Good morning, everyone. Thanks for joining us to have a conversation with Chief Strategy Officer, Mickael Chane-Du, with Adagene. My name is Arthur He, a Senior Biotech Analyst at H.C. Wainwright. Mike, first of all, thanks for coming down to talk. Maybe to kick off, could you give us a brief overview about Adagene? We know Adagene is a platform company with the leading asset targeted CTLA-4. How does that making you guys unique in the CTLA-4 space?
Yeah. So thank you for having me, Arthur. As you mentioned, Adagene's lead program is a masking CTLA-4 called ADG126. We know that the issue with anti-CTLA-4 is not really the efficacy. It is really the, I would say, the lack of tolerability, right. We design our CTLA-4 such that it comes with an increased therapeutic index. It is much safer, we believe, than the first-generation CTLA-4 inhibitors. We can dose it so much higher thanks to an improved safety profile. We got that better safety profile thanks to our SAFEbody Platform, masking technology platform that is wholly our own and proprietary. The whole idea is to have a protease-sensitive linker. So the linker, the mask, is removed. The antibody is active once certain conditions are achieved.
We believe that those conditions are more likely to be achieved in the tumor microenvironment, number one, high concentration of certain proteases, and number two, high concentration of the target, here, in this case, CTLA-4. One data point, an important proof in the pudding is the fact that we have been dosing patients up to 20 mg per kilogram, even in the context of a combination with PD-1 pembrolizumab. Where historically CTLA-4 have struggled to go above 1 mg to 3 mg per kilogram. I would mention the fact that our discontinuation rate due to adverse events is less than 10%.
Okay. So I think for what I am saying, because the SAFEbody Platform, you guys can dosing probably about 24 more than ipi. Could you give us more what kind of that room giving to the patient to get a-
What can we bring to the patient as a result?
Yeah.
We think that, number one, that CTLA-4 inhibition is a very dose-dependent mechanism of action. We believe that the higher the dose the better in terms of response profile. Thanks to our ability to dose higher, again, thanks to the masking, thanks to the better safety profile, we believe that we can, as a result, fully unlock the potential of CTLA-4 PD-1. I will give a few data points, for example, in the context of late-line microsatellite stable colorectal cancer without metastasis to the liver. We know that historically, PD-1 inhibitors as monotherapy are not so efficient with response rate close to 0%. We also know from a randomized phase II that durvalumab, tremelimumab, PD-L1, CTLA-4 from AZ, generated a 2%-3% response rate in that same setting. We so far, especially at the relevant doses, we have generated the confirmed responses between 15% and 36%.
You touched on the ADG126, the data there. You guys updated the OS data in the first half this year. Could you give us a little bit of color on that? I guess the question is you are moving for the 20 mg per kilo. My question is that top of the curve or you guys can push a little bit higher?
Oh, you meant we. Yes, we disclose OS data and overall survival curves from several dose cohorts. We combine the 10 MPK cohorts. You had two subgroups there, 10 MPK Q3W and 10 MPK Q6W. We had a median overall survival close to 20 months, and a very nice trend in terms of long-term OS with a 48% 24-month rate. There was a trend towards really good survival benefit as well from the high-dose cohorts. We will update the dataset probably next year. I would mention the fact that we so far we see a very good response profile, better response profile, a trend towards better duration of response from the high dose. Let's see how the data evolves.
Okay. Let's take a look at the safety side. I believe for the 10 MPK you get like 15 grade three and for the 20 you get a little bit higher. Slightly over 30%. How should we reconcile this number with the dosing or the tolerability profile of the ADG126?
Yeah. First of all, in the context of late-line metastatic colorectal without liver metastasis, I'm just going to say late-line from now on.
Yeah
it's shorter. If you look at the 20 MPK cohort and the number you quoted, it's an average number. It's a combined number. If you look into the details, we know that the loading dose of 20 followed by 10 MPK came with the higher grade three incidence, which was 50%. But two things. Number one, we had no discontinuation due to adverse event at that dose. That's number one, the very important data point. Number two, yes, we did have 50% grade three, but it came from 14 patients, and we had notably one patient that had some late onset of grade three, where it was a long-term responder, and we saw two grade three in the same patient beyond 12 months. It's probably also a matter of small N.
I guess for that part, FDA are okay with you guys with pushing to the phase II study,
Yep
with the higher dose. Could you tell us a little bit more about the phase II design and what you guys try to achieve through the phase II study?
Yes. Thank you. We have this ongoing randomized phase II for Project Optimus. We're testing two doses in that trial. ADG126 at 10 mg per kilogram every three weeks, so Q3W plus pembro, as well as ADG126 at 20 MPK Q6W in combination with pembro full dose. What we would like to see is that we replicate the data that we have seen in the phase I-B.
As a reminder, we saw a confirmed response rate between 15% and 25% from these two doses. But I also invite our investors to look at the totality of the data. You want to look at response rate, obviously, also duration of response, as well as progression-free survival. As you remember, we showed a median PFS very close to five months in our phase I-B. It will probably be too early next year in the first half of 2027 to get a median overall survival. But certainly, we believe that we will have a trend in terms of PFS.
Okay. Speak of that for let's look fast forward for next year when you look at the data. How should we kind of make a judgment or you guys internally thinking to picking which arm is better arm in terms of the dosing regimen wise? What if they are kind of looking very similar? How is that?
We will look at the totality of the data again. We will look at ORR, the trends in terms of duration of response, PFS, and safety of course. Based on that, we will make the decision to move the right dose in a pivotal setting.
Okay. Sounds good. I guess as we said, registration is going to become right after you guys picking the dose. What is the gating item like for you guys have the first patient dose in the pivotal trial?
First we need the data. Number two, we need to have an end of phase II meeting with the FDA where we will present the data to them. Then we will discuss the trial design for the future phase III randomized phase III trial in the setting that we are targeting. Those are the key factors before we initiate and dose the first patient.
How have you guys think about the phase III, how the design or setting up could be? I know you haven't finalized, you have to talk to FDA after data first, I get. Generally, what's the setting for?
Yes. At high level, I think I believe that investors should expect a randomized phase III trial comparing ADG126 at the relevant dose plus KEYTRUDA versus depending on the population that we target, you could have a select control arm, could be fruquintinib plus one or two bevacizumab, could be physician choice of therapy. If you look at what a direct competitor did not so long ago before deprioritizing the trial, it was in later line patients. I believe that the control arm was physician choice of therapy that included salvage therapy, fruquintinib et cetera. To be determined. I believe we have a good view on what could be the control arm in that study. Two scenarios in terms of endpoints. I believe that the base case scenario for people should be primary endpoint of overall survival.
Okay. Then there's a second scenario that needs to be discussed with the FDA, which is having a co-primary endpoint of response rate alongside overall survival. We have seen other trials where we have seen precedents about that where response rate could be used for interim analysis and the interim analysis could be used to discuss potential accelerated approval in the context of a randomized trial. But you should see that scenario as an upside scenario.
Okay. Let's take a pause on the 126 now. We all know that partnership have been always your part of your story which I think it's kind of a little bit unappreciated there. First of all, for 126 itself, you have a multiple clinical collaboration with Roche before and with Sanofi ongoing and also I believe recently the Incyte, right? Could you tell us a little bit more about that? What's the rationale you guys pursuing that for the collaboration?
All these trial collaborations. If you take a step back and talk about the lead program of ADG126 first, we believe that ADG126 could be a phenomenal combination partner not just with anti-PD-1 but also with a lot of bispecifics, so broader combination regimens. Two great examples would be the Sanofi collaboration and the Incyte collaboration. We are currently evaluating novel combos, so novel anti-PD-1 IL-15 with ADG126 with Sanofi in solid tumors and you should think of the warmer tumor types. The other one that is also very exciting is a collaboration with Incyte in msCRC, with and without liver metastasis. We are combining ADG126 with their bispecific PD-1 TGF-beta.
We unbelievably believe that that anti-PD-1 TGF-beta is a better combination partner in the context of microsatellite stable CRC because that bispecific has shown a 15% response rate in late-line msCRC, including 12% response rate in patients with liver metastasis. And those numbers are significantly above not only the anti-PD-1 monotherapy data, but also versus any standard of care so far. We believe, Incyte and Adagene, we believe that the addition of CTLA-4 could address an important mechanism of resistance, and we can improve upon the data that Incyte generated at ESMO 2025.
Also previously, you had the collaboration with Roche, tested
Yes
126 in their liver cancer, right?
Yeah.
It seemed like even though the data presented at the AACR and even though the cohort number is a small number, for me, it looks interesting data there. My question is there a path you guys can take to this asset or in this indication further? I mean, in what kind of sort of form possible?
Yeah. The collaboration with Roche was another great example of ADG126 being part of broader mechanisms, broader regimens, broader mechanisms of action. As a reminder, we generated in a randomized setting, even though in a small number, a trend towards better response rate, better PFS, and better overall survival for the triplet combination of ADG126 at 6 mg per kilogram every six weeks on top of tecentriq plus avastin, so Atezo/Bev. Atezo versus Atezo/Bev and that was part of a platform trial called MORPHEUS. We were very happy to see that kind of data. Unfortunately, that trial, MORPHEUS trial, was deprioritized some time ago. That said, we at Adagene believe that first-line metastatic liver cancer is a very interesting and important indication for ADG126. Number one, we believe that people don't fully appreciate the size of the addressable market.
Number one, it is the sizable incidence number in the U.S., more than 15,000 patients are treated every year in first-line metastatic HCC. Number one. Number two, the median duration of treatment could be pretty long. I would remind people that the median PFS, not duration of treatment, but median PFS with Atezo/Bev or PD-1 CTLA-4 that are approved currently have generated PFS in the high single-digit number. We also believe that the competitive intensity is not as high as in other settings. So we like first-line HCC a lot. Now, to answer your question, how could we address that tumor type? Remember that we at Adagene have an important Chinese lineage. We have a strong heritage from there. So we want to leverage upon that. We could enroll a lot of patients in China, generate further proof of concept data in a very capital efficient manner.
I would remind people that HCC in China comes with a significantly higher number. If we were talking about 15,000- 20,000 patients for first-line HCC in the U.S., we're talking about more than 200,000 patients in China.
And also, I guess on the same side of story, you guys also mentioned about the non-small cell lung cancer as another large indication potentially that ADG126 can make a dent there. So I guess my question, in what kind of situation you guys are willing to take that in that direction?
We are looking at the whole field, obviously. You may have noticed that the CTLA-4 inhibitors have attracted a lot more attention and capital recently. We noticed indeed that BioNTech with gotistobart generated very interesting data in the context of, I believe, second line squamous lung cancer. So it does show to the world that CTLA-4 is far from a dead mechanism of action. It could be a very important one. It is just that people have been underappreciating it for some time. For now, we do not have a plan to do a randomized trial in the context of second line squamous NSCLC. But we recently raised $70 million in April with U.S.-based investors after generating updated data from our phase I-B and after announcing the trial collaboration with Incyte. Again, we have a very important Chinese heritage and lineage. We want to leverage upon that.
We believe that we can generate POC data in a very capital efficient manner. I am not saying here that we are going to do for sure everything, but we want to be selective. I explained to you what is the rationale for first line HCC. We also very much like neo-adjuvant, adjuvant CRC. We like metastatic CRC. But again, we want to be selective.
Gotcha. I guess another question in terms of pipeline-wise, now you are resourcing more focus on the ADG126 for now. What other early assets in your pipeline are you very excited about or you want to highlight for us?
I would like to highlight ADG138. It's our dual Masked HER2/CD3 T- cell engager. This is a program that could be moved potentially in the clinic. We can use the China playbook, where we generate some early proof of concept data there. I want to emphasize something. I talk a lot about China right now, but all our data sets are global. We have fantastic relationships with people in the U.S., South Korea. We are a global biotech company. We believe that for early POC data generation, going to China is a very important one. ADG138 dual Masked HER2/CD3 T- cell engager, I believe is an asset that investors should pay a closer look at.
Awesome. To close, could you remind us what's the catalyst for Adagene in the next 12 months and what's your cash position there?
Yeah. I would mention on the clinical side, number one, our randomized phase II trial in late-line metastatic CRC for Project Optimus. We will have the end of phase II meeting with the FDA, which will lead hopefully in 2027, initiation of a randomized phase III trial. I will also mention that we have an ongoing randomized trial. It's an investigator-sponsored trial evaluating ADG126 plus pembro in neo-adjuvant CRC, a setting that we have not talked a lot about today, but we are very excited about it. We believe we can be very differentiated there, and people should expect data also in 2027. We want to remain very active in terms of business development. We have proven our ability to bring in non-dilutive capital and sign smaller licensing deals. Please stay tuned.
Awesome. Thanks, Mike.
Thanks, Arthur. Thanks for having me.