Welcome everyone, and thank you for joining us at another great session at the 2021 Jefferies Global Healthcare Conference. Really happy to have here with us on this fireside chat, the President and CEO of ALX Oncology, Jaume Pons. Also with us, the Chief Medical Officer, Sophia Randolph. Thank you for joining us today. We were briefly just chatting, of course, about so many things going on. I know Sophia's quite busy with so many trials getting up and running. I would just love to just start off first with a bit of a high-level question that I think is on the minds of many investors, maybe to Jaume, is trying to parse out the CD47 landscape because there has been a lot of different companies popping up. I would just love to briefly hear about why you think ALX148 is differentiated from some of those others that we're hearing about. That would be a great place to start off. Thank you, Michael. I can talk about that for a long time, so I will try to be brief. CD47, I think it's a good target. Not only it's because it's overexpressing cancer cells, so not because it's a tumor-associated antigen. It's a good target because it's a checkpoint modulator in the immune system. It is a checkpoint modulator for dendritic cells and macrophages. The companies split a little bit in the way that they approach this duality. Many companies are choosing to make molecules that have an active FC. Therefore directly can bind and directly kill cancer cells. They are using CD47 as a tumor-associated antigen. That would be great if CD47 were only expressed on cancer cells. That's not the case. CD47 is also expressed in most normal cells. It's expressed in red blood cells, platelets, neutrophils, actually any single normal cell in the body. It's a marker of self. I think this approach has brought to many compromises in terms of which effector functions they use, which affinity they pick, with the result that at the end, they don't have single-agent activity or not a strong single-agent activity, and they have to develop the assets in combination. Do you feel that there, I don't want to use the term hand-waving, but other companies who claim to just have a different epitope and claim to still be able to have an active FC, that they think that's good, but have somehow gotten around anemia and some of those companies have partnered, et cetera, and that's what they're saying. They have some data, but it's hard to interpret. Do you think that ultimately will still not be as good? Yeah. I would say that even in those cases, those molecules do bind normal cells. They have shown in their own data all these molecules do bind normal cells. Maybe they bind less red blood cells, but they still bind platelets, for example, or T cells or other normal cells. Also in those cases, they are taking compromises either in the FC function, so an IgG4, which is less potent than IgG1, so it's not able to produce full activity. Picking a low affinity molecule that actually is less able to block the pathway. Still, in those cases, they are reaching compromises in the site of single-agent activity. Again, they have to be developed in combination. We designed the molecule to be used and developed in combination. To completely focus in CD47 as a checkpoint modulator. We believe that in that setting, in the combination setting, as a checkpoint, we have a superior molecule. Right. The other issue with the combination approach, which is required, is potential additive toxicity. Teasing out the therapeutic window. Do you think that ultimately will become an issue? A lot of these companies are still against single agents, just to get safety before you can go into commerce. What do you think about that? That's an essential difference. Our molecule has already shown in the clinic that it can be combined with multi-agent cytotoxic therapies. That nobody else has shown, combined with checkpoints, combined with anti-cancer antibodies. Not only shows safety, also we have shown efficacy in the solid tumor setting, in where we are completely unique as well. I think if CD47 is a checkpoint modulator, we have the best molecule. I draw a parallel to that with PD-1 and PD-L1 molecules. Of all of them, of all the PD-1, PD-L1 molecules, there is only one with effector function. That's BAVENCIO. All the other ones choose to treat PD-1, PD-L1 as a checkpoint, not a tumor-associated antigen. BAVENCIO chooses to try to do both. BAVENCIO is not the best of the PD-L1 molecules. That's interesting. That's another example of where they would have wanted to dial it out as an inhibitor, right? Yeah, my guess is that they wanted to have both. Wanted to have a checkpoint and effector function against cancer cells with the result that it didn't work as well as just having a pure checkpoint modulator like Pembrolizumab. Right. That philosophy and that specific strategy has played out now in data. Let's talk about the gastric cancer data and the head and neck data. Maybe we take each one of those separately and talk about why you were excited about that data. Small numbers of patients, why you're excited and where that takes you for the next update. I don't know if that's a good place for you or for Sophia to talk about. No. That's better for Sophia. Yeah. Sure. No problem. The data that we have in head and neck and gastric, and I'll start with the gastric, is really exciting for us. All of these data coming from our first-in-human study has propelled us into our mid-development program. In terms of gastric cancer first, most recently we presented at SITC this past year. There we presented some initial data in 14 patients of our drug plus trastuzumab on top of the standard of care ramucirumab plus paclitaxel in patients with second-line HER2-positive gastric cancer. There we saw an objective response rate of 64.3% in those 14 patients, and at that time we had a median follow-up of about 5.3 months. This was extremely exciting for us. The benchmark there, RAINBOW study, is about 28%, and then overall response rate. Even the more recent phase III with ENHERTU in patients who had failed one prior trast, objective response rates there were about 41%. The data of ours, 64.3%, was exciting and early. Coming up at ESMO GI this July 3rd, we'll be presenting an update on that now fully enrolled cohort of approximately roughly around 20 patients. We're excited to see now response rates across that full cohort as well as the longer median follow-up. It was, I'd say, a quadruple combination, but two of those, ramucirumab and chemo, are a standard option for patients with 2nd-line gastric cancer. You're saying that people had, was it 28% response rates in general? They actually, with the quadruplet, we had a 64% response rate. The backbone of ram pac would be the 28%. Exactly. Right. That's really exciting because you're doubling it. Now, you say, "Oh, well, is the evorpacept doing anything?" Your answer was, "We'll look at something like ENHERTU," I think is what you said. Go ahead with that. That was higher, that's as a single agent, that wouldn't explain it either. Yeah. Even when you look at ENHERTU, which is an antibody-drug conjugate, so trastuzumab hooked onto a deruxtecan chemotherapy payload. There you're seeing an objective response rate of about 41%. With the direct cytotoxic chemical conjugate. What we did do, because it is a question that we get, which is, well, you have a four-drug regimen, how do you know what your drug is adding into that mix? So what we had done, and we also presented at SITC this past year, was this updated data from a cohort looking at ALX148 plus trastuzumab, so a chemo-free regimen in the same second-line setting. So there we saw out of 19 patients a 21% response rate. This is significant because, as we just discussed earlier, our drug isn't anticipated to have much monotherapy activity by design based off of the design of the molecule. When we combine it with an antibody like trastuzumab, which is also known and already has been published to have minimal activity in the second-line setting, so these are patients who have already failed prior trastuzumab. Th at activity via HER2 signaling, patients just don't respond very well to it beyond chemotherapy. If you were to parse those pieces out, there's certainly no data to suggest that it should be this robust. Therefore, you feel good that the hypothesis of the mechanism is playing out. Given that we'll have more patients, I guess, presented and more follow-up, what is good data? What do you come away saying is good? Is that consistently high response rates? Is that a specific PFS that's better than ramucirumab? How do we benchmark that to give us confidence for the next step? Yeah. The first thing that you definitely we would want to look at is objective response rates, and certainly we've talked about the benchmarks already for that. Durability of response is important. RAINBOW as the backbone was about 4.4 months as well as its median PFS. Anything significantly above that would be exciting for us. Of course, ultimately the gold standard is always overall survival. In this phase I cohort, the primary thing that we'd be looking at in addition to safety would be objective response rate and the durability. Okay. Now just to be clear, it's six more patients, so it's 14 now going to 20. Is that what you said? We'll be presenting it mid-year, but approximately 20. Okay. It's six more incremental patients, so it's not like there should be huge swings of the data, right? Because it's just incremental. It's approximate, so approximately that number. Approximate, okay. Yes. We'll have a few handful of additional patients to look at response, but then also the longer durability of those who are already on. Are those all at a higher dose, those new patients, presumably, so you should feel good about that? Right. All of the patients with the quadruplet therapy, the majority of those patients will be looking at ALX148 at 15 mg per kg q week, and then there's a smaller group at 10 mg per kg q week. Have you decided, we'll get to head and neck in a second, have you decided what you want to do? Are we going to hear an update or is there an analyst call after that data? How will we hear about what you want to do next? Go ahead, Jaume. Yeah. Just in terms of what we're going to do, obviously in the poster we're going to describe everything. There will be a press release. If we think it's necessary, we'll do an investor call, but we haven't decided yet. Okay. And I want to note that. Do you want to take it forward, though? Do you want to take it into a phase II-B, kind of like head and neck? Yeah. We're completely ready to phase II-B, so this will be starting shortly. Maybe Sophia can comment on that. Sophia, I think the number of patients is 18, right, for this. Yeah, the formal number, at this point, is 18. Yeah. We'll have 18 patients. Yeah. It's a small number more, again, we'll get more patients. It's more about follow-up. Does that inform you've had some of the data since SITC, just about what the next step is? I don't want to spend too much time on it because it's a smaller market, does it inform at all what the next step is? I guess talking with the FDA is, you want to move forward. Yeah. Absolutely. We will be working on a randomized phase II study. We'll be looking at not only sort of definitively teasing out the contribution of ALX148 to a trastuzumab-containing regimen, but then also, ultimately looking at the randomization between that and ramucirumab paclitaxel. We'll wait for that update. In the meantime, what was most intriguing to me was that you had some great head and neck data, but that that was discussed with the FDA already, and that you guys have been able to, and I think the words are, say, potentially pivotal study. Maybe you could talk about that. To have a potential pivotal study started now is a pretty big thing for a small biotech. Maybe just talk about the head and neck data like you did with gastric, what the response rates were versus what you'd expect, and what did the FDA say about this next study that you can do? Right. For head and neck, as you just mentioned, at SITC this past year, we presented two cohorts, and I'm just going to highlight, these are the patients who are checkpoint-naïve. New data we had was in four patients who were first-line checkpoint-naïve patients with head and neck cancer. In those first four patients, we had two PRs and one CR. Obviously, incredibly small numbers there. That is a group that we've now built out and will be presenting towards the end of this year. There, with those responders, we had, interestingly, responses in patients with CPS scores of zero up to 50. The benchmark there is KEYNOTE-048, objective response rate of 36%. That's the benchmark for our subsequent randomized phase II that you alluded to. The other population that we updated at SITC was now second-line head and neck patients who are checkpoint-naïve. There we had 10 patients. Previously reported four PRs, but a median PFS of 4.6 months, median overall survival of 22 months. CPS scores, again, in those responders ranging anywhere from zero to 40. The KEYNOTE-040 is a reference for those patients. Benchmark is an objective response rate of 15%. That compares well with the 40% objective response rate that we saw. Again, small numbers, but provides the rationale for starting a second phase II study, which we've now enrolled our first patient already. That will be looking in the first-line setting, checkpoint-naïve, looking at our drug plus pembrolizumab versus pembrolizumab alone. Okay. You, if I remember that right, doubled the response rates in first line, doubled the response rates in second line, and you again, feel that that should validate the mechanism again, right? Both because they have, I guess you were applying low checkpoint scores, but also because it follows along the gastric data. It's really multiple things combined here that are putting together a story. Is that fair to say? Very fair to say. Okay. What did the FDA say? You showed them this data, and I'm personally surprised that three out of four patients, although I guess there's more coming later this year. Is that 10 or 15 patients? How many patients is it? By the end of the year, when we report, we've completely accrued. This was a phase I dose escalation cohort. We have a total of 13 patients, so we'll be presenting that data. The data in support of our Fast Track designation as well as in support of the phase II is really the totality of the data from our phase I study. Okay. You have gone ahead and started a first-line study. Is that correct? Correct. We have two, p hase II randomized studies. The first one is the one I just mentioned, ASPEN-03, so our drug plus pembro versus pembro alone, and that has dosed its first patient. The second trial will be looking similar population, but here it is in patients with any CPS score, and there we'll be looking at ALX148 plus pembro, plus chemotherapy as a standard versus pembro plus chemo. In first line. Both of those are in first line. All right. If you have low scores, you get the chemo added on. Yeah. This is all built off of the label for pembrolizumab. If you're pembro positive, the label supports a backbone of pembro monotherapy. If you're CPS score agnostic, meaning any CPS score, so including being PD-L1 negative, you can get the added-on chemo. That's exciting because, look. Just kind of, what did the FDA say specifically? It will take some time, but you got to enroll, and they got to get the data. That's a pretty big event. Maybe just talk about that. Yeah. Essentially what they've communicated to us is that this study is exactly that. It's potentially registrational. Obviously, it depends upon the data and discussions with them, but just from a structural standpoint, it is a trial that could support approval. Yeah. Both of them. Yes, both of them. Both studies. Right. Just to be clear, now, both of them are designed similarly. To be honest, I think you would probably be surprised if one worked and one didn't. Right, the idea, because I don't know how many patients it is, but I would be shocked if just one study served as an approval. Presumably, it's the combination of both, but that totality of those two would be more obvious to support an approval. Is that fair? Again, we'll see how the data pans out in both, but certainly, their general stance is two, I think, well-conducted randomized studies. Certainly, these are two well-conducted randomized phase studies. Okay, good. Let me kind of round that out, because what everyone's really seen a lot of is MDS data, and that's, of course, what led to Forty Seven's acquisition by Gilead. Interestingly, Gilead has not committed yet to filing. They're supposed to announce something this year, we're waiting on that. You're going to have your MDS data coming up. Maybe comment about how that study's going. It's phase I. You believe you're going to be at doses that are active. How do we look at this data and what you're going to get? Tell us what we'll get, how do we compare that? How should people think about that versus just pulling the last MDS data from Gilead at ASH, we look at that? That's not necessarily a fair comparison, right? Maybe talk to that. The structure of our MDS, it's a phase I/II study, so the phase I portion, we anticipate presenting that before the end of this year. In the phase I portion, it's a traditional dose escalation, and it's a population of both relapsed/refractory MDS as well as patients with treatment-naive, higher-risk MDS. It is a blended population. Whereas Forty Seven was only first line? In their most recent data that they presented, yes, it's only in the treatment-naive. Right. On top of azacitidine. While the CR rates were good, it was a first line, meaning again, you'll have patients. We want to parse that out, right? Right. It's important to look at the patients, exactly. Okay. That's number one, look at the patients. Okay. Right. Also, we're looking at three different dose levels. We're looking at a 20 q week, a 30 q week, a 20 every other week, a 30 every other week, and then a 60 mg/kg q four weeks or q month. The idea there is that because of the exemplary safety profile that we've seen with ALX148 across the program, the idea is that we can increase the dose of the drug without really sacrificing toxicity. In that way, we can stretch out the administration schedule to make it more convenient to dose with the monthly azacitidine. That could be interesting. I guess in a really good world, the data would show high CR rates across these populations and across the doses, and that there wouldn't be a fall-off, I guess, at monthly dosing? How do you think about those scenarios? Yeah. Ideally, the 20 every other is a slightly lower exposure level, right? That's more equivalent to 10 mg per kg q week. The 30 and the 60 should have similar exposure levels. That's equivalent to a 15 mgs per kg q week that we've used in the balance of the program. With the small numbers, I don't know if you'll see formal differences because the numbers per cohort are small. Overall, they are all active doses. We would hope to be able to see something in the way of complete responses in some of the patients. Do complete responses happen in a reasonable timeframe? Because I recall that Gilead's data, the CRs got deeper over time, or PRs maybe. The CR rates went up. All I'm just saying is, if you're taking a first look at it, help me. Is the first CR rates a snapshot and that investors should compare to the first snapshot? Of Forty Seven? Do I got to go back to the Forty Seven data from 2019? Yeah. For all of these, and really not just for MDS, but even across the program, we do see deepening over time with this class of agents, meaning in terms of responses. We see that also in the solid tumor setting as well. When it comes for MDS in particular, even the AZA label, it takes time for these agents to work. For example, patients have to be on for at least six cycles, or six weeks before you even evaluate them. There is a timing about this as well. As we look at the different individual patients, their individual histories as this is a phase I, just really looking to see improvements in those blast counts, whether or not that flips into an actual objective response rate, looking at transfusion dependence and independence as well, looking at durability of response. All of these metrics become super important as we evaluate these patients. Well, look, I think Wall Street's going to go look at CR from 2019 and 2020. Promise you. You also have a second-line population, so that's not directly comparable, so that's its own apples. Also, the anemia and all that wouldn't necessarily be so much, but you believe you should have similar CR rates and possibly better dosing. Is that a fair statement? Yeah, I think that's our hope. In addition, once we get through this phase I, then we would be moving seamlessly into the randomized phase II portion of the study, where the randomization obviously becomes important. Would you expect, I ask this because people think it's going to impact ALX148, would you expect that Gilead probably should be able to file, and if they don't, should we read that as a problem? As an ability to be Fast Tracked here? It's a great question. Yeah. Hard to know based off of what's in the public domain. We do know that their pivotal study is approximately 500 patients, so it will take time for that to accrue and to read out. Either way, t hat they have shown proof of principle that this target is important in MDS, and I think that helps all CD47-targeted agents. Well, if they don't, that's the point. It's going to go for a while, let's hear what they say. I look forward to the updates. I know we're out of time, this was a quick gathering. Thank you guys for joining with us. Data coming up, a lot of data coming up, we look forward to following you throughout the rest of this year. Thank you, Michael. Great. Thank you, Jaume Pons. Thank you, Sophia. Thank you. Bye.