Adagene Inc. American Depositary Shares H.C. Wainwright 28th Annual Global Investment Conference

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 milligrams per kilogram, even in the context of a combination with PD-1 pembrolizumab. Where historically CTLA-4 have struggled to go above 1 to 3 mg per kg. I would mention the fact that our discontinuation rate due to adverse events is less than 10%.

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 AstraZeneca, 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%.

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.

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 3 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 3, but it came from 14 patients, and we had notably one patient that had some late onset of grade 3, where it was a long-term responder, and we saw two grade 3 in the same patient beyond 12 months.