Adagene Inc. American Depositary Shares H.C. Wainwright 4th Annual Immune Cell Engager Virtual Conference

Sure. Arthur, thank you for having me, and let me put this. At Adagene, our mission is straightforward: targeting tumor, spare healthy tissues. That's our SAFEbody platform. Our clinical pipeline lead is muzastotug, is a masked anti-CTLA-4 designed to deplete intra-tumoral Tregs. We have extensive clinical data at a higher repeat dose, and with long-term follow-up to assess the response rate, ORR, and the DOR, and the OS benefits. Also assess the late onset toxicities at the 10 to 20-fold higher dose than Ipi used. Our pipeline, in addition to CTLA-4, a rich franchise pipeline and the masked antibody are the focus. We would also like to introduce other masked antibody pipeline. Especially today, the ADG138 is a dual masked HER2 CD3, and using our clinical validated, SAFEbody platform in this HER2-directed T-cell engagers.

We believe this enhanced therapeutic window is essential. I would like today to walk you through the clinical data and the upcoming milestones.

Sure. I think there is a common thing everybody, the technology we mentioned about uses protease cleavable masking peptides.

Yeah Or the masking peptides.

There is a very different twist and flavor for specifically how to develop, design and develop that masking peptide, and with tumor-specific activations. Just like ADCs, it sounds like a very generic drug attached to an antibody. But the differentiation among different ADC we know is a huge difference, right? In HER2, after so many years, people realize we eventually have ADC technology for big blockbuster drugs. I think for masking technology, I believe over the last 20 years or so, eventually we have seen the light for this masking technologies. I think the major difference, if you ask me, I could call a keyword, precision.

Basically, how do you develop your masked peptides in a precision way, which could be tailored to your specific antibody binding interface to do that specific masking with precisions.

Also, how do you activate this masking moieties in tumor microenvironment in the right time and space? Again, it's a precision to control the other activation process. This kind of difference could make a huge difference in clinics. That's why I'd like to say our masked CTLA-4, a target almost every masking technology originally developed around this CTLA-4 targets. Because there, the challenge is really how can you put your mask on this antibody, allow the mask to stay on and in blood circulation for more than two years or even longer with a continuous dosing, with 10 or 20-fold higher dose. The second, how this mask allow you to activate in the tumor microenvironment clinically, without the leakage while in circulation in the blood, to create that differential therapeutic windows.

I should say, you can describe your technology as much as you could. But in the end, you have to show clinically it actually delivers the kind of clinical result match with what you promised in the very beginning. For this, I could say we're perhaps one of the deepest clinically to develop our masking technology. For example, our muzastotug anti-CTLA-4. Right now, we're working with those patients for more than 250 patients through monotherapy in combination with PD-1, and then in combination with standard therapy in triple combinations, to show how this masked CTLA-4 allow you to dosing at the 10 or 20-fold higher dose, achieve a therapeutic window more than 10-fold higher, and with longer circulation in cold tumor like MSS CRC. We already have the FDA's fast track designations.

Also in first line, like HCC, we have shown a triple combination when we add our drug masked CTLA-4 on top of atezolizumab versus atezolizumab in a randomized trial done by Roche to show a longer, first of all, the ORR almost double, if not triple, the control arm with the doublet. The OS is still not reached after two years follow-up, while the control arm already reached about 18 months. So still with very robust safety profile, for example, is the MSS CRC was going to share with you at the 10 MPK and 20 MPK, and in the first-line HCC, essentially, we can maintain that doublet or triplet, at the 6 MPK, two times higher than Ipi approved in combination with the PD-1, and those are the patient more than two years now, still on treatment, not yet reached the OS.

Yes. So here for, as we know, the TCE has been a very hot topic for the last two years.