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All right. Welcome, everyone, to Jeffrey's 2026 Global Healthcare Conference. My name is Roger Song, senior analyst at CoverSmithKai Biotech. It is my pleasure to have a next fireside chat with AOX Oncology. So welcome, Jason and Barbara. Thanks for having us. We appreciate it. Right before happy hour now. Here we go. Yeah. OK. Awesome. Last but not least, and then maybe the best. So, all right. So, Jason, do you want to give yourself and Alex a two-minute state of art? Yeah, sure. Again, thanks, Roger, to you and the Jeffries team for hosting us. Really appreciate it. It's been a great meeting for us. And at ALX, really coming off a strong ASCO and a lot of momentum over the last few months. So as a reminder, we're advancing two programs, both in the clinic. First is a 4-percept, which is our lead program in CD47. We've been working on CD47 for now close to a decade and really have been pleased over the last year to see the original thesis, the original vision of Vorpacept pan out in the clinic. Dating back to the company's inception, we took a different approach to the target. CD47, of course, is utilized by cancer, frankly, all cancers, to evade the immune system. And there's no question about the importance of its biology. What has been challenging is that it's literally expressed everywhere, and that is made for a difficult target. And our approach, again, dating back to the beginning, was separating the don't eat me signal from the eat me signal. So EVO blocks the don't eat me signal, utilizes an FCA active antibody to drive the eat me signal, taking together that drives targeted phagocytosis against tumor. That has played out. It's played out now in five different clinical data sets. And the other thing that's become very clear is that CD47 is also a very strong and predictive biomarker. So, that's been news for us over the last year, again, supported by data both in HER2 positive breast as well as HER2 positive gastric cancer. And that really has been an important transition for the company as we're truly a targeted oncology play now, and we believe CD47 is an incredibly big opportunity, and we have an opportunity to be, you know, the answer, we think, for those patients that over expressed CD47. Our second program which we'll get into AOX 2004 is a novel EGFR targeted ADC. You know I think invalidated targets in oncology EGF are still not yet cracked. It's been a difficult target for an antibody drug conjugate and we spent a lot of time internally developing AOX2004 to address this. So we have a unique antibody. We are the only ADC in development using metuzumab as our epitope. That provides some really unique differentiation. We also spend a lot of time optimizing the linker payload construct. That program is also really doing quite well in dose escalation, and we continue to escalate dose and are really encouraged by what we're And so all of that taken together is what led us to raise $150 million back in February, brought in a really strong group of new investors as part of that, and I think our conviction in both programs, frankly, is higher than it was when we closed the financing. So a lot of things to be excited about right now. Excellent. All right. I know it's interesting, I think we just caught up earlier before the talk, is that folks are interested in either Evo or the 2004 programs, and then it seems that people have a different focus. But today's conversation, let's get evenly distributed or just touch on both, and maybe we'll focus on the Evo for a moment right now. The recent data in terms of the biomarker-driven CD47, Palliative, and then in both, you said Gatrick and Breast, it's very impressive, right? You see the clear difference between express servers an expressor. Then now you're doing the phase two, Aspen 9, and then you, I think at this point, you're guiding towards the mid-year next year for the initial data. So what is the profile you're looking for on both efficacy and safety? Yeah, sure. I'll let Barb talk about where we see the bar. I think what, again, is most encouraging is in two positive, HER2 positive tumor types with breast and cancer, we've seen a really strong overall response rate. In our randomized setting in gastric, we had a roughly 40% delta in ORR versus control. And then in the new data we shared at Esmo Breast just a few weeks ago, we showed that all patients, five out of five patients in our combination with Zanidatumab responded with 1CR. So I think in terms of response data, we're really excited by what we're seeing but perhaps most encouraging is the durability and and where we're seen dor of 20 months roughly in pfs in the case of our gastric study over two years that's the type of durability you hope to deliver with an io mechanism like cd47 and i think we're we're saying that in the in the data and barb do you want to speak to where we see the bar Yeah, thanks. And yeah, with the focus being really what's the bar for the Aspen 09 study? So maybe I'll stop, take a step back. Aspen 09 is a single arm trial. It enrolls HER2 positive breast cancer patients who have all received prior in HER2. The reason for that is that's where the unmet need is. In HER2 is quite an active agent, the most active agent seen to date in HER2-positive breast cancer, and it's moved up and solidly first-line therapy now. Unfortunately, afterwards, what had been first described anecdotally is that available therapies just are not producing the outcomes that were expected, and now we've seen several large real-world data sets confirm that with response rates post and HER2 15% in a couple of studies, PFS about four months. The two studies, real- world studies I'm thinking about, a Japanese study of over 600 patients by Nozawa and then Boston group Tarantino, both in manuscript form. And so what do we need to see in Aspen-09 single-arm study post in HER2? First of all, I want to make sure that I'm well above the comparator. And like I said, the comparater is not very good. So that's one thing. In terms of what have we actually seen when you combine avorpicep with trastuzumab or zanidatinib to various HER2 antibodies. Jason just talked about some of those data. So in gastric cancer, HER2-positive gastric answer, in second and third line, patients that all seen at least trastuzumab or maybe other HER2 agents, 65% response rate. And And then in Xanidatinib, and that is in patients who express CD47-high overexpression. In that similar subset, confirmed HER2-positive status still in those patients, CD47 high. We had five of five CD47 overexpressing HER2 positive patients respond. That was the data just at ESMO breast just a couple of weeks ago. So we're seeing fabulous outcome, but I think what we really only need to see, and this is the bottom line, what we need to say is somewhere in the range of about 30 percent response rate and a PFS of about six months. And that gives us quite a buffer in a future phase three, thinking that we could double response rate or better, and we could enhance PFS by 50% or more, and that would be a real win for patients with those outcomes. Got it. Great. And then the other thing is one of the very important component is the CD47 cutoff or the expression level. The good thing is so far, as long as they are expressing and then the, you know, it's not that sensitive to the level of the expression. Maybe it's a good thing, but on the other side, it's the Aspen 09. You will refine the cutoff and then how we should make the decision on the cut off and then as you design the Phase III. Thanks. Yeah, exactly. Aspen 09, we have great data. Why do we need to do another Phase II study before moving on to Phase III? Well, one of the questions that we want to address is have we identified the optimal cut point because we would envision a phase three being a selected patient population only enrolling the CD47 high so we need to really understand how to define that. We are enrolling all comers in the Aspen 09 meaning we are testing retrospectively for CD47 levels, and we will look to see where a threshold segregates patients who have a very high response rate from those who have lower response rate, and if it's anything like our prior data, as you said, it could be more or less an on-off. For gastric, we presented a data table where we showed a variety of different cut points, And as long as you had any expression of two or three plus IHC for CD47, essentially, there was a near 40% enhancement of response rate and a PFS hazard in a randomized phase two with a hazard for PFS of around 0.4. So really extraordinarily good results. And it wasn't a cherry-picked cut point. We saw similar results across a whole range of levels. In breast cancer, we also saw in the Xanidatinib trial a cut point. The patients who were considered low in that trial had either 0 or 5 percent total membrane staining. The patients that were considered high were 20 percent or more. But it was a small data set. Those were across 9 or 10 patients. So now we have the opportunity to run a larger study, up to 127 patients, really get this cut point right, and then be able to utilize that applied to a phase three. So we're moving down. The other thing I'll say is that this will be a companion diagnostic. We're working with Ventana, Roche Diagnostics to be ready for a phase 3 with all of the companion diagnostic work that needs to be done. far away of developing the companion diagnostic and then before you decide the cutoff can you start to work on it and then once you get that you can quickly you know slip in the numbers absolutely aspen 09 is a rather large trial for phase 2 at 120 patients it is open label so there might be opportunity we've talked about having patient data on 80 patients for example and then you know, by middle of 2027, and we can apply some of the learnings to fine-tune it. So anyway, I do think the process will move us from a research prototype assay to a locked formulation assay. There's a process that we go through, and that is what is occurring during the Aspen 09 phase 2. Excellent. Okay, great. And then fast forward, the interim data looks supportive. Can you use that data set to talk with the FDA, you know, discussing the potential pivotal program at that point? Yeah, absolutely. I think the plan, again, we've guided to mid-year next year for 80 patients of data from this study. I think we feel really quite confident in that guidance. And at that moment, we'll go to the FDA. We'll have certainly a lot more data to share, both on the cut point as well as overall efficacy with, you I think some encouraging durability is what we would aim for. And at that point, you know, we'll be able to lay out the phase three, which should be very similar to what we're running right now. So it would be EVO plus TRAS plus chemo versus a TRAS chemo comparator and anticipate having those conversations next year. Okay, good. And then how much the treatment landscape is going to change in the coming years? Because I think, Barbara, right now the standard of care is pretty bad, right? So 15% and the format is PFS. But how do we think about the future post-inheritance to breast cancer? And then what is coming and what's on your radar to benchmark? Yeah, I mean, I think right now, unfortunately, the unmet need is really quite high. I mean, if you look at patients that progress, as Barb mentioned, what the real-world evidence is highlighted is irrespective of what they receive, whether it's TRAS, various chemo, the TKIs, the response rate consistently is around 15% with a few months of PFS. So therefore, we see a lot of opportunity there. perhaps one of the most exciting and interesting things for us with this focus on cd47 is that we in essence are the only cd 47 therapeutic in development certainly at this stage at this point it's due to how this played out with our competitors with fc active antibodies that approach largely didn't work you know it took two very large acquisitions and randomized data to prove that. But the result of it all is this program essentially standing on its own and not having a ton of competition. So our goal is to focus on CD47 high. And whether it's breast or gastric or heme malignancies, we do not see competition in that segment. And again, we know that patients that over-express CD47 do even worse, and that's what we're focused on, is really being the answer, ultimately, in the CD47 high population. Excellent. Yeah, we really look forward to that data set, and then they can change the treatment particular for the post-inheritance population. Okay, I gave you my promise that we're going to spend nearly half of the time talking about the 2004, which I think I got, you know, quite a few investors ask about this program and some of them are very excited about it so tell me why you think egfr adc you know your program can be different from the past because in the in the past we have a couple company tried but it didn't that it was not that successful yeah sure so egfr is an incredibly well validated target and i think what we saw in the space when we first embarked on um on this effort was a real need to approach it differently if you look at the top targets that are validated on oncology there's no question that adc or egfr is in the top five but yet there is no approved uh egfr adc and there's really open field even in terms of late stage development and what we tried to do and again this was an effort in-house back in 2021 we pulled together a very strong team in palo alto led by jama pons and and Maria Virgic, who are just incredible ADC researchers and scientists, to work on this. And one of the things they did was go back through the history of EGFR development to understand what has been done on the antibody front. And through that work, we identified an antibody called metuzumab, which was developed by Merck-Sorono, specifically with unique binding to EGF-R to avoid the on-target toxicities associated with cetuximab and panetumumab. That is a very key difference. Not only do we think it will result in improved toxicity, but almost all of the bispecifics and ADCs in development utilize cetuxumab as their epitope. So if you think about an escape mechanism post-cetuximumab, it's very likely that the tumor has mutated off of that, and by applying a different epitome, we believe we're gonna have a unique advantage there. So that's part of what we're working on. And then again, I think the linker payload construct also really goes back through the history of ADC development. We know Topo has been the best payload for ADCs. There's in HER2 is perhaps the best example. So we're utilizing that as our payload and spent a lot of time optimizing the link or payload to maximize the bystander effect and really nail the on-target delivery. And I think that design is what we've now seen translate. We've seen it translate into the in vivo work. We saw it translate in to the NHP work where we did not see a lot of the traditional skin-related issues. We did not ILD associated with the payload and really had a clean signal, which then led us to the clinic. And as I mentioned, we've continued to dose escalate the clinic we started at one doubled to two then doubled again to four and have been able to escalate beyond four so again i think there is a lot of opportunity for an egfr targeted adc and in these spaces that we're looking at for example headed neck we think we have a really good opportunity to be the first topo topo based adc in that space so yeah excited about that program as well great um just clarify you say you starting with one and double to two four now you are in eight or you're cleared we've gone double to double to four we've got beyond four go down four um you know i think we we look to the other adcs in terms of therapeutic window we'd expect four and above would would be now entering the therapeutic window um and that's what we continue to target got it okay good and then in terms of the skin and then the iod that you don't see that signal in nhp not you didn't say that's in the clinical yet yeah i would just say so far so good i mean we've been able to escalate really quite rapidly we started dosing patients back in august and have continued to be able to um yeah move forward really quickly with that program we're planning an additional safety update later this year you know continue to have a lot of confidence in that guidance and looking forward to sharing more at that point got it and then uh what what kind of a tumor type you are enrolling and then prioritizing uh considering the uh expression level also it's a phase one so yeah sure yeah we have a uh restriction in the phase one even of four tumor types that all have high expression of EGFR, so that would be head and neck, esophageal squamous cell cancers, non-small cell lung cancer, and colorectal cancer. So from the very start, we are targeting a patient subgroup by indication that has a higher likelihood of responding because of their EGF-R expression levels. Okay, got it. And then in terms of the data we're going to see later this year, how meaningful the data set will be? I know you're focusing on the safety, which is right, because we know the limitation for the past ADC GFR is the safety. And then outside of safety, how big the data set you will feel it's meaningful to show the safety? And then also, how likely we're gonna start to see early activity, you see, above four eugerae is the set of predispositions? Yeah, I mean, I think, you know, this is dose escalation characterized by relatively late line patients across the four tumor types that Barb mentioned. So certainly tough patients that were enrolling in the study. What we want to see and want to share with investors is answers to some of the safety questions, right? Can we dose into therapeutic range without seeing a high rate of ILD? can we avoid significant diarrhea GI tox can we avoid skin and rash and some of the EGFR related tox and is the rest of the you know safety profile manageable that's the goal I think that is very important if you're able to do that at therapeutic therapeutic range call it for and better it's an important milestone for an ADC I don't think it's lost on us that activity is also important and so hopeful about sharing you know some signs of activity as well when we get to get to that point got it and then in terms of those tumor types how how do you look at the distribution because it's a phase one unit right and then you know non-small cell learn you have a lot of options maybe esophageal is less so so tell us yeah I mean I think we've taken a pretty thoughtful proactive approach to that um of course you know late line crc patients are easier to enroll just given the high unmet need there but as barb alluded to it's very important for us to have data across all four tumor types with a particular emphasis on head and neck and lung i think we see real opportunity in those and those spaces for an egfr targeted adc so as we've gone through this and again i think barb and the team has done a great job of this is just ensuring we have a good balance so in terms of expectations i would expect to see a good mix of of those different tumor types later this year okay at this point do you want to guide how many patients potentially you're gonna show us you know on the safety number and then advocacy yeah no i mean i think we you know we want to get 10 15 or more um you know i think enrollment has gone quite well. We had a great ASCO on both programs. We spent time meeting with investigators that focus on all four of these different tumor types, and I think the enthusiasm is high and building. So I think we'll be able to provide some good insights as to where we are on these different cancers as well as at the right you know doses if you will okay great as I said I think EGFR ADC is highly interesting and then I think you're not gonna gonna give us the first data set and then the how you think of this first data is they're gonna guide you next or you will start you back feel or think about the expansion you mentioned the head neck and then You said that for a reason, based on the data, or that's your strategy? No, I think our strategy with this program is getting to the right dose and then speed. I mean, I thinking ADC development, it's really important that execution is tight, and so from our perspective, once we get through this phase, it'll be quickly into backfill, to expansion and doing so in in settings that are going to be relevant for our phase three so second line head and neck second line long is very important you know and I think we would and will very quickly pivot to that and that all enable us going into next year to have data set that's in the right patient population and we think provide a real clear look as to what the activity is for the drug. Awesome, right, look forward to that. Maybe just ask the minutes, you know, what else you want to highlight and then also the the cash in the wrong way and then cover the catalyst upcoming? Yeah, sure, I think we're well capitalized at this point coming off the raise. We have about 170 million as of the last quarter that'll fund us well into mid 28 which will get us through um you know most if not all of what we just talked about we're going to have really robust data and aspen breast again we see incredible opportunity to be the first cd-47 directed therapeutic and then with alex 2004 i mean we're certainly focused on safety that's what's most near term the cash will get us well through a lot more than that so again I think next year we're looking to have true proof of concepts in indications that matter with 2004 and ideally our internal goal is to have two programs that are ready for randomized you know registrational grade trials by the end of next year and that's what we're shooting for. Excellent, thank you Jason, thank you Barr, thank everyone. Thank you, appreciate it.