Good afternoon, everyone, and thank you for coming to the UBS Biopharma Conference here in beautiful Miami. I'm Colin Bristow, one of the biotech analysts. It's my pleasure to have ALX Oncology with us here today. On behalf of the company, we have CEO Jason Lettmann and President and Chief Scientific Officer Jaume Pons. So thank you for being with us here today. Thanks for having us. So maybe let's start with a sort of, you know, a relatively broad question around the, the CD47 space. You know, what are your current thoughts about the overall CD47 field? We've seen some sort of reasonable, I'd say, disappointing data from competitors. So, you know, what is your current thinking, excitement, and how do you see evorpacept as being differentiated? Sure. Well, thanks again for having us. Appreciate it. These are very comfortable chairs, so we'll try to stay awake and keep you all awake through post-lunch. You know, I think since founding the company in 2014, you know, a lot has changed in CD47, but in many ways, the story's still the same for ALX. You know, we, you know, really pioneered the first approach to block CD47 with a dead Fc, which is a very differentiated mechanism to what has been tried. And at the time of the company's founding, it was really about two mechanisms. One was in combination with anti-cancer antibodies, and two was in combination with checkpoint inhibitors. So as things have played out, those two theories, if you will, are still very much intact, and frankly, with the recent gastric data, which I know we'll talk about, has only validated that more. And over the, over time, a third mechanism was tested, which was in combination with azacitidine, which is, of course, what, 47 and others have done, which, you know, unfortunately didn't pan out. But for us and I think for the space, what we're most excited about is what we're seeing with, in particular with anti-cancer antibodies, and we'll see soon with checkpoint inhibitors. In terms of some of the competitive disappointments, you know, any you've got the dead Fc, anything specific or anything in addition you would call out or on their assets that you think were driving those sort of, you know, disappointing data sets? Yeah, I think, again, Jaume should weigh in on the mechanism and the scientific, genius, frankly, behind the approach. But what we feel you have to do is separate the don't eat me signal from the eat me signal. Obviously, CD47 is very widely expressed. It's one of the common ways in which the immune system recognizes self, and so it's very difficult to achieve both safely in one molecule. And so what we're doing is separating the don't eat me signal from the eat me signal. And that is what has resulted in our superior safety and what we're seeing in efficacy, and I think it highlights how it's very different from what magrolimab and some of the others have seen. Yeah, so exactly what Jason said. So it is the key here is that CD47 is expressed in every cell of the body. The competition tried to make molecules that kill all CD47-positive cells, with associated toxicity. We decide from the very beginning to separate toxicity from efficacy by separating the signals, as Jason said. So when you ask me about the field, I think the field is very healthy. If you look at one company, this one. He's not biased, so. That's right. He's objective. The data speaks. It's true. That's right. So you've got 9 ongoing studies across 7 tumor types, and, you know, I think there's a lot of investor focus on head and neck and gastric. You know, as you look across the suite of studies you have, you know, which ones do you think are sort of underappreciated or overlooked by investors, in terms of either sort of probability of success or just the sort of risk-adjusted opportunity? Yeah. So I think the way we like to think about it is mechanistically, so it's really the two mechanisms. One, with anti-cancer antibodies, to harness the power of the macrophage, and then two, it's in combination with a checkpoint inhibitor to harness the power of T-cell activation. And so on the first, of course, what we're most excited about is what we've shared recently with the gastric data, which is ASPEN-06, which is the first randomized study in the solid tumor setting in the CD47 space. So there, you know, with a 30% delta versus control, and we were guiding and hoping for 10%, in terms of response rate, I think we're very, very bullish on what we're seeing. I think that's driving confidence in the full data set, which we'll disclose in Q2. We feel like that is a great validation, of course, in gastric, but that is a great validation with any anti-cancer antibody. If you look at the consistency of the signal, for example, what we saw in combination with atezolizumab in earlier studies, we think that our drug works with any anti-cancer antibody. So when you look forward, I think that is underappreciated, perhaps. Then, of course, it's the second mechanism. Again, these are two very different mechanisms, but the second mechanism of checkpoint inhibitors, we're gonna have the first randomized data in that space back half of next year. That is also, I think, very exciting. In that case, we're testing evorpacept in the first-line setting in head and neck, which, you know, I think represents a huge opportunity as well. So those are the ones we're most focused on at this point. Yeah, what I would say is that people tend to think about hematology versus solid tumors. We do not think that way. We think it's specifically anticancer antibodies and checkpoint, which, for example, we have isatuximab combination with multiple myeloma, that we are very excited about. But it's the same mechanism as combining with Herceptin in cancer, in gastric cancer and, but that's hematology, right? So, I don't think we want to be boxing hematology versus solid or only solid, not hematology. We are combination with anticancer antibodies and combination with checkpoints. And anticancer antibodies include CD47. Okay. I think, you know, it's a good segue to ASPEN-06. Yeah, I think a common question or, yeah, a common discussion we've been having with investors is just the ORR for the control arm was perceived or a concern was that it was just underperformed. It was 22% ORR. You know, I think if you look at, there's a small Korean study. I think there's a 54% ORR. Just how do you rationalize that? You know, what do you think are the nuances that drove that? Yeah, I think that has not been a surprise to the clinicians and the investigators involved in the study. I think what's interesting and certainly great for patients is that the treatment paradigm has evolved across oncology, but in gastric as well. And ASPEN-06 is one of the first studies to look at globally, what does the current standard of care look like in the second line? And so to see something in the 20s, when many of these patients have seen a checkpoint, when they've seen Enhertu, you know, again, second- and third-line patients were enrolled here. You know, it's a population that's in dire need of a new therapeutic. And so, you know, again, we don't think that that's low for a global study. And then I think your other, the second part of the question just referenced the HER-RAM study out of Korea, which was a single country-focused study that was pre Enhertu, that was a relatively healthy population, and there they showed a 50-some% ORR. And I think what's interesting is that demographic is very similar to what the, our study that we ran, our phase 1b study, where we showed a 72% overall response rate. Again, Korea only, very similar patient population. So again, I think some of that's apples versus oranges, and that's why we're running a randomized study. And, again, with ASPEN-06, we're pretty confident in what we're showing there. But, you know, to follow on to that, just also on the DOR, there was, you know, we saw despite the lower response rates in the TRP arm versus HER-RAM, the median DOR of TRP in Aspen-06, I think, was 7.4 months. And that was greater than what we've seen in HER-RAM at 6.7. Anything you can say around that? I think it's, you know, you have response rates, durability and survival, and again, I think durability and survival is where, a lot of the noise can get washed out. So to see consistency with our control arm and what they saw, is encouraging to us, particularly when you compare with what we're seeing, which is we have not reached DOR, at the interim. So that's particularly encouraging, particularly given that I think the average duration of follow-up is about eight months at the time of the interim. So, you know, we are encouraged by what we're seeing in, on the durability front. And, you know, I think, again, it's consistent with what we've seen in the prior studies, too. What should we expect to see from ASPEN-06 in Q3 next year in terms of survival data and the maturity of the overall survival? Yeah, you know, we're gonna, we're planning to share what we have at that point. We've guided to Q2. Of course, when you think about survival and PFS, that's gonna be event driven, so I think we'll be happy if it's not reached at that point. But you know, again, I think one of the challenges you have with interim is we're still actively recruiting patients. We're in the middle of the study, you know, and certainly want to preserve all options with FDA. But, you know, I think as we've communicated, once we get to Q2 and on the final, we're gonna share what we have on all fronts. You've discussed plans to seek a potentially accelerated approval based on ASPEN-06. And to what do you view as the sort of must-haves in terms of survival benefit? And can you remind us of the powering for the survival endpoint? So the primary ASPEN-06 is overall response rate. You know, I think the good news in gastric, which, and we could talk about head and neck, but response rate has been predictive of survival in gastric, which is why we're powering the study off of that as the primary. In terms of accelerated approval and how the agency will look at that, of course, you know, we don't want to play FDA. That never ends well, so that'll be a review issue for them. But again, I think what they recognize is in this contemporary, you know, environment, with so much for patients in the first line, that there's a real need in the second line. Again, to see the type of response rate we've seen so far, we feel relatively confident that should translate into, you know, some good conversations with FDA, but too, too soon to tell at this point. Makes sense. On tox, you've noted the incidence of cytopenias was evenly distributed between the, the evorpacept containing arm and the control arm. So you know, is it a fair inference there that evorpacept doesn't contribute to any anemia? And another thing is the TRP triplet was reported to lead to high rates of neuropathy. And can you just say what you saw in the study there? So I think on the safety front, again, our safety profile has been very consistent and very differentiated from what has been seen in the space. And CD47 is so widely expressed, particularly on blood cells. You know, what the others have seen has been a very significant heme tox signal. And we have not seen that. We have not seen anemia, we have not seen the grade 3, 4, you know, very strong neutropenia, cytopenia signals that others have seen. Again, that goes back to the mechanism. I mean, we are going to see the tox associated with the backbone of the triplet. But again, I think that's consistent with any, you know, HER2-targeting agent plus chemo. But if you look at the evorpacept contribution beyond that, it's been a very clean, very encouraging safety profile. Great. So, the phase 3 engagement you initiate in the second half of next year, just what's the rationale? How do you justify the use of ramucirumab, as the active control when the standard of care is kind of shifting towards Enhertu? Yeah. So that's, you know, an active area of exploration and conversation for us as well. You know, I think right now, if you were to look at the guidelines, ramucirumab is still second line, you know, level one evidence. And HER2 certainly has come on the scene in the second line as well, and I think that's why we're mindful of the comparison. Ultimately, we have to look at the full data set to know how we compare, and then we're going to be making some decisions based off of that. But again, I think what we're seeing so far is very encouraging, and then once we get to the final, we'll be able to share more as to how we're thinking about the final study design. Yeah, but the study design as it is now, was endorsed by the FDA before we started the phase 2. Yeah. The study design was already agreed with FDA before we started the phase 2. Okay. And will you meet with the regulators sometime between now and the final ASPEN-06 readout? Is there anything planned there? We're not disclosing FDA interactions. But I think, you know, for us, when you have interim results like this, it's great to see such a strong signal. So we're going to be taking into consideration that and, you know, I think, you know, talking about what we should be doing with FDA as well. But certainly, when you see a 30% delta, I think it allows us to be more aggressive. When will you be in a position to give us sort of more granular detail on the phase three design? That'll be around Q2 as well. Again, we wanted... You know, you asked about survival, PFS, full, you know, the full data set, if you will. And, you know, we also want to see that before making any, major decisions around the design. Again, super encouraged, and I think interim results like this allow us to get started, but want to see the full before we, you know, commit. Makes sense. So switching to head and neck, you've got two readouts in the second half of next year, ASPEN-0 3 and ASPEN-0 4 top line in first line head and neck. Can you talk about your dose selection strategy? So you looked at 10 milligrams per kg and 15, Q weekly in the phase 1b. Now you're looking at 45 milligrams per kg, Q3 weekly in phase 2. Can you walk us through that and the data that's supporting it? Yeah, I mean, the best way to think about our dose is we will be matching our dose with, with whatever combination agent we're going with. So it's effectively the same dose, it's just different frequency. Do you want to? Yeah. So the way it works is that 10 mg per kg or 15 mg per kg weekly, right? So 15 mg weekly is equivalent to 30 every other week, 45 every three, 60 every four, right? And we have shown in PK that we have the same exposure with all these different regimens. So that's an advantage of our safety profile. And from bringing up the initial dose and cover the loading interval. And while we are doing that, we are always in combination. So we don't want the patients to have to come every week to the hospital to get a dose. So we combine with Herceptin every other week, to 30 every other week. We combine with pembrolizumab, which is dose every three weeks, we do 45, every three. When we're combining with the atezolizumab, we were doing 60, 34, because it's essentially in four weeks. I think that's a huge advantage of our drug design. Other companies, they have to go weekly when their drug was 34, or to say that, I think that is advantage for the patient too. I'm glad Jaume explained that. That's a lot of math post-lunch. Okay. On ASPEN-04 or the chemo-containing regimen, you didn't see a great sort of separation and or improvement in OR reported in the phase 1b with the evo Keytruda chemo combo, versus what we saw in KEYNOTE-040. So what's your expectation going into the phase 2 readout? And what's the bar, or what's your threshold that you need to see to move forward? I think in head and neck, even post keynote, as we've seen with the lead study, the correlation between response rate and survival is not as strong as it is in gastric. And I think there's been many programs who have been led astray by assuming in head and neck that the response rates are going to be predictive. And so what we're trying to do is get to OS. And again, I think we're confident in that because of what we saw in the 1B. You know, we saw over 80% OS at one year, which we don't feel has been demonstrated elsewhere. And again, I think what's been a little underappreciated is how things have played out in head and neck, because ultimately, if we can deliver 12-month OS, that's going to trump everything else, which is what we're shooting to share back half of next year. So again, and I think, I mean, Jaume can talk about it mechanistically, but it's our agent plus Keytruda's two immunomodulatory agents. So we don't necessarily have a hammer in that case, and you'd expect things to take a little while. And again, I think that's consistent with what we do. Yeah, so this is important here, right? So if you look at the KEYNOTE-040, KEYNOTE-048, where KEYTRUDA was approved, in neither of the cases, KEYTRUDA had any impact in our response rate, and it was approved in overall survival. So that is one point that we know for about this mechanism. In the case of combined chemotherapy, where chemotherapy has a huge debulking effect in cancer cells, we didn't expect to see a change of overall response rate when we have an immunomodulatory compound. In the case of ASPEN-03, where there is no chemotherapy in the phase 1, we did see improvement- Right. in the response rate. We'll see it in the phase two, hopefully, but mechanistically, that would make sense. Mm-hmm. Because there is not a big debulking effect of chemotherapy. Yet, in the KEYNOTE-040, when KEYTRUDA was approved, for KEYTRUDA alone, did not show, response rate difference either. So you can see that we're even better than KEYTRUDA, because KEYTRUDA didn't show that. Any specific thresholds you're willing to put out there in terms of, you know, your go-forward decisions? The primary endpoint is overall survival per month. Okay. That is the well decision point, and response rate is our second endpoint. We are going to be judging for both studies in overall survival per month. Mm-hmm. Maybe in the last few minutes, let's switch to ADC and the ALTA-002. Can you talk about your ADC platform that, you know, from the ScalmiBio? And what are some of the targets that you're looking at? Yeah, we're talking about business targets for obvious reasons, right? So ADC is very competitive, so I would not show it as factually as possible to be able to have an advantage there. But what I can tell you about the platform, that it has two components. One is an in-house payload linker that our company owns completely. And second, a masking technology that will be activated only in the tumor. For different candidates, we mix and match too. Some of them will have both, some of them will only have the payload. The payload, as you could imagine, is a topoisomerase-based payload, which in my opinion, is the highest priority to success at this point. Okay, that's helpful. And the ALTA-002, is the IND still on track? I think it's for 1Q next year timeline still there? It is. Yeah, it's still on track for the Q1 IND for ALTA. Will we see any preclinical data from that at all? Yeah, so we have a poster in fact the last year that all you have seen. Yes. Where it show very significant synchronizing activity, both in tumors expressing SIRPα and tumors not expressing SIRPα. So I think that, I see this molecule as a very big hammer, is a molecule that it will show itself quickly. This is one, because, you know, it is designed to have a very, very strong synchronizing activity if the animal data reproduces in humans. Just, I guess, you know, just taking a step back, what are the mechanisms or targets of interest to you right now? And, you know, just the current sort of biotech valuation backdrop, sort of increase your appetite for business development and just being opportunistic. Yeah, I think it does. We're in a strong cash position. We have a great group of investors. We've done a number of collaborations with pharma, continue to have strong interest there. And I think to Jaume's point, you know, we have a pipeline that's underappreciated, but in an incredibly hot space where we have a lot of expertise. But there's certainly opportunity to bring in additional programs, and that's something that we're going to be looking at as well, probably over the next, you know, two or three quarters. Fantastic. And maybe could you just remind us on your cash position in ALXO? We, so we closed the financing of, I think we netted roughly $60 million off of the gastric data. We have cash now into early 2026. So, you know, we have a long list of catalysts coming up next year, and we'll be able to see through all of those without any financing overhang. So well, well-capitalized and in, in a good place from a balance sheet perspective. Super. And maybe just to kind of wrap things up, could you just walk us through what are the most important catalysts that we investors should be paying attention to over the next sort of 12 to, you know, 12 to 18 months? Yeah. I think it's ASPEN-06 final, of course, final randomized data in Q2. It is ASPEN-03 and ASPEN-04, second half of next year, which are again, first randomized studies in the checkpoint space in this field. We're running two programs with ADCs that we haven't talked about, that we're also excited about. We have a program with at MD Anderson to test kind of the heme hypothesis. And yeah, I mean, if you look at the milestones coming up next year, it's a pretty long list. So we're excited. We think we validated the anti-cancer antibody hypothesis with 06, and, you know, from here, there's just a lot to look forward to, so. Yeah, something like 3 randomized and 2s and 3s, and 1s here, so it's not too bad. There's just a few things going on. Yeah. We're- You guys are busy. Yeah. Well, we're looking forward to following it. Well, I think that brings us to the end of time. Jason, Jaume, thank you very much for this. Thanks, everybody, for coming. I think we'll wrap it there. Thank you.