Okay, great. Thanks everyone for continuing to join us here at the Guggenheim Biotech Conference. My name is Brad Canino, senior analyst. Very happy to be sharing the stage with the next fireside with Crescent Biopharma. We've got Ellie Im, the CMO up here, and Jonathan McNeill, President and COO over there. Thank you so much for joining us. Great. Thanks, Brad. We appreciate you hosting us today, and just a reminder, we'll be making some forward-looking statements today, so please refer to our SEC filings for more information. But at Crescent, we're focused on advancing life-transforming therapies for people living with cancer. It's a very exciting time. We're extremely well-positioned to deliver for patients in what we believe could be a $100 billion+ market. And we're advancing a matrix portfolio across next gen IO bispecifics, ADC, and standard of care combinations in our selected area of interest, which includes thoracic, GI, GynOnc, and head and neck cancers, and we have a multi-pronged strategy. Mm-hmm. The first element is CR-001, our PD-1 VEGF bispecific that we believe can be a best-in-class IO backbone. We're delivering on our ADC portfolio well, as well. That includes CR-002, a PD-L1 Topo ADC, and CR-003, which is an integrin beta-6 Topo ADC. Then we're also exploring synergistic combinations of CR-001 with a variety of ADCs, both in our pipeline and with external partners. Mm-hmm. Late last year, we announced a transformative partnership with Kelun-Biotech, which is a leader in developing and advancing commercial stage ADCs, and we're very excited about this. This is a validating partnership for us. Kelun-Biotech selected to work with us on CR-001 because they believe it can be a best-in-class, next-generation IO backbone for their full portfolio of ADCs. As part of that deal, we in-licensed the CR-003, our integrin beta-6 Topo ADC, outside of China, and Kelun-Biotech received rights to develop CR-001 in Greater China across their full portfolio of clinical stage ADCs. Mm-hmm. What this has done is set us up for a very exciting 2026. We're gonna initiate at least four clinical trials this year, which puts us on track to deliver clinical data across both monotherapy and standard of care combinations beginning in Q1 2027. And we also announced in December a $185 million PIPE, which gives us runway into 2028 to pass these clinical catalysts. So a very exciting time for Crescent, and look forward to discussing more today. Okay. Maybe we can drill a little bit more into CR-001, the PD-1 VEGF. Talk about how you're positioning it relative to the competitors, and maybe is there any angle of differentiation you have around certain aspects of the construct that you'd like to highlight? Sure. Ellie? Yeah. So it's, it's a really important question, and thanks for asking that so that we can address it here. Understanding how, immuno-oncology drugs have been developed so far, from PD-1, PD-L1 inhibitors, we know that introducing any changes to the construct, or potency or any types of functionality, including PK, can have an impact on clinical profile. And likely, we will need to run a randomized phase III trial to truly see how the changes that we've introduced in the laboratory setting affect, OS data or PFS data or long-term safety data. And looking at HARMONi-2 data of ivonescimab, versus KEYTRUDA with a hazard ratio 0.05 or so, with that data, we were convinced that this is a compound that has ability to demonstrate superior efficacy to KEYTRUDA with favorable safety data. Instead of trying to develop something that is better by introducing changes, we wanted to keep the key features of ivonescimab, including the VEGF binding site, PK part, as well as the functionality of PD-1. But we, of course, wanted to improve upon the part that where we could, and that's where we did with the PD-1 scFv domain. Currently, ivonescimab is produced at 10 mg per ml with a relatively low concentration, and that's what we see with the scFv antibodies. The stability is usually a problem, and they produce at low concentration. And with our proprietary amino acid chain engineering, we were able to push the concentration up to 150 mg per ml, and we are working on even achieving higher concentration with CR-001. So what it means is, we were able to produce a drug that is replicating cooperative pharmacology and PK and key features of ivonescimab, and then that reduces the risk of us going into clinical development. But also with improved stability with the scFv domain of PD-1, now we have addressed IP issue, and then it becomes a new molecular entity, and we have freedom to operate. And our strategy is very different from how the most of PD-1 VEGF compounds have started their clinical development, where they started in China, right? And then companies that adapted that design is now trying to figure out how best translate that to global clinical strategy. Whereas us, we are starting with our ASCEND phase 1 trial, that's the name of the study, in global setting. So we have sites in the United States, Europe, as well as APAC. And while we are doing that study, we also have our partner, Kelun, will be doing phase 1 trial of CR-001 in China as well. So we are addressing that question head-on of the translatability, but also have a very efficient way to generate data in a clinically meaningful way. So from the construct of the compound, by matching the key features of ivonescimab, which is the only PD-1 VEGF that has multiple positive Phase III study data, but we improve the stability, will give us a lot of benefit, including manufacturing capability, as well as potentially going into sub-Q later in the development stage. And then with global stage development from the beginning, we'll have a lot of efficiency in terms of getting to phase I study and then de-risking based on the early clinical data and going into registration-enabling trials. Got it. And now PD-1 VEGF has been an area that's had a lot of strategic transactions around it. Mm-hmm. A lot of that taking an asset from China- Mm-hmm. As you mentioned, though, you have a more U.S.-focused, global development focus. Mm-hmm. So maybe, Jonathan, how do you think that aspect of that development focus being more global is impacting your strategic discussions with pharma as you go forward? Yeah, look, I mean, I think it, it's a purposeful strategy. Mm-hmm. And at a high level, all the questions around the translatability that you see in this sp- Mm-hmm ... this space between Chinese and Western patient population- Mm-hmm. We just will never have to answer that because we will have the data. Mm-hmm ... in hand, generated in parallel. As everyone knows, these are global programs. We have, both for the PD-1 VEGF, but also ADCs, we're committed to develop them globally. So the element of that, having that data from the beginning, clearing your dose of three mg per kg for our phase I- Mm-hmm ... which is 10 times the starting dose of ivonescimab based upon our preclinical data, it is helpful in strategic discussions. But more broadly, as we think about the landscape here, we're focused on generating our clinical data. Mm-hmm. We have an opportunity to bring pharma and other potential partners along over the course of 2026 as we generate this data. But we are focused on generating clinical data across CR-001 and our ADC portfolio because we think that is when it'll be the opportune time to have those meaningful conversations on partnerships. Those partnerships could take many forms. It could be a selective partnerships focused on a specific ADC that's applicable to a certain tumor type, where a synergistic combination could make sense. It could be a larger global partnership, such as what you saw with BioNTech and BMS. There's various forms that could take, and again, that, the transaction we have with Kelun allowed us to generate meaningful data across a range- Mm-hmm ... of ADC combinations, while also maintaining control of our assets outside of Greater China. So we think it provides us a lot of flexibility from a partnership perspective. Mm-hmm. Got it. Okay, and now, well, 2026 is a big year of operationalizing- Mm-hmm ... the first development of CR-001. You're going to be generating data for next year. Mm-hmm. How do you expect external catalysts in the PD-1 VEGF space to shape the view of the class this year? You want to start there. Yeah, yeah. So this year, we are anticipating data from HARMONi-2 and HARMONi-6, potentially OS update, as well as HARMONi-3, initial data in the second half of the year. And of course, there will be additional data of more earlier phases study data coming from multiple different tumor types. From HARMONi study updates perspective, so far we've been seeing clinically meaningful benefits of a PFS and OS, as well as safety perspective, pretty consistent and favorable data. And so, we don't have a crystal ball in our hands, but as long as the OS data remains somewhere around where it, it's considered as clinically meaningful, I think this is an opportunity for all of us to learn what is the best way to develop this class of drug. 'Cause so far, what we are seeing is that this is a real class of drug that can potentially become the, you know, next generation IO backbone and besting KEYTRUDA. And so as long as the OS data shows that that potential is continuing, then I see this as an opportunity to learn how best to develop it with the indication selection, inclusion, exclusion criteria, and then the statistical design of the studies to further improve probability of success in the global development setting. And so, that's what we see that as a catalyst event. But from our perspective, we also have indications that outside the lung that we are focusing on in phase I trial, as well as our strategy is differentiating with the combination possibilities with our own ADCs, or potentially ADCs, or other assets that have shown promising data from the outside as well. So, it's a really great catalyst events that everybody is waiting for, and we will learn from those events how best to develop this drug. But overall, I think we will be very focused on executing our study and generating the data, and thinking about what our future strategy would be for the registration trials. Great. Maybe talk a little bit about the status of the CR-001, phase I, and then importantly, how are you designing the first-in-human studies to maximize the speed and value of information gained to understand its profile relative to ivonescimab? ... Yeah, so we are very happy to report that we had IND cleared, and then our starting dose is at three mg per kg, which is a very important point, because looking at ivonescimab data at 10 mg per kg, they had meaningful anti-tumor activity. So within weeks of starting dose escalation, we are getting to those relevant dose levels. And execution perspective, operationally, we are making really great progress. Happy to report. So we have a site globally, United States, EU, and then APAC, and we will be achieving first patient dosing initiation soon. As we mentioned in the previous release, as of first quarter this year, so we'll share that update. From a study perspective, we have eight different tumor types that we are prioritizing in the therapeutic areas of Thoracic, GI, and GynOnc, and we have chosen sites accordingly. So while we are doing dose escalation, we have a tumor type-specific backfill cohort that we will be opening. So what it means is, for example, at 10 mg per kg, after we clear that dose, we can open non-small cell lung cancer backfill, for example, 10 patients at that dose level, colorectal backfill, up to 12 patients, endometrial backfill, up to 10 patients. And this is an iterative process. So you can imagine, while we are doing dose escalation, we are also generating a lot of meaningful data that we can interpret it. So with the safety tolerability, PK, as well as, preliminary anti-tumor activity, normally, in phase I trial, you would see all comers and two lung cancer patients, three colorectal patients, and one ovarian patient. How can you interpret the data? But here, because we have chosen these tumor types that we think we have a high probability of success, and we can generate a clinically meaningful benefit with the PD-1 VEGF. So we will have operational efficiency, and then with this design, we are also generating the data that we can truly talk about what is the clinical profile of CR-001. But at the same time, we want to emphasize that in the backfill, as early as this backfill cohort, we are generating data in first-line non-small cell lung cancer patients. So first-line non-small cell lung cancer is an important element because, this is the indication where, as a monotherapy, ivonescimab has shown really robust anti-tumor activity and has, most amount of data so far. If we enroll first-line patients, and then the data shows, matching key features of ivonescimab, then we are addressing this question head-on. Safety tolerability, pretty similar. PK is pretty similar. And then, in first-line non-small cell lung cancer patients, we have a relevant and comparable efficacy data, and this will, this whole, data package will be, a opportunity for us to de-risk and then really show everybody that this is a real class of PD-1 VEGF. And going into the registration enabling trial after that point, then we have a higher confidence, understanding that, ivonescimab is the only PD-1 VEGF with multiple, positive phase 3 study results. So unlike traditional PD-1 VEGF trials out there, where other phase I studies, we believe our innovative study design allows us to generate comprehensive data in an efficient manner, and especially the first-line patient data set, it's a really critical way for us to look at the preliminary anti-tumor activity of the CR-001 pretty early in the development, and then we'll address a lot of questions. I think the key thing is, with that data set- Mm-hmm ... that we're going through Q1 2027, it allows us to connect the dots between the rational design of the molecule- Mm-hmm ... the preclinical data demonstrating cooperative pharmacology we have, and then the clinical data that Ellie just articulated. Uniquely, because of the design of CR-001, we believe- Mm-hmm ... it de-risks the later phase II, III registrational studies we would execute, both monotherapy and combination. Mm-hmm. That's a unique element of CR-001 because of the design that we made, right? Mm-hmm. If you think about that, all the data Ellie just articulated is from our own ASCEND trial outside of China. In parallel, Kelun will be generating data. Mm-hmm ...... CR-001 monotherapy in combination in China. Mm-hmm. And so it's going to be a very robust data set across- Mm-hmm ... relevant patient populations that we'll be able to start sharing in 2027. Mm-hmm. Great. So a lot of that was focused on monotherapy. What is unique about the way you have approached ADC combos relative to some of the other PD-1 VEGF competitors? Yeah. You want me to start, or either way? Yeah, I mean, I think it's a rational choice, right? Mm-hmm. So if it's a matrix portfolio where we looked across the areas of interest- Mm-hmm ... Thoracic, GI- Mm-hmm ... GynOnc, head and neck- Mm-hmm ... and we tried to select what are the best ADC combos- Mm-hmm ... either internally or externally sourced to address those, right? So the way we think about it is that we have differentiated PD-1 VEGF, as we just articulated, but each ADC and its rational design, we believe, is differentiated based upon its antibody linker and payload combination, right? Mm-hmm. So for CR-002, the PD-L1 ADC, we optimize the antibody for internalization and enhanced potency. The linker is the same one used in HER2, and we think that that de-risk it as well, and then we have a DXd payload. And if you look at that in combination, it's different than the MMAE payloads that are out there for other PD-L1s and some of the other linker technology used from some competing molecules. For CR-003, the integrin beta-6 that we in-licensed from Kelun-Biotech, it's an integrin beta-6 that's fully humanized on the antibody portion with a distinct epitope from Pfizer's two molecules, but the linker and payload combination is an enhanced version of that used in sac-TMT, which I think all of us are aware has generated extremely positive data in the Trop2 setting. Mm-hmm. We think each of those assets is differentiated, and then- Mm ... we have the opportunity to combine them. And as we think beyond our own internal pipeline, the Kelun has the opportunity to take CR-001 with their full portfolio of ADCs, which includes integrin beta-6 ADC in China, but obviously others, including TROP2, HER2- Mm ... claudin, Nectin, and other undisclosed targets. That data generation also has value to us as we think about our ADC strategy on a forward basis. Mm-hmm. So it's quite a robust combination strategy. Mm-hmm ... that allows us to pick the best combos to make a difference for early line patients across a range of solid tumor indications. I guess, you know, most of pharma seems to be prioritizing TROP2. Mm-hmm. Obviously, you have access to one with the Kelun, but your ones that you'll be developing are PDL1 and integrin beta-6. Why focus on those two targets in terms of what you brought in-house over a Trop2 or something else? So as Jonathan mentioned, we evaluated the targets with existing clinical data, 'cause initially, our strategy was not to take biological risk, and so we wanted to choose the ones that have a clinical data, and that's where we started. And then we looked at our matrix portfolio that we are building and what are the best targets that we can utilize, but also, we thought about how we want to compete with existing assets, and then where they are in terms of development. That's where PDL1 ADC and integrin beta-6 ADC came to the top two because of multiple tumor types that we can prosecute, and it fits well into our portfolio. By innovating antibody, linker, and payload, and utilizing topoisomerase payload, we thought that we could really differentiate from existing compounds that are slightly ahead in terms of their monotherapy or combination with conventional IO drugs in a couple of indications. So that it came about as looking at the probability of success, how much of risk that we want to take from a biological perspective, but how it fits into our portfolio, and how do we want to compete with the existing drugs that are in development, and then creating the differentiation that we need to potentially have the best-in-class profile. I think we're not done expanding the portfolio, right? Mm-hmm. There is an opportunity, of course, to access additional ADCs that we can combine with CR-001. Mm-hmm. Whether that's internally developed, externally developed, via partnership, that there's an open question there. And as we generate more data and see where there might be opportunities to make differences in specific indications- Mm-hmm ... that's certainly an area of discussion that we could have from a BD perspective. Okay. And then within Crescent- Mm ... do you consider these first two ADCs to potentially have independent value of their own with- Mm-hmm ... monotherapy development paths or non-PD-1/VEGF combo development paths? Yes. Like, yeah. Yes. I mean, and look, look what happened to, with ImmunoGen and, and HER2, right? Yeah. So we each of these independently could be very valuable assets. Mm-hmm. Although we do see the potential of synergistic combinations- Mm-hmm, mm-hmm ... and are very likely to pursue those, but yes. Mm-hmm. You know, it's a scenario where, again, if you look with the matrix portfolio- Mm ... certain indications we'll likely pursue synergistic combinations. Mm ... with standard of care chemo. Mm-hmm. In others, it will be with the ADCs. So it's not a blanket statement, but yes, we see each one has an independent value. Yeah, we're, of course, we have to assess monotherapy clinical profile of these ADCs carefully, and that's the initial step of development. And so while we are doing that, we will assess different indications and different settings. There's, you know, front line setting, but then the second line, third line setting, we're even going into earlier setting of adjuvant and neoadjuvant. So, our ADCs, the way that we have improved the capabilities of all aspects, will have a chance to create differentiated profile, and then we will assess it in all the settings as monotherapy, as well as in combination. And then this aspect also is important even for us to do the combination, 'cause contribution of component part is what FDA is really looking into before they approve a combination therapy. So we'll have a pretty comprehensive clinical development strategy for our ADCs. Help us understand how and when you start to generate ADC combo data with CR-001 and when that might be delivered? Yeah. So, we've said that there's gonna be at least one combo study initiated- Mm-hmm ... with CR-001 in partnership with Kelun this year. We haven't disclosed that target yet because it'll be from Kelun's pipeline. But then, as Ellie articulated, as we generate the monotherapy data- Mm-hmm ... with CR-001, CR-002, and CR-003, there's an opportunity for us to initiate combo data, both CR-001 and CR-003- Mm ... next year, so 2027- Mm ... and then CR-002 and CR-001 as well. Mm-hmm. All those combinations are there, and we'll start to see that data in 2027. Okay. Then maybe just to close out, current state of the balance sheet and runway, where does it bring you through in terms of these milestones we've been talking about? Yeah, so we did $185 million PIPE last year, so we had $246 million pro forma on the balance sheet as of September thirtieth. Takes us into 2028, so beyond all of the clinical milestones that we just articulated. Okay, wonderful. Well, perfect. Thank you, Ellie. Thank you, Jonathan, and thanks, everyone, for listening in. Great. Thank you.