ALX Oncology Holdings Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Sure. Well, thanks for having us. Appreciate it. Always a good meeting. Harish is our CFO today, but given we do not have Barb, our CMO, he is also here for any super hard Top pressure.

clinical questions. No, pleasure to be here. It is an exciting time for the company. Appreciate all the support from Cantor over the years. As a quick background, we are developing two programs, both we think have the potential to really change care in oncology. Our lead program is in CD47, evorpacept or EVO. We have been pursuing that program since the company's founding. I think the story with CD47, like a lot of things in biotech, you could probably write a couple of novels on. Certainly, a lot of ups and downs and changes in the space and failures. CD47 historically has been a tough target. The reason it is so hard is because it is how our immune system signals to essentially be left alone. It is how our healthy cells communicate. Cancer hijacks this, and because of that dynamic, it has been a really tough target to pursue.

There's no question that it's an incredibly important target, and for us, what has been unchanged is our approach to that target. Dating back to the company's founding, we took the approach that we really had to separate the "don't eat me" signal, which CD47 is known as, from the "eat me" signal. That approach of using EVO with a dead Fc to block the "don't eat me" signal, and then combined with an Fc active antibody to provide the activation and the targeting, is how the company was created and what we're still pursuing today, and what is really, we think, built into a really promising program. We can talk about what's changed, but I think what's really important for this program, and frankly for IO, is our ability to predict what patients will respond. That's been a real shift in our approach, really.

We're now focused on bringing a targeted therapeutic to patients. Our second program, which we'll also get into, is ALX2004. This was a homegrown, internally developed effort out of our labs in California, really led by a strong group of protein engineers and chemists who have put a lot of drugs on market. ALX2004 is an EGFR-targeted ADC. Certainly, EGFR is a very well-validated target, and it's also been a tough nut to crack for ADCs. Our approach is very different. We're the only ADC that we're aware of using rituximab as an epitope. We think that's going to give us some unique advantages. We also spent a lot of time optimizing the linker and payload architecture, utilizing a topo-based payload to really put an ADC together that we think has the potential to drive strong potency as well as a wide therapeutic window.

That's where we're at right now. Again, exciting time for the company, and happy to go through some questions.

Sure. If you look at where we've combined EVO with an Fc active antibody, we have five different clinical data sets to support that mechanism.

We've combined with Herceptin, we've combined with a HER2 bispecific zanidatamab, we've combined with rituximab. That whole body of data, including a randomized study with gastric, has really supported the drug's activity. As I mentioned, I think what we've learned from our global ASPEN-06 study, our gastric study, as well as the study that we did with Jazz, with Zani, is that CD47 is also a very strong and predictive biomarker. It's been known for a long time and well-published in the literature that CD47 high is a negative prognostic. Patients that overexpress CD47 typically do poorly. What hasn't been really elucidated is can you use it as a biomarker?

Both in our gastric study, our HER2 positive gastric study, as well as the HER2 positive breast study that we did showed that the patients that had the best response to our drug were CD47 high.

Again, I think it's really important, as a former investor, I think one of the things that always scared us about IO is there's been a lot of failures.

Whether it is IDO, STING, you could put a long list up, there is really only one PD-1 story.

Yeah. To me, it is not that those pathways were not active and the targets were not valid.

It was how do you identify the patients that can respond best?