Crescent Bio coming back. I think it was just a year ago that we had the first opportunity to showcase the story. We have the full management team with us today. We have Josh Brumm, the company's Chief Executive Officer, Jonathan McNeill, the company's President and COO, and Ellie Im, the company's CMO. We also have Amy Reilly in the audience, Chief Communications Officer. Thanks Crescent team for being here. Obviously, a big 12 months or so that we have upcoming. Josh, before we get into too many details, maybe just give us the lay of the land for those who are a little less familiar with you. Yeah. Great, Eric. Thanks for the invite today, and thanks to Cantor. Just as always, we may be making some forward-looking statements, so please refer to our SEC filings in that regard. Eric, you are totally right. It is crazy it has been a year. What we have been able to pull together in the last year has been pretty fantastic from our perspective. It is an exciting space. There has been a lot of involvement in the clinical data in our space. I think it is a great class of drugs here that we are developing for oncology, and our background really started in October 2024, when Peter and Fairmount Funds decided to put together a company called Crescent Biopharma, Inc. around next generation I-O therapy and a bispecific for oncology. But really did it in the premise of belief in combination therapy. We have the CR-001, our bispecific asset that is in phase I/II study now in the clinic, as one part of our strategy. But on the other sleeve of our strategy, we have our own ADC portfolio, and we believe in combining the next I-O backbone therapy of CR-001 with ADC assets and other modalities in time to really benefit patients in cancer. We have had a great run over the last year. We did a big partnership with Kelun-Biotech, which we can talk about, bringing in a second ADC that is in the clinic now, CR-003, which is an integrin beta-6 Topo1i ADC that started dosing in China through our partnership with Kelun-Biotech in Q1 of this year. At the same time, we put CR-001, our bispecific in the clinic. CR-002, our PD-L1 Topo1i ADC will be in the clinic this year, so more to come on that soon. And we really have driven the portfolio deep into the clinic now. We will have three assets total here relatively shortly in the clinic, and we have a slew of data coming starting in Q1 2027, and we can talk more about that as well. A lot of progress indeed over the last 12 months. As we look ahead for the next 12 months, what do you think are the top two or three things that are going to move the needle for investors? Look, clearly everyone's paying attention to HARMONi-3, right? That's out there. We'll see how that reads out. I think from our perspective, the recent update from Akeso on BTC was a big injection of confidence into the space. Again, I think what we felt from pharma going into ASCO and then coming out of ASCO on the HARMONi-6 data, was a big move. I think probably 50/50 was, "Hey, I'm committed to the space. I think it's going to be a real class of drugs" prior to ASCO and HARMONi-6, and now I'd say if it's not 100%, it's close to it. If you got an ADC or an oncology portfolio, and you're big pharma, you're believing in this space, and so there's a lot of activity there. I do think that's something that we're obviously paying attention to. Okay, great. Let's get right into it and CR-001. Just first eye level structure, remind us of where this molecule came from, how it was designed, and why it was designed that way. Yeah. Ellie, you want to take that? Yeah. It was internally developed by Paragon, and of course, Paragon has done a great job of producing antibodies, and that is a foundation of many successful companies at Fairmount. When we looked at the HARMONi-2 data, initial PFS readout in 2024, that is when we decided to keep the key structure and the functionality of ivonescimab, building CR-001. Because deviating from that structure or potency can lead to different safety or efficacy profile, and in I-O, we have seen many of those studies that failed at phase III. Instead of us spending too much time in the lab space trying to differentiate for ivonescimab, we know that this structure works, so we wanted to keep the key features of ivonescimab, but we wanted to improve upon the two things. One is a PD-1 binding part. We use the domain that is matching pembrolizumab instead of a penpulimab. We also improved upon the stability of the compound by engineering scFv domain of the bispecific. As a result, ivonescimab is currently being manufactured at 10 mg per ml, which is a relatively low concentration, and given their recommended phase II dose is 20 mg per kg, the volume of infusion is quite high. Whereas ours, with our preliminary run, we were able to push the concentration up to 150 mg per ml, and we did not see any aggregation. What it does for us is the manufacturing perspective, and the vial size perspective, infusion volume perspective, it gives us huge advantage. But down the road, we can also look into the potential sub-Q administration, which KEYTRUDA just recently did successfully as their life cycle management. What our strategy allows us is we have already demonstrated in the preclinical setting, in vitro setting, that it matches the functionality of ivonescimab cell binding anti-tumor activity of the mice and the PK of the monkeys. We are running ex-China global phase I trial of CR-001 right now. In dose escalation and backfill part of the study, if we can demonstrate safety tolerability, PK, receptor occupancy, serum VEGF neutralization, and anti-tumor activity matches that of ivonescimab, then we will accelerate our late-stage development by combining with various agents of standard of care chemotherapy or ADCs that we have already started with a Kelun-Biotech partnership, as well as other compounds. What it helps us is the time for us to start those registration studies, and also checking the box for probability of success of the compound. Do you expect or do you know what your targeted dose will be? Will it be 20 mg per kg as well? We will follow our data. We are making great progress on the phase I study. We expect to report out that comprehensive data in 2027. Any reason to think ballpark it won't be in that range? I think our base case will be quite similar or comparable to what ivonescimab has done. Okay. The one aspect of your molecule that is somewhat differentiated from ivonescimab is the PD-1 binding domain. I think you went with a higher affinity binding domain, or you affinity optimized that binding domain. Just talk a little bit about how that compares to what's being used in ivonescimab. ivonescimab used the penpulimab, which is a PD-1 inhibitor developed by Akeso, and it is approved for nasopharyngeal carcinoma in China. It made sense for them to use their own PD-1, whereas for us, we use the one that is matching pembrolizumab. Of course, there is no direct comparison of the two PD-1 inhibitors out there, but I am sure everybody understands how many trials pembrolizumab has shown efficacy and the safety in a successful way. We feel pretty confident with our strategy of going with a pembrolizumab binding domain, and then keeping the other features relatively similar to that of ivonescimab. Yeah. I would just maybe say, as you asked about catalysts in the space, I think bringing it back to our catalysts, Eric, the design of the molecule, testing it out clinically now, showing that what we saw pre-clinically and seeing that clinically, that is really the first of kind of three major reads coming for next year. If it is okay with you, maybe just talk about those for a minute. We are going to get to that. Okay. But let's just give us quickly the lay of the land of the VEGF PD-1 space first. Sure. Again, you've tried to match ivonescimab as closely as possible. How many others out there do you think are of similar ilk, and how many of those are unpartnered assets at this stage? I don't think anyone can claim that they know all PD-1 VEGF inhibitors that are being developed out there, especially in China and ex-U.S. space. What's unique, I think about our case is that we are doing global development. I think up to date, all assets that have been in-licensed or collaborated by strategics have been coming from China. Right? Their early-stage data is coming from China, and then they are doing various work to then bridge that into global development, and which we've seen some of the challenges, right? How that development can sometimes slow down where they need to modify their development strategy. Whereas in our case, we are matching the key features of ivonescimab, and then we have that confidence, building that confidence with the clinical data, and we are generating global clinical data, and then that will allow us to then go into global registration trials in a timely fashion. In that way, I think we are very uniquely positioned. Yeah, I would just maybe add that I think we've talked about this before, but I think ivonescimab, clearly LonoVA, Merck's asset, and BioNTech are the ones that we're paying the most attention to. When we first started, we got asked a bunch of questions like, "How can you catch up?" And, "How do you compete against all the bispecifics in China?" I think the execution that we've been able to process over the past year really now puts us in a place where, and we'll talk about this more this fall, how quickly we can generate phase III study starts. It'll be tough even for Chinese assets to come in and catch us from a global perspective, and that was the goal that we had, and we've made some great progress on that. If I were to redefine my question by saying how many VEGF PD-1 bispecifics are there in global phase I or later development that are unpartnered, you would say one? One. One. Yeah. Okay. Great. Let's get into the development program. First, you mentioned that you're looking at the competitor, ivonescimab, in the HARMONi-3 trial. How, if at all, does that impact what you will be doing in your phase I development? I think there's lots of lessons learned, right? Ellie touched on it already about just starting with the Western patients. We think that's the big advantage. We can talk more about that. I think the lessons learned from the first-in-class asset is something that we're paying attention to very closely. I think also the success that they're having across multiple phase III studies. They've done great work. I think they validated the space time and time again. I think that because the space is so big, there's room for multiple players here clearly, and we'll leverage those lessons into our phase I, II study designs. More importantly, as we learn from those studies, thinking about the phase III studies we're going to start, where we start those studies, what indications, are all things that we're leveraging as we think about really trying to get to revenue. Okay. Remind us of your phase I trial design. I know it's quite innovative. Yeah. We are enrolling eight different tumor types in the phase I/II study. We have non-small cell lung and four GI indications, including colorectal, gastric, hepatocellular carcinoma, biliary tract, and then endometrial, ovarian, and cervical indications. We have a dose escalation as a monotherapy, and as we are clearing each dose level, we have an opportunity to open tumor type-specific backfill cohorts of select tumor types. For example, after clearing 20 mg/kg, we can open non-small cell lung cancer backfill cohort up to 12 patients in that dose level, and colorectal backfill up to 12 patients, or biliary tract backfill up to 12 patients. This can happen at each dose level as an iterative process. You can imagine that we can generate safety tolerability PK receptor occupancy data, as well as anti-tumor activity data in a very efficient fashion. Also, this will allow us to look at the safety and efficacy per tumor type instead of all backfill put in together. You might have two ovarian patients, three lung patients. It's very difficult to interpret that data. On top of that effort, we will also include frontline treatment-naïve non-small cell lung cancer patients as part of monotherapy backfill. What will allow us to do is to clearly demonstrate anti-tumor activity of PD-1 VEGF, our CR-001. If the ORR is somewhere around 50%-70%, as other leading PD-1 VEGF bispecifics have shown, then this is a clear way for us to demonstrate that, yes, safety tolerability, PK, pharmacodynamics, as well as anti-tumor activity. In this early stage study, we are clearly demonstrating that CR-001 works quite comparably. Okay, let's, for a moment, put aside the backfill cohorts and the tumor-specific histologies and just talk about the dose escalation and the need or desire to show safety, PK, some sign of tumor activity, et cetera. Yeah. When will we see that data, and what would constitute proof of concept from that aspect of the study? Yeah. So of the backfill in dose escalation cohorts, the Q127 data that we promised is on track. That really for efficacy, we're focused on the first-line cohort of 12 patients in non-small cell lung cancer. That's where we're going to be looking for the 50%-70% efficacy that we're looking for. Is that at a lower dose, Josh? I'm sorry to interrupt. That'll be at likely a much higher dose, so 20 or 30, but in a dose we would take forward, potentially. Okay. Yeah. It'll be meaningful. From the second-line plus data from that study, we'll have, we've said, triple digits worth of patients for safety, PK receptor occupancy. We will look at half-life, all the things that we think really matter from a comparability standpoint to ivonescimab. We have got the efficacy. We knew the second line plus is going to be messy as far as efficacy. That has been out there from 10%-20% the BioNTech and ivonescimab studies. We wanted the first line to compare efficacy, but then we have got a much larger pool of patients for safety and tolerability. What kind of follow-up would you expect on the 12-patient cohort in frontline lung? We will mainly focus on, as an initial read, response rates and then durational response. Of course, we will have follow-up data to show the durability. In that study, we talked about it as three buckets of data, but we will also have data coming from standard of care combination in frontline as well as late line patients. That data will complement in terms of efficacy data, not just as monotherapy, but in standard of care combination, how CR-001 works. Then we will provide longer follow-up data with maturity. Yeah. That is the second bucket of data which will be coming in mid 2027. By then, we have said we will have hundreds of patients enrolled in the study. That will be standard of care chemo combinations, plus our internally developed PD-1 VEGF across multiple tumor types. More to come on what those tumor types are, but you can imagine that GI, thoracic, and gyn will be areas of interest. That is middle of the year. What that is designed to show is that you are having the activity in combination with chemotherapy that positions CR-001 to be a potential best-in-class I-O backbone that works well with standard of care chemotherapy combinations. We recently saw the data from Akeso and first line biliary tract showing the potential of PD-1 VEGF in China with chemo combinations. That is something that we are going to replicate, but in our global study that is currently active across the U.S., Europe, and South Korea, across multiple tumor types. This would be positioning CR-001 to position well with chemo. The third bucket of data which we will touch on is our ADC combo data as well, all of which is coming in 2027. Just to put a patient number on it, those expansion cohorts will be at least 20 patients. So there will be 20, 30 patients worth of data per indication from the standard of care chemo combos. Again, looking at multiple chemo agents across multiple indications, multiple line settings, first line, second line, you are going to really have a good idea about the ability for this drug to be a backbone foundational therapy. Between now and the first data release in Q1 of 2027, are we going to get any play-by-play with regard to where are you in the dose escalation and also the simultaneous expansions? I think we will come out with an update sometime this fall around what to expect in more detail for next year. Clearly talk about the indications that we are going to be studying in the standard care chemo combos. CR-002 update will be coming as well. As we said, that is going to be in the clinic this year as well. Then, we will probably give an update on our relationship with Kelun-Biotech and what they are doing for that third bucket of data, which we will talk about as far as the ADC combo data. As you know, they have started dosing now in a sac-TMT CR-001 combo. It will be the first bispecific combo with sac-TMT that is going on in China. Likely see that expand into different indications as well, as well as potentially expand the relationship beyond just sac-TMT into their other ADC portfolio. All of that, I say, is on the docket for this fall, and stay tuned on that. Okay. Then just sticking with CR-001 for a moment, how are you going to make the decision on different histologies? Well, we're going to follow the data first and foremost. That's why we designed the study we designed. We're also going to follow the competitive landscape. Right? The question for us is how many studies can we run and how quickly can we get those started? I think that will be part of the update this fall as well, is when we intend to start phase III studies. I think that will be important for investors and patients both to hear. Like, "Hey, when can we get our hands on this drug, and how quickly can we get on the record towards revenue?" I think we will follow the data, we will follow the competitive landscape, and we will look across those 40+ indications, plus opportunities to expand the label like we've seen in colorectal. We will decide what foundational revenue we want to go. It will be some mix potentially of first-in-class opportunities where nobody's at right now, with a bispecific. It also could potentially be where we fast follow in large market opportunities, so it will be a combination of both of those. Okay. I got one, but you can go first. You mentioned some lessons that you've learned as you've watched other sponsors go from China trials to global trials. Can you maybe just go into, quickly, sorry Eric. No, please. What those lessons are, especially as it pertains to HARMONi- Sure 3, perhaps continuing? Ellie, you want to touch on this one? Yeah. We'll, for example, use HARMONi study, right? Because that's the one that has most information available. The HARMONi-A trial, EGFR mutated non-small cell lung cancer trial in China, was done first and demonstrated the PFS and OS benefit. Summit then took over global development of that asset in the same population, and they started enrolling patients in China. There was a little bit of lag between Chinese patients' enrollment and ex-Chinese patients' enrollment. So at the time of their final survival analysis, which was last year right before ASCO, they had just a small miss, very near miss of a survival benefit from the statistic perspective. A lot of KOLs saw that as clinically meaningful, but nevertheless, it missed the statistical significance. Summit shared from their press release that the Western population that came in for the study did not have sufficient follow-up to demonstrate the survival benefit. That's why they missed the statistical significance on survival analysis. They actually did a great job on following analysis. The longer follow-up, sufficient follow-up in Western population did provide improved survival benefit in the Western population. This is one example of how you start with the Chinese data, and then how do you want to then start working with the global sites, operationalize it, working with the FDA, EMA, or KFDA, or PMDA to align on the strategy, data analysis, and then statistical analysis time point. So that's one of the examples of how the fact that we are generating global data and then working with the FDA and EMA from the very beginning, will help us execute seamlessly. Also learning from the data that's out there and utilizing our own expertise on how to execute the study and improve the probability of success of that study. Yeah. You heard a similar response from Summit with the HARMONi-3 PFS interim look, right? At ASCO, they had the call and talked about that Western patient data was just probably immature, and timing was an issue. Those are some lessons that you can apply to how you think about the timing of your stats and the program you are developing. Eric, you had a question? Well, thank you for that question, Andy. Just back to the discussion of disclosures later this fall on phase III indications. What would be the rationale for giving us phase III strategy even in advance of kind of- So we are not going to talk about indications. We want to talk about the timing of when those could start. So that gives people an opportunity to understand, when do we start the march towards revenue. Got it. Thank you. All right. Maybe we should, in the last five minutes, move on to CR-003 and the Kelun-Biotech partnership. First of all, just tell us what your learnings are, your take home messages from the Pfizer data. We understand that Pfizer is still keen on their asset, their SP. Yep But any thoughts you have there? Yeah, I mean, overall, I think we've said this before, that we thought that study read out as expected, right? I think that obviously Pfizer's spent a lot of time talking about the size of that opportunity prior to the readout, validating the size of that market opportunity. They have a second asset in development as well. They're very much committed to the target. So we just feel like that from our perspective, how we designed all three parts of the molecule, how Kelun-Biotech designed all three parts of the molecule, and why we did the deal with Kelun-Biotech gives an opportunity to really optimize on that target and to have some real benefit here for patients, both in the monotherapy setting, but also in combination with CR-001. You doing anything differently at all post-Pfizer? On our strategy for clinical? No. Okay. Okay. What is the next disclosable or communicable event on CR-003? Yeah, CR-003's already in the clinic. There's an ongoing phase I/II study in China run by Kelun-Biotech. We're on track to report data from that study in Q1 2027, so that'll be monotherapy CR-003 data. On the back of that, we'll have the opportunity to initiate global monotherapy studies, but then also to work with Kelun-Biotech to initiate a combination study of the integrin beta-6 Topo1i ADC CR-003 with CR-001 or PD-1 VEGF in China as well. That speaks to our broader combination strategy. We mentioned that there's already an ongoing CR-001 sac-TMT combo study. Kelun-Biotech, as part of our collaboration, has the opportunity to use CR-001 with any ADC in their portfolio. They've disclosed B7H3 ADC, Nectin-4, Claudin ADCs, among others. So we're very excited for them to continue to generate data there, which we get access to. In addition, we have our own internally developed PD-L1 Topo1i ADC, which perhaps we can touch on next, which we're excited for that data as well. All right. One more question, maybe two more questions on CR-003. Just with regard to the Q1 data release from Kelun-Biotech, knowing that it's out of China, what would constitute differentiation or a best-in-class profile relative to the Pfizer asset? Yeah, I think we'll have to wait for Kelun-Biotech to tell us exactly what they are going to share. We can't get ahead of that. Obviously, we have some thoughts on that, but we'll let Kelun-Biotech talk more about what and when they're going to ultimately share that data. Do you think it will be evident that there's a best-in-class profile from a phase I trial in China? Could be. I think it could be. Obviously, people will want to compare that to the Pfizer readout and the earlier phase I data from the B6A program, so that'll be something that we're aware of. I think there could be some differentiation there. Okay. Josh, I can't help but come back to your comment earlier about a potential to expand the partnership with Kelun-Biotech and what you mean by that. Yeah. What I mean by that is from Kelun-Biotech's opportunity, people have to remember that Kelun-Biotech is competing with Akeso, right, in China. That's why they in-licensed our CR-001 asset. They needed something to combine. They never had a first-gen PD-1, so they needed an I-O agent to combine across their 10+ portfolio of ADCs. They will likely expand, looking at combinations beyond sac-TMT with CR-001. As they do that, we'll talk more about what other ADC targets that they use to combine with CR-001. That's when I talk about expanding the development of CR-001. It's with their portfolio. Not bringing in additional assets. There's always that opportunity, so I wouldn't say that's never off the table. We certainly are very much in agreement with their view on combination therapies, and we're constantly looking for ways to combine ADCs, whether they're approved ADCs, whether they're late-stage clinical ADCs like sac-TMT, or early-stage clinical or pre-clinical ADCs with CR-001. Because I think going back to the opportunity here, it's rare you have an opportunity to replace a massive label of the current first-gen PD-1s with what we call backbone revenue, foundational revenue. That allows us then to get to the best-in-class opportunities and execute on our strategy of our belief in combination therapies. We are always looking for combination opportunities with CR-001, so I would say that's never off the table. Okay, thank you. Jonathan, I know we only have a minute, but I can tell you really want to tell us about the latest on CR-002. I'll just say I don't want it to be the stepchild because it's going to be entering the clinic in the near future, and that's our internally developed PD-L1 Topo1i ADC. So that'll be entering the clinic. That's a study that'll be run by us globally outside of China, and we'll have data on that asset in the second half of 2027. So we have so much going on that it's often lost, but we're very excited about that asset and think it has a potentially differentiated profile from another Pfizer ADC and also Henlius as well. Very fair. Team Crescent, thank you for being here today. We appreciate it. Thank you.