People here with us, and I would love to give the opportunity for, perhaps Jason, to make some opening comments about where ALX is now. They obviously are interrogating an anti-CD47 antibody. There was gastric results. They talked with FDA about it, but there's no doubt they continue to have a lot of promise on that, with other modalities, ADCs, et cetera. Talk a little bit about that and where you are with that program. Yep. Then, importantly, since we were just at ASCO, there is a new program, which they had a whole analyst day about regarding their new ADC, antibody drug conjugate against EGFR, and that looks promising, albeit early. You got a lot of things going on in brewing despite the low stock valuation. Tell us a little bit about why we should be excited about the anti-CD47 and then the EGFR antibody. Yeah, sure. Thanks for having us, and thanks for the time. So, yeah, quickly, we have two drugs now in the clinic, one being Evorpacept, which I think we've been working on since day one. Mm-hmm. You know, as you know, it's the only and is the only CD47 and developed with a dead Fc. Importantly, we are seeing no on-target-related issues that have dogged the class for many years. I think that's what differentiates us. Okay. That's what has set us up for, the two new studies we'll talk about. Yep. in breast and in colorectal. Yep. I think the bottom line is, that initial hypothesis, if you will, dating back to 2015, has really played out in the clinic. We have five positive clinical data, clinical studies to support that. That really provides the foundation for what we're doing. We also, over the last three years, have been working on ADCs, and in-house, we've been busily working with a really strong team of engineers led by Jaume Pons, to develop a novel ADC against EGFR. Yep. We, by intent, did not disclose that publicly up until this past March, and recently have now shared with the street our plans there. We think we have a real opportunity to both be first and best in class against a validated target like EGFR. Yep. We are very excited about that as well. Tell us about, I mean, can we go in order, or do you want to talk about EGFR? You're in charge. All right. Let's talk about Evorpacept. Tell us about the ongoing studies. I am definitely keenly aware, and Wall Street is, about some of the promise with ADCs. Yep. You said that you're obviously looking at this, therefore, in breast cancer, also because, to be clear, there's definitely activity, with, anti-cancer antibodies. Right. Maybe put those two pieces together 'cause there's two angles there that are interesting. I know I said ADCs, that's an important one, but also, obviously, anti-cancer antibodies as evidenced by the gastric study, which everyone agrees looks very promising. Yeah. Probably we don't want to necessarily run huge randomized studies in gastric. Let's apply that to a much bigger tumor type like breast cancer. That's why you've got a breast cancer study going directly with an anti-cancer antibody. Yeah. I mean, it goes back for us to the mechanism. Yeah. It's a simple mechanism. We use Evorpacept to block the don't-eat-me signal. We use an Fc active antibody, or in the case of the study we did with Zanidatamab, a bispecific, working together that drives ADCP against tumors. That thesis has continued to strengthen with the breast data that we shared at San Antonio in December. Mm-hmm. We had an oral presentation in January at ASCO GI. Those studies then form the foundation, as we mentioned, for the breast study, which we're launching, which is a randomized study that'll be posted in HER2, as well as a colorectal study that we're also launching. Can you tell me the, yeah, so let's talk about that. Yeah. I like to sort of understand the design of the study, talk about the probability of why that would work, and then actually when the data comes. Tell us about the breast cancer study first. Many of us obviously are familiar with a lot going on in breast cancer. We all just came from ASCO. Tell us about a post-HER2 type of indication. Yeah. I'll let Alan talk about the design. Yeah. You know, in terms of why we're excited, and, and as you mentioned, Mike, coming off ASCO, I think there's no question to most that, in HER2, we'll soon be frontline in HER2-positive breast. Okay. The data's very strong. Okay. Now it's really, what is next? What will we have for those patients post-HER2? Why the San Antonio data for us was so important is that we showed a roughly 55% ORR in patients that had all seen HER2 and a multitude of other HER2-directed therapies. Yet, with our drug, the novel mechanism that our drug brings, have seen really strong responses. Can you, I'm sorry, can you summarize that just to be, that sets us up into why this works? What was the breast cancer data that was shown? This was Evorpacept plus Zanidatamab. Yeah. Which is a HER2-directed bispecific. Yeah. On average. Is that Zanidatamab? That's the, it was Zymeworks, and now it's Jazz. Yep. Okay. So, partnered with Zyme and then Jazz to run this study. Yeah. Why it's important for us is because we've, we showed activity post-HER2. Mm-hmm. In Cohort One of that study, 100% of our patients had seen HER2, and had seen on average, I think, five or six HER2-directed therapies. What we do is use Herceptin or any Fc active antibody in a different way. To see these patients that had progressed on a multitude of prior HER2-directed therapies and yet see activity really confirms for us what we're doing. They had failed many lines of therapy. This is obviously HER2 breast cancer. Yep. They had seen everything, probably including in HER2. Yep. All of them saw HER2. They get Herceptin, which is an older antibody and certainly should not work alone in fifth-line breast cancer. They got that plus your drug, and they had a 50. No, so. Just to clarify, the study that we're talking about was with Zanidatamab. Yeah, okay. Yeah. Right? So, with another different HER2 antibody. So, bispecific. Mm-hmm. Another important aspect, 'cause we've been asked questions about, all we've been doing were monoclonal antibodies. Yes. The key component is the active Fc. Yes. Zany is a bispecific. In this study, and just to go back, you're right, it was six, the median of six prior HER2-based regimens, all of whom had received in HER2. The other aspect of it that builds upon the gastric data, there were 21 patients total who were positive by archival tissue for HER2. When we look at a subset of nine patients who were centrally confirmed pathologically and were known to be via fresh biopsy positive for HER2, of those nine, as Jason mentioned, five responders. The median PFS was 7.4 months. The DOR has not been reached. That, again, furthers the information that we learned in gastric that, not surprisingly, if you've got a targeted therapy, you need the target present in order to have the best activity. Yes. We're now moving to a randomized phase II study. Given the fact that Evo has no single-agent activity itself, it's very important to do the randomized component. What we'll do is, these are patients who will be post-HER2 or sort of line of therapy agnostic in this study, 120 patients. The control arm will be monotherapy for chemotherapy, along with Herceptin. It'll be dealer's choice as to what chemotherapy is used. The experimental arm will be the same, plus the addition of Evorpacept. This is something that should start imminently, soon, the middle of this year. We expect to have some data available, interim data, second half of next year. Okay. Just to clarify, thank you. The initial data where you saw strong activity in breast cancers was with Zanidatamab, you said. Yep. Is that a HER2-CD3 or what is the bispecific? It's HER2-HER2. HER2-HER2. Yep. Okay. Basically, Pertuzumab and Herceptin. Okay. And you showed a strong overall response rate. Therefore, you're going to this. Now, I thought I heard you say you get chemo or dealer's choice stuff. Is that what you said? Yes. And Herceptin. Yes. Right. Yes. That's to eliminate and make sure that they are getting a HER2 thing because on your side, they're gonna get a HER2 as well, plus your drug. Right. To show that you're adding on top of HER2 and there's HER2 in both arms. Standard of care for patients in this setting is Herceptin and chemo. Yeah. What we don't know, and another rationale for the randomized portion of the study is, what we don't know is what are patients going to do with Herceptin and chemotherapy in the post-HER2 setting? Mm-hmm. The response rate's around 20-25% currently, but many of those are in patients who have never had in HER2. We don't think the response rate's gonna get better. We suspect it could even be lower, but we don't know. That's why we'll, that'll be helpful for that, as well. Okay. So, you're enrolling patients now? And how soon? Very soon. Very soon. Very soon. Very soon. Just trying to put the pressure on Alan. you're helping. You're helping. Thanks, Mike. Thank you. It's soon. You said that based on enrollment, there's gonna be an interim analysis on overall response rate. Correct. Yep. That will happen in the second half of 2026. Right. Yes. Okay. That seems reasonably plausible, like the gastric study, that you should have higher response rates than chemo and Herceptin. We, you know, at ALX, there's probably been over a dozen studies that the company's done over the years. What's great about that is we know where our drug works, and we know how to pick the right patients, and we know where it doesn't work. Those learnings are now what drives this study design and why we think the probability of success is high. Okay. Yep. I'll just add one. Just one. Quick thing, Mike, if I may. Please. The selection of the patients, so, that's obviously very important that we continue to identify patients that are known to be HER2 positive, right? It's challenging to request, require fresh biopsies on every single patient operationally. What we learned from the gastric study was that CT DNA was a very good surrogate marker for that. What we're going to do is all patients will be tested for, and entered on based on their CT DNA component. We'll allow fresh biopsies if they come in, et cetera, of course. The key element will be positive CT DNA. That'll be our. Okay. Let me repeat that. Yes. You can do a CT DNA test instead, which has very high concordance with. Yep. Fresh biopsy. Right. I I actually think you looked at that in the gastric study. We did. Okay. That's. So. Again, where we're building off of what we've learned. Yeah. if, in that study where we had CT DNA positive or fresh, you know, we showed a roughly 30% delta in ORR. Okay. So, again. Is this, this is a, even though it's a phase II, quote unquote, but it is randomized. There is not a lot after in HER2. You said standard of care is Herceptin. Right now, that's. Chemo. That's frontline is Herceptin plus chemo, essentially. First line is in HER2, right? It will be in HER2. Posting HER2. It will be in HER2. Standard of care after in HER2 is Herceptin plus chemo. And. If we can beat that. Yes. That would be great. Right. Okay. Now tell me about, you mentioned, colorectal. Mm-hmm. Are we doing a [TUX] study or what are we doing here? Exactly. So, again, you know, across our five positive clinical studies, what we have de-risked is combining with an Fc active antibody. So, when you look at colorectal EGFR antibodies, that's been a staple of care for many years. Mm-hmm. In this study, we're gonna combine with Cetuximab, an Fc active, EGFR targeting antibody, that is used in the first and second line. Given what we showed in gastric, which is a somewhat similar pathology, to do that here, we think has been de-risked. We know there's a significant unmet need for patients in colorectal. There's been a real lack of new therapeutics for a long time. Again, we think, yeah, we think Evo should provide a nice combination potential. Is this second line colorectal after failing one EGFR antibody? No, in this case, they will not have had, so it's FOLFIRI is the chemotherapy. Okay. So, it's an irinotecan based. So, no prior Irinotecan, no prior Cetuximab. Okay. So. Taking a slightly different approach than the Herceptin because of the fact that you, because of the fact that there's a need in the second line setting. Basically, we're looking to see how we can put these three together. We believe it should be done very swiftly, but we're gonna start with a dose escalation component. Just to be clear, 'cause I like to get these details correct. So, first line, I would assume if you're an EGFR colorectal cancer. Yes. That you would be getting an EGFR antibody in first line. Avastin is also used quite. Okay. Right. Avastin is your first line. Then, if you're an EGFR patient, you're gonna get an EGFR antibody plus chemo in the second line. And here, we want to add your antibody on top. Is this a randomized study? No, single arm. Single arm. Okay. Yeah. Dose escalation. We want to obviously see that we have better and higher response rates than what historical shows for Ritux plus chemo. Correct. Yeah. Proof of concept. Yep. Yep. Exactly. Yep. Okay. Fantastic. And so, what's the status of that study? Alan's gonna enroll that very soon. Also, just. Very soon. About to. Just. We're gonna have some updates soon. Got it. I shouldn't be here. I should be out working. Yes. All right. Maybe you're opening some New York sites. I don't know. That's right. Columbia's right up the, right up the street. Yeah. So, what about, so those are the, those are the two. Now, tell me then next about the EGFR targeted antibody drug conjugate. Can, can I shift to that or do you want to talk about the ADC combination? No, I think that's right. Is that still going on, the ADC combo? Yeah. I mean, for us, where we've tested Evo is across three different mechanisms. Yep. Right? The antibody story, the ADC story, and the checkpoint story. I think the checkpoint story, as we've read out with ASPEN-03 and 04, did not play out like we hoped. Yep. I think the ADC story is still open for debate. Is there a story going on? Is there a study going on? Yeah. We're, we're right now, we have an ongoing study with I-SPY. Oh, okay. That's testing in HER2 plus Evo. Yes. that's ongoing. It's a, one of the arms in a gigantic, I-SPY consortium study. Yeah. A A gigantic consortium. Within HER2. Yep. That'll be, I think, instructive. From a capital allocation and a focus perspective, we are absolutely focused on the antibody story. Very good. We've talked a lot about colorectal and breast. We also have an ongoing collaboration with Sanofi in multiple myeloma. Perfect. and it's a very similar story with SARCLISA. Okay. So. Hey, by the way, Alan, is the colorectal study, is that an update in the second half of 2026 as well? Colorectal study? It's open to single. So that one, we may, we should have some safety and maybe early efficacy the first half of 2026. Okay. Because remember, it's small. We like randomized studies. So, we will hold you to. Yeah. A more complete picture of a randomized study in breast cancer second half. All right. Let's talk about the EGFR antibody in the last, perhaps 10 minutes, if that's okay. Yep. All right. Here we have EGFR antibody drug conjugates, seem logical against EGFR, but there have been historical challenges. Walk through what the challenge is and what have you come up with that's so great that's gonna be better than the ones that have failed. Yeah. I mean, that is the question. I think what we're excited about and what we see within monospecific EGFR ADCs is some real room to innovate and potentially be first and best, as I mentioned. As you mentioned, Mike, EGFR ADCs has been a challenging place for drug development. Both AbbVie and Amgen have had programs that have failed. Yep. EGFR has known on-target tox. Skin tox is very common, and is well known in the field. The challenge is when you add a payload onto an EGFR targeted antibody that you see those tox issues and you see them in spades. That's what's happened with the prior programs. They've had a very difficult time getting the therapeutic window right. What we did is optimize the payload, the linker, and the antibody to really bring a unique ADC. We're using a Topo1 based payload, which, I think as most know, is the most validated payload out there within HER2 and others utilizing that payload. We have a novel payload linker where we spent an incredible amount of effort. This was developed in-house over the last four years to get that right. We designed about 700 constructs. We synthesized 60, and we tested this specific design meticulously to get here. The third piece is the antibody. We're using a unique epitope. Historically, in EGFR ADC development, everybody's picked the known, approved antibodies, right? You'd start with Cetuximab, you'd start with Panitumumab, and that's led to some of these on-target issues. That's what we're excited about. Again, we've now shared with the street as of two weeks ago, not all, but a lot of our preclinical work to support it. Probably most exciting from that is that in the primate work we've done, we've been able to dose up to 10 mg/kg without seeing these on-target related issues, like derm, like skin tox. Again, preclinical, we need to see how it behaves in the clinic. We have been very excited over the last couple months to be able to disclose this program. One would believe that the skin tox, which has been skin safety adverse events tox, is certainly related to the underlying antibody such as Panitumumab, Vectibix, not being specific enough for mutant over wild type. That is why you're gonna get some tox, because if it's hit in the wild type in the skin, right, epithelial tissue, you're gonna get tox. Right. Amgen's a pretty decent company, but, you know, Panitumumab's a pretty old drug. You have come up with a better EGFR that is more specific or selective for mutant? It's a unique epitope that can hit both wild type and mutant. Okay. Where we tune the affinity in such a way in order to allow us to not have the on-target related issues. Okay. This is where we discuss posting analyst day. Can you break that down? How can one select for not having skin tox if you're hitting wild type and mutant? It's a great question. I think what we know is through using this epitope, there's data to support that you don't see the same on-target related issues. The affinity is reduced a bit. As which may be one of the components, a different epitope may be another of the components as well that will do that. I think the key thing to know in ADC development is that in NHP work, there's actually been a pretty strong correlation to the clinic when it comes to derm related issues. I believe that, right? The non-human primate is gonna get rash too. Right. How does, just to be clear, because presumably the mutant form is more in the tumor and the wild type is in that. Can you just clarify that? Just to. Because we're, I gotta be clear, we're not, we're not fully understanding how it's selective to not have the tox. Right. Because it must not be able to hit the wild type in the skin. Yeah. Just to be clear though, this isn't necessarily an EGFR mutant directed. Fair. Fair, fair enough. Just to be clear, my understanding is that you just don't wanna hit wild type because wild type is in epidermal tissue. Right. This is not about to do with EGFR because that's the tumor. It has to do with EGFR wild type cells are in the tissue of the skin. Yep. Yeah. I think the key thing to note is if you look at the history of EGFR developed antibodies, there's been many antibodies that developed. Okay. There's been many that have gone in the clinic, and some of those have been able to solve this challenge, hit both wild type and the native and not have this issue. Okay. We went to school on the history of. Okay. EGFR. I feel like there's a secret sauce here. Maybe it's like an epitope that is somehow not exposed to the EGFR tissue. I mean, I think, I don't understand. Yeah. The company was super intentional given how competitive ADCs are. Okay. and we were very quiet, frankly, to get to this point. We were not gonna disclose this program until we approached IND. Okay. Now we're there. I think, yeah, we've spent a lot of time on the design and getting this right. Okay. So, where are you with this? What's the plan? What's the clinical plan? Where are you? When will we get the answer to prove to Jeffrey C? We have. Skin tox. Yes. We have IND cleared as of April. Okay. Alan's also working on this. But I, you know, I think. Oh, you're sorry. IND's cleared as of April. Yep. Okay. Yeah. So, you're starting. We're starting. There we go. Yeah. We've guided to mid, mid-year. We're on track. Okay. We've guided to mid-year across all three of these studies and are executing across all three well. I think what we're encouraged by is given EGFR is a validated target, given there's these questions around tox. Yes. We're gonna have safety data relatively soon. Again, we know EGFR is a validated target. I think once we check the safety box, if you will, it'll be an exciting inflection. What, this is a phase I dose escalation? Is it, what tumor types, et cetera? Yeah. Yeah. I'll give you a little color on this. Traditional dose escalation, what we've decided to do is restrict it to those tumor types, four tumor types that are known to be dependent upon and overexpress EGFR. That would be head and neck, non-small cell lung cancer, colorectal cancer, and then squamous cell carcinoma of the esophagus. We're not doing one dose escalation grouping all four of those histologies together, and then have dose expansion subsequent as we look at the appropriate dose. Then we'll also be mindful of dose optimization. Also having the ability to choose which of those four, potentially all, but which of those four are the ones to take further in phase two. All right. Safe to say that these are, you know, pretty late line patients in those tumor types, failed a bunch of other stuff. So, obviously, any response rates you're gonna be pleased with. Like, what are you gonna be looking for here? Yeah. These will be previously treated patients. And, you know, in some cases, most of the cases will probably have had an EGFR directed therapy of some sort, of course. I think one of the reasons we designed it as such is since we know there's some dependency on the EGFR pathway, we would anticipate the ability to identify some level of efficacy or activity, I should say, early in the course, along with safety. Where, where, when you look back at the Amgen data and I guess AbbVie too, what did they show? Did they show any activity or they just ran into all the skin tox in advance or like? They had a, I mean, the challenges were around dose escalation. If you look at both of those programs, they were never able to dose above 2 mg/kg. Okay. They really found themselves in a therapeutic window challenge where they were dialing the dose down. I'd say there was some signal, but it's a little hard to extrapolate. They were using in one case an MMAE payload and another a different payload altogether. Again, I think our goal was to take advantage of those learnings, take advantage of what's now known in ADCs in terms of what works. A lot of our clinical, our preclinical data that we shared shows how we used in HER2 as sort of our benchmark and then optimized off of that. You know, that gives us some confidence that we'll be able to dose more highly than they were. Also, I think, you know, it should be different in terms of efficacy. Okay. There is certainly, yeah, there was reasons to believe from both of those programs. You just basically said, or I got you to say that multiple studies are starting soon. You did this analyst day, maybe a month ago or so. Mm-hmm. To disclose this program. You have about $100 million of cash at the end of Q1. I think you said that you've kinda worked the expenses and now you're going to the end of 2026, but there are definitely readouts, but most of those readouts are later in 2026. How are you thinking about capital? I don't know if you have an ATM or whatnot, but how are you thinking about that and whether some of these could be partnered, like obviously Evorpacept could be versus the antibody drug conjugate? What types of things are you thinking about, Jason? Yeah. I mean, I think, you know, the good news is, is what you said, which we were guiding to Q1 of next year. Now we're guiding to Q4. Yep. It gives us time to execute on these studies with the internal goal and frankly mission of putting up, putting up data on this money. I think, as we do that and in parallel, we continue to have great conversations with pharma. Mm-hmm. you know, we're developing in Evo's case, a combination agent where we've now shown is safe in over 750 patients and can combine with any antibody or bispecific. It's a powerful message to take to pharma. We're gonna continue to have those conversations. On the 2004 front, we've now introduced to the world a novel ADC against a validated target. Yep. Of course, there's gonna be interest. We're gonna continue to advance those threads with pharma. On the investor side, I think you look at some of these milestones we have coming up, I think we're gonna have some windows in which, you know, we could think about potentially, you know, accessing the markets. I think for us, we're focused on execution. We're focused on running a very tight ship. We now have reduced burn quite a bit. I think that gives us some flexibility as to how we think about balance sheet. Sorry if I, sorry if I didn't catch that, but the ADC data, is that, that since it's just getting underway, that's probably also sort of a mid 2026 thing. That's what I was gonna add, Mike. I would say the breast is the one that's more towards the end of next year. Yes. The other two are actually in the first half of the year is what we've guided to. Then we also, just as a reminder, all three are open label studies. Sure. You could imagine that'll give us flexibility in terms of, of course, we wanna make sure we're looking at the data with robust and we have some signal. Right. We do have that flexibility as well. Jason, let me just close 'cause you were just at ASCO. I mean, do you feel like you continue to have good conversations on Evorpacept? I mean, you kind of said that that's something that could be. Yeah. A partnerable interest. I mean, that's, you know, that's been our focus for a while. I think coming off December with the breast data, ASCO GI with the gastric data, we now have a very clear picture of where our drug works. Yep. How it works and where it works best. That takes a lot of time, right? It took us 10 years to get to this point, but that's what we know. I think when we pitch that to potential partners, it's compelling. Coming off ASCO where we had a number of conversations, I think we're feeling very encouraged. Mm-hmm. And yeah, I mean, drug development is hard. It takes time. Mm-hmm. You're gonna have some hits and some misses, but we now are capitalizing on our hits and we know where we're going. We had a great ASCO. Very good. Thank you very much. Thank you guys for the update and we'll keep track. Thank you. Yeah. Appreciate it. All right. Thanks everybody.