Perfect. Welcome everyone to the 30th Annual Healthcare Conference with Credit Suisse. I'm Tiago Fauth. I'm a biotech analyst here at Credit Suisse. We're joined today by ALX Oncology. For fireside chat, feel free to email me any questions that you guys wanna. I'll try to work those in. We're joined today by Jaume Pons and Sophia Randolph from ALX Oncology. Basically we can always start with some brief remarks on some of the highlights of 2021 for ALX Oncology so far. We'll talk a little bit about the competitive landscape and then dive into some recent data updates. Jaume, you can take it away for a brief intro and we'll follow up from there. Yeah. I think that this year has been a good year for us. We have a lot of things coming out, and we have started many phase II in other solid tumors that will be coming in the following years. We're very excited about our data so far, both in hematologic and solid indications. I think that our initial hypothesis that we made when we started the company so far is hitting expectations. Got it. To that point, I guess so we could get nonstop questions about the derivative differentiation, right? CD47 became a relatively crowded, at least perceived to be a relatively crowded competitive landscape. What's the biggest opportunity for differentiation for your assets specifically, how it does differentiate from other, CD47 programs out there, and how can that may actually show up in clinical data? Yes. In my opinion, CD47 is a mechanism that is going to show its potential in combination settings. The main differences between us and everybody else is that we design our compound to be used in combination. Therefore, by inhibiting the CD47, we have a much better safety profile. We have the ability to dose higher. In the clinic, we have shown that higher dosing translates to more efficacy. All the other companies design compounds that try to have some single agent activity. The single agent activity has been extremely modest. Then that's always all of them being developed with the compound, mostly in combination. I think our advantage is that the compound was designed to be in combination. We'll be able to go to earlier lines of therapy in combination with chemotherapy, for example, because we are not going to have toxicity. At the same time, we are able to move in combination with multiple agents that we can carry without safety concerns, because our toxicity was low. These combinations will be possible. In two words, we designed the compounds to be in combination. It's been developed in combination. Everybody else design their compounds to show single agent activity. We develop in combination, and it carries some baggage in terms of safety. Got it. What are some of the key features from a safety perspective then that in clinic has kind of differentiated you guys relative to the competition? To be fair, like, so sometimes when I speak to physicians, they seem to be comfortable with the overall profile so far for most CD47 agents. When does that potential safety differentiation actually plays out? Does it necessarily require more combination trials and moving earlier in the treatment paradigm? How can that play out for you guys? I will start that and then Sophia you can as needed. The way I see it is that so far all patients from other CD47 molecules have been mostly in hematological settings where transfusions are usually part of treatment for second-line AML. The main tox of our CD47 molecules is a hematological tox. In those settings where transfusions are used very frequently, this hematological tox can be hidden by the transfusions that you give to patients. When you move to other indications where patients are not transfused frequently, is when anemia, thrombocytopenia, neutropenia, and other CD47 molecules shown in the clinic are more relevant. Especially if we want to move in the first line or earlier lines where patients not usually transfused all the time. Sophia. Yeah, no. Exactly. It's important when you think about the clinical development strategies for a compound, because ultimately you do wanna get into the earlier lines of therapy where often chemotherapy or other cytotoxic agents are commonly used. With evorpacept, unique safety profile, it allows for those types of combinations to be well tolerated. To date, we haven't been adding any toxicity to the backbone of whatever our combination partner is. It allows us to escalate to higher exposure levels as well as bringing up into earlier lines of therapy where we've been able to combine with multi-agent chemotherapy regimens and other apoptotic type cancer regimens. Got it. No, that's perfect. I mean, solid tumors is definitely one of the key drivers for the story here. Perhaps before we go into that discussion, maybe just a couple of a few minutes talking about hematologic malignancies, right? You recently had an ASH abstract in Higher-Risk MDS. There was some noise relative to the abstract and the press release and how exactly to contextualize those data. We're talking about five patients worth of data, right? To be frank. A lot of speculation from above to the small sample size or perhaps what is the best way to look at those data in your opinion? How does it actually stack up with the prior therapies in CD47 space? I'll ask a couple follow-ups on that. Okay. Yes. Yeah, I just want to go back. It's five patients. You know, aggressive here to go over it, but you have to take it with five patients. If you look at the five patients, you know, representative is looking good. It's not any reason to believe that it's going to be any worse than magrolimab. No. Sounds okay? Yeah. Definitely between both the abstract and the press release, what we were able to present with that abstract data at ASH over the past couple of days has been two parts of data. The first part of data from a response evaluable perspective was looking at five patients who were newly diagnosed with higher risk MDS and then another five patients who were in the relapsed refractory setting. The data was really encouraging. Essentially within those first five response evaluable patients, all of whom just happened to be TP53 mutated disease, of those five patients, we had two who have achieved complete responses. It is five patients, it's about 40%, which is on par with the 40% that's been described previously with magrolimab as well in their phase I b. Certainly encouraging compared to the backbone, which would be azacitidine alone. Our combination was evorpacept plus azacitidine, where you would expect somewhere around 17%-20% as a response rate. The relapsed refractory side, there also very interesting. We saw two patients who presented with a marrow CR. Anything in the relapsed refractory setting is considered exciting. I don't think magrolimab has actually published. At least I'm not aware of any data that's been published in the looking at magrolimab plus azacitidine in relapsed refractory. They do have a monotherapy data out there where they saw, I think, one marrow CR out of 10. Between those two pops of data, we're encouraged. The drug's been well tolerated, as was stated in the abstract. The goal was to get up to 60 mg per kg every four weeks, which we were able to do. Remember, given the size of the molecule, that's equivalent to 120 mg of antibody. Safety-wise, not adding on to any toxicity profile beyond that of azacitidine alone or the disease itself. We'll be presenting more data at ASH in about 20 patients. With 20 evaluable patients, is that a mix of relapsed refractory and newly diagnosed or? Yeah, it'll be a mix of both. Possibly 20 with TP53. Those who are response evaluable will be a slightly smaller group that it will be. Anything that allude to at least the TP53 treatment patient from different characteristics. Is there anything else that we should take into account when trying to comp this versus magrolimab? How important is actually that specific mutation in terms of characterizing prognosis and in context of the overall data? Yeah. TP53 in general is considered a poor prognostic characteristic. The actual response rates in TP53 patients who have TP53 mutations for newly diagnosed MDS, response rates are not that far off from the wild type population. It's more about how do they go on to progress and their overall survivals where they have a worse prognosis than those who do not. Even with the magrolimab MDS data in patients who have TP53 mutations, they've only presented really data on four patients in their earlier data. Of those four, two had a CR. It's in line with, I think, some of the TP53 data that's out there from other competitor agents where TP53 response rates, wild type response rates are fairly similar. It's really more about how those patients perform as time goes on. Got it. I guess since we have fewer benchmarks for the relapsed refractory patient population, I was wondering if you guys could outline as you mentioned, almost any activity would probably be perceived as positive. What's the hurdle rate for that market? In all honesty, is that how big of a market could that even be given how rapidly progressive the disease can get at that stage? It's a very aggressive patient population. Really, anything that you know the medical need is most there, right? Where patients really don't have much in the way of treatment options. The bar for objective response rate in that population is extremely low. I think first, you know, the point, can we see a clinical improvement? That's always the first step. That's the data that we'll be presenting at ASH. You know, worry about the market size after that. Whether or not you can actually see you know some improvement from are we providing clinical benefit in that population. Got it. No, that's fair. Perhaps just in terms of trying to understand expectations for the fuller data set of the presentation. You did show some kind of responses relative to the abstract, and I'm assuming that was mostly just a function of the cutoff date before submitted for the newly enrolled patients. Is it fair to assume that the actual full, fuller presentation with more patients will have a more mature data set? Or is there a chance for this data to be in a continuous spectrum where you can see better responses with a longer follow-up in a subset of those patients, just trying to understand how mature do you think your data set will be at ASH? Yeah. The data that was in the abstract and the press release are all from the same- Same type of patients, yeah. The difference between the two is just as you note for as you're evaluating patients with toxicity, there are a lot of components that go into the final overall response assessment for a patient. At the time of the abstract, not all of that data had come back yet. With the press release we were able to update with the complete response data set for each of those patients. They all have the same assessment date. For ASH poster, we will have more mature data set on all of those patients. You would expect some additional data coming from both types of data sets, yeah. Got it. No, that's perfect. I guess we can pivot probably to solid tumors. Just deeper picture, and different CD47 companies have taken a different strategy towards solid tumors, right? Not necessarily a whole lot of overlapping indications relative to solid malignancies where everyone's kind of pursuing a similar playbook to some extent. What drove your choice of indications specifically relative to perhaps what Forty Seven was doing or some other companies that you're familiar with pursue? What we were looking at initially at sub 32 different product compound, we had to think about indications where there were drugs that were approved, and they didn't work very well. Actually we had a window to see improvement over those drugs. We were looking about the selected CD47 expression, so relatively high. Also presence of macrophages in the tumor. We found the gastric and head and neck tumor indications. We were looking in terms of mechanisms as well. For each one of these indications, we're testing a different mechanism. In the case of gastric cancer, we're testing the combination with anti-cancer therapies which are targeting the cancer antigen presenting receptor in the case of gastric. In the case of head and neck, we're testing the combination with checkpoint modulators. That’s the other aspect of, okay, selection of the two indications. One, testing one mechanism and the other one another mechanism. Got it. I'm assuming that also kind of addresses the question that you've probably gotten a few times, which is the rationale to pursue solid tumors, given that you haven't really seen a lot of success previously with other agents. Perhaps it's about just finding the right indication or the right combo and mix of phagocytic signals and checkpoint inhibitor synergy. Is that the right way to think about it? Yes. As usual in oncology, to find the right tumor for the right patient. Another aspect is that, because we have a very good safety profile, we have been able to dose very high in those indications. Also as Sophia told you that our molecular weight is half of an antibody. Potentially we have a better tumor penetration in a solid tumor setting. Also our affinity is the highest one with a picomolar molecule. Actually in the limiting amounts of molecule that find its way inside a tumor, we may have enough affinity to block the mechanism where others may not. I think all these three plus now the chosen combination partner explains why we think that we have been successful where others have not. Got it. Understood. Understandably so, there's been a lot of focus on the upcoming head and neck, especially for front line data. It's mostly because you've had some pretty interesting results, but in a small sample size as well. Four patients worth of data in the front line, though far exceeding what would have been expected from benchmark, a fairly comparable benchmark in the space. For the update, as you think about growing that sample size, what should be expectations in terms of number of patients or reversion to the mean? Is it most important to look at response rates or perhaps duration of response, overall survival? What are going to be kind of the same drivers and the best way to look at that combined data? For the head and neck population, for SITC we will be presenting data on about 13 patients who have been treated with evorpacept with pembrolizumab, 5-FU and cisplatin. That'll be the new data that we present. We'll be in the first-line setting. We'll be also presenting follow-up survival data and more on that survival question right after this. We'll be presenting survival data on the original cohort of 10 patients who were in the second-line setting for head and neck, who were checkpoint-naive. Those patients received evorpacept plus pembrolizumab, the doublet. Those are the two parts of data that we'll be presenting. In terms of the newer cohort, chemotherapy combination cohort. With that particular group, in terms of benchmarks, you're looking at KEYNOTE-048 is a relevant benchmark where you had patients receiving pembrolizumab plus 5-FU and cisplatin versus the EXTREME regimen, which was cetuximab plus 5-FU and cisplatin. One thing that it's important to note from there, anything that you can see in terms of objective response rate is significant. In terms of approval of pembro plus 5-FU and cisplatin, it was really based off of the survival data, and it has to do with immuno-oncology agents and their impact on longer time points such as overall survival or later line in terms of PFS. As we move forward with the data that we show at SITC, anything that we can see above benchmark in terms of objective response rate is important. In addition, looking at survival-based endpoints as surrogates for clinical benefit in this population is important as well. Similarly for the second-line setting, again, any improvement in objective response rate is definitely important. It's also important to look at the longer time points that are the survival-based endpoint. We'll be presenting all of that data at SITC. Got it. This is perhaps a fairly subjective question, but whenever we're running a trial without a control arm, what's the magnitude of improvement that actually gives you confidence about translating to a real signal in a controlled fashion? If you're talking of progression-free survival of 14.9, right? I think for high-grade, are we talking about months? Are we talking about a 20% improvement? What would be interesting enough that would warrant further development, I guess? If you can frame what would be some of those expectations? Sure, sure. I think in terms of for head and neck, really again, as you go back to KEYNOTE-048, the endpoints that were particularly predictive of response were actually the overall survival metrics and overall survival rates. There is where you started to see those Kaplan-Meier plots split apart between the test and the control arm. There, you know, looking at something, you know, 30%-50% improvement would be again, the gold standard of overall survival or overall survival-based metrics like OS at 12 months. That would be definitely distinct and actionable. It's, you know, the single arm study, you know, you're always limited because you are comparing to historical controls. Over the course of time, patients are treated differently in the prior lines of therapy. Sometimes that can impact how you can interpret your results. Ultimately, you want to get to randomization. That's the key. That's what we started now with our ASPEN-03 and ASPEN-04, both studies in the first line setting, evorpacept plus pembro chemo versus pembro chemo and then in ASPEN-04. Sorry, that was ASPEN-04. ASPEN-03, evorpacept plus pembro versus pembro. Those two phase II studies are actively accruing now. Got it. Perfect. Can I ask just a quick update on gastric and kind of what the status for that program overall would be helpful. For the gastric program, again, as Jaume mentioned earlier, there, we're testing a slightly different mechanism of action. We're looking at evorpacept plus a anti-cancer specific antibody. Looking at a combination with trastuzumab. At SITC, we will also be updating the data that we showed at ESMO GI, where we were looking at that doublet, ALX plus trastuzumab, on top of the current global regulatory standard of care, which is ramucirumab plus paclitaxel. At SITC, we'll be presenting updated data on those 18 patients who received ALX plus trastuzumab ramucirumab paclitaxel. It will have some longer duration of exposures and therapy and responses that we'll be updating there. The data even from ESMO GI, where we saw the 72% objective response rate to your benchmark for ramucirumab + paclitaxel is about 28%, and a median overall survival that hasn't been reached, and is doubling, more than doubling with median PFS. That data was extremely encouraging in that expansion cohort, and it's the reason for us working towards our ASPEN-06, our randomized phase II/III, where we'll be looking at the triplet versus, in this case, first-line ramucirumab + paclitaxel. That's coming up. The study is up on clinicaltrials.gov, and we're working on activating the study. No, that's perfect. If there's anything else within solid tumors that we haven't covered that might be worth highlighting to investors at this moment? Otherwise, I'll just jump in from business development perspective and a couple of questions there. I don't think so. Other than that, we'll continue running our study with, Zymeworks dataset. That's correct. Perfect. From a business development perspective, I mean, here we get a lot of questions on M&A potential in the CD47 space, right? You have Forty Seven, you had Trillium as well. Given there certainly seems to be a lot of interest in, from a strategic perspective from our considerable companies, how do you think ALX kind of stacks up versus on your own compared to CD47 assets that are still potentially available, I guess, for a potential transaction? And how should investors think about that potential? CD47 in terms of design of the molecule and clinical development path, we were very differentiated. We have a molecule that was designed to use in combination and is being developed in combination. With a strong sensitivity for solid tumors as well. In that we are very unique. All our acquisitions were mostly focused in hematological malignancies. I think that this is very good space for us, actually, the market for solid tumors project. I think that as we progress in our development, this potential for negotiations. At this moment, we are completely focused in our job actually developing. Fair enough. Yeah. Yeah. You also had a couple of recent acquisitions coming by. What's actually behind the rationale of ALX Oncology's strategy in terms of doing a couple of partnerships here, a tuck acquisition there. Where do you think that how do you think it complements your current pipeline, and what's the overarching strategy here? Yeah. We are in the process of building a pipeline. So far 100% of our focus was in the heme side. Actually the next is our collaboration with ALX to have a received process CTG compound, which I'm very excited about, and we should be filing IND next month or next year or so. ADCs is something that was always an area of interest. I think that, at this moment that we have proven that we have increased the efficacy of antibodies and as well potentially chemotherapy. ADC makes a very good partner for ALX in particular. There are not that many interesting approved ADCs in the solid tumors setting. We decided that it was time for us to have our own set of ADCs as well. Obviously at this moment we are starting our compounds to get a bigger market. Why don't we do it with our own compounds? That's the idea of starting an industry effort, developing compounds that would expand on themselves, so they wouldn't be designed just to be combined with the ALX, so they will have a life of their own and indications of their own, and also put the enhanced. No, I see that makes sense. Great. Honestly, that kind of runs through most of the questions that I've got and that I had prepared. Is there anything else that you think investors are kind of missing around the story? Stock has been volatile around data updates. The question is always kind of the same, which is just how do you compare against the rest of the landscape, right? Without any head-to-head data, I think it's kind of difficult to make any extrapolation. Perhaps one last one for me that is related to the competitive landscape, but you do have an upcoming officially pivotal readout for magrolimab in MDS. I don't know, based on what the clinical experience in MDS for your own molecule, what are the potential features that you could have from that readout to you and perhaps to the CD47 class more broadly? In my opinion, the data from magrolimab in MDS and AML completely proves the mechanism. I think the mechanism is proven in the clinic, which is what is most important for me of the work of Forty Seven now Gilead. I personally don't think that Gilead will get approval with a single arm study in MDS, and I think they will have to finish the study, which is also an opportunity to be able to catch up if that is the case. Got it. Is that mostly from a sample size perspective or a data? Like, what informs that opinion? That's my opinion that it will not be. That's obviously a personal opinion. But I think that in a combination with something like azacitidine, which is active. We have recently had a few studies where the outcome for azacitidine has been bouncing. Got it. There's just not a lot of certainty and inclusivity. That's a fair point. That's- It's also a very heterogeneous population, so you can get differences depending on who's actually enrolling. It's one of those diseases that's very complex in terms of the baseline characteristics of patients. That's fair. You probably could. You don't necessarily have a lot of precedent comps to inform you on that. Right. Got it. No, understood the point well taken. Great. No, I think that's it for me. I don't know if you guys have any final remarks, but extremely helpful. I do appreciate you spending the time with us. Hopefully it's a productive conference for you guys as well. Thanks a lot for your participation. Appreciate it. Thank you.