Adagene Inc. American Depositary Shares Morgan Stanley 24th Annual Global Healthcare Conference

Welcome. Thanks for having me.

Of course. Adagene is a protein engineering company. As you mentioned, we're developing our own masking technology, wholly owned, wholly proprietary. If you take a look at what we do, we have our lead compound called ADG126, a masked CTLA-4. I will mention the fact that the compound is protease cleavable. I'll also mention that as far as ADG126 is concerned, we don't only need high concentration of protease within the tumor microenvironment for the mask to be cleaved and removed, but we also need a high level of expression of the target here, in this case, CTLA-4. The story of Adagene is not just limited to CTLA-4 and colorectal. We have a very broad library and early-stage pipeline. For people who are listening to us, keep in mind that we also have, for example, among others, a masked T cell engager going after HER2 and CD3.

We have other interesting things in the pipeline, but I'm just going to mention this for now.

Sure. We know that CTLA-4 is a very de-risked target from both from a clinical perspective as well as from a commercial perspective. You have the IMJUDO, the tremelimumab or the ipilimumab, YERVOY of the world that are now generating revenues close to $3 billion-$4 billion annualized. We know it works in a number of tumor types such as lung cancer, melanoma, RCC. Now, when it comes to cold tumors, especially looking at microsatellite stable colorectal cancer or MSS-CRC, with or without liver metastases, we know that immuno-oncology agents, and in this case PD-1/CTLA-4, unfortunately, that kind of regimen doesn't really work. We know, for example, that PD-1 monotherapy has a response rate of close to 0%, including in patients without liver metastases.

When you look at some data from a randomized phase II for tremelimumab, the response rate was 2%-3%, again, in patients with late-time MSS-CRC without liver metastases. The fact that we at Adagene with ADG126 in combination with pembrolizumab, we have generated a response rate at the relevant doses between 15% and 36%, admittedly in a small data set, small population, small N. We believe that this is a very strong signal. The other thing that I want to mention, so we have SAFEbody. The whole idea of SAFEbody is to improve upon the safety profile of CTLA-4. The safety profile, the tolerability profile of CTLA-4 is very well established, you know that you come up with things such as pneumonitis, colitis, et cetera, and a lot of discontinuations due to adverse events.

In our data sets in more than 60 patients with MSS-CRC, our discontinuation rate due to adverse event was less than 10%, even though we are dosing patients at really high levels, up to 20 milligrams per kilogram. For those who are listening to us for benchmark, the first generation of CTLA-4 has been tested and approved at doses more around 1 to 3 mg per kg. If you are closer to 1 to 3 mg per kg, if you look at YERVOY ipilimumab, for example.

It is really the safety data that we have generated, as mentioned, in more than 60 patients with MSS-CRC. We see a very controlled incidence of grade 3 adverse events, no grade 4, no grade 5, despite the combination of ADG126 with pembrolizumab, and again, at a dose of up to 20 milligrams per kilogram. A dose level that has not been reached by any other CTLA-4s. The fact that we have this efficacy that seems to be very differentiated versus the PD-1 of the world or the first PD-1 CTLA-4, and more particularly durvalumab, tremelimumab in that setting of MSS-CRC without liver metastases, is telling us that we do have a differentiated therapeutic index.

Sure. If you think of MSS-CRC, microsatellite stable CRC, the initial addressable market for us would be late-line, non-liver mets. We are talking about a little bit north of 10,000 patients just in the U.S. We and some third parties do estimate that global market to be a little bit north of $1 billion. We are addressing this initial market through the combination of ADG126 plus pembrolizumab. Keep in mind that we also have, nowadays, a trial collaboration with Incyte, which is evaluating a combo of ADG126 with PD-1 TGF-beta as I specifically said. That PD-1 TGF-beta has generated, we believe, a very differentiated response rate compared to the pembro of the world. Again, close to 0%, where Incyte generated a response rate of 15% in ITT, 23% in patients without liver metastases, and 12% in patients with liver metastases.

Okay. Thanks to that combo, we now have access to a broader late-line population.