line with the PFS benefit that we've seen from last year's ESMO. In this indication, pembrolizumab was able to demonstrate with survival around 17 months from their earlier trial. If we assume that, and then clinically meaningful OS benefit of four to five months is demonstrated, that's what I think everybody's anticipating, then this will be seen as a new standard of care that's providing meaningful survival benefit in this hard-to-treat population. Of course, we have to also remember that safety aspect of it. Everybody was wondering how VEGF-related toxicities will be managed with ivonescimab, and we saw that high-grade VEGF-related toxicity was much less frequent than when Avastin was given systemically. Given this great safety profile, and then if the OS data shows meaningful benefit that is matching PFS data, then I think that will be a highly validating event for the entire field. Yeah. Look, this is already a class of drugs. You're seeing this. You have multiple phase III trials. You have significant pharma investment and a number of molecules in development. We think we have a differentiated strategy across both CR-001 and our matrix portfolio with ADCs. 70,000+ patients have been treated with ivonescimab to date. We think this data will be further validating, and we've also been encouraged by the translation we've seen to Western patients in previous studies as well. Okay. I know in the opening you talked about Kelun and how that partnership allows you to accelerate the data generation. They've initiated clinical development on CR003, which is the integrin beta-6 that was part of the collaboration, the ADC. I know they intend to look at that in combo with CR-001. I think one of the other important milestones that we find ourselves asking, or I guess answering a lot of questions about, is this upcoming Pfizer phase III data, where they have an integrin beta-6 with an MMAE payload. It's in a phase III study head-to-head versus docetaxel. I think they're guiding to data now sometime around mid-year. Just any thoughts on the trial that they've designed? I know that they've enriched for squamous patients or non-squamous patients. I know that they're looking at integrin beta-6-high endpoints specifically. Just curious what you think about that trial and the prospects for success? Ellie? Yeah, we are waiting for the study results from Pfizer's SGN-B6A. As you mentioned, the trial was optimized for non-squamous patients, also they have implemented a biomarker strategy looking at integrin beta-6 high patients, as well as all comers, and they're looking at PFS and OS. When we chose our compound of CR003, we carefully looked at the targets that are available, and integrin beta-6, we thought it's a really ideal target for ADC because it's overexpressed in multiple tumor types, whereas its expression is quite minimal in normal tissue. We agree with Pfizer that this is a really great target. How we built this CR003 was to improve the probability of success and create differentiated efficacy and safety profile. The biomarker strategy and the histology, probably that is most linked to how we are tackling heterogeneous expression of integrin beta-6, and then how these antibodies are getting internalized into the tumor cells. Our antibody that we have chosen was specifically selected for internalization capability, not just in the high express cells, but in the low express cells as well. Of course, the linker part is also important, looking at the overall systemic toxicities, how we can prevent that with improved stability. The payload that we are using is a topoisomerase payload, whereas Pfizer is using MMAE. When we look at Pfizer's compound, using Q2-week dosing schedule, and then we are seeing MMAE-related toxicities, which is a class effect such as neuropathy or neutropenia. Improved stability of our linker is designed to prevent systemic toxicity and bone marrow toxicity. Also topoisomerase payload, so far we have, is known to have a better therapeutic index compared to MMAE ADCs. Our optimized profile of ADC, looking at the antibody linker and payload, we think that it will give us a great chance to demonstrate differentiated clinical profile in terms of efficacy as well as safety. I mean, lung is one of our key indications, but we are also excited to study in multiple other indications such as head and neck, GI indications or gynecologic indications as a monotherapy as well as in combination with CR-001. Yeah. It sounds like Pfizer will actually have some phase I data looking at that ADC in combination with pembro and PD-L1 high expressing lung- Yes at ASCO as well, which I would imagine is probably of some interest to you guys. Maybe talk about the other ADC really quickly. CR-002, this is a PD-L1 targeting topoisomerase-equipped ADC. Again, Pfizer has an MMAE version of this. I think there's a Chinese company with a topoisomerase version of this. You talked about internalization. Has that same enhanced internalization, has that been built into CR-002 as well? I guess I ask the question because I know that there's a little bit of either observation or pushback that PD-L1 doesn't necessarily constitutively internalize as well as some of these other better-known solid tumor antigens. Do you think internalization is or could be rate-limiting to this development effort? Or do you think that's a problem that's just kind of a problem of other assets that we've seen at other companies? Oh, yeah. Internalization is one of the key mechanisms about how ADCs are going into the tumor cells and release a cytotoxic payload and then leads to tumor cell killing. Internalization is one of the key steps, right? We screened many antibodies targeting PD-L1 when we developed the CR-002, and specifically chosen the one that has best internalization capacity and also that leads to cytotoxic cell killing. We understand how the PD-L1 and then PD-1 angle is working together to improve immune-mediated toxicity as well as the cytotoxic cell killing. Our strategy was to choose the antibody that binds and then also internalizes the best, and then release a cytotoxic payload. From our perspective, we really like this target because the tumor types that are expressing PD-L1 matches really well with our matrix portfolio, and then combining PD-L1 ADC with the CR-001 PD-1 VEGF bispecific can provide a synergistic effect. This program is on track to file an IND middle of this year, and that's a Crescent run program. We'll have data in the second half of 2027. Again, another data readout as part of our broader portfolio. Is there any universe in which you're pursuing single agent registration for either of these ADC candidates? Yes. Yeah. We designed both these ADCs and selected them for both their activity as monotherapy and the potential to have a synergistic combination with CR-001. The goal here is really to be driven by the data and to where we can make a difference in multiple solid tumors and drive toward earlier lines of therapy. We'll pursue both of these as monotherapy and of course, in combination with CR-001 based upon the data that we generate. All right. Maybe just last question to finish up here. Maybe just speak to the state of the current balance sheet and what that allows you to execute on? Yeah. We ended Q1 with $180 million in cash, and that gets us into 2028, which is well past the plethora of data, robust data coming from the four clinical studies we'll start this year and read out throughout 2027. We're in a very strong position. Lots of interest in the space, and it really does put us in a great position to execute on what we have in front of us for 2027. All right. Very good. Really appreciate the conversation. Looking forward to the next couple of months here. It's going to be interesting. Thanks again for the time. Thanks everyone for listening. Appreciate it. Thank you.