ALX Oncology Holdings Inc. Common Stock Wells Fargo 21st Annual Healthcare Conference

Yeah, thanks for having us. Always a great meeting. Appreciate it.

Yeah, sounds good. Well, again, thrilled to be here. Harish is our CFO, but he's also our acting CMO on this panel.

All right. If there's any tough clinical questions, Harish is the man for that.

It's an exciting time for the company. ALX has been at this for about 10 years, and I think there's really been a lot of data, a lot of advancements in the field, and certainly, I think from our perspective, we're just at a really interesting inflection point with both programs. As a reminder, we're pursuing evorpacept, really a first-in-class and best-in-class CD47. As is often the case with biotech, you could write a novel or two around the history of CD47. For us, the story of CD47 is really a target that's still very, very relevant and important. There's no question about its importance in oncology, and it's been a tough nut to crack.

Our approach has really been one that is different, and we'll talk about that later, but we do think we just continue to see a clinical signal there, and a targeted signal in the patients that we think will most benefit from evorpacept. The new program, ALX2004, we developed that program in-house. I think these days, that in of itself can differentiate. Dating back to 2021, we really set out to develop new and novel ADCs. We saw an opportunity at EGFR, again, a very relevant and important target, and at a really exciting inflection point there as well. We've been dosing patients in our dose escalation now since August. I think we've been pleased with how it's been translating. With this data set, we're expecting to share, call it 20 or more patients.

We've shared in the past that we were able to start at 1 mg per kg. We were able to double to 2 mgs per kg and double again to 4. Over the summer, we shared that we've been able to escalate beyond 4. In terms of what we hope to share, of course, we want to be able to give investors in the street a sense of safety. It's an important thing in this class. It's been difficult to target EGFR with an ADC, so we want to take off the major EGFR-related toxicities, if you will. So skin, grade 3 plus diarrhea, et cetera, as well as we hope to answer some of the major questions you'd have with a topoisomerase-based ADC, such as ILD.

We, of course, understand we also need to share activity. Again, I think we're hoping to share what we're excited about on the activity front as well.

Right. Well, the good news here is I wasn't constructing anything. Just a non-PhD, I think is good for everyone. But we were really pleased to assemble an incredible team at the time, led by John Mapons, who's probably one of the most successful drug hunters that I know. His goal was really to look at EGFR in a new way. Historically, and I think it's still the case today, whether it's a bispecific or an ADC, they've looked to the approved antibodies. So they've looked to cetuximab and panitumumab to form the backbone, to form their epitope. Our approach at ALX was different, because we knew that cetux and pani both have EGFR-related toxicities. So we chose an antibody known as rituximab. We believe, and we think we are, the only ADC in development with rituximab as our epitope. We know in ADCs, epitope matters.

rituximab was developed as a way to avoid the on-target skin related EGFR issues, and we thought it was a perfect vehicle to deliver a payload. Parallel to that, we spent a lot of time optimizing the payload linker. I think what was also unique is we used ENHERTU as our benchmark. Of course, ENHERTU is the best performing topoisomerase ADC out there, and we used that to really develop and benchmark both our on-target internalization as well as our bystander effect. We found that this ADC is better on both. So what we're hoping to deliver is an incredibly potent molecule that is safer than what's been done in the past.

Yeah. I think the good news is our assumptions going into this have largely held, which is at four, we were hoping that would be entering the therapeutic window, and we continue to feel that way.