Good morning, everyone. Thank you for attending Jefferies Global Healthcare Conference. My name is Kelly Shi, a senior analyst on the biotech team here. Please join me in the welcome Mr. Mickael Chane-Du, Strategic Advisor, IR and the BD of Adagene for this first chat session. Welcome.
Thanks for having me.
Maybe for investors not very familiar with Adagene, could you provide an overview of the company and what you are focused on at the moment?
Sure. Adagene is a company focused on developing biobetamolecules. Our lead program is called ADG126. It's a masked anti-CTLA-4 that is currently developed for a very cold tumor, microsatellite stable colorectal cancer without liver metastasis. I'm going to say MSS for the remainder of the discussion. We just have generated updated data at ASCO, and I'm very happy to say that our poster was very, very well attended with way over 100 people that came there. We sense a very, very good momentum with physicians, investors, and pharma.
Fantastic. Maybe could you lay out data details on both efficacy and safety front, and how does it compare to the available therapies?
Sure. We are talking about the data set in the context of a late-line MSS CRC without liver metastasis. In this very context, I'm going to start with the standard of care. Standard of care, be it for fruquintinib or TAS-102 plus BEV, has a response rate in the mid-single digit. All right. There is very good data on that from several phase III trials. That is the standard of care. Unfortunately, the patients do not live long. For example, if you look at the FRESCO trials, specifically in the subgroup of patients without liver metastasis, the median OS does not go above 12 months. All right. That is for the standard of care. Because we combine with PD-1, it is important to tell you what PD-1 single agent has done in past trials. It is close to 0% ORR, and we got confirmation of that speaking with potential partners.
PD-1 single agent does not do much in this setting, unfortunately. Now, if you look at the, let's say, the more direct competitors, I am going to mention, for example, Agenus with Botensimab, Balstilimab, CTLA-4, PD-1, they generated an ORR of 19% in the phase II, great for them, and their median overall survival was circa 20 months. Unfortunately, this is a very potent anti-CTLA-4 thanks to Fc enhancement, but it also comes with toxicities. I will mention the discontinuation rate due to adverse events in their phase Ib, which was 34%. They do not disclose it in their phase II. You can make some speculation on where that could be. Xilio Therapeutics at ASCO had a poster as well that confirmed. The top line ORR was, I believe, 26%, but they had some unconfirmed partial responses. It could be one, I believe, that would not confirm.
Please to be confirmed with people from the audience, etc. But the confirmed ORR from these guys, if I understand correctly, is 22%, and they're dosing, they're trying to, let's say that their dose is much lower than our compound. All right. This is the context of where things are. What have we shown at ASCO? We are dosing patients with ADG126, again, a masked anti-CTLA-4 at doses up to 20 mg per kg, and we have two cohorts. One, we call it the loading dose. You start with 20 mg per kg followed by 10 mg per kg every three weeks. Okay. That's the loading dose. The other cohort is 20 mg per kg every six weeks. So continuously. I'm happy to share with the audience that we had a confirmed response rate of 29% and that all responses are ongoing. Okay.
More importantly, because it does demonstrate in our view a differentiated therapeutic index, we have a very manageable safety profile. So far in both cohorts, no patients have discontinued due to adverse events. More specifically in the 20 mpk Q6W cohort, we had less than 20% grade 3 adverse events. We even showed in the poster that these grade 3 adverse events were transient. We are very, very happy with this data from the new cohort, but we also updated, we also updated people on the 10 mpk cohorts. We had two cohorts here again at 10 mpk. We had Q3W and Q6W. The ORR from the Q3W was 17%, including one unconfirmed partial response. The confirmed ORR, to be fully transparent, was 14%. We had no responses at 10 mpk Q6W. Combined, you had roughly 10% ORR confirmed from this cohort.
That being said, we showed our median overall survival, which is 19 months, and we were very happy to share this curve with the world because we had very, we did not have a lot of sensored events. Please look at the curve. It does tell you that not many patients drop out, and it is thanks to our safety margin. All right. I am going to say that another company had a median overall survival very close to that, and that the curve had many more sensored events early in the curve. I believe that our curve is very reliable. Remember, 10%-ish ORR confirmed from these cohorts, and we had 29% of confirmed ORR at the higher doses. Already the responses seem to be more durable in the higher dose cohorts.
We're looking forward to sharing the overall survival data from the 20 mpk cohorts whenever the data is more mature.
Fantastic. Maybe just on several points, I would like to clarify for the 20 mg two cohorts, what is the median follow-up time?
The follow-up?
Yeah.
It's a few months. It's definitely less than 10 months. I cannot remember the exact number, but it's really less than 10 months. On the other end, the 10 mpk cohorts had a median follow-up of close to 18 months. Just to give a little bit more color as well, the loading dose cohort, if you remember, we showed data at ASCO GI 2025. Nowadays, the follow-up in that cohort, I believe, is north of five months. It's really above five months. We started to recruit patients within the 20 mpk Q6W cohort really earlier this year. We had seven patients who were efficacy evaluable at the time of the data cut-off date, but more to come. We have enrolled more patients since.
I see. Do you think of this 10 mg cohort and 20, which has more mature data and OS, median OS, seems pretty impressive? Do you feel is this time to communicate with the FDA with the available data sets and think about the next step? Maybe a question built on top of that is from the PK, do you think you can continue dose up beyond the 20 mg?
Okay. I'm going to answer the first question on regulatory interactions. We have told the world that we would give an update by Q3. We're very much on track. We're very much on track and looking forward to update investors and everybody else at the right time. On the second question, can we go above 20 mpk? I think we're pretty happy with 20 mpk so far, especially, again, it's still early. We need things to mature, but I'm personally very happy with 20 mpk Q6W. The PK modeling seems to suggest that this could be a very good, this could be a very good middle ground between the loading dose and the 10 mpk Q3W cohort where you can have, so far, remember, we had the same confirmed ORR, small number, than the loading dose, but we have way less grade 3 adverse events.
Great. Also on safety, you mentioned a 20% grade 3 a year. Would you be able to elaborate on some specific toxicities? You mentioned it's mostly actually transient. Can you also provide more color on that?
Yeah, I can share with you a little bit of details. It's actually two grade 3 adverse events out of 12 patients. Right. So remember, it's a small data set. Those patients have not discontinued. They had immune-related adverse events, but those patients have not discontinued due to, again, to the occurrence of those grade 3. They're still, I don't remember if they're still on treatment. Actually, we said that we have not had discontinuation due to adverse event. Now, whether they progress or not, I don't know that, to be fully honest.
Great. This cohort also, just to confirm, only enroll patients without peritoneal and liver metastasis.
Oh, that's a good question. This new cohort of 20 mpk Q6W did enroll patients with peritoneal involvement. We actually had a case study showing a patient with this particular peritoneal involvement, and it was a patient with a partial response. We no longer exclude patients with peritoneal metastasis, and the path forward will likely be in patients without liver metastasis, but still with peritoneal involvement.
Any feedback from investigators on the trial regarding the liver metastasis cohort? I think we all know it's very hard to treat, but also there's high unmet needs. It is also important that it constitutes actually a big portion of the patients. From this study case, any plan on this population for the future?
We believe in metastasis. A good question. I don't think that we've done a good job at explaining everything to the market and to people. We are currently enrolling patients on ADG126 plus pembrolizumab plus standard of care. Standard of care being either for fruquintinib or TAS-102 plus BEV. The reason we're doing this, and to my knowledge, we are the only company with a CTLA-4 doing, at least in late-line MSS CRC, doing these broad combination regimens thanks to our safety margin. We are enrolling these patients as we speak. Okay. Those patients will be without, but also with liver metastasis. Just a data point to keep in mind, for fruquintinib, that's had the same activity in patients without and with liver metastasis. Still has a low ORR. We're talking about something in the 4 %.
Okay. Great. There's also investigator-initiated phase II trial for ADG126 in neoadjuvant CRC. Could you talk about the opportunity in this setting and what's the status of the development here?
Sure. The incidence of MSS colorectal without liver metastasis in the U.S., we estimate that to be 10,000 patients roughly. All right. When it comes to neoadjuvant patients with colorectal in the U.S., and we're talking about stage two, phase three, stage two or stage three patients, we're talking about a number way north of 100,000 patients. All right. The good news is, kudos to the Agenus team. They did generate data in a very similar setting with Botensimab, and they had, in my view, what is a pretty interesting pathological response profile. This phase II will help us to understand where ADG126 sits in terms of efficacy as well as in terms of efficacy as well as in terms of safety. I'll just say that we have said publicly that the dose of ADG126 is a high dose in that trial.
Just look at, it's going to be one of the two doses that we tested in the late-line CRC world. Right. So it's either the loading dose or the 20 mpk Q6W. And I believe that we said that we are giving two doses of that versus one, I believe, for Agenus.
Fantastic. As we are waiting for the feedback from regulatory agency in Q3, could you share your thoughts? What would be the, if you have to guess, what would be the most likely regulatory path for the next phase of the development for CRC?
We stick to our guidance of providing an update by Q3. Okay. Your question is, in my opinion, what could be, listen, there are a lot of different scenarios. I cannot give you all the details, but let me just say this. You can imagine that the agency could be very supportive of a safe regimen that has shown a very high response rate in the tumor type where the ORR is normally closer to 5%. The question is, does the team, will the team do a good job at explaining everything at the FDA to the FDA?
Okay. Great. Based on the CRC clinical evidence, what other tumor types do you think could be potential expansion opportunity for ADG126?
Very important question. I cannot say too much for now, but we know that CTLA-4 does work in a number of indications. Right. Yervoy, Opdivo, Keytruda have a number of indications on their label. They have NSCLC, liver cancer, RCC, et cetera. Let me say that we will update the market when the time is appropriate on how we think about this. There are tumor types that, in my view, could be super interesting for a drug such as ADG126. It is very important for, we believe, for CTLA-4 to be dosed very high, number one, but also that the concentration within the tumor microenvironment is high enough. Without giving all the details, various data from academic centers, including Gustave Roussy, suggesting that if you do intratumoral injection, you'll get really, really good responses.
It is very important to get as much CTLA-4 as possible in the TME. The first generation of CTLA-4 has generated, they have generated very interesting data here and there. We think we can push the efficacy higher thanks to a high-dose CTLA-4 and thanks to our masking.
Okay. Fantastic. Maybe beyond ADG126, could you give us your thoughts on what could be the next interesting pipeline target, a pipeline program you're going to focus on?
All right. We have publicly said that we have a number of preclinical assets that could come, that could enter the clinic whenever we can, as long as we have the right funding. One of them is a HER2 CD3 engager with a double mask. This is the one that is the closest to the clinic. I believe that it is IND ready. Right. In the clinic, you remember that we have the CD137. I think this one is, let's say that we're pausing the effort, especially since we're very happy with the recent developments of ADG126. I joined the company as an executive a few months ago, and I'm discovering what the platform can do. I actually gave a lot of ideas for the future. Here again, we will update the market when the time is more appropriate.
Okay. Great. Besides the Q3 update, FDA feedback, any other catalysts that we should expect in the next 12 months?
Yes. We do not commit to any specific timing, but I think I would believe that investors would like to see at some point an update from the 20 mpk Q6W cohort, especially since we have enrolled more patients. That is number one. Again, I do not want to commit to any specific timing, but this is certainly something that we know and we will, again, do when the time is more appropriate. That is number one. Number two, yes, we will update the market on the regulatory interactions. Stay tuned. Number three, we hope to share some preliminary data from the phase II IST in neoadjuvant colorectal cancer. We said that we would do it before year end. Right. It is in the 2025 milestone agenda. We have also said very publicly that we want to, we want to have additional partnerships. It could be licensing agreements, et cetera.
We have said publicly, we do get inbound calls, but we also want to make sure that we do things, we do the best things for our stakeholders, shareholders.
Okay. We will wrap up our session here. Thanks, Mickael, for a great discussion and looking forward to a news flow from Adagene.
Thanks, Kelly.