Conference Transcript - CBIO 2026-06-03

Speaker 2

My name is Manoj. I'm an associate in Agha's team, and it's my great pleasure to introduce Crescent team. Maybe we can start with, so we are all back from ASCO. So how do you view the Harmony 6 data point at this point? So it came like slightly better than in terms of overall survival. So how do you view the Harmony 6 data?

Joshua Brumm, CEO

Yeah, thanks. I think from our perspective, ASCO is very exciting across the entire portfolio and strategy for Crescent Biopharma. I think very validating for our view on really replacing first-gen PD-1s with the new backbone therapy for IO around the biospecific class of drugs. I think that question was substantially answered with the historic data that Akiso and Summit put out with the Harmony 6 data. I also think from a longer-term strategy around our focus, which has been from the beginning around the ADC combination therapies, also the SAC-TMT data was also very strong. And so from our perspective, it was a very exciting and validating ASCO for this year. In regards to the Harmony 6 data, maybe Ella, if you want to take a few minutes to comment on our perspective.

Ellie Im

Yeah, we thought that that data was really validating the class and then answering some of the key questions that we've had thus far. The first one was PFS benefit translating to OS benefit. So PFS 해설 ratio was 0.6 and OS 해설 ratio was 0.66. And so we are now seeing how PFS benefit is directly translating to OS benefit. And what was also great was regardless of a PD-L1 expression of the subgroup, the patients benefited across those levels. And in terms of safety, which is also important because some of the key concerns of this combination with chemotherapy plus PD-1 VEGF was coming from Avastin, causing a lot of bleeding issues, especially in squamous population. So now we are seeing that long-term safety data compared to last year's ESMOS data maintaining comparable to what we saw at ESMO. And then overall grade 3 or higher grade events compared to the two arms, PD-1 arm versus PD-L1, PD-1 VEGF arm, we're not seeing major differences. So all those things to us is mainly a positive and huge validating point for entire class.

Speaker 2

So maybe kind of thinking about like, yeah, yeah, yeah How's it going guys?

Speaker 3

It's going great.

Jonathan McNeill, COO

We just finished talking about Harvey six.

Speaker 3

Yeah, yeah, exactly By I'm warning you guys all right, I will go over so where was the next one? I preemptively apologize It's good seeing you guys. We all just came back from ASCO So, you know, I wanted to maybe start off with, again, if we think about PD1 by Jeffs, class is real. I think the big takeaway I think Minoja and I had is really trial design matters.

Joshua Brumm, CEO

So, you know, can you hit on what were like the big takes in terms of trial design that your team is going to be incorporating after we've seen some of the data sets we got from Biontech and from Summit? yeah look i think that's a very savvy point i we spent uh the the last few days talking about uh just that point the class of drugs now i think is completely validated it's validated we started with that while you were getting out of the elevator i think that um you know the harmony six data validates the class of drugs you have sac tmt from asco that looked great you had the crc data from uh from summit as well talking about label expansion from the first gen pd ones all on point for our strategy to company right and where we want to go i think that um even looking forward to the questions that summit will need to answer around harmony three i feel like your point is exactly well taken that's a summit question for us the class of drugs and thinking about how we want to design our study the lessons learned to be a fast follower to build on our focus around developing oh one is the backbone therapy best in class by specific partner of choice uh for this transformation and paradigm shift from first generation pd1s is something that we're very excited about and there are some key lessons to be learned from this data so maybe i'll you could talk a little bit about that yeah yeah so um overall we thought that this was really landmark data we've been waiting for uh something that can do better than ketria plus chemo in

Ellie Im

squamous cell non-cell lung cancer it's been more than a decade finally showing pfs benefit translating to os benefit and overall a perspective everybody thought that it was acceptable uh safety profile so overall we are very encouraged by this data uh the few a few things that we could draw from the results of course how to define inclusion exclusion criteria for safety perspective who should be included because they can tolerate the drug or who have a higher risk of immune Mediated adverse events or VEGF mediated adverse events that we should not include, right? What are the sample size we should use and then what is the right benchmarking for the standard of care arm? So we were talking about Median ways for the competitor arm would it be 19 months versus 24 months, right? And then if you now see the when the curbs are separating which you pointed out rightly so in your report Now we have a better understanding of how long a follow-up it should be for us to really detect right amount of benefit that can be statistically significant and also clinically meaningful. And of course, last but not least is the stratification factors, what really matters and how we can use the right stratification factors so that there's no critical imbalance between the two arms that can lead to potentially, you know, one or the other way of results. Yeah.

Speaker 3

You know, to that point, I mean, there's kind of this interesting discussion, which is like, okay, well, there's a different dynamic in terms of elderly patients versus, you know, younger patients, but is that actually a false signal? It's actually more about ability to tolerate, you know, standard of care, and that, you know, it just happens that age is a stratification. So when you think about, again, things that you would apply to your studies, are you thinking, is it an age cutoff? Are you thinking it's about prior lines of therapy in order to enrich for the patients who would be responsive with your drug? What's the right approach to amplify the right signal?

Ellie Im

So based on that question, which has been pointed out by the discussant and heavily debated. And we actually looked at the Harmony A study, Harmony 2 study, as well as other monotherapy data and combination data in many different tumor types. Based on our knowledge, I think this is the only study that showed relatively big difference in the hazard ratio of younger or older patient population. And then the safety and tolerability perspective, I don't think there's any data to speak to that age 65 and older patients have a lot more toxicities. So I think it's more related to this study specific. And then Summit did a great job of explaining there were two major factors that could have contributed to it. The tumor size, patients with a larger tumor size, and patients with a brain metastasis. there were a higher proportion of patients with such features were allocated to ibanesimab treatment arm in the age 65 or older. And so now we know this, and it looks like the summit is already stratifying based on those two factors, which will potentially mitigate foreseeing such discrepancy in terms of age affecting tumor benefits.

Speaker 3

Right. So to you, it's like less about the age. it's more about just how inherent like the older you are the more severe you actually were with your cancer okay that would make sense that would just say is people take time to digest and come back and start to look at the data yeah like you know the chinese patient data versus the global data those answers are existing in harmony and harmony a dig into the harmony too if you dig into that those data sets there's a lot to be gleaned there already understood now i'm sorry like i didn't think i i got a read i figured i was gonna leave asco and be like okay we're gonna get a sense on how much alpha you know uh some spent on the harmony three readout i don't know if i got one someone in the audience wants to chime in it's fine but um i mean did it have to be 0.6 it had to be 0.65 it had to be 0.7 i mean there's a range of outcomes here so and we're all dealing with a sensor empty right so when you think about again like there could be a red flag where it's like, hey, we are seeing as we go into a global trial that the data isn't one-to-one translating, which often happens. That doesn't mean it's not a real signal. It means it's not translating one-to-one. So when you think about, okay, we got a four-month delta in Squamous.

Ellie Im

If you were powering a phase three study today, what would be the absolute OS delta that you think should be the target in any well-controlled phase three trial in a U.S.? in a more global population like right how much wiggle room does four months give you so that's a really good question and again you pointed out in in your report so i i'm glad that i have a chance to talk about this so we are looking at the shape of the curve between the two arms and how widely they're separating and in terms of reducing the risk of death and that's how hazard ratio is calculated and that was a 0.66 median is just the one point of the number that's representing the survival benefit right so it's more of looking at the oval curve how it looks like so around month six or so the curves started to really separate and then the separation became wider with time right so with the longer follow-up this was a 38% data maturity for survival analysis. The longer follow-up might give us even better hazard ratio and again median is just the one point that you are looking at one time point and see how Long of the patients lived at the 50 percent percentile. So overall risk reduction of this trial showed 34 percent. So that's something that we need to look at. And also how the computer arm is performing. So Keynote 407, overall survival for the Keytruda arm was 17 months. So here, the PD-1 plus chemo arm was 24 months. Depending on in which region and how your population uh is performing that control arm can be different right so then how you consider that and choose the right uh sites and countries and then also control the enrollment rate and when is the right time to perform an analysis so that patients enrolled in the study have a follow-up sufficient follow-up to demonstrate the difference in efficacy as well as a safety perspective so all those things are really great lessons for us yeah and then we are here learning from all the great data that's coming out very encouraging not just in non-small cell lung cancer but from multiple tumor types yeah i mean we'll talk about it here yeah and then we are executing and generating our own data of a cr001 ascend which is phase one two trial of our pd1 vegef and so So we'll generate our own data and then learn from all the great lessons. And then that will give us a chance to then decide on which tumor type and then what combination we should choose to improve the probability of success of our registration trials.

Speaker 3

Dr. Justin Marchegiani I understand a very helpful answer. I mean, Josh, this might be also a question for you. Again, you have to, I think what the summit management team, and again, I think there's very very impressive team there's no doubt about it but you have this kind of unique circumstance of you have to be you're competing with the big guys you need to create catalysts you need to raise money and that's something you're going to have to deal with as well but you know i can't help but think like i would be powering these studies for os and just not messing around like no more pfs interims like we know this class works that's fine but if you went and said look we are running our trials fully powered for os we are not spending alpha because ultimately that's what, by the time we get on the market, that's what regulars are going to go for. And that's really what we, you know, we want to put forward. And then to your point, if the curves get wider over time, they may have actually hurt themselves by, you know, doing an interim a little earlier than expected. I mean, is that the right read, right? Like, how do you balance the need of a headline, you know, which could help with capital raises versus, you know, making sure these trials are powered correctly in your seat?

Joshua Brumm, CEO

Yeah, look, I think it's a great perspective. Our view is that this really is a unique position to be a very fast follower and the opportunity here we're talking about it doesn't matter who you talk to what farm you talk to some of it ourselves this is a hundred billion dollar market opportunity paradigm shift and then our strategy and focus on the adc synergistic combination piece of this from the beginning i think has been a clear differentiator in our clinical strategy and i think you know our view is that we're learning rapidly from these studies and again i always say it's a great credit and you know bold leadership to open up this next class of of uh backbone therapy for io and so we'll learn from that um we will think about is this os only are we going to think about um how we want to run these studies but it is such a massive opportunity we're just talking about lung right and so for us as we think about this over the next couple of years we're going to be able to generate a foundational piece of revenue out of this changeover paradigm shift with our 001 asset i think what's unique to us is we we own that asset right and there's only a few people out there that have the opportunity to be a player in this next generation backbone therapy and cr001 with the three the three buckets of data we're generating now the q127 monotherapy first line non-small cell data that's coming again within 12 months here within actually nine months and then within 12 months that second bucket of data where we're going to take O01 and combine it with various standard care chemo agents. We're going to see various tumor types, various reads across being able to combine safely and efficaciously with various chemo agents, and then leveraging the partnership we have with Colune to generate that third bucket of data, which is O01 combo with ABCs. And as of this week, we now know that we're going to be able to be talking about the CR001 stack TMT combo that our partner clune's running in china i'm shocked additional ladies that was the adc cool i had no idea right so we're very first of many we're very excited about being in the middle of this entire field but generating data across all three of those buckets will allow us to be able to have a a claim that we could be best in class partner of choice and so how we think about designing these studies where we go how broadly we go and how we go with partnerships uh capital raise, et cetera, the data will give us the ability to generate that position of strength from a capital perspective and a partner perspective. And so I think we have some incredibly valuable assets. I think our strategy will pay off. And I think being a very fast follower and the things that Ellie and the team are already thinking about implementing into our study design are going to be incredibly impactful for us.

Speaker 3

Now, you know, it's interesting. You look at the Lenovo data. It's clear where Merck's head was at. You had an NSCLC backfill cohort. 80% of your patients were PD-1, 1 to 49%. Like, and where have they not run studies in lung is, you know, the 1 to 49. And of course, we'll get the Colun less than 1% data in non-screening shortly. But knowing that, and we think about your combination data set, and really, you also have a backfill cohort in first-line lung. What's the, when you think about the data we've seen so far, and we're not just thinking about broadly first line, but we're thinking about subtypes, right? Where do you feel like the benefit of a PD-1 VEGF is best positioned relative, you know, like relative to just Pembro alone? Is it the one to 49? Is it less than 1%? Or at your point, no, actually, we see, you know, across all subtypes, you know, that's really where we're going to be enrolling for patients. Or when you do, when Kloon does that trial, they're going to go for that really biomarker specific population, similar to what Merck did with Wanova. Allie Chandra.

Jonathan McNeill, COO

Well, I'd say first, we don't want to get ahead of our partner, Colun, around describing what the 001 SAC-TMT study is, and we'll be excited to share more about that when that's But we're excited to generate that data because I think that will inform the question you asked, which is, is this applicable across all subtypes? What are the best tumor types for SAC-TMT and 001? More broadly, what are the right tumor types for other ADCs, such as the integral beta six topo adc that we also partner with colun we have rights that outside of china plus oh one as well too so i think that we will make a data-based decision on that the data to date and the data that colune released at asco suggests that it could be applicable across a wide variety of non-small cell and potentially other tumor types as well but that's something that our data and the field's data will guide us on i don't know if you guys anything but um yeah no i we we are looking at the data from monotherapy as well as a combination perspective of ADC as well as chemotherapy.

Ellie Im

So I think it depends on which strategy that we are referring to. One thing that has been really great to see with the PD-1 VEGF as a class compared to PD-1 antibodies is that regardless of PD-L1 expression, we are seeing similar degree of benefit. So having said that maybe Delta can be greater in patients who didn't receive a lot of benefit from PD-1. So that gives us a little hint. But it all also depends on are we doing it as a monotherapy, or are we combining with a standard of care chemo, or are we combining with ADCs that have specific activity in these tumor types and then PD-1 expression.

Speaker 3

So we have a lot of options of generating the data and then making decisions based on that now not all chemotherapies have the same side effect profile not all adcs have the same side effect profile um i think one of the things we see with sac tmt is a that four make per kick dose was kind of a breakthrough for them i think they were higher dosing they were pre-dosing with cgsf you had a lot of neutropenia yep they found kind of a dose which balanced i think their ae profile but can you talk about again less ILDs but stomatitis, you have diarrhea, you have neutropenia. Why could SAC-TNT potentially be the right side effect profile that would be combinable with the side effects that you get with a PD-1 reg f? Why is that maybe the right fit here?

Ellie Im

We are very encouraged to see what Colune and Merck had done to optimize their dose. I agree with you that five mc per kick those was associated with a higher number of a greater three were higher grade events on those diarrhea stomatitis as well as other neutropenia and other adverse events so at four mcpercate it was well tolerated and then we saw very low number of patients with a great three were higher grade AEs or AEs leading to discontinuation or death, right? So based on that data, what we know from PD-1, VEGF versus PD-1, immune-mediated adverse events perspective, the rates are similar. And then the VEGF-mediated adverse events perspective, most of them are grade 1 or 2. Right. And then the grade 3, where higher grade events are very rare.

Joshua Brumm, CEO

So that gives us a lot of confidence that when SEC TMT was safely combined with Keytruda right the profile of what we know safety profile of what we know of PD-1 VEGEP also we should be able to safely combine with the SEC TMT and provide that benefit okay and I might just add on that I do think it is worth pausing and just acknowledging that there are a number of biceps in development yeah but they are not created equally and i do think that safety is going to be one of the key issues of can you really be a backbone therapy if you're going to generate the next pertuxin or the next ketruta you need to be able to be combined across various various agents safely and that's why these three buckets of data that we're generating that we'll have out middle next year will be so impactful because it'll it'll give people a look across you know monotherapy multiple chemo agents multiple ADCs in a very short period of time and, you know, a solid number of patients, is CR001 safe and combinable across multiple agents? And so that's why we're designing the study this way, because we are positioned this to be the best-in-class backbone.

Speaker 3

I want to stake one more question on your partnership with Kulun before we'll end on B6A. Like, Kulun, and we've gone to Shanghai, we've gotten to know that management. It's a very remarkable organization. They have great sites. Like, the more we meet them, we really do think they're super impressive. They think about novel payload delivery, whether it's, you know, even RNAIs, steroid delivery, I mean, degraders. They're working on some pretty interesting stuff. What is your relationship with them? Because you have two ADCs you're sharing. But I can't help but think, A, I think a lot of things people don't understand about the deal you did is they actually now kind of have some skin in the game in terms of there's something specific with your company. They have an ownership stake. And you're going to get data not just with SAC-TMT, but there's a ton of ADCs they have in their portfolio, Nectin-4 and some with Merck, some not. Would I be surprised if, let's say, we generate some of that data and then you in license or you have the ability to actually bring those products into the United States, right? Is that possible that we shouldn't just think about the Kloon partnership on the PD-1 VEGF and these two assets, but actually something that could be more expansive?

Joshua Brumm, CEO

I'll ask Jonathan to talk a little bit about that, but first I'll just say that we couldn't be happier with our partnership with Column. Dr. Guh, their CEO, and I personally have become friends. We have a very shared vision across both companies to really become leaders in this field.

Jonathan McNeill, COO

And so I think there's many things that we expect we could see that will build upon this first initial collaboration, and we couldn't be happier with that relationship. yeah i would only add that as you alluded to we design the economic incentives and the structure of this relationship to truly align that as we generate meaningful clinical data the value we create is shared together and we see that as a foundation of what could be a relationship that ship that expands further as we continue to advance our assets across not just oh one and sac tmt but oh one and the integral beta 6 adc and then potentially other adcs as well okay that is interesting um all right last uh thing to hit on here uh obviously we got the pfizer announcement

Speaker 3

sounds like the decision was made months ago oss uh os itt no more b6a high b6a low we're gonna go for it um i like i want your just gut reaction when you heard that was your first thought again there's two two ways to think about it ah these guys missed on their pfs this is their last shot of hitting on os and you know it's going to be a modest effect size or the other read is i look at that publication they had a month ago they talked a lot about dose optimization and we're seeing with these adc's actually pfs understates sometimes the os benefit especially if you're going headed against chemo the longer you stay on the drug again with longer time that

Joshua Brumm, CEO

that actually ends up being a good thing and these guys are making a smart decision so those are those are the two thoughts in my head jesus um what was your team's internal read on that pfizer announcement yeah look i think we take pfizer uh for what they said right they said this is something they've been discussing for quite some time they haven't seen the data um and and that they are obviously committed they've made a number of changes to the protocol here throughout throughout the study uh but they're they're very committed obviously to the integrative ethics target with the first gen program that's reading out as you're as you're talking about but also the second gen program they have um we really do think that this is an interesting target it was top of our list it was one of the reasons that this colune deal got done um and so um i think you know we'll let the data speak when when they're ready to let it speak but i think they're clearly committed to it they're excited but they've seen a lot of data um and so we're just going to let that be and see when the data comes and i would just say we'll learn from that data just like we will from otherwise in terms of biomarker strategies, trial design.

Jonathan McNeill, COO

But if it is positive, that's wonderful for the field. It's also wonderful for the opportunity we have to have a best-in-class integral beta-6 ADC. If the data shows some MME-related toxic liabilities, again, we have a very different molecule across antibody linker and payload. And although that would be unfortunate, we'll learn from that.

Speaker 3

And as long as it validates integral beta-6 target, we're full steam ahead. i will say albert was he had a fireside chat with our ceo he said b6a could be the biggest dragon visor five one so on that note uh again guys i apologize for being stuck in the elevator apologize to the management team too but i think we cleaned it up at the end hey thanks so much