Good morning, welcome once again to Cowen's seventh Annual Oncology Innovation Summit. I'm Phil Nadeau, one of the biotech analysts here at Cowen, it's my pleasure to do a chat with Crescent Biopharma. We have with us today Josh Brumm, CEO, Ellie Im, CMO, Jonathan McNeill, the President and COO. I'll hand it to you guys first. Can you give a brief state of the company overview, biggest strengths, biggest challenges, what does Crescent need to achieve to drive outperformance over the next year to year and a half?
Great. Thanks, Phil, really appreciate having us on today. Before I begin, just a reminder, we're making some forward-looking statements, please refer to our SEC filings for more information. At Crescent, we're really focused on building the leading next-generation biotech oncology company. As you may know, we're doing that with two specific strategies.
One is developing the next generation IO bispecific with our CR-001 asset, also our belief in where the puck is moving in the space around combination therapy. We're also building our own sleeve of ADCs and thinking about how we can develop best-in-class opportunities for patients living with cancer. This year we'll be initiating four clinical studies across three of our programs. That will really, in turn, set up 2027 to be a year flush with data across the entire portfolio.
We will be leveraging our relationship with Kelun-Biotech that we set up in the end of last year as part of that data release. I think there's kind of three key buckets of data we're looking for next year and generating from our one program around some monotherapy frontline on small cell data that we've talked about in Q1 2027. We talked about from our expansion cohorts looking at combination standard care chemo combos in the middle of next year.
Also again, leveraging that Kelun-Biotech relationship, seeing CR-001 combined with ADCs in the Kelun-Biotech portfolio, as well that data coming mid-next year, as well as data coming from our ADCs, our CR-003 asset, which we licensed from Kelun-Biotech, integrin beta-6 topo ADC. That data will be coming in Q1 2027. That study's already underway, CR-003 in China with Kelun-Biotech.
Then our own ADC, our PD-L1 topo ADC, will be in the clinic mid this year, generating data as well in 2027. We're really set up in a nice way to really start leveraging the portfolio to generate meaningful clinical data. We're financed across all of those milestones, and we're looking forward to a really exciting 2026 year of execution. The data coming is starting in early 2027.
Great. With that overview, maybe we'll dive into each of the programs in turn, starting with CR-001. For those less familiar, can you describe its design and what preclinical data in particular are there that suggest that it's very similar to ivonescimab?
I can address that question, Phil. Thank you for that. The design of the CR-001 is coming from us trying to replicate cooperative pharmacology of ivonescimab. We kept the key functional features of ivonescimab. That includes finding domain potency as well as aspect of PK. Last year at SITC, we presented preclinical data, including both in vivo and in vitro data, showing CR-001 demonstrating comparable cooperative pharmacology to ivonescimab, and that included in vivo PK data as well as anti-tumor activity data in mice study.
That's very helpful. For those listening, are there any additional modifications for CR-001 that were not in ivonescimab?
Yeah. As part of our designing the molecule, we thought about what we can improve further upon based on what ivonescimab has. Ivonescimab has shown great safety and tolerability data as well as anti-tumor activity. Currently, it's being manufactured at 10 mg/mL, which is a relatively low concentration. We have incorporated a proprietary amino acid chain in the scFv domain, and as a result, we were able to push the concentration up to 150 mg/mL, which is about 15 times higher than where currently ivonescimab is being manufactured.
We think that this will give us a great benefit in terms of manufacturing and potential commercial Biosize as well as looking later life cycle management and going into sub-Q, which Kisunla submitted to extend their patent life with their trial.
With our proposed design of the CR-001, we successfully demonstrated cooperative pharmacology in the preclinical data, and then in the clinical study, what we are doing, proof of concept data from this study will help us then demonstrate the similar PK safety and efficacy data from CR-001. Once we demonstrate that proof of concept data, then we will have greater confidence going into the later-stage development.
You referenced the ongoing study. Can you remind us of the trial design, and in particular, which tumor types are being included?
ASCEND is the name of the study. It's a global phase I trial of CR-001, and we have successfully dosed patients in February of this year. It's progressing quite well, and then it has a dose escalation, backfill, dose optimization, as well as expansion cohorts. In this trial, it allows us to generate comprehensive PK safety tolerability pharmacodynamics as well as anti-tumor activity data in tumor types of our focus as monotherapy, as well as in combination with the various chemotherapy.
The tumor types that we are focusing on as part of this trial includes non-small cell lung, and then GI indications, including colorectal, gastric, biliary, and HCC, and then gynec indications, including ovarian, cervical, and endometrial cancer.
As Josh mentioned, there'll be initial data in Q1 2027. Can you provide a little bit more detail on what investors can expect from that disclosure? For example, will you present data from all tumor types, and what type of measures will be disclosed?
As part of our initial data release, which is anticipated in Q1 2027, we will include the data from dose escalation as well as a backfill of ASCEND the trial. The data set will be quite comprehensive, and we will have a safety tolerability, as well as anti-tumor activity data as a monotherapy, and the PK and the pharmacodynamics data as well.
As part of anti-tumor activity data in the backfill, we will include previously treated patients of the various tumor types, as well as first-line non-small cell lung cancer patients' data, which is probably the clearest and most direct way for us to compare efficacy of CR-001 to ivonescimab and other PD-1/PD-L1 inhibitors that are out there.
Yeah, maybe I'll just add onto that, I think, as I talked about those three buckets coming by mid 2027. I think it's really important to kind of pause here and dig into why we expect from each one of those buckets. As Ellie mentioned, the easiest and cleanest way for us to say, look, not only did we show pre-clinically that we replicated the proper pharmacology of ivonescimab and why we designed the molecule the way we did, which I think is going to have major benefits for Crescent and our patients that we're treating going forward.
We could show that pre-clinically, but clinically quickly being able to be in the front line setting lung where most of the data are generated, we could show efficacy and safety tolerability that's similar in the clinic to what we saw pre-clinically.
I think that's going to allow us then to leverage our strategy of how we design the molecule quickly into registrational studies, but it's also going to help us understand where we want to go and where we want to focus from an indication perspective. I think that's where that second bucket from the expansion cohorts, if you really think about replacing the first gen PD-1 backbone, you've got to be the partner of choice.
You've got to be safe and efficacious. I think looking at multiple tumor types in combination with standard care chemo and multiple chemo agents, and having that data across multiple tumor types, showing the safety and efficacy, not just where PD-1 first gens have worked before, but potentially where you could expand the label from the good, the bad, or the bispecifics in areas like CRC.
I think that's going to be very important for us to be able to show those first two buckets and then combine that with ADC combo data from our partner Kelun-Biotech to really by middle of next year say, look, CR-001 is truly the best-in-class bispecific and partner of choice for patients and for combining across multiple tumor types to be successful for patients. I think that's where we want to drive ourselves to by middle of next year.
It's in the triple digits of patients, right? These are the cohorts that we're looking at, the expansion cohorts from the non-small cell front line, the monotherapy from the backfill. These are 12 plus patients a cohort. Not ones and twos, but meaty, meaningful cohorts that we can look at and really see real value from the data we're generating.
Can you talk a little bit more about what the bar will be to moving forward into registrational trial in any one of the subtypes? How will you prioritize speed to market with fast follower versus first to market in a different indication? What's necessary in each of those situations to justify pivotal straight away?
Yeah, I think that's where we leverage the matrix portfolio that we have and why we built the company the way we did with the 001 for next-gen bispecific foundational sleeve for IO therapy backbone, but also the ADC and the combo perspective. I think that as we look at areas like lung, where we get asked often, "Do you think lung is still open? It seems to be crowded."
With our ability to think about combination therapy and where that puck is moving, we think lung is wide open, and that's a best-in-class opportunity. There'll be other areas where we can go and tick off first-in-class opportunities that haven't been yet focused on from those that are out there running late-stage studies in lung, just starting in CRC and other areas where we can still compete for a first-in-class/best-in-class.
There's a matrix approach we have where a number of first-in-class opportunities combine with best-in-class opportunities and leveraging across the portfolio, that's our current portfolio. Also, as we want to demonstrate those three buckets of data for CR-001, we think there's plenty of opportunity to work with other payloads and companies that have tumor-specific areas where they want to focus that we could then leverage CR-001 as well.
There's lots of opportunities for us to think about where we want to go and focus our registrational studies. We've got the plethora of opportunity based on the data we have and the portfolio we built and the way that we built it.
Josh, you mentioned the potential for development in combination with ADCs. Can you go into a little bit more detail about that opportunity? Which ADCs do you think could be complementary and therefore highest priority? Maybe which tumor types would be most amenable to a combination of 001 and an ADC? Yeah, Jonathan, you want to take this one?
As Josh alluded to, we're advancing a matrix portfolio across CR-001, our PD-1/VEGF bispecific, our ADCs, which include our integrin beta-6 topo ADC and our PD-L1 topo ADC. As we think about this, we're going to explore these as monotherapy, in combination, and in combination with standard care chemotherapies to develop and advance a database decision of a matrix portfolio of where we can make the biggest difference for patients.
Our partnership with Kelun we announced late last year really exemplifies and accelerates, and expands this strategy. As all are aware, Kelun's a leader in global ADC development. They are a commercial stage company with their most advanced asset being sac-TMT, which is the subject of 17 global registrational studies in partnership with Merck. Kelun shares our commitment to developing CR-001 and ADCs in synergistic combinations.
As part of our deal, we in-license the integrin beta-6 topo ADC for all regions outside of Greater China. Kelun-Biotech has the opportunity to develop CR-001 as monotherapy in China, which is a study they recently announced that they have initiated in China, but also in combination with their full portfolio of ADCs. There's a number of Kelun-Biotech ADCs that are eligible to be combined with 001, including against targets around Trop-2, HER2, claudin, and Nectin-4.
In the recent data Kelun-Biotech shared at ASCO, we're looking forward to seeing more of that on Friday, where you combine pembrolizumab with sac-TMT to lead into very compelling results, further exemplifies our combination opportunity around CR-001 and ADCs, particularly topo ADCs. We're very excited to explore combining CR-001 with our own internal pipeline, as Josh alluded to.
ADCs with Kelun-Biotech, such as sac-TMT, which is eligible as part of our collaboration. That could be an interesting combination study to explore, and potentially additional partners that Josh alluded to. We will make a database decision to make a difference for patients across multiple solid tumor types based on this strategy.
What do you expect to learn from the sac-TMT/pembrolizumab combo on Friday? Anything in particular you're paying attention to?
Well, I'll hand over to the team, but at first, even from the abstract release we've seen, what it shows is a couple of things. First is the safety that we've seen from Kelun's ADC pipeline. As a reminder, our integrin beta-6 topo ADC, CR-003, was created by Kelun from the exact same platform that made sac-TMT, so it's an enhanced version of that linker and payload.
Though safety is a read-through to CR-003 monotherapy, but there's also the element of the opportunity to combine Kelun's topo-based ADCs with IO agents. If you see positive data from sac-TMT and pembrolizumab, we are very excited about the possibility of employing what sac-TMT and similar ADCs could do with a PD-1/PD-L1, both in terms of enhanced efficacy and potentially enhanced safety as well. We're excited to see the data in more detail and believe it has important read-through to our synergistic combination strategy and CR-003 as a particular asset with Crescent.
Yeah, and I would just piggyback on that just to quickly say this is where the value of the Kelun relationship, and we've gotten to be very close with Kelun since we've been working together almost one year now and thinking about how we can drive the value of CR-001, which is the next logical step, right? You've got the Keytruda plus sac-TMT.
The next step is the bispecific plus sac-TMT, and thinking about not just sac-TMT and their pipeline of ADCs, but across their broad pipeline should generate a wealth of data for the class of bispecifics, but it'll be with our CR-001, which we think again, will be the partner of choice in best-in-class bispecific, and that partnership can help validate that very quickly. That's helpful.
Maybe one question that we get quite often is what does Crescent expect to learn from Summit's plenary presentation this weekend of Ivo plus tislelizumab, or Ivo plus chemotherapy versus tislelizumab plus chemotherapy in the first line advanced squamous cell lung cancer, the survival results? What are you guys looking forward to in that data set? What in particular are you going to pay attention to?
Yeah. Ellie, you want to take this one?
Yeah. Thanks for that question. It's a highly anticipated presentation at ASCO plenary session, and given that we will have a chance to look at the survival data from this frontline study, I think it's quite important for us to look at the details and then what it showed, in terms of how ivonescimab compared to PD-1 in this difficult to treat population.
In terms of overall survival benefit, we are interested to see how that data translates to clinically meaningful benefits. Far, ivonescimab, these three trials have shown clinically meaningful data, and clinicians all seem to think that if this drug would be approved based on the profile that they understand, they're willing to treat their patients with ivonescimab.
Considering that finding, if we see similar clinically meaningful benefit of survival in this HARMONi-A trial that shows PFS benefit we've seen from last ESMO is translating to OS benefit, I think it will be a huge catalyst for the entire field, addressing one of the critical questions that we've been having from the very beginning of a PD-1/VEGF bispecific development. From our side, we are very excited to see this data, we will learn a lot from the patient population they enrolled and how the safety and efficacy data look like. Based on this, we will gain a lot more confidence in developing CR-001.
Because we have intentionally designed this compound to match the key features of ivonescimab, if we demonstrate that CR-001 has similar early clinical data from ASCEND trial, we will have a lot more confidence going into the later stage development.
I'll just add on to that. I think what Ellie said is right. If we see that four-plus months of survival benefit, we think that's going to be incredibly successful. I think if you see that, you're going to have then a bifurcation between this clearly being further validation, almost unnecessary validation, that this is a new class of drugs, versus what the market reaction may be based on which side you are on the stats and OS and et cetera. I think that's more of a market issue, not an issue for where this class of drugs will go long term.
That's helpful. Maybe moving to CR-003, can you talk a little bit why integrin beta-6 was a high-value target and a compelling opportunity for Crescent?
Top of our list from a target perspective, but maybe I'll just give a little background here.
Yeah, integrin beta-6 has been our target of priority for a while. It's because it's an ideal target as this integrin beta-6 is overexpressed in multiple solid tumors, whereas its expression is very low or undetectable in normal tissue, which makes this an ideal target for ADC in general. Also, the tumor types where integrin beta-6 is overexpressed, the list is quite well matching with our matrix portfolio. When you look at the tumor types that we want to study with integrin beta-6, it complements the types of tumors that we are studying in ASCEND the trial with the CR-001.
Right. Pfizer is evaluating its targeted ADC in a phase III trial in lung cancer in combination with pembrolizumab. Data is expected mid-year, so any day. Can you describe how Crescent is going to evaluate the results from that trial? What will provide confidence in the class, and what results would make you more pessimistic?
I think we sit in a great position here as we look to learn from that data, but maybe Ellie or Jonathan, one of you want to give our perspective?
Maybe I can start, and then I'll let.
Yeah
I mean, look, from our perspective, it's like a win-win for us regardless of the outcome of that data because of the differentiation of CR-003. If the data is positive, that's wonderful for patients, reinforces the opportunity with the integrin beta-6 target, and also just demonstrates the size of this market. If it's mixed because of something that might be ascribed to either the linker or payload that Pfizer has picked, again, it points to the opportunity you have a best-in-class integrin beta-6 ADC.
As a reminder, we designed this asset with Kelun to have a differentiated safety and efficacy profile. The antibody is optimized for internalization and for both high and low antigen-expressing cells. The linker, it's stabilized with a potentially superior PK profile compared to the vc linker that's used in the historical Seagen, now Pfizer molecule.
Of course, our payload is a topoisomerase payload that optimized for tumor cell killing with a bystander effect. This is all based on the sac-TMT platform, an enhanced version of that, so it's also clinically validated as well. Just further reemphasizing Pfizer's commitment to the target, they are advancing a separate integrin beta-6 molecule with the same antibody, but with a topoisomerase-based payload. We're very confident. We think we will learn from this data. We think it's a very positive situation for Crescent, somewhat regardless of the outcome here. Ellie, anything to add?
No, I think you touched all the great points. The way that we have optimized the CR-003 for internalization and an Fc-silenced antibody to potentially address the risk for pneumonitis as well as a linker payload that could provide us wide therapeutic index. All these things could give us a chance to create highly differentiated efficacy as well as a safety profile for multiple tumor types, of course, including non-small-cell lung cancer.
Maybe one last question on this program, and that's the phase I/II study that you referenced previously with data in Q1 2027. Can you go in a little bit more detail about what tumor types will be investigated, kind of the general design of the study? What should we expect in terms of size, scope, and other measures in the Q1 2027 readout?
Yeah. I mean, look, it's a robust phase I/II study. We don't want to get ahead of our partner, Kelun-Biotech. What's been disclosed, it's around 256 patients across three elements, dose escalation, dose expansion, and then an indication expansion as well. They haven't disclosed what tumors are going in, but you can imagine it's multiple solid tumors. We're well aware of the integrin beta-6 expression profile that Ellie alluded to across different tumor types.
As we think about this study, we'll have elements across those cohorts in Q1 2027, then we're going to leverage that data from China to initiate our own phase I/II global study. What that does is accelerates our global development timelines. For example, on dose escalation, we won't have to repeat the full dose escalation, likely because we can leverage the data from Kelun-Biotech. We're very excited about the opportunity for this ADC, both as monotherapy and in combination with CR-001.
Great. With that, we are just about out of time. We've asked you a lot of questions today. Anything that we didn't get to that you'd like to highlight for investors?
Well, I just say don't sleep on CR-002. We didn't talk about that in detail, but that program will be in the clinic middle of this year, data in 2027 as well. Just thinking about the ability, not just the monotherapy, as it was mentioned for CR-002 and 003, but also the combination of 001. Again, as you think about the matrix portfolio, lots of ways for us to play and win across all indications, even some that may seem to be crowded at first glance.
We're really excited about really leading that with meaningful clinical data generation starting Q1 2027. I think we have put ourselves in a position to generate across these at least four studies we're initiating this year. At least one will be with Kelun, and a 001 plus an ADC combo, could be more.
That just really sets us up for a very robust, data-rich 2027 in which we want to follow the data and continue to serve patients. We're in a great spot. As I mentioned, we're well-capitalized to get through all those key milestones from these four studies and really just looking forward to generating the data.
Great. With that, we are out of time. I'd like to thank the team for coming in and giving us an update.
Thank you.
Yeah.
Thanks, Ellie.