ALX Oncology Holdings Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Great. Thank you. Thanks for having us.

Yeah, sure. I think CD47, like a lot of things in biotech, there's been all sorts of ups and downs. I think you could write a novel about the history of drug development in that space. That's what makes it fun. What we get to do each day is it's unpredictable. As we like to say, it's not the target's fault, however, that things played out like they did. I think there's just been no question over the last 15 or 20 years of research that one of the fundamental ways in which cancer evades the immune system is via CD47. It's a tough target because it's also how our healthy cells signal to our immune cells to be left alone.

Because of that challenge, that fundamental challenge of expression, where you have expression on healthy and you have expression on cancer, again, that's what required a unique approach. If you think back to our company's founding, there was really two schools of thought. One, the conventional one, was let's design an Fc active antibody, one antibody that will both activate, drive "eat me," and then block "don't eat me." What that ended up doing was causing all sorts of significant on-target issues because of the fact that CD47 is so widely expressed, they had really significant on-target toxicities that really weren't apparent until after those acquisitions when they ran the randomized studies.

Okay. That for us, was what we tried to solve at the company's founding.

We bifurcate the "eat me" signal. We have a dead Fc, so we provide full blockade of the "don't eat me" signal, and then we use an Fc active antibody like Herceptin, for example, to provide the activation. That mechanism is the same that we're pursuing today, and it's been a beautiful thing to watch that translate in the clinic. We are far, far safer after dosing over 800 patients here. We know it's safer, and frankly, quite safe in general, and we know that the activity has been quite strong when we get that combination right as well.

Yeah, we need to be working hard. As much fun as investor meetings are, Harish and I get to do this, but everyone else back at the office is doing the real work. I didn't mention our second program that you alluded to, which is ALX2004, which is our EGFR-targeted ADC. We're super proud of that molecule. We designed it in-house by a really great group of world-class chemists and protein engineers. Since 2021, we've been pursuing that in-house. We started dosing patients about a year ago. That's been a very competitive space and also a very challenging one. Targeting EGFR with an ADC has been tough. We think we've cracked the code, as we'll get into. We have a novel epitope called matuzumab that we're using. We think we're the only ADC in development that utilizes that backbone.

And we think our linker payload architecture is quite unique, too. As you mentioned, our goal internally is by the time we're sitting here next year is to have both programs on the doorstep of a phase III. And I think so far so good. Execution has been really quite strong across both.

Yeah. I think the program's progressing quite well. We started dosing at 1 mg per kg. We then doubled to 2, and we've doubled to 4, and now we see signals over the summer that we're now beyond 4, and I think that's really important. For most TOP1-based ADCs, 4 and above has been in and around the therapeutic window. I think first things first, we want to show that we have a therapeutic window to play with, so to speak. I think what's really key to remember about this study is that it is a U.S.-only site.