Okay. Good evening. My name is Bob Klingenberger. I'm an Executive Director with the Morgan Stanley Healthcare Banking Team. It's my privilege to welcome the Crescent Team here this evening. Before we start, I do have to read a brief disclosure. For important disclosures, please see the Morgan Stanley Disclosure website. If you have any questions, please reach out to your Morgan Stanley sales representative. As I mentioned, here with the Crescent Team are Josh Braun, the CEO, Jonathan McNeil, the President and COO, and Ellie Ng, the CMO. Welcome. Thanks for being here. Josh, I thought I would just start with you. Obviously, you all kind of recently entered the public markets with the closure of the reverse merger in June.
Maybe you just want to give us sort of a background on the Crescent story and kind of how this all came together and an overview of where we're at today.
Yeah. First of all, thanks for the invitation. It's great to be here with the team. Lots of interest in the space, as you can imagine. Lots of data coming out even today, right? Multiple pieces of data coming out. Look, I think for us at Crescent Biopharma, really exciting time for us to be in this next-generation immuno-oncology bi-specific space. I think what's important for people to understand about Crescent Biopharma is that we really are differentiated in our strategy. We're not just focused on the next-generation immuno-oncology play, which we have with our own CR-001 bi-specific antibody, but we're also in our other sleeve of business on the ADC side. We say ADC Plus because we're really focused on multiple ways to win and think about combining that part of our business synergistically with our CR-001 asset. We came together about, I think, October of 2024.
Peter Harwin and the Fairmount team had the idea to put this company together. Jonathan McNeil and myself, Amy, and others joined the company in early April. We found our Chief Medical Officer, who's been fantastic and really has a nice story to tell about her experience here. Ellie, so I'll like her to introduce herself quickly, in a second. Suffice to say that this is a busy time for us. I think we have a great shot to be a leader in this space. We are rapidly approaching dosing patients in early 2026 with CR-001. We'll be taking our second asset, CR-002, our first ADC, into the clinic in the middle of 2026. Really operating next year in our dual strategy between our CR-001 asset in the bi-specific sleeve of our business and the ADC side of our business with CR-002. Pretty exciting place to be. We're well capitalized.
I will say it's just great to be working with people that you know, you've worked with in the past, know how to execute. I think this is a long game we're playing, right? This redistribution of this $100 billion market opportunity, between the immuno-oncology space and the PD-1s and the ADCs. It's a long game. It's a nine-inning game, and we're in the top of the first here. Every indication that we want to go after outside of lung is wide open, first-in-class opportunities. We're building a portfolio of first-in-class opportunities and then fast-following where it makes sense in areas like lung, which are major markets. I'm pretty excited about what's in front of us.
Yeah, that's great. Did you want Ellie maybe?
Maybe Ellie, just give a quick background for people. I think it's important that people understand your background and where you helped us.
Okay. Thank you, Josh. Ellie, and I'm the Chief Medical Officer at Crescent Biopharma. I'm a medical oncologist by training. In my industry career, I had a chance to work on two PD-1 inhibitors that got approved. The first one is Keytruda. I worked on the KINO10 study, which led to the first global approval of Keytruda in non-small cell lung cancer. When I finished the piloting of that study, I went on to join a biotech and then worked on a compound, Cogentrol, currently owned by GSK. They are learning from what I've done at Merck and other PD-1 inhibitors, quickly developed a clinical development strategy that led to excellent approval in a couple of indications. Ultimately, Cogentrol became the first PD-1 inhibitor to be approved in frontline endometrial cancer. Currently, they're looking at $1 billion plus revenue in this year.
That shows how going into the clinical development stage of the program in a timely fashion, but utilizing that smart strategy and how to execute it can matter. After that time period, I worked on ADC development for two and a half years. When I saw the pipeline of Crescent Biopharma, I felt like it feels like glove. Of course, ibinastinab has met data that everybody loves and wants to talk about. Finally, we have a compound that tested Keytruda in first-line non-small cell lung cancer. We've been waiting for this for 10-plus years after Keytruda development. Believing in that data, from both efficacy and safety perspectives, I wanted to join Crescent and provide this opportunity of developing new IO backbone of PD-1/VEGF, as well as developing ADC programs as monotherapy and in combination, and then providing transformative changes for multiple indications.
Yeah. Maybe just to add a little bit, Jonathan McNeil and I have been together for quite some time. I think maybe, Jonathan, I didn't touch on it in my open, but just how we thought about designing CR-001, why that's different, and why that's exciting for us.
Yeah. For CR-001, our lead asset, the notion there was how do we make sure that we can replicate the cooperative pharmacology that's led to the positive clinical benefits of ibinastinab, but also engineer a molecule that's a new molecular entity and has additional advantages. We think we've accomplished that. The SCFV domains of CR-001 are novel, and they allow us to formulate the molecule at up to 150 micromoles, which allows us to have the potential for subcutaneous dosing over time as we think about lifecycle management. We believe that the opportunity we have ahead of us is to connect the rational design of 001 with our preclinical data, which has recapitulated the cooperative pharmacology of ibinastinab, with the clinical data that we'll touch on that we'll be generating in late 2026 or early 2027.
With that, we'll have a very high conviction of what we'll see in the phase two, three studies in select indications that we'll initiate on the back of that phase one. If you have a different antibody format, if you have different targets, others in the PD-1/VEGF space, it will be very challenging to have a similar level of conviction, even if your early phase one studies show promising results. As we know in the IO space, phase one results do not often translate to larger phase two, three. We think that this puts us in a leadership position, both for our first-in-class indications and our fast-follower indications for 001.
Yeah. I think we should jump right in. I know, Josh, you sort of made reference to it, more data today, even, from ibinastinab, rather, over the weekend.
Maybe just comment a bit on how you've seen the recent data readouts from the last, call it, three, six months, play into the strategy you all have developed and how that's impacted the plans going forward.
Yeah. I mean, I'll ask Ellie to comment specifically on some of the data. What I would say is if you would have asked the Fairmount team and Peter Harwin back in October 2024 and said, "Hey, look, the data is going to read out this way over the next, you know, year. How do you feel about making that investment and building this company?" I think people would have just been jumping up and down. I think what we've seen over the initial ibinastinab data, KISA Bio data has been quite, quite terrific. I think that even the data today, why it didn't hit the endpoint and people are kind of, you know, regurgitating over that, I think it did have a very good response in a very difficult population where PD-1s historically haven't worked.
I think it really just shows that this is clearly a new class of drugs. It's a long game to be played to see how you redistribute this class. I think we're just very excited about having an opportunity to see all that data being validated, the number of phase three studies that are out there with positive data now from ibinastinab, and how our molecule fits just, you know, in this category and the opportunity in front of us. Maybe, Ellie, if you want to just touch on a little bit more specifically some of the data from today and historically what we're seeing.
Yeah. Harmony data, right, over the weekend, they released longer outlook data for PFS and OS, and also highly anticipated data from Asian patients versus non-Asian patients. We thought that data was highly validating and encouraging at the same time because PFS benefits maintained with the longer follow-up. OS data, finally, we got to see the difference between the Asian population and the non-Asian patients, with median overall survival data pretty much identical between the two populations. Again, addressing that concern, one of the concerns that people had, what if we are not seeing consistent benefit, but the data suggests that we are seeing consistent benefit. What was also great is that with the longer follow-up in the non-Asian population, I think we are seeing more of a separation between the two arms, and the benefit is now looking similar to that of Asian patients.
This is also aligning with what KISA Bio recently released about their Harmony A study, which is the same study that's done only in the China population. Their final OS analysis hit the statistical significance. The longer-term follow-up data is suggesting that there's a nice separation of the overall survival. Again, considering that this is a population where PD-1 inhibitors, where VEGF inhibitors as monotherapy, or in combination with the standard of care, did not have great success. We think that this data is highly validating. We hear a lot of people asking about statistical design of the study and the subgroup data and how the hazard ratio and p-value look like.
That's also a great point, and the valuable lessons that we are having because the difference between the Asian population and non-Asian population, the follow-up timeline is what we think created some of these results that we are seeing from May versus now. Now understanding this, and because we are in the position where we are starting with a global site, doing the right statistical assumptions and study design and understanding what regulatory bodies want us to focus on, which is critical for our execution endpoint as well as the likelihood of getting the drug approved. All these things are highlighting that PD-1 VEGF is a real drug with a consistent benefit that we are seeing between Asian and non-Asian population, a consistent trend with the PFS and OS.
Some of the executional issues that we've raised are giving us a great lesson, and we will be able to de-risk further.
Yeah. I think just on that point specifically, an important question I know you all have talked about, and I think, Jonathan, you touched on a little bit, is just your design, your sort of plan for CR-001, right? I know you haven't disclosed all the tumors you might focus on in some of those later studies, but maybe just to give you all an opportunity to lay that out in the detail that you've disclosed so far.
Yeah. I mean, I think from our perspective, one of the key updates that we're looking forward to coming out with soon is just what's the phase one study design look like? What are the lessons learned from the studies that are out there? I have great respect for Bob and his team. I've been working with Bob and Pharmaceuticals and knowing how hard they pushed this and the courage to take it into this kind of population. I think there's great lessons learned there. I'm sure that if they could have started from scratch, they probably would have designed some things differently too. We'll take those lessons into our phase one study design. We haven't disclosed what indications we're going after yet, but we have said we're focused on thoracic, GI, and gynoch.
I think the piece that's a little bit different for us maybe than others in this space is, again, we have these two sleeves of business. We have the IO piece, and then we have the ADC piece. We're building the integrated matrix of a product portfolio where we're thinking about those indication selections and tumor types across the different categories that we may be focused on between monotherapy O01, standard of care with O01 combo, and then other ADC combos. That plays into how we're thinking about our portfolio strategy. Again, highlighting that it will be a first-in-class beachhead program for us, with O01, and then a fast-follower approach in indications like lung, which are very, very large, and being second or third or fourth, that's real significant revenue opportunities. Also thinking about that ADC approach and where we combo that.
I think what we'll do is we'll have a very robust phase one study. I think we're focused on three types of data that we want to generate over the next 12 to 18 months. We have to generate the data that we need for regulators on the dose finding, safety, PK, etc. That's traditionally going to be done in second-line plus patients. That's a little bit more messy data coming back, but we have to generate that data. What if we can generate that data as we need to develop the drug in a very robust, high-quality way, in a timely fashion, and then parallel that with some frontline data, which I think will answer and check the box for what really investors are looking for. Also thinking about, are there ways we can generate combo data with CR-001?
If we can do those three things, we've obsessed about what's the clinically meaningful data we could generate. We think those are three buckets, and if we could generate that data in a timely fashion, in that kind of Q4 2026, early 2027 timeframe, that's really going to move the needle. We can then start talking about what are the specific indications we're going to go after because we're going to follow our data, and we'll also follow the field. If others are going into areas that we thought we might want to, and maybe that's not first-in-class, we have the flexibility across those three indication types that we're looking at to be, again, first-in-class.
For CR-001 specifically, in that development plan that you just laid out, the key timelines are clinic by, dosing patients by Q1. By Q1.
Sort of that late 2026, early 2027 timeline for that initial data.
Yep, in those three buckets.
In those three buckets.
Yeah.
The next steps are in 2027.
Next steps is when you push, you know, how broad you go, how many indications you go. I'm going to just maybe jump ahead, but it ties into our partnering strategy and our partnering.
Yeah.
Maybe Jonathan could talk a little bit about that.
Yeah. On the partnering front, just like there's two sleeves of our business, there's two sleeves of how we think about the partnering perspective. First, with CR-001, clearly, there's been a lot of interest in the space. There's been multiple billion-dollar plus deals, but what we see is that there's value for us generating clinical data before we think about doing a CR-001 partnership. We can drive CR-001 ourselves, but given the breadth of opportunities across 40, 50-plus indications, we see the value of a potential partnership, but we want to generate that clinical data first as a key value inflection point for both ourselves and potential partners before pursuing a strong partnership in CR-001. For the ADC pipeline, we have the ability to generate ADC candidates internally, but there's significant interest in combining ADCs with PD-1/VEGF bi-specifics. There's been promising data of combinations of ADCs and PD-1 inhibitors.
Now a lot of the ADC developers want to combine their ADCs with best-in-class PD-1/VEGF bi-specifics like ours. There is an opportunity for us to pursue deals in the near term to accelerate combo data in indications of interest in the ADC space. That's something that we have actively ongoing dialogue about.
Maybe just to move to one of the points, Josh, you made on watching out for other data. We talked about data that came over the weekend. There's obviously been tons of disclosure. It feels like every week there's almost an update in the space. What are the key data sets that you all are kind of watching maybe through the end of the year into early next year that may or may not impact the strategy, I guess, but just that you are kind of keeping a close eye on?
Yeah.
Yeah. Harmony data that we just saw was quite helpful for us to understand how the drug works and how we want to best develop this compound. The Harmony 6 data, right? It's a chemo combo data in first-line squamous non-small cell lung cancer patients in Chinese population. We are anticipating that data will be available sometime, like maybe at ESMO, right? Harmony 2 data, which is monotherapy ibinastinab data in PD-L1 positive non-small cell lung cancer patients, had earlier release on preliminary OS data. We are hoping to see longer follow-up data and how that OS data looks like. This is just non-small cell lung cancer data. That's the only indication that we have phase 3 data from. Now we are seeing more indications such as small cell and other tumor types. It's an earlier phase trial.
We are also carefully watching those indications and see how the data is evolving.
Yeah. Maybe I'll just add to that quickly. I think, you know, we get asked that question a lot. People are trying to figure out if this is a class of drugs. How do you guys build the company? You know, how tethered are you to could you design the molecule to be like ibinastinab? If that, but the OS doesn't hit, what's going to happen? I would just point out to people now about the breadth of data we have in this space. This is clearly a class of drugs.
Mm-hmm.
How you design a study, powering, etc., absolutely matters. If you go back and look at the Opdivo versus Keytruda initially, you know, that ended up working out for Keytruda in a way that I don't think people thought when that initial data went out with Opdivo, they missed the phase three study, right?
I just would remind people that we have enough confidence and conviction that this is a class of drugs. Mm-hmm. We have seen enough data and the way we've designed our molecule that with the right strategy, the right clinical development plan, the right, you know, stats behind it, we are a little bit now insulated, I think, from that, hey, is OS going to hit or not hit?
Mm-hmm.
Reminding people that we have the ADC part of our business that also, you know, de-risks our strategy. I just think that it's a great question, and we clearly are monitoring every single piece of data coming. It's part of the fun, right? I think we need to build a building for CI just literally because it's all we're doing half the time. I think that it is bigger now than just the OS data coming from Summit, right?
Yeah. I guess maybe to that point, how much stock do you all take? Obviously, given the purposeful design of CR-001 with respect to ibinastinab, BioNTech, I think, had data today, right?
Yeah.
How much are you all focused on that versus in some of these other indications? How do you kind of balance that versus the design?
I think that there's four molecules that we view as like that matter most in this space. Yeah, clearly, we believe in our own molecule. It's ibinastinab, but the BioNTech molecule, and then the Merck Lenovo molecule, right? We think, and why are those four? Because we think that they are most similar to ibinastinab in design. Other molecules, they may succeed, but they've done changes in antibody formats, targeted, etc. Those are the four molecules. We monitor all data in this space. To your point, we do put more stock in those molecules because we think that they most inform what we're trying to do. The BioNTech data is a great example, which was largely successful data in terms of efficacy and safety in small cell lung cancer. It is something that we can learn from, right?
We will also learn from molecules that are showing different data sets in this PD-1/VEGF bi-specific space that perhaps is not as promising. That's also an important learning for us as well. We've seen that with some of our competitors too.
Yeah. I do want to spend a little because I know the two sleeves of the business, right, as you've described it. I do want to spend a little time on the ADCs. I know you all haven't disclosed necessarily the targets for CR-002 and CR-003. Talk just a little bit maybe sort of broadly around that sleeve of business, how you've kind of conceptualized it, from a top O target. Just sort of broadly how you think about that, especially on the combination side. Sure, we can talk a little bit about timelines as well.
Yeah. I'll ask Jonathan to talk more about the strategy specifically. I'll just kick it off by saying that I think, you know, we understand that if you're reading the tea leaves of where this is going, where you can make the biggest impact is in frontline monotherapy or frontline standard of care and combinations, right? I think that's where you're going to have the biggest impact in this redistribution of this class. That's why we built the strategy the way we have. I think we all have some experience in our previous life of working with antibody-drug conjugates. We have hired a Chief Scientific Officer in Jan Pinkus, that spent his life in ADCs coming from ImmunoGen. We understand how to, you know, balance, delicately the difference between taking the risk and reward in this space.
I think there's a lot that's been learned in the ADCs, and we'll apply that to our strategy. Maybe I'll ask Jonathan to talk a little bit more about that.
Yeah. At a high level, we haven't disclosed our targets for competitive reasons. We'll adopt you to do so as these molecules advance toward the clinic. As Josh noted, what we're looking at for our ADC targets are validated biology. At this stage in the company's evolution, we think there's an opportunity to differentiate based upon antibody target, but also linker and payload design versus taking biology risk with novel targets. We have the opportunity to pursue validated targets. We have the opportunity to use our own linker and payload combinations. We've highlighted the opportunity for topoisomerase payloads because we think that those are very promising. That being said, we have the flexibility to use MME or other payloads as well. Validated targets, likely topoisomerase payloads. What we're looking for are ADCs that both have activity as monotherapy, but also synergize well with CR-001.
Our initial targets will have the opportunity to be used across a breadth of solid tumors. It'll be necessary to run the dose escalation like you would for any molecule with the ADC themselves. We'll have the opportunity to quickly move into combination therapies with CR-001, which will allow us to build this integrated portfolio where for each indication, we can decide when do we pursue monotherapy, where do we pursue CR-001 with standard of care chemotherapy, and where do we want to take CR-001 with an ADC. We'll have that opportunity to look at that as an indication-by-indication basis as the landscape evolves. Importantly, although we do have internal ADC development capabilities, this is where that BD element comes in, which is there's a lot of inbound interest in combining ADCs with CR-001. That's something we'll evaluate as well.
Yeah, I was just going to ask, you know, there have been a number of, you know, sort of partnering type deals on the ADC side. You mentioned that the space seems to be kind of going that way, especially for probably the frontline patients. Are there targets in particular? I obviously haven't disclosed yours, but broadly that you all have seen that are kind of of high interest that you're monitoring?
The target for CR-002 is obviously clearly interesting to us. We'll all disclose that at the right time. CR-003 likewise, right? We also have our list of other things that we're working on currently, or things that we are looking to, you know, combine with externally. We've got that list. I think as Jonathan mentioned, taking novel biology risk around the targets is something that, you know, isn't wise for us to do at this point. In the broader vision of this company, and the company that we believe we can build, I do think that would be something down the line that we would look at, but it's just kind of how you stage that and how you prioritize that.
Yeah, I think we have an opportunity to differentiate without taking that risk, right? Because if you make an effective ADC and then you synergize with CR-001, that in and of itself could be a differentiated therapeutic regimen versus either ADC monotherapy or potentially ADC combined with PD-1, which we're starting to see promising data from. I mean, if you look at CR-003, the PD-1 data was very promising and very different than CR-003 as monotherapy. We're learning from that. We'll have the opportunity, and I think many see that opportunity in this space.
Yeah. As you all are, as we're sort of approaching, you know, obviously entering the clinic and you have a lot going on, the company just became, you know, completed the reverse merger in June. Can you kind of remind just everyone, you know, kind of cash runway, what is it, what is the kind of current runway get you through in terms of, you know, data?
Yeah. Cash is $153 million as we close the second quarter. That gets us through 2027. It gets us through all the data we talked about. It gets us through those three buckets of data that I talked about earlier, and puts us in a real strong position to execute on the broader strategy that we have and build on this vision. I think that one thing that we have been super focused on right now, and I think is also going to be a differentiator for us, is just the clinical operations part of the business and getting ready to run this global study. I just want to make sure I give a call out to the team back in Waltham, who've been doing an amazing job on getting us ready. I can't tell you how we started in April.
We had a quick turn on this one, leveraged the team that we had in New, and Ellie's team has done a great job. I think that's going to provide us a lot of ability to drive quickly in a very exciting, robust phase one study that this capital we have on the balance sheet will allow us to read out on.
Yeah. As you think about some of that, we've talked about some of the differentiation in terms of the way you design the molecule. Maybe if we could just drill down for a moment on some of the lessons you feel like you learned from the current development, and in the way you purposely designed the molecule, how you might see that differentiated play out in the clinical data.
Yeah. So we designed CR-001 to match the key functions of ibinastinab. The reason behind this is what Josh mentioned and what Jonathan mentioned, that in immuno-oncology drugs, introducing new changes would take a long time. Many patients of data usually randomize phase three data for us to truly understand. The new changes that we did introduce were with the amino acid chain in the SCAB domain, which helped us achieve excellent stability. We were able to push the concentration up to 150 micrometers per mL compared to currently ibinastinab vials that are given to patients at 10 micrometers per mL. This excellent stability and high concentration provides us an opportunity with the manufacturing feasibility, but also down the road, we will have an opportunity to do the life cycle management as well. With our phase one trial, based on the.
I'll stop you, just so people know.
Yeah.
Yeah. Okay.
With our phase one study design, as Josh mentioned, we've studied, we've been studying competitors' data very carefully and what is the best way to do the dose binding work, which is very critical because finding the right dose is a key step for the success of the overall plan. Generating that data helps us choose the indications for registration or trial, right? That means preliminary anti-tumor activity data, and then getting into the first line where most of the robust activity has been seen. Then how to pivot there from monotherapy to combination with the standard of care and also with the novel agents. All those plan steps that we have will help us efficiently develop this drug. That's combined with what Josh just mentioned with our operational plan. This is a global setting study.
Right now, Summit Therapeutics and BioNTech are the two companies that have global clinical data of a PD-1/VEGF bi-specific. We will start dosing patients first quarter in 2026, so not far behind. From there on, we will have a global footprint and answering the question on how the Western patients versus Asian patients, how do they do with the safety and efficacy, what's the right dose for CR-001, and what's the indications that we want to prioritize for the registration trials. Of course, addressing the regulatory requirements from the FDA, EMA, and the global bodies. All those work we are planning on will help us de-risk, but also accelerate overall development plan as well.
I think what people don't realize is that because this space has been so hot just on Wall Street, right? It's taken up a lot of mind share. Operationally, in executing these studies, because we're the first company starting with the Western patient population, everything else has been started in China and brought here. There's still not a ton of activity in the U.S. sites. The U.S. sites are hungry to get going, and they're excited to work with the bi-specific. In some of these sites, we're leading, we're the first. We're leading the charge. It's just a reminder for me, at least, that we really are at the head of the front of the line in this long game we're playing. It's exciting to be some of the first, the first company to work with some of these big U.S. sites that just haven't had a bi-specific yet, right?
Yeah. Obviously, a lot of exciting things to come for you all. I know we're running a couple of minutes left here. As you maybe just take a step back, obviously, started in April, been a quick turn to get to here in five months or so. I guess if we take a little bit of a big picture view, three, five years down the line, how do you envision, obviously, hard to predict the future, but how do you, where do you see the future for Crescent?
Yeah. Thanks for that question. People sometimes think you're crazy when you answer the question, but you got to put it out there for people to believe in. We've said this when we looked at the opportunity and Jonathan and I and Amy, Rick, and the team came over. We truly believe that we can build the next biotech oncology company. CLG Next is a great comp. I think that with the two sleeves of our business, the valuation you're seeing in Summit already with their validation and their data, you look at ImmunoGen and what they sold for with, you know, one ADC that had some great data. Can we build a $30-40 billion company? Yes. It's right there for us to go do.
Having the team in place that knows how to work together and the culture that we work with, I think, is absolutely required to do that. Having the assets behind it, I think this is an incredibly exciting time. I think we'll look back 10 years from now and we'll just see how long did it take to play this baseball game and where are all the players, who's on what base, and what the score is. It won't be final, but it's going to be deep into the seventh-eighth inning and it's going to be a complete redistribution from where we are today. We're excited to play the game.
Top of the first inning. Thank you to the Crescent team for being here. I'm just about out of time, so thank you again for the time.
Thanks for the invite.
Thanks, everyone.
Thank you.
Thank you.