Mid-biotech team at BofA. pleased to be joined with Crescent Biopharma, with Joshua Brumm, the CEO, and Ellie Im, the CMO. Thanks for joining us, guys. Thanks for the invitation. Yeah, maybe just at a high level for a couple minutes, just could you introduce, you know, the company's sort of PD-1 × VEGF space and sort of the recent developments, what you're looking forward to? Yeah, for sure. I mean, look, I think, Crescent's vision is to build the world's next leading biotech oncology company, and we do that through a two-pronged approach. The first approach is on our next gen foundational IO bispecific program, CR-001. The other side of the coin there is our ADC portfolio, and really with our vision towards winning in the front line setting in various tumor types and indications around synergistic combinations. That's been the strategy for the company for quite some time. We have started this year in the clinic with our first program, CR-001, which went in and started dosing patients in early Q1. Our second program, which is partnered with Kelun-Biotech, for our first ADC, our ITGB6 topo ADC, CR-003, it is now in the clinic dosing patients as well. Yesterday, Kelun-Biotech announced that our 001 program was IND accepted in China, so it's starting there as well. We've got 3 INDs cleared so far this year. Our second program, in our ADC stable, our 002 asset, our PD-L1 topo ADC, will be in the clinic middle of this year. We plan to start at least 4 clinical studies across those 3 programs this year. We're in a really good position to drive towards real data creation, starting in Q1 2027 with the 001 program and the 003 program in China. We're really set up for a real nice run of robust data coming in starting Q1 2027. Yeah, that's helpful. Maybe, you know, at a high level, I think when people think PD-1 × VEGFs, most people think lung cancer. I guess, you know, there's potential for 40, 50 potential label indications, maybe even more. How do you guys decide which indications to prioritize in development and commercial opportunity as a sort of following pembrolizumab's path? I mean, look, I think I'll let Ellie Im talk about this a little bit too, but what we've been out saying is that in our CR-001 program, we're focused on generating 3 buckets of data by mid 2027. The 1st bucket of data from our ASCEND study will be from our backfill cohorts, which will be our 1st line non-small cell frontline data. I think that's gonna be really important for us to validate clinically, you know, how we design the small molecule to be similar to ivonescimab. We've seen that from a preclinical perspective, but now having the clinical data to replicate that will be really important. That 1st bucket of data will be Q1 2027. The second bucket of data that we're really focused on is looking at CR-001 combination with standard care chemo, multiple chemo agents, across multiple indications, you know, 12+ patients per arm. S O we can really get a robust response and really validate that we can work and combine CR-001 across multiple chemo agents and think about, getting back to your question, where we wanna take the program from a registrational perspective and what indications. The third bucket will be through our Kelun-Biotech partnership and the ADC combo with CR-001, which we'll announce that study, at least one study that'll start this year sometime in Q3, Q4. We're really gonna be guided to know what indications we wanna go into by data. Driving towards those three buckets of data by mid 2027 will really enable us to have the data in hand, as well as monitoring the competitive landscape on where we wanna go with our program. It's not just the CR-001 program, but it's also the CR-001 program plus ADCs in combination. We'll really step back and look at where we can make the biggest impact, where we can think about being first in class versus best in class, and let the data drive those decisions. Yeah, that's helpful. Maybe speaking about that Q1 2027 data package, can you just maybe speak to, you know, patient numbers, follow-up, durability that we expect to see in that, and then maybe, you know, how important it is that you're showing first-line data, whereas, you know, typically you see later-line studies first and then movement in the earlier lines. Sure. I'll just quickly say that, look, we understand the value of creating meaningful clinical data. What we didn't want to do is spend time debating second line plus data with others that have been out there before. We know that data anywhere from 12-25% response rates. It depended on if you had PD-1 pretreatment, what line of therapy you came from, and how many% of those patients per line of therapy were in that data set. We really wanted to be able to quickly identify efficacy and separate. That's why we wanted to show that first line non-small cell. As far as what we expect to see in some of the patient numbers and what not, I'll let Ellie talk about the ASCEND study a little bit. Yeah. We have a global phase I/II trial of CR-001, our PD-1x VEGF bispecific, studying 8 different indications, lung cancer and then GI, as well as a gyn-onc indications. The data that we will present early next year will have a very comprehensive safety tolerability, efficacy, PK, and pharmacodynamics data from our dose escalation, as well as a tumor type specific backfills. As we are escalating the dose, for example, we have 3, 10, 20 and 30 mg per kg. As we are clearing these dose levels, we have opportunity to open tumor type specific backfill cohorts, for example, non-small cell lung, backfill, colorectal backfill or endometrial backfill. This is an iterative process that we can generate multiple number of patients' data at each dose level, and it will include frontline non-small cell lung cancer data as well. With this data set being shared in early 2027, we will then have clinical data to really compare how CR-001 is working compared to ivonescimab as well as other leading PD-1x VEGF bispecifics. Yeah, that's helpful. You know, when we think about the PD-1 x VEGF space, I think a big debate is always, you know, sort of global data, Western data versus, you know, China data. What are your thoughts on that? You know, given you guys are running a global trial, is that an advantage for you? Sort of maybe thinking about, let's say the data looks good. What's the path forward to registration? You know, is it, you know, all shots on goal? How do you think about capital allocation, potential partnership as well? Ellie, why don't you talk about HARMONi-6 a bit and the read-through that we've been getting asked quite a bit around, you know, what does that mean for Western patients? Yeah, yeah. Versus Chinese patients, and the discounts that people are trying to apply there. I think, you know, probably not a great idea to do that. Maybe just walk through some of that data, and then I'll talk about capital allocation. Regarding your question, I think that's one of the biggest questions that's out there, as long as well as overall survival benefit of this class. For us, it's great that we are running a global trial of ASCEND. It's studied in the United States, Europe, as well as Asia Pac. We also have our partner in China, Kelun. They will do CR-001 phase I trial as well. We are generating meaningful data from China as well as a global stage. What's great about this is that we don't have to worry about data translatability and then working with the FDA, now the different endpoints and how to do the registration trials and powering all those things that we are seeing, some of the difficulties that we are seeing with the Summit case. We don't have to worry about any of those things, as we are learning all the great lessons from Summit and others that are ahead of us. To Josh's point, now we are anticipating HARMONi-6 overall survival data at ASCO plenary session, which is really exciting. A lot of questions that we are getting is a HARMONi-3 trial, which is the same population that's studied in the global setting, squamous non-small cell lung cancer patients in combination with the chemotherapy. What we are seeing so far is that HARMONi study, which is a global study, they studied the EGFR-mutated non-small cell lung cancer patients. Compared to the study, HARMONi-A study, the same population done in China, we are seeing great translatability of survival benefit between Chinese population and the Western population. We are also seeing meta-analysis data coming from global phase III oncology studies. Survival benefit perspective, Asian patients and the global population, that translatability is quite good. Overall, we feel really confident about PD-1 x VEGF as a class, and then the data translatability that we will see, and more data coming out, everybody, including the patients, investigators, investors, as well as the pharmas and strategics. We are gaining a lot of confidence that this is a next generation IO backbone that has a full potential to replace PD-1 inhibitors. Yeah, that's helpful. Then maybe, you know, on the link between PFS benefit and OS benefit, I guess just thinking long term about, you know, what bar you need to see versus PD-1s to see, you know, uptake. Then I guess looking at the PD-1 x VEGF class as a whole, you know, is it sort of a one winner takes all space, or do you think there's optionality for multiple players to compete across, you know, the potential 40-50 indications? Yeah, I mean, I think our experience is telling us in the field, right, having now dose patients been in the clinic, working with investigators, it's about clinical benefit, right? I think we feel like 4 more months of benefit is enough for people to get really excited about this and see this, you know, new class of drugs kinda replace the first generation PD-1s. I think that's what we're kinda looking for out of some of this data that we're gonna come see at ASCO. You know, I think that puts us in a great position with our strategy with CR-001 and how we design these studies. I think, you know, it's very, very much a focus of ours to generate that data and be in position to really be a best in class bispecific partner of choice with our CR-001 program by middle of next year by generating data across the three buckets and having the design of the molecule replicate the cooperative pharmacology of ivonescimab. I think that's the key piece that we are looking to win on long term. I don't think it's a winner take all strategy. I think if we can replicate the cooperative pharmacology and the clinical results of ivonescimab and the safety of ivonescimab in the clinic, I think that, you know, you mentioned earlier 40 plus indications that are on label for PD-1s now. The opportunity and indications like CRC, where you see label expansion, and some of the nice data there in the phase II studies in CRC in China, 80% plus response rates with the bispecifics. I think those are areas in combination with chemo standard of care. I think those are some of the opportunities where there's just so many ways to go, whether you want to be first in class in an area where people aren't working with bispecifics right now in combination with standard of care, like endometrial, one that Ellie Im is quite familiar with, or you want to go in combination therapy and go win in non-small cell. I think all of it's open. It's just a matter of where you want to place your bets and how you want to devise your own clinical strategy. Plenty of ways to win here. Yeah, that's helpful. Maybe switching to the partnership with Kelun-Biotech. You know, a big debate in the space has been sort of Chinese biotech and the speed of development there. I guess, can you speak to how your partnership maybe allows you to quickly inform go, no-go decisions for ex-China development? Yeah, I mean, look, I think, first of all, we really appreciate our partnership. I think it's a unique partnership, and I think people are just now starting to understand the value of what this partnership could potentially deliver. I think that, you know, encourage you to talk to Kelun as well. I think we both are working extraordinarily quickly. I think that they are also pleased with the speed at which we're working, and I think together we're working at a pretty rapid clip. I do think that, as Ellie mentioned, you know, we have the ability to start the study globally with 001, kind of getting around some of the issues that previous, you know, people have had to deal with in the space. I think having the supplemental data from 001 from China is gonna be helpful. Having them run the CR-003 program, our ITGB6 topo ADC, which we're really excited about, in China early, and then getting that data, thinking about how would then we how and when we file the IND, how we, you know, move forward quickly here with our development in outside of Greater China with CR-003 and in combination with CR-001, is something that, you know, really does allow us to accelerate that development, maybe shaves off 1 to 2 years of development timeline. It's a really good partnership, and we have the ability to work together to find the best ways to bring these combination strategies forward for patients. Yeah, that's helpful. You mentioned CR-003, the integrin beta-6 topo ADC, which is already in phase I in China with data expected Q1 2027. I think you designed it with superior internalization in low expressing cells and a stable linker to reduce toxicity. I guess, how does that optimization over prior programs translate into a differentiated clinical profile? You know, can you frame what we can expect in that readout in Q1 in terms of tumor types, patient number, follow-up, et cetera? Yeah. We intentionally designed that integrin beta-6. Kelun-Biotech did a really great job. Kelun-Biotech is known for their expertise in building quality ADCs, such as the sac-TMT. When it comes to antibody, of ADC, it's about internalization, how you can internalize and then release that cytotoxic payload. To your point, they use the antibody that have a potentially superior internalization power, not just in the high-express cells, but in lower-express cells as well. That can overcome the issues around the tumor heterogeneity. With the more stable linker that they have used, it can reduce the risk of systemic toxicity as well as releasing free payload in the systemic blood. The topo payload that we have is a excellent bystander effect, and of course, is known to have a wider therapeutic index compared to some of the other payloads that are out there, such as MMAE. All this differentiation that Kelun-Biotech put in, and we love this asset for that, it gives us a great chance to create differentiated efficacy profile, not just in non-small cell lung cancer, where Pfizer is doing phase III trial, which is the readout planned for the middle of this year, but additional indications as well. Also, we have a opportunity to combine with CR-001, which is a PD-1 x VEGF. We can win as a monotherapy as well as in combination in multiple indications. Yeah, that's helpful. I think we're unfortunately at time, but I wanted to thank both Joshua and Ellie for the great conversation today and, you know, looking forward to all the updates in the space, both from you guys and broadly. Thanks again. Thank you.