All righty. Let's go ahead and get started. My name is Ashleigh Acker, a Biotech Analyst on Allison Bratzel's team here at Piper Sandler. Thank you for joining us at the Piper Sandler Healthcare Conference. It's a pleasure to introduce ALX Oncology. Joining us for a fireside chat, we have CEO Jason Lettmann and CMO Barbara Klencke. Thank you for joining us for the fireside chat. This is meant to be informal, so if anyone from the audience has a question, just raise your hand. Before we jump into Q&A, just to level set for investors, Jason, can you give a quick overview of the company, the story, the setup into year-end in 2026? Yeah, sure. Well, thanks for having us. Appreciate it. Appreciate all the support. ALX was founded in 2015 with a really different approach to CD47. Our lead program is evorpacept, and I can get into the differentiation. We also have a new program, ALX 2004, which is now in the clinic, which is an EGFR targeted ADC. On the CD47 front, it is a very important target and an important pathway that's been well established over the last 15 years. But it's been very difficult to drug. It is one of the most fundamental ways in which the immune system communicates to healthy cells. It's known as the "don't eat me" signal, and it's expressed on just about every cell in the body. And so that's been a challenge: to get the targeting right, if you will. And so our company's approach, dating back to the early days, was to separate the "don't eat me" signal from the "eat me." And really, that insight and that fundamental difference is what we've now taken into the clinic. So we are the only CD47 blocker in development with a dead Fc. We provide full blockade of the eat me signal, and then we use an Fc active antibody to provide the eat me signal. And working together in that way is what has allowed us to have a very targeted approach. And that's what we've seen now translate in the clinic. We've seen it now in four different clinical studies and is really the basis for what we're driving forward with now. And that approach, we think, is really well validated and, frankly, the only CD47 to date to have that level of validation. And then the second program we'll get into is our EGFR-targeted ADC. Excellent. So let's talk about some of the mechanisms that you've explored. So the focus for evorpacept has been on three combination hypotheses: one in combination with anti-cancer antibodies, one with ADCs, and the other in combination with checkpoint inhibitors. In recent months, we've seen a strategic shift away from combination with checkpoint inhibitors and a focus on combination with anti-cancer antibodies. So as a lead into the data that we've seen with the latter approach, maybe walk us through the mechanistic rationale here. Yeah, sure. So CD47 signals both to healthy cells, and it's also hijacked by cancer. And we know that the signaling is both to dendritic cells as well as to macrophages. And so dating back to the company's founding, it was really of high interest to test both. So to test how it works with the macrophage as well as test how it works in terms of the potential to better cross-prime and activate T cells. And I think what we've learned over 10 years and now over a dozen clinical studies is where it works best. And what we know is in combination with an Fc active antibody is where we see the most activity. Without question, we see the most potency. And so that's what really is the basis for us going forward. That approach is what we're now advancing with our breast cancer studies. So combining evo with Herceptin, which is an Fc-active antibody, and we see a really unique and large opportunity to benefit patients that overexpress CD47. And again, we've now demonstrated that in the clinic in terms of combining with both tras as well as zani, which is a collaboration we did with Jazz. So we've now shown in two HER2-positive cancers our ability to impact those patients. And that's what really provides the basis for our strategy in breast. Excellent. So let's talk a bit about your ALX Oncology Holdings trial in gastric and GEJ cancer. So this is a phase 2 trial that evaluated evorpacept plus TRP in HER2-positive second-line plus gastric patients and had a control arm of just TRP. So as a reminder, you saw 41% ORR versus 26% in the evo arm versus control, and DOR and PFS hazard ratio did show benefit. When you looked closer, patients with fresh biopsies and ctDNA analysis showed significant benefit. So you actually plan to make the case that these results were convincing to merit accelerated approval. And we learned in May that per FDA guidance, it wasn't eligible for accelerated approval based on the availability of Enhertu. And you chose not to pursue a full phase 3 in second-line HER2-positive gastric. So can you just walk us through that data a little more closely and kind of the interactions with FDA and where you stand in terms of a full phase three, given that you plan to potentially advance this through developmental partnerships? Barbara, do you want to take that? Maybe I'll address that. So the gastric study was 127 patients randomized phase 2, so a very robust-sized gastric cancer study in the second- and third-line patient population. And one thing we know about gastric cancer, HER2-positive gastric cancer, is that you can lose the HER2 positivity. It's a bit more heterogeneous. And so we, from the very beginning, had planned to really look at the population that retained HER2 positivity. We did so by requesting fresh biopsies, which we got in something like 48 of the 127 patients. So we got a fair number of people to agree to a fresh biopsy. And we did ctDNA in everyone. So as you said earlier, the response rates were better in the overall population. We had a 41% response rate, which is very good in gastric cancer. When we look at the 75% of patients who retained HER2 positivity, we see an enrichment of response rates. We saw 49% response rate versus 25% response rate in a control arm. We also saw some nice durability with a 15.7-month duration of response and a hazard for the progression-free survival of 0.64. So that's what we discussed with the FDA. But at the time, as you said, Enhertu had just received full approval. And what we decided at that point was really to refocus our efforts into the breast cancer population. Excellent. During your Q2 update, you shared data from a pre-planned exploratory analysis of the ALX Oncology Holdings ASPEN-06 trial. Can you just walk us through some of that data and their significance as it relates to your overall strategy? Yeah, and I think this is probably the most interesting aspect of the study itself. The overall results were good. It was enriched with HER2 positivity. But we chose here to also look at CD47 expression. And despite a long history of different agents attempting to block CD47, this is a nice, large randomized phase two where we were able to look at CD47, and we see a really transformational benefit in the patients who had overexpression or high CD47. So here, what we see is a 65% response rate and a median duration of benefit of response of 25 and a half months. And that compares to the control arm, which really stayed very similar to the ITT patient population. So we saw a 65% response versus a 26% response rate in the TRP alone arm. When we look at progression-free survival, the hazard was 0.39, and the median duration of PFS was 18.4 months versus 7, and we also see a similar trend in survival, where the hazard was 0.63 and 17 months median progression-free survival. So again, we're really impressed with that data. We think that the biology of HER2 disease is similar across diseases. Breast opportunity, much larger commercial opportunity. So that's where we've really focused our efforts going forward. Great. When it comes to identifying HER2-positive and CD47 high patients, can you just remind us of the study flow diagram that you used in order to identify these patients? Yeah, in the gastric study. So we enrolled 127 patients. There were a number of patients who agreed to a biopsy subsequent to their prior HER2 targeted therapy, but we also got the HER2 ctDNA on everyone. In the gastric study, we found that 75% of patients retained HER2 positivity based on either biopsy or ctDNA. And then we looked at the CD47 breakdown. We looked at a whole variety of cut points. We really think that almost any expression of high-expressing cells produced a benefit. We really see very consistent benefit across a variety of cut points. We chose the numbers I told you here. We chose the cut point of at least 10% of cells expressing CD47 to the IHC 3+ intensity. Excellent. So where are you on a potential ALX Oncology Holdings partnership in light of the ALX Oncology Holdings CD47 biomarker data? I think the last time we spoke, you were pursuing an ALX Oncology Holdings Asia partnership. It was very much on the table. Has that changed at all? No, I think we still are. I think, as Barb mentioned, we've now validated this mechanism in a randomized study. I think what's been new to our story is this biomarker analysis that we did. And as Barb highlighted nicely, that's very much on mechanism, right? Our drug needs HER2 expression, and we need CD47 expression. Have that, it's clearly working in a transformative way for these patients. So it's been exciting to roll that out to partners. That's been a new element to our story and very much still interested in pursuing that. Certainly, gastric is an interesting opportunity in the U.S., but it's a much larger patient pool in Asia, which I think lends itself well to BD opportunities. So continue to do that and investigate BD as a way to move the program forward in gastric. Great. Let's talk about a potential companion diagnostic. Can you elaborate on your companion diagnostic development? Are you developing this in-house, and how does it integrate with your clinical programs? CD47 has long been recognized as so important to the immune system and to immune evasion by cancers. So there's a large amount of data looking at it from a prognostic standpoint and looking at which cancers and how often is it overexpressed. And it's very ubiquitous. So you find almost any tumor type has high expression. You find it as a poor prognostic marker across the board. What hasn't been done is it has not yet been matched to a therapeutic. It's not been used as a predictive biomarker for patient selection for treatment decision-making. Now, at this fork in the road, it really is taking what has been a research-based assay and translating that into a potential companion diagnostic. We're certainly talking to partners. We're thinking a lot about that. We're utilizing a similar assay on our forward-looking breast study, which we'll talk about, a phase two study, as we used in the gastric study. But certainly, if we were to go forward in a phase three, we would need to really have a companion diagnostic process. Excellent. Actually, let's pivot to the ALX Oncology Holdings trial. This is a phase two study evaluating evorpacept plus Herceptin plus chemo in the HER2-experienced HER2-positive population. And it's evaluating efficacy by CD47 expression levels. And you've guided to the first patient in this quarter with interim data expected in Q3 2026. This trial underwent protocol amendments to incorporate CD47 and HER2 as biomarkers. Can you walk us through the amended clinical trial protocol and the rationale behind these changes? Yeah, this trial is a single-arm trial of 80 patients. It was originally, as you say, it was amended. It was originally thought that a randomized study. But what we really have decided is that with the outcomes that we saw in the gastric study being so transformational that we can really have confidence that if we can replicate anything anywhere close to that in a single-arm study, that we have a nice benchmark of a response rate of 15%-20% in the breast cancer population with Trastuzumab and single-agent chemotherapy alone. So we're really looking for a large treatment effect, which could be easily identifiable in a single-arm study. What this study is really going to help us do is to look at the cut point for CD47. We want to replicate we've seen it twice now. We've seen good data in the gastric setting and HER2-positive gastric. I've already just described that. We also had a study in combination with Zanidatamab, run by Jazz. And that study showed a 56% response rate with evorpacept plus Zanidatamab in the HER2-positive breast cancer population. And those were all post-Enhertu. So we want to do this for a third time. But what we want to do now is look prospectively at archival tissue or fresh biopsies, whichever we can get, and look at CD47 and determine if there's a cut point that we would take forward in a future phase 3. Excellent. With regards to regulatory interactions, anything you can share from discussions with FDA regarding the trial design and the use of CD47 as a biomarker? What kind of feedback have you received? As normal process, we submitted the amended protocol. Received pretty standard feedback proceeding with this study. We really look forward to being able to have a data-driven discussion with them as the data from this study comes out later in late 2026, 2027 as we complete the study. Is it too early to say if the phase two study could be registrational? I believe there was some commentary on your recent earnings call about what a registrational study could look like. Is it too early for this to be registrational? Are there any updated thoughts on what a potential phase three could look like? I think the potential phase 3 is the same type of treatment, a control arm with chemotherapy and Trastuzumab. In the past, the control arm outcomes, the outcomes with this type of control arm would be about 20%. But what we're seeing more recently, for example, at ALX Oncology Holdings, there was a large real-world evidence study reporting about 600 patients post-Enhertu in the HER2-positive space with a 15% response rate, thereabouts. And so I think post-Enhertu, we're only seeing control therapy, the standard of care options for patients becoming even less effective. Our therapy post-Enhertu, we anticipate a very good outcome based on the Zanidatamab data. So we anticipate being able to randomize Trastuzumab chemotherapy versus Trastuzumab chemotherapy and evorpacept. I think in the phase 3 study, utilizing potential predictive biomarkers, selecting patients for high expression of CD47, and then utilizing ctDNA potentially for confirming HER2 status would be our thought going forward. In terms of talking to FDA, I think we'll see the data and make a decision at that point as to what our options might be for whether there might be an early approval process or going forward into phase 3. Excellent. So I also wanted to spend some time on ALX 2004. So this is your EGFR-targeting ADC developed in-house by ALX. How does its design differentiate it from other EGFR-targeted ADCs in development, and what preclinical data has supported its advancement thus far? Yeah, sure. So back in 2021, we made the strategic decision to pursue ADC development in-house. So as part of that, we acquired a company, company in quotes, a small company. It was about a dozen protein engineers, chemists, etc., and Palo Alto to pursue ADC development, and at the time, they had some really interesting linker payload constructs, interesting ideas around novel toxins as well as a shield approach, and we took that and from 2021 up until just early summer of this year, largely didn't disclose the program or the efforts, and I think part of that was just due to interest being primarily on CD47, but it was also just due to competitive reasons and wanting to keep the program under wraps, and I think what we saw at the time, and is still the case today, is that although most spaces in oncology that have validated targets like EGFR are very, very competitive, we saw an opportunity for a monospecific EGFR ADC to address some of the challenges in the past. AbbVie, Amgen, for example, had programs. They developed ADCs against EGFR that have failed, and we felt by really optimizing the linker payload as well as spending a lot of time on the epitope, again, we know epitope selection is really important in ADCs that we could address some of the challenges of the past, and through disclosing our preclinical work over the summer, I think it's generated a lot of enthusiasm and pleased to now be in the clinic. We've cleared the first dose cohort as we announced that earnings a few weeks ago, and I think the program is really off to a good start. Again, EGFR is a very well-validated target, and we have the opportunity to be first in class there. Excellent, so let's talk about that phase one trial, so this is being run in multiple solid tumors. What steps have you taken to optimize 2004's therapeutic window? What can we expect to see with initial safety data in the first half of 2026? Yeah, the study, as you say, is in multiple tumor types, but we actually selected four tumor types that are allowed to be enrolled. We did really look at several important things. One is responsiveness to EGFR therapies. The other is responsiveness to TOPO1 inhibitors. So we narrowed down to non-small cell lung cancer, colorectal cancer, head and neck, or esophageal. Out of those patients, we think that gives us a good chance of seeing potential activity even during the phase one study itself. In terms of how we might really maximize the therapeutic window, we are very pleased with our preclinical tox studies. Our GLP tox studies allowed us to start at one milligram per kilo, which is a really good, robust dose. As we announced at our earnings, we were able to double that and go to two milligrams, having cleared that one milligram cohort rather easily after the start of the study earlier this year. We anticipate having some safety data in the first half of 2026. Excellent. What data are you looking at to help the company make a go or no-go decision with this asset? And if you're able to say, when might we see efficacy data from this study? Yeah, I think there's no question, just given some of the history in the field, that safety is important. We know that both the naked antibodies Cetuximab and Panitumumab have had skin-related tox, and we know it's been a challenge for the field. First up is safety, as Barb alluded to. We're going to have that first half of next year. And then shortly thereafter, we haven't provided guidance on efficacy. But again, as Barb highlighted, the four tumor types that we're targeting should be tumors where we see activity. And the goal, I think, looking into the back half of the year and into the following year is to put up efficacy data as well in one or two of those tumor types. Excellent. So maybe zooming out a little bit, how do you view the competitive landscape for EGFR-targeted ADCs? And where do you see 2004 fitting in? Yeah, I think we have a really unique asset against a validated target. And I think that's rare in ADC development right now. We certainly have competition from China-based ADCs that have been advancing various programs. But to the best of our knowledge, our asset is truly unique. Our epitope is unique versus the competition, and our linker payload construct is also unique. So we believe we have an opportunity to be first. We believe we are first at the moment in terms of treating U.S. patients. And I think with good execution and continued pace against the dose escalation, we'll be able to, yeah, I think advance this program very quickly. Excellent. Maybe just to wrap things up, how does your current cash position support the advancement of your programs? And what is your expected runway? Yeah, sure. So we have cash in the Q1 of 2027. If you look out from here over the next 12 months, we have a number of really important catalysts. We talked about 2004, getting to safety is going to be important. We've guided the first half of next year for that with efficacy to follow. I think, again, given how well-validated EGFR is, it's an important milestone. Then on the evorpacept front, the breast study is on pace to initiate soon. Getting the interim data on that will be really important. We've shown good data in two HER2-positive studies with our ALX Oncology's ASPEN-06 results and then our work with Jazz combining with Zanidatamab. To be able to do that in a third study, I think, will be really important. We've guided to Q2 2026 for that. A number of really important milestones in the short run and cash through early. Wonderful. I think that's our time. Thank you so much for joining us today. Thank you. Appreciate it. Thanks.