Good morning, everyone. Thanks for joining us today. My name is Arthur He, Senior Biotech Analyst at H.C. Wainwright. Thanks for joining us to have a conversation with Mr. Mickael Chane-Du, the Chief Strategy Officer of Adagene Inc. Adagene is a clinical-stage biopharmaceutical company focused on developing next-generation antibody therapies to treat cancer, based on its proprietary platform, including NEObody, SAFEbody and POWERbody. Mickael, welcome. Thanks for having me. Mickael, for those who are new to Adagene, could you give us a quick overview of your current pipeline? Sure. Thanks for having me, Arthur. Adagene is a company focused on small-cap biotech, focused on antibody engineering. Our latest program is called ADG126. It's a novel masked anti-CTLA-4. A couple of things about ADG126. Number one, we have the antibody itself is novel in the sense that it binds to a differentiated epitope compared to ipilimumab or tremelimumab. Thanks to that, we have this enhanced ADCC. We have a very potent anti-CTLA-4. That's point number one. Point number two, we apply our proprietary masking technology to this antibody, which helps us to have what we believe is a significantly improved therapeutic index versus naked antibodies. We are able to dose very, very high, which at the end of the day results in a much higher concentration of the active antibody in the tumor microenvironment. Thanks, Mickael. Speaking of the SAFEbody technology platform, could you help walk us through the SAFEbody platform, how it works, and how it's using the ADG126? Sure. The SAFEbody masking technology is protease-sensitive. We need a certain concentration of these enzymes, and we believe that these enzymes are more likely to be found in the tumor microenvironment versus the periphery. That's the point number one. When it comes to ADG126, more particularly, we just don't need only a high concentration of these proteases. We also need a high expression level of the target, here in this case, anti-CTLA-4. You really need these two conditions to have this activation of the antibody. Gotcha. Because of that SAFEbody technology platform, you have struck a very strong partnership and most recently got expanded with Sanofi. Could you help highlight that collaboration and what that means for the ADG126 development? Sure. Thank you for bringing up Sanofi. For people in the room and on the webcast, we recently announced an equity investment from Sanofi for an amount of up to $25 million, and we received an amount of $17 million concomitantly to the signing of it. Three points. Number one, people should keep in mind that Sanofi is actually very familiar with masking technologies. They acquired Munich, I believe, back in 2021 for an amount of $1 billion. Very familiar with masking tech. That's point number one. Number two, we have had a discovery collaboration with Sanofi for some time, since 2022. They really know intimately what we're doing, not only with ADG126, but from a platform perspective. That's point number two. Number three, it is not just an equity investment that helped us with the funding of the phase 2. We have expanded the collaboration with them. Discovery collaboration, funding of the phase 2, but also we have a trial collaboration. They have committed to a phase 1b/2 where they will evaluate one of their novel bispecific antibodies in combination with ADG126 in solid tumors. They want to enroll more than 100 patients in solid tumors. Let's get into a little bit deeper on the ADG126 asset. First of all, I guess some people still do not fully understand the mechanism for the ADG126 versus other CTLA-4 therapies. Could you help to explain what's the big differentiator for ADG126? Compared to? To the epitope or other CTLA-4. Yeah, that's an important question. We applied our proprietary masking technology to a novel anti-CTLA-4. As I mentioned earlier, we need two conditions for activation. Number one is a high expression of certain proteases. The proteases are going to cleave the masking moiety, and the antibody can bind to its target. That's number one. We also need a high level of anti-CTLA-4. Again, two conditions for activity, for activation, right? At the end of the day, let's look at the clinic now. We are able to dose ADG126 at a very high level. You know that, Arthur. We started from 10 mg/kg every six weeks, but we are now dosing patients all the way up to 20 mg/kg every six weeks. We believe that thanks to our safety margin, and we believe that such levels are necessary to unlock the true potential of anti-CTLA-4 in combination with Keytruda. I see. You mentioned about the clinical you have seen in the clinical for the ADG126. Could you tell us a little bit more about that? What part of clinical data is more resonating with the physicians here? It's not just one data point that resonates with key opinion leaders or investigators. I'm going to start with safety, because from safety, you have everything, I believe. Our discontinuation rate due to toxicity is fairly low, even at high dose. Right now, I'm not saying that this is going to be the case with a larger sample size, but even from the two cohorts where we evaluate ADG126 at 20mg/kg, we haven't had patients discontinuing due to toxicity. That's point number one. We allow patients to really receive several cycles of treatment, A. B, we don't have a cap on the number of cycles that we can give to patients. C, patients do not stop treatment early on because of tox, etc. We believe that this is very important, not only for the quality of life of the patients, but also for overall survival, ultimately, right? That's the safety part. Patients can stay on. Number two, because again, we are able to dose very, very high on these patients. We have this very high concentration in the tumor microenvironment of active anti-CTLA-4. We have, and let's see how the data matures over time, but we have so far what we believe is a very good response rate in the high 20% from our 20 mpk cohorts. CTLA-4, taking a step back, CTLA-4 is a very well-known mechanism of action that is dose-dependent. The higher you dose, the more likely you're going to end up with responses and hopefully better survival benefits. All right. Then my natural question is, when are we going to expect the next data update from the ADG126 program? What kind of data can we expect? I'm going to give you a softer guidance, but I would say that 2026 is a more likely timing, early 2026, for updated data from our phase 1b data set for ADG126 in combination with Keytruda. Going back to your prior question of what is exciting for key opinion leaders or anybody who are testing the drug in the clinic, we have published data from the low dose for ADG126, if you remember, 10 mpk Q3W and 10 mpk Q6W, where our response, the response rate combined, stands in the teens, right? We have shown this median overall survival of 19 months. Nineteen months of median overall survival, you're going to ask me, how does it compare to the standard of care? The standard of care right now, if you think of frequency, for example, mid-single-digit response rate and a median overall survival of 10 months- 12 months, right? Nineteen months so far compares very favorably with the standard of care. I believe that it also compares nicely with what the competition has shown to date. This is from the low dose, where we got, again, something in the teens in terms of response, in terms of response rate. We have data from this data is still maturing, but we have data from 20 mpk cohorts. So far, our confirmed ORR stands at 29%. If you believe that anti-CTLA-4 is dose-dependent, you know, from a response perspective and an overall survival perspective, I believe that this is what makes investigators very excited. Awesome. I know you most recently get aligned with the FDA on the trial design for the randomized phase 2, as well as also later on for the registration trial. Could you tell us a little bit more about what's the outcome from that meeting? Sure. Very nice in the phase 1 meeting with the FDA. We basically got everything we asked for. We got alignment from the FDA on the future phase 2. The phase 2 will be randomized, and we will test two dose levels. Dose level one will be a low dose, 10 mg/kg, 10 mg/kg every three weeks, and dose level two will be a higher dose, 20 mg/kg every six weeks. We're doing this to identify a dose for the future phase 3 and to meet the optimist requirements. How about the endpoint? The primary endpoint will be response rate. For both or just for the phase 2? For this phase, yes. For this phase two, yes. Thanks for asking. I want to manage expectations here. This is a phase two that is not going to be pivotal. We plan to do a phase three afterwards. More likely, phase three randomized with a control arm, active control arm. More likely than not, the primary endpoint will be overall survival. I see. Let's take fast forward mode, like see if the ADG126 getting approved, what you see, how this fits into the current treatment landscape. Sure. So about the future, you're asking, let's assume that we continue to have positive data, positive and more mature data. If we have a response rate that continues to stand above 20%, in this 20%- 30% range, that would be clinically differentiated versus the current standard of care, right? From a response rate perspective. As you and I know, responses with immunotherapies tend to be associated with very long duration of responses. Immunotherapies also have these sometimes long stable disease. If you also have something safe, good quality of life, you have the perfect cocktail to achieve a survival benefit, right? Ultimately, what we would love to see with ADG126 is a long OS curve, right? If that's the case, let's see how the standard of care evolves. Right now, the standard of care shows a median overall survival in the 10 months- 12 months. I see. If we can show something that is above that number, we believe that ADG126 in the context of patients without liver metastases could be well adopted. That is the first step, late-time MSSCRC without liver metastases. Then you have the subgroup of patients with liver metastases. I cannot comment too much on this. I am just going to say that so far, we have an ongoing cohort. We have some ongoing cohorts where we evaluate ADG126 with PD-1 as well as standard of care, here in this case for quentinib. We are not enrolling patients with liver metastases yet, but this is something that we could do. I see. Just a quick follow-up question. Have you guys or are you planning looking beyond the CRC or more specifically try the one combo, the 126 with Pembro or other PD-1, PD-L1 in those indications where the PD-1 works? It's a very good question. CRC, before I answer straightforwardly, I want to remind everybody that late-time MSSCRC is not a low-hanging fruit. PD-1 single agent doesn't work. The first generation of PD-1 CTLA-4 did not work. If you remember the data from durvalumab, tremelimumab, the response rate in patients without liver metastases was 3%, right? PD-1 or PD-1 plus CTLA-4 were not able to bridge into late-time MSSCRC, right? We really, quote-unquote, "started" with far from a low-hanging fruit, right? As you mentioned, there's a number of indications where CTLA-4 is known to work. It has brought a benefit to patients. At the right time, when the cash position allows it, you can imagine that we at Adagene will consider other tumor types. MSSCRC could be one of them. Gotcha. Let's switch, looking beyond the ADG126. Other than 126, which program are you most excited to want to highlight for us? Very excited about ADG126, but since you're asking about the rest of the pipeline, I would say that ADG138 is a very interesting early-stage candidate. It's a double masker, HER2/CD3 engager. We have shown in preclinical models, including monkeys, that we can dose this T-cell engager very, very high. Our MTD is pretty high compared to your typical CD3 engagers and CD3 HER2 engagers. It is an asset that is IND-ready. We're not moving this asset forward by ourselves right now. It is an asset that we would move in the clinic more likely with a partner, more likely than not. Okay. Yeah. Let's say that, again, the preclinical data package is pretty strong in my humble opinion because, again, we are seeing very strong activity in very hard-to-treat models, and we are able to dose pretty high with a good safety margin. I see. Let's move on to my favorite questions. What are the major catalysts for Adagene over the next 12 to 18 months? Number one would be more mature or more data from our phase 1B. At ASCO, we got a lot of traction, a lot of enthusiasm, be it from investors, investigators, investors, and non-investors. We had seven patients, those at 20 mpk Q6W, and 14 patients at, sorry, 20 mpk followed by 10 every three weeks, right? That's the data at ASCO. We will show more mature data from disroding those cohorts. Again, 20 mpk followed by 10 every three weeks. We will have more patients from the 20 mpk Q6W cohort, and we hope to share that early in 2026. That's point number one. Point number two, let's see, depending on the enrollment, depending on how the data matures, but 2026 could be potentially a good timing to release data from our triplet, triplet combination of ADG126 CTLA-4 plus PD-1 plus frequently. All right? Number three, those are the clinical highlights or updates. Stay tuned. We are working very hard on the BD side. You saw that we announced this equity investment, trial collaboration with Sanofi. Following our data at ASCO GI and ASCO 2025, we got a number of inbound calls for ADG126. We're talking about a lot of different things, and it could involve some additional trial collaborations. Gotcha. The last question is, could you remind us your current cash position and the runway? Sure. We had $63 million at the end of June, but that was right before the equity investment from Sanofi. You can upgrade that number by, I believe, $17 million, if I remember correctly. This allows us to fund operations into 2027. Gotcha. Thanks, Mickael. Thank you very much. Thanks, Arthur.