Awesome. Thanks so much for everyone for joining us. My name is Akash Tewari. This is day three of our Jefferies London Healthcare Conference. The time flies. I have the Crescent management team. Why don't I hand it off for some intro remarks, and we'll get started. Great. Thanks, Josh. Josh Brumm, CEO. Great to be here with Ellie, our Chief Medical Officer, and Jonathan, our President and COO. We will make some forward-looking statements, so please refer to our SEC filings for more information on that front. It's great to be here in London. It's a great way to kind of wind down the year with being here and talking about the Crescent story. I think what's important about the Crescent story is there's really our focus and delivering on our mission to build the world's next leading biotech and oncology company. I think for us, it's really driven by two really distinct strategies. One is led by our CR001, our next- generation PD-1 VEGF bispecific. We'll talk a little bit more about how and why we designed that molecule and how we think that's the backbone of our strategy going forward. The other part of our business, which is equally as important, is our ADC pipeline. While we haven't disclosed yet those targets, we will be doing that relatively soon. What you'll see is that we have a very complex matrix portfolio between our CR001 bispecific and our ADCs, which would allow us to really generate a pipeline of monotherapy, monotherapy standard of care for CR001, and then also thinking about where the puck is moving in this business, really to synergistic combinations with our ADC pipeline. We are really excited about what we're building here. The team could talk more about the design of our 001 and why we think that's going to be important going forward. I think of note, we will be in the clinic dosing patients here in early Q1 with CR001. We are excited about that transformation to clinical- stage company. Our first ADC, CR002, will be in the clinic about six months behind, so mid next year. We are really just on the precipice of transforming into a clinical- stage company and driving benefit for patients in this landscape. Yeah, it is great to be here. Thank you. Yeah, absolutely. It's great to have you. Look, it was interesting. I asked Merck this on the Q3 call, where I said, is the way to think about their approach 1.0, 2.0, right? They have an ADC. They're generating data there. Then kind of 2.0 is, OK, now you're adding a PD-1 VEGF to everything. They gave a nuanced answer. They're like, we don't really think about it that way. I think one of the things I'm picking up, not just from Merck, but really kind of more broadly in the space, is a PD-1 VEGF kind of has two distinct strategies. You're going for the big thoracic indications, I think everyone else is. This is something that your team's interested in. But then there's also kind of areas where PD-1 VEGF biology is, there's less competition, and there's a really interesting kind of additive benefit, right? Like even I was at the BioNTech R&D day, and they're looking at a HER2 ADC, an HR+, with a PD-1 VEGF. So there's creativity here. As you look at the moving pieces in the space, where are you seeing markets and opportunities where, you know what, it's not just about NSCLC, but other indications where a PD-1 VEGF could really play a role? Yeah, I mean, look, I'll respond first to the comments that you're going to discuss with Merck. It'd be a lot easier for Merck to have that conviction if they had CR001, right? I think that's for us where it starts. I think that's why the multi-sleeve approach to our business is really important. CR001 will be the backbone, I think, of all these ADC synergistic combination programs that move forward, right? I think how we intentionally design CR001 to mimic the cooperative pharmacology of an sugemalimab, we've improved the stability and the ability for that to be sub-Q long term. We think it's the best in class bispecific. We just haven't had a chance to prove that out with our data yet. Our preclinical data looks sparkling clean. It looks just like what we thought it would be, how we designed it. I think for us, that's the power of having CR001 in our pipeline. Taking that to your point, thinking about where do we take that in monotherapy, if at all? Where do we think about leveraging not just one, but our multiple ADC pipeline? Thinking about, can you be best in class in lung and kind of leapfrog where some of it is today? Absolutely, right? Can you think about other combinations or other areas, even in monotherapy, outside of lung? Absolutely. I think that clarity in our strategy, along with our ADC targets and how we built this portfolio, will be something that we'll be looking forward to talking about very soon. Understood. Now, I was at ESMO, and I was there at kind of the HARMONi-6 presentation. Obviously, that's a big card flip for understanding the PD-1 VEGF space. Because again, now you're thinking about chemo synergy, right? Like you can see as a monotherapy, you have lower discontinuations. The question is, of course, once you add upon systemic chemo, are you going to be able to maintain this kind of PFS edge that then translates, hopefully, to OS? One of the concerns I had with the ivonescimab data was when we look at duration of response, those curves were touching with both arms. I think the question is really, how do the curves really evolve over time? I'd love to get your take. What was your team's internal view of the HARMONi-6 data? What are you learning from that? Maybe some of the revised stat plans that Summit's now taking. Lots to learn from the studies that have been before us. Maybe, Ellie, you want to take this question? Yeah. It is a really great question. We have been waiting for HARMONi-6 data for a long time. Everybody, including the KOLs, was very pleased to see robust PFS benefit, as well as the safety profile of ivonescimab plus chemo combination in squamous cell non-small cell lung cancer patients. Regarding the DOR curve, there were clear separations at the beginning and then towards the end where we saw a lot of censoring because the duration of follow-up is not as mature. That is where the curves were touching a little bit. The long-term follow-up data will give us a better sense of how the duration of response looks. We also have to remember that the comparator arm was PD-1 plus chemo, so the patients who are responding from PD-1 treatment also tend to have a very durable response. Sure. That's one part of the data that with time, we would like to see how it evolves. What I was really surprised and then also pleased about was the safety profile that is matching also with efficacy. Overall, immune-mediated adverse events between the two arms were not that different. Patients who are on the ivonescimab and small molecule anti-PD-1 arm had a little bit of increased risk for Avastin-related adverse events. When it came to the higher-grade events, the numbers were very small and very manageable. Compared to what we knew from Avastin treatment and side effects that were related, we are seeing different types of or superior types of safety profile with ivonescimab and small molecule anti-PD-1. I think that's why we are all excited to touch a little bit upon your previous questions, too. In the indications where PD-1s have worked well, now we have a chance to improve further upon. In indications where PD-1s did not work as well, right? That includes, as you mentioned, the hormone-positive breast cancer, EGFR-mutated non-small cell lung cancer, and MSSCRC. In those indications, now we are seeing very encouraging preliminary activity of PD-1 VEGF. This gives us really a chance to provide next-generation IO backbone treatment for the broader indications. We are very excited about the opportunity. We thought that HARMONi-6 data was highly validated. Interesting. I think that's a valuable perspective. One of the other parts about HARMONi-6, and you kind of alluded to it, is there were differences in response rate depending on PD-1 expression, which I think was a little surprising for us internally. I'd love to get your take. What did you think of that signal? Were you surprised about it? How do you think about that in terms of impacting your clinical development strategy? What I was pleased to see was the overall how the patients in the PD-L1 low expression and PD-L1 negative expression. Yep. So, overall benefit in the PD-L1 high population, we already know that those patients do well when they receive pembrolizumab. That is only one-third of the population. Even then, not all of those patients respond, maybe 50% when we combine with chemo. The rest of the population, 70% of them, have relatively lower response rate when they receive PD-1. What we are seeing with the PD-1 VEGF is in those populations, the 70% of the population who did not do as well when they received pembro, now they are doing much better with the PD-1 VEGF. We think part of the reason is now intensified PD-1 blockade, you know, and then also VEGF coming in and playing a role. What is great is that now all the patients who are benefiting from this treatment is broader. The safety profile is not that different from when they are given pembrolizumab. The superior efficacy that is being provided to a broader population matched with the safety profile, that's where we got really encouraged with the HARMONi-6 data. Interesting. You know, there was a big readout in HER2 expression gastric for our coverage with Zymworks and Jazz. Actually, I was catching up with the Zym CEO. You made an interesting comment. I'm curious what your take was. They have HER2, HER2 bispecific. We've seen with the KEYNOTE-811 study that in PD-1 low expressing patients, pembro really doesn't add that much. Ken made a comment. He's like, actually, when we're taking targeted therapy that might have complement-dependent cytotoxicity, we're actually supercharging the effect of PD-1 low expressing. We've seen, I'm going to jump a little, you see Summit and they're doing targeted approaches as a part of their clinical development strategy, not just ADCs, right? When you think about the impact of, A, having efficacy in PD1 low, turning cold tumors "hot," how much does targeted approaches play into your clinical development strategy and not just ADCs here? So, one great thing about PD-1 VEGF so far, what we are seeing is its superior efficacy in multiple tumor types. Because of its safety profile, it can be combined with various agents. That includes standard of chemo, ADCs, and then targeted therapies for radionuclear treatment. That is the foundation and then potential of PD-1 VEGF. We are going into clinic, and then we will start our global phase I trial early first quarter next year. Based on our data, we will have a comprehensive assessment of safety, efficacy, and then PK profile. From there on, in the indications that we are seeing great activity of CR001, we will then have a robust combination strategy for not just the ADC, but the targeted therapy or standard of care chemo or as a monotherapy. So, having this solid profile of CR001 would be our first step. From there on, we will have a robust plan for expanding our pipeline. Understood. Maybe I'll just add that I think what I've stated publicly is that the most important thing Crescent can do right now is to run a very robust phase I study, CR001, understand our dose, understand this drug in the clinic, replicating what we think we will see, right? Our very aggressive and I think diversified strategy on our portfolio on how we think about building the ADC side of our business, both internally and externally, and other ways that we can, because of the safety of 01, then combine. Maybe I'll just ask Jonathan quickly to touch on some of our thinking around our strategy on partnering and that internal external development. Yeah. On that topic, we have the opportunity to combine 01 with our internally developed ADCs. That has the opportunity for both monotherapy, but also combination therapy in multiple oncology indications. One other benefit we have is once we generate the robust data with 01, and particularly [guess-DRAVQ] RP2D, then we have the opportunity to leverage external collaborations as well for select indications and assets that we do not develop internally. That speaks to the breadth of opportunity in the PD-1 VEGF space. One could imagine a situation for tumor type A, we're combining 01 with 02. For tumor type B, we're combining 01 with an external asset that we either in-license or establish a global partnership for. That's how we're thinking about our BD strategy on the back of generating the meaningful clinical data with 01. I think it's important that people don't miss this specific, I think, benefit that we have. We intentionally designed CR001 to mimic the cooperative pharmacology of ivonescimab. I think we're the closest bispecific to that molecule, which means once we have our phase I dose and really understand that, we can accelerate in development very rapidly with other combinations. I think it's interesting. You've seen Pfizer come out. You've seen BMS and Pfizer come out recently in the last month, both talking about where this puck is moving and synergistic combinations. That was our strategy from the get-go. When we get a chance to come out and talk about our ADC pipeline, talk about our targets, talk about our matrix portfolio, you're going to see this thinking that's been in place for quite some time and how quickly we can leverage and accelerate that in clinical development because of how we intentionally designed 001. I think this is an important point to make to people. Understood. You know, it's interesting. I literally just came from hosting Pfizer, and they are talking about that 3SB io asset. One of the things that they were able to kind of achieve is they generated a big data set in China. They're alluding not just in CRC, but maybe potentially in three or plus other indications. They might be able to go directly into phase III. There comes that question of, if the FDA is comfortable with just China data, why is it important that you're generating data sets not just in that population? I think that's a perception, but I don't know if that actually reflects the reality. In your strategic conversations, how important is it that you're having geographic diversity out of the gate, that you're having data in U.S. sites and you can really adequately control the benefits you're seeing here? Yeah. I would say that it really goes back to what I mean, I think if Summit could turn back the clock and redesign these studies from the get-go and not have to mesh in Western patients and Chinese data and all that stuff, we get that benefit, right? We get to sit back and watch things that we change and how we power and run the stats for these programs. We're starting in a global study ex-U.S., so we can do this right from the beginning. I think that's the power of it. I don't necessarily believe that if it's a certain demographic, right? I think it's more about setting your study up right from the beginning with the right power in the stats, taking what we've learned from the data that's out there and applying that filter to our study. I think that's going to provide extraordinary benefit to how we think about the design of the studies. I think you'll see that when we talk about our phase I study design. Understood. You know, I think also just maybe thinking about external partnerships. This is actually unsolicited advice I gave to Summit. I said, you know, when you think about "these multinational corporations," oftentimes they might have capital, but they do not really have assets internally to combine. I think it has been interesting. Sometimes the best combination partners are not the big guys. It is actually the mid-cap emerging players. You are seeing more and more that these biotechs themselves are becoming multi-asset stories. That is certainly your kind of starting ambition. When we think about external partnerships for Crescent, should we be focused on the big multinationals or is it actually maybe these emerging mid-cap oncology players that might actually offer more for your company? Yeah. I'd say that really it does always start with the focus on benefit for patients. And so thinking about where we can go, leverage the intentional way we design 01, and find best-in-class synergistic combinations that ultimately will win for patients. I think you're right. I think I can tell you for sure we are focused on looking at all the ways to do that, right? I think there is always that big pharma partnership that's out there for us potentially after phase I, after we get this phase I data in a very robust, high-quality way. And that's where the couple of billion dollar front value deals have been done. We've seen those deals. That's clearly out there. There are so many people that still need a bispecific. We can go through the list of names. We are open for business on looking at ways to benefit patients and building best-in-class synergistic combination with 01. I think once we have that phase I data and understand our dose, late-stage clinical molecules, ADCs that are out there, other things to combine with, or approved therapies that are out there, we can move super rapidly. I think that's been our strategy from the beginning. Those conversations have been ongoing for quite some time. I would just say stay tuned on our thoughts and how we might do that. Understood. Now, you mentioned that phase I, and I think obviously that's a critical study. Can you talk about when you look at maybe some of your peers in China, the size of the studies they enrolled, the types of patients they enrolled, also just in terms of tumor types, how will your phase I maybe differ from what your peer group's done historically? Yeah. Yeah. We are in a great place for a couple of reasons. One is we have intentionally designed CR001 to match the key functionality of ivonescimab, which is the only PD-1/ VEGF bispecific with multiple successful results from randomized phase III trials. We can definitely leverage that feature and then build upon that confidence. But the second part of it is that we are seeing a lot of data emerging from PD-1 VEGF bispecifics in general. Also, I'm well- versed in how PD-1 and PD-L1 inhibitors have been developed. Based on that, we are building a robust phase I trial in a global setting. That includes not just doing a dose escalation in all comers, which is a good place to start, traditionally speaking, but it's hard for us to really understand the comprehensive signal of an oncology asset, understanding comprehensive PK, safety, tolerability, and then efficacy. All this data will help us get to finding the recommended phase II dose and then registration enabling indications in an efficient manner. We are thinking about all these different things when we design the first in-human trial, which will start in just a couple of months. Starting from a global setting in the United States first gives us a chance to first talk about our strategy with the investigators. And then if we are successful, these are the investigators who will enroll into our phase II and phase III trials as well. Establishing this footprint is very important for us. And then one of the key questions that analysts have been asking is, would Chinese data translate into the global setting? We do not have to worry about that. We will address that question from the get-go. And then working with the FDA, EMA, and other regulatory agencies from the beginning and understanding what their expectations are from this study and then going into registrational trials, all this is a strategy that we are building on. Utilizing competitors' data and also running our comprehensive trial will really put us in a great position. We are very excited that we will be, I guess, one of the first few companies who will generate this global stage data of a PD-1 VEGF bispecific. Understood. Just help us understand the timing of that release. Getting into the clinic shortly, this sounds like a back half of 2026 event in terms of when you're going to start showing maybe some dose escalation data. Let's put it this way. In that release, let's say in the back half of next year, are we going to get, here's our dose, XYZ indication? Number two, when we think about the capital commitments after that point needed to, because again, I think your team has talked about, let's go for the big guys. Let's also look at a couple indications where we really have a faster market strategy. Can you talk about the capital needed to pursue both of those approaches? Yeah. It's a great question. Obviously, it's on people's mind, the cost to fund these phase II, III studies. I think we'll be able to accelerate those studies very quickly on the back of the phase I study design. I think what I can tell you today is we are very close to coming out and having a discussion around the phase I design, what data is going to be available, when it's going to be available, what are the indication areas that we're focused on, what is the ADC program, what are the ADC targets, how does that combine, and then a whole slew of data that will be coming out of the pipeline. It's not just 001, but you'll have 002, you'll have combination data. I would just say be patient. A few more months or less, somewhere in this timeframe between now and dosing first patient, we're going to come out with a pretty big discussion and conversation and look forward to having that, but it's not today. Understood. Maybe just lastly, as you think about, I think the trope two story is fascinating. I was even meeting with Tubulin. You're having a lot of these targets that people have written off on the ADC side. Then it's like suddenly, hey, maybe I have site-specific conjugation, better stability, and then suddenly therapeutic window changes. We're seeing it really manifest on OS. I mean, that's certainly what I was seeing at ESMO with sac-TMT. A lot of trope two ADCs. One is suddenly showing a really remarkable overall survival benefit. Again, you have the benefit of kind of learning from your peers. When you think about assets to partner with and you think about the right approach when you think about designing your own ADCs, what are the maybe high-level lessons you're learning right now? Yeah. Yeah. I mean, I think what you alluded to is one of the key lessons. I would not even say it's something, I mean, Ellie has experienced ADCs. A number of us came from antibody-oligo conjugates, all this. What we take away from that is that every element of the design matters. So, that includes both the target, how do you engage the target, what's the linker, and then what payload do you select, right? So, our focus is on identifying best-in-class assets to combine in a synergistic way with 01. And then we, frankly, make a decision around should we develop those internally, which we will decide to do with, for example, 02 and 03, or should we go out and get an asset and try to partner for one that allows us to really make a difference for patients in that space and drive toward not just later line, but earlier lines therapies as well. The lesson we take is that, as you're alluding to, not all of these assets are created equal. You can't say every trope two ADC is the same, every trope two topo ADC is the same. It really does come down to the nuance of the asset and then how does it synergize with us. One benefit we have is that we can make a decision based upon the interest we have on that best-in-class next-gen IO backbone, which is 01, to really decide, does it make sense for something for Crescent to build internally, or should we partner those? That is part of those active discussions that you alluded to, not just with large pharma, but also some of the mid-cap players that you have alluded to. I know you can't give the indications. Can you give us therapeutic areas where you're seeing interesting emerging ADC data? What we've said is thoracic, GI, and reproductive are areas that we're focusing on. Jonathan's point and your question, the way we design the molecule, and we're going to be within 12-16 months from that data, right? That's very fast in this business. That's not lost on partners. So, people coming to us wanting to talk about combinations, ADCs, other, that we aren't Merck, right? We don't have, we are quick and nimble. I think because we have the asset, we're going to have a lot of opportunities that others may not have because 01 is going to attract those suitors. That is something that we're also working through. I think, and just circling back quickly to your capital question, we have capital through 2027. Our big POC 01 readout, in addition to other things that we'll be putting on that catalyst map, is late 2026, early 2027. We're really well funded through that period of time. The big spend, when you think about the phase II, III studies, comes on the other side of that. I think we've got multiple optionality of thinking about how we fund that way. We haven't done that big partnership yet. That data would allow us to raise more money. We'll find some mix between a partnership or equity to fund those big phase II, III studies. The real value of the flexure point from where we sit today is that end of 2026, early 2027, 01 POC, plus some other things we'll put on that catalyst calendar that will allow us to think about how the best way to fund the larger studies on the other side of it. Understood. I was a little late, so I went a little over because you guys deserved it. Thank you so much for the time. I appreciate it. Appreciate it.