Greetings and welcome to the ALX Oncology First Quarter 2026 Financial Results Conference and Webcast. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please note this conference is being recorded. I will now turn the conference over to your host, Jason Lutman, CEO. Please go

ahead, sir. Thanks, everyone, and welcome to our Q1 2026 results. Really appreciate you all spending time with us this morning and are looking forward to sharing these updates with you. On slide two, and before we start our presentation as housekeeping, here are our forward-looking statements for your review. On slide three, here's the agenda and plan for today. We're going to be providing an update on our key accomplishments in the first quarter of 2026. Most notably, we are very excited to share with you the data set that was presented yesterday in Munich at ESMO Brest 2026 from the analysis of our trial evaluating Evorpisept and zanidatumab, which clearly showed, again, that CD47 expression is a key predictive biomarker for increasing durable clinical response in heavily pretreated HER2-positive patients. This further validates the results we saw with EVO and HER2-positive gastric cancer from our ASPEN-6 trial. We are also very excited today to be joined by Dr. Sarah Hurwitz from the Fred Hutch Cancer Center at the University of Washington, who is a well-recognized expert in metastatic breast cancer. She will be presenting the ESMO breast data in detail and also share her views on Avorpacept's significant potential within the current treatment paradigm for HER2-positive metastatic breast cancer. Our CMO, Barb Quinky, will then recap our findings to date with EVO and HER2-positive cancers across now two different independent trials and indications, showing that patients with high CD47 expression derive the greatest benefit across all key efficacy markers, including overall response rates, duration of response, and PFS versus those with low expression. These results support our targeted oncology approach with EVO, notably our ongoing ASPEN-9 Breast Cancer Phase 2 trial. Barb will then provide an update from our ongoing Phase 1 trial with our novel EGFR-targeted ADC, AOX 2004, which also continues to track the plan, and we are enthusiastic about its potential to also change care in EGFR-expressing cancers. So, on slide 4, we continue to advance both our programs, EVO and AOX 2004, and are pleased with the progress on both fronts over the course of Q1 and remain well-positioned to report on significant data readouts from these programs in the coming 12 to 18 months. On the EVO front, CD47, as you know, is incredibly important in oncology and has been a very difficult target to crack, yet it plays a fundamental role in tumor evasion and resistance. We've been happy to see EVO's differentiated approach to this target further validated in the clinic over now five different datasets, including randomized data. Further, the new data from this week's ESMO meeting and over the last year support CD47 as a strong and predictive biomarker. These new findings further support the drug is working as designed and also enables a targeted strategy, which allows us to focus on the patients who will benefit most. On ALX 2004, as you know, it is a highly differentiated EGFR-targeted ADC, which was developed in-house by ALX and has the potential to be a first-in-class EGFR-targeted ADC. EGFR has also been a difficult target for ADCs historically, and ALX 2004 was designed to address this with a novel epitope and linker payload construct. We have been pleased to see the strong preclinical data to date translate to the clinic, and with the continued strong progress in dose escalation, where we have been able to further increased dose. Overall, both programs remain on track and well positioned. Now, on slide four, Q1 was a quarter of continued good execution and additional positive data, as well as completion of key hires and a strong financing. As you'll hear more about shortly, this week's data validate again the power of CD47 in a late-stage patient population. Here, we observe that all patients who were confirmed HER2 positive and CD47 high, achieved a response, including one complete response. We also, yet again, saw the durability that one hopes to see with an IO mechanism, with a median duration of response of 20 months and a median PFS of 22 months, which is clearly far improved over the benchmarks. While the focus for today will be on this new data set with EVO, ALX 2004 is also progressing through dose escalation very well and remains on track for initial safety readout in the second half of this year. We remain as excited here about its potential as we do with EVO. Further, the financing from February, which was anchored by very strong investors, further strengthens the balance sheet and enables us to execute through these important data milestones. And last but certainly not least, we added Jeff Knight, who is now our Chief Development and Chief Operating Officer, which really further strengthens our leadership team. Jeff, as you may know, is one of the best operators in biotech in terms of building companies at our stage through the next phase, including commercialization. On slide six, briefly, this just highlights the execution, clinical development progress, and timelines which remain on track for both programs. Our Avorpisept Phase II breast trial continues to progress well with strong enrollment globally and increasing site enthusiasm. Overall, clinical timelines remain on track as we're expected to read out 80 patients mid next year. ALX 2004, as I mentioned, is also progressing well with enrollment and dose escalation ramping and are on track there for an initial safety readout in the second half of this year. Our goal and vision for both of these programs also remains unchanged as we aim to have both programs ready for registrational studies by end of next year. On slide seven, in my last slide, here is also a snapshot of our clinical pipeline. As you know, we're advancing two novel cancer treatments with key near-term catalysts. And again, Aspen Breast is on track, and we continue to also be encouraged by our ongoing study with our partner, Sanofi, testing EVO and multiple myeloma. Our two studies in HER2-positive cancers have now been completed, as we'll focus on today, and ALX 2004 also remains on track. I'd like to now turn the call to Barb, who will provide a quick reminder of our MOA, which is very important, as we're clearly seeing it translate to the clinic. And we'll then turn the call over to Dr. Hurwitz to review the new data. Barb? Thank you, Jason. These next few slides describe

Evorpisept's mechanism of action. What's so compelling to me is that the mechanism of action is entirely consistent with what we see in the clinical trials. So, let me just go through this. Cancer cells commonly upregulate CD47 expression to evade immune detection. Evorpisept blocks the CD47 signaling, but it does so without an active FC domain. So, Evorpisept by itself does not engage the phagocytic activity of a macrophage. We need to combine avorpicep with an anti-cancer antibody and then the combination together strongly augments the ADCP activity of the antibody and that's likely what results in the efficacy that we see in the studies that we'll talk about today. Essentially, the antibody stimulates the eat-me signal and the avorpicep inhibits the don't eat me signal. Therefore, the combinations of Orpicep with an antibody are selectively enhancing or augmenting macrophage phagocytosis of cells that express HER2, for example, in the case of a HER2-targeted antibody, while also blocking the don't eat me signal. On the next slide, we see how this mechanism of action translates into safety. Our clinical safety database is now more than 800 avorpicep-treated patients. And it also, the clinical safety data is also entirely consistent with this mechanism of action that we show here. Avorpicep was designed, again, without an active FC domain. That's shown on the right side of the slide. So when we block the don't-eat-me signal on normal healthy cells, such as red blood cells, There is no macrophage activation, and we avoid on-target toxicities. This is really fundamentally different than what's been tried in the past by conventional CD47 inhibitors, which have essentially failed in the clinic. They attempted to use CD47 as a tumor-associated antigen with both an active FC domain to activate macrophage at the same time of blocking CD47. That ended up being an indiscriminate approach because CD47 is so widely expressed on healthy cells, especially hematologic cells in particular, and that led to the potential for significant on-target toxicity. So with that description of avorapicep, its mechanism of action and its differentiation, let me now turn the conversation over to Dr. Sarah Hurwitz. On slide 12, you can see her background here. She is a steering committee member for our ASPIN-09 Phase II study of avorapicep in HER2-positive breast cancer patients. She was an investigator on the Avorpisep and Zanidatinib trial that we'll discuss today. And she's a senior vice president, a professor of clinical research, and the director of the clinical research division at the Fred Hutch Cancer Center at the University of Washington in Seattle, where she's also the head of the Division of Hematology and Oncology and the Smith Family Endowed Chair of Women's Health. She's an expert in the management of breast cancer and in the development of novel targeted therapies for breast cancer.

Thanks, Barb. I'm really excited to be here today. There have been remarkable changes in the management of HER2-positive breast cancer, especially since 2020, with new agents like trastuzumab, dirextecan, and tucatinib demonstrating benefits in pretreated disease. And with the results of Destiny Breast 09 showing benefits with TDXD in combination with pertuzumab, we have a new standard of care according to our NCCN guidelines as of this February. What we don't know is how we should be treating patients after they've received an HER2. This remains an area of unmet need. On slide 14, you can see this graph showing the outcomes that we have from patients who've received prior in HER2 treatment with the median progression-free survival of only 4.1 months. What we don't have are randomized prospective data telling us as clinicians how we should manage patients after TDXD, but observational and retrospective data sets are fairly consistent showing that PFS rates of under six months is what patients experience post-TDXD. On the next slide, on slide 15, you can see the list of HER2-directed therapies that we have approved and in late stage development on the left side. These include HER2-targeted antibodies and bispecifics, HER2-targeted antibody drug conjugates, and HER2-targeted tyrosine kinase inhibitors as well. What we don't have are immuno-oncology therapies approved or in late stage development outside of evorpacept. And so this remains an area that's very exciting to see developed now. On slide 16, you can see the range of CD47 expression in normal cells versus tumor cells. As explained before, CD47 is expressed on all cell types and is a marker of cells, and cancer cells can take advantage of this by overexpressing CD47, allowing them to hide from the immune system. Focusing on the left there, you can see highlighted in blue breast cancer cell lines, which actually do have higher expression of CD47 in tumors compared to normal, which is highlighted in black. On slide 17, you can see a meta-analysis of 38 cohorts across 17 publications, which included over 7,000 patients, demonstrating fairly consistently that CD47 overexpression was correlated with shorter survival in patients with cancer. So it's a negative prognostic biomarker. On slide 18, there are data here relating to CD47 expression in breast cancer, in particular in HER2-positive breast cancer. On the left, you can see that CD47 expression is higher on HER2-positive breast cancer cells versus HER2-negative on the right. High expression is denoted in the dark blue, moderate expression in green, and low expression in blue. So HER2-positive breast cancer cells appear to have a lot more CD47 expressed than HER2-negative breast cancer cells. And in fact, if you look on the right side, you can see that CD47 high cells are more common in recurrent HER2-positive breast cancer, shown on the left side, compared to primary or initially diagnosed breast cancer. And so, these data provide strong rationale for us to be evaluating of Orpicep in HER2-positive recurrent or metastatic pretreated disease. On slide 19, you can see some elegant data demonstrating that TDXC treatment may actually upregulate expression of CD47, again providing strong rationale to treat HER2-positive recurrent TDXC pretreated breast cancer with Avorpacet. On slide 20, you can see the title slide for the data presented recently at ESMO breast. This is an exploratory biomarker analysis from our phase 1b2 trial of Xanidatamab, a HER2 targeted bispecific in combination with the Vorpacep in patients with HER2 positive metastatic disease. Slide 21 gives you an overview of the study design. This is a phase 1b slash 2 study and we presented the safety dose escalation cohort data from three patients with HER2 positive breast cancer enrolled and data from cohort 1 where 21 patients with HER2 positive breast cancer were enrolled who had received at least three prior regimens. The exploratory biomarker analyses focus on these 24 patients, and it's notable that all of the HER2-positive cohort received prior TDXC and a median of five prior lines of HER2-targeted therapies. This is extremely heavily pre-treated disease. The patients were allowed to enter the study based on prior local HER2 testing of their archival tissue. However, fresh baseline biopsies were obtained in most patients and tested retrospectively for HER2 status by central assessment. And we'll be reviewing outcome results based on the central assessment as well as the intent to treat population. In addition, patients' tumors were tested for CD47 expression on the fresh baseline tumor biopsies or on archival tissue if fresh biopsies were not available. Patients were treated with sanidatumab at 1,200 milligrams for those patients weighing less than 70 kilograms and at 1,600 milligrams for patients 70 kilograms or greater. The avorpacept was given at 20 mg per kg for these three patients enrolled in the 1A or at 30 mg per kg IV every two weeks for the rest of the patients. Going on to slide 22, we're jumping to the efficacy outcome data. What you can see here are the confirmed objective response rate on the top row based on all 24 patients, which is 33%. I find personally these data to be quite impressive in patients who've received a median of five prior lines of therapy, including TDXD. If you go down to the duration of response, those patients who experienced a response had a duration of response of 20 months and a median progression-free survival of 3.6 months. This next column shows the outcomes for the six, excuse me, for the 10 patients who had essentially confirmed HER2-positive breast cancer, where the objective response rate was now 60%, the duration of response was 20.2 months, and the median PFS was 8.3 months. These data, I think, are impressive as we reflect back on the fact that our retrospective and observational data suggests that patients pre-treated with TDXD have a median PFS of less than six months. So I find these data to be quite compelling and exciting. Those patients who did not have centrally confirmed HER2-positive disease had a lower objective response rate of 14%. On slide 23, we can now see breakdown based on the tumor CD47 expression levels. Using a cutoff of at least 20% for CD47 expression, there are five patients who had both centrally confirmed HER2-positive disease and CD47-positive or greater than or equal to 20% expression. All patients had an objective response in this cohort of five patients with a median DOR of 20.2 months. However, those patients whose CD47 expression was less than 20%, that's four patients, only one had an objective response. So this is beginning to give us data that CD47 expression level may be a marker to help us select patients particularly responsive to this targeted therapy. On slide 24, you can see a Kaplan-Meier curve for progression-free survival based on CD47 expression levels. So, the progression-free survival with a CD47 expression level of at least 20%, you can see the PFS is 22 months. For those patients, less than 20%. percent. The PFS is 3.4 months. Again, although these numbers are very small, we're talking about nine patients total, the data are quite interesting, and I'm excited to see them hopefully confirmed in the larger study. On slide 25 are our conclusions for this exploratory analysis of our FASE 1B-2 study of Orpicep and Xanidatamab showed promising anti-tumor activity in patients with heavily pretreated HER2-positive metastatic breast cancer, median of five prior lines of therapy, all of whom received prior TDXD. Greater anti-tumor activity was seen in patients with centrally confirmed HER2-positive disease. Durable responses were seen in this patient population and seemed to be largely observed in patients with higher CD47 expression, supporting a CD47-dependent HER2-driven biology that resulted in this prolonged progression-free survival. It's notable that most patients with centrally confirmed HER2-positive disease remained HER2-amplified at progression with TDXD, supporting the continued use of HER2-targeted therapies. And so, a biomarker-driven approach incorporating CD47 may optimize patient selection for this combination regimen and warrants further study. So, with that, I will turn it back over to

Barb. Thank you, Sarah, for that excellent presentation. As we've seen, all of the patients who were centrally assessed as HER2-positive and who overexpressed CD47 in their cancer cells achieved confirmed response to the combination of avorapacet plus anidatinib. What's new on slide 27 in the table on the right side of this slide are the individual CD47 expression levels and the confirmed response assessments for each of the 10 patients with centrally assessed HER2-positive disease. An IHC assay was used to quantify the total membrane staining for CD47. A positive result was defined retrospectively as a score of 20% or higher, which we observed in the patients shown in the top five rows, highlighted with deep blue. All five of these patients with CD47 expression responded, including one patient with a complete response. That patient happened to be the only patient from the dose escalation cohort that was centrally assessed as HER2-positive. There was no evidence of CD47 overexpression in the four patients highlighted in light gray, one of whom responded to the avorpicep and zanidaptinib combination. And then in the last row in this table is a patient who was unevaluable for either response or CD47 expression level. On slide 28, I want to highlight the consistency that we see between the results of the avorpicep zanidaptinib trial in HER2-positive breast cancer patients and in the previously reported HER2-positive gastric study. On the top half of this slide, you'll see the data that we've just reviewed. This includes the 33% response rate in the 24 patients enrolled based on archival HER2 status, the 60% response rate in the 10 patients centrally assessed as HER2-positive, and the 100% response rate in the five patients who were also CD47 overexpressing. On the bottom half of this slide, you see the data from ASPEN-06. This is a randomized phase two study of Avorpacept, Trastuzumab, Paclitaxel, and Ramisurumab versus the TRP regimen alone. Here you see the response rate climb as we look across the slide at the same subsets. In the ITT, the response rates in patients randomized to the avorapicep arm was 41%. Response rate was over 49% in the patients that retained HER2-positive disease, and it was 65% in patients whose tumors also expressed CD47. And recall, this was a large Phase II study of 127 patients. As you see, the data trends here are consistent across these two independent trials of a Vorpicep when combined with a HER2-targeted antibody. On slide 29, I'm again showing the results of the EVOZANI study on the top and the ASPEN-06 HER2-positive gastric study on the bottom. These graphs show the duration of response in the subset of patients who were HER2-positive and CD47 overexpressing in the two independent studies. The duration of response was remarkable in bulk settings at 20.2 months and 25.5 months, respectively. On slide 30, the same consistency across the two independent studies is seen with the PFS results in the subset of HER2-positive CD47 high patients. Both studies show remarkably long PFS, especially in light of the later line settings for both indications. On the left, we see the median PFS for these patients in the avorpus absanidatinib study of 22.1 months, while the median PFS for those without CD47 expression was only 3.4 months. And then in the gastric study shown on the right, The median PFS was 18.4 months for the patients in the Vorpicep arm, and the hazard ratio in this subset in the randomized trial was 0.39. So, these data are really why we're so excited about moving forward with the development of Vorpicep in HER2-positive breast cancer. Slide 31 shows our ongoing ASPIN-09 study in the HER2-positive breast cancer setting. Like this antidatinib the Vorpicep study population. All of these patients will have had to have had prior INHER2. This is a single-arm study that will enroll up to 120 patients and has a primary endpoint of response rate in the subset of patients who overexpress CD47. We're making very good progress with enrollment, and we're very much on track to achieve our stated milestone of having interim top-line data from approximately 80 patients by the middle of 2027. On slide 32, we show the market opportunity. Ultimately, our aim, of course, is to bring this drug to market. We estimate that there are approximately 20,000 addressable patients who are HER2 positive and overexpressed CD47, representing a $2 to $4 billion market opportunity in the United States to five major European markets, and Japan. I'm not going to turn for the last few minutes of this talk to our second molecule. Slide 34 shows ALX 2004, our EGFR antibody drug conjugate. This is actually a very unique molecule. It was designed by protein engineers and cancer biologist within ALX. EGFR is obviously a very validated target, but it's been very difficult to target EGFR in the past with an antibody drug conjugate. We selected a metuzumab-derived EGFR antibody to minimize off-tumor skin toxicity and to maximize the therapeutic window. Also, the epitope is distinct from that of FDA-approved EGFR antibodies minimizing the likelihood of resistance to prior EGFR antibody treatment. The proprietary linker allows for liposomal cleavage of the linker payload like other D-Rox-Tcan ADCs, but the stability of the linker antibody has been enhanced to minimize systemic payload release. The molecule also contains a proprietary Topol-1 inhibitor payload. It has an antibody drug ratio of 8, and the payload has similar direct cytotoxic potency, but it has enhanced bystander activity compared to D-Rux-C-Can. On slide 35, we show the phase 1 design. This is an ongoing study, and the study is designed for dose escalation, dose exploration, and expansion cohorts. The study is limited to patients who have lung cancer, head and neck cancer, colorectal cancer, or esophageal cancer, as EGFR expression is higher in these indications. And in this study, we're also making very good progress with enrollment. We are certainly on track to achieve our stated milestone of reporting initial safety data within the second half of 2026. We previously publicly released information that we began dose escalation at one milligram. We then said we escalated to two milligrams, and then we announced that we had escalated to four milligram per kilogram dose cohort. But as we advanced the enrollment and dose escalation in this trial, we are now shifting from providing granular updates to reporting initial safety data in the second half of 2026. And I'll now turn the presentation back to Jason.

Thanks, Barb. And also a big thank you to Dr. Herberts for joining us today to share her views. At ALX, we're advancing two novel cancer treatments with key near-term catalysts that have the potential to be both best-in-class and first-in-class and change care. And with this new data today, we have now demonstrated in two studies and two HER2-positive cancers that EVO is a very active drug and that a CD47-targeted approach can drive transformational benefit to patients. And again, although not the focus for today, we remain as excited about the potential of our EGFR-targeted ADC, which is also progressing quite well. We now have a stronger balance sheet to fully execute through key milestones over the next two years, and this really sets us up well for further execution and further catalysts. In sum, Q1 was a strong quarter for us in terms of new data, new leadership within our team, and a new financing. So the message for today is one of building momentum as our conviction in both programs remains high, and we're looking forward to additional updates very soon. with that I'll turn the call back over to the operator for questions and again thanks again for the time this morning thank you we will now be conducting a

question-and-answer session if you would like to ask a question please press star one on your telephone keypad a confirmation tone will indicate your line is in the question queue you may press star two if you would like to remove your question from the queue for participants using speaker equipment it it may be necessary to pick up your handset before pressing the star keys. Again, that is star one to ask a question.

And our first question will come from Michael Yee with UBS Securities.

Hey, guys. Thanks for taking our questions. Congrats on the updates and progress. This is Kyle Yang for Michael Yee from UBS. Two for us. The first question for management. So, congrats on the data today. So, for your upcoming interim data readout, in mid-2027 from your ongoing Phase II Aspen breast study. What would you say is compelling results in terms of ORR and also DOR? And do you plan to put out data on NPFS? And what would be good data for NPFS? The second question for Dr. Hurwitz, Could you please help us understand how do you plan to use this drug in the clinical setting if this is approved? Do you expect to test everybody for CD47 expression? Thank you.

Appreciate the question. So, yeah, on the first one, and I'll let Barb weigh in as well, I think, you know, we've been very pleased with enrollment to date on our breast study. It's going quite well. certainly this data, which we've been able to share just over the last couple months with the investigators, has furthered that enthusiasm. So I think as Barb highlighted well in her comments, feel very good about our timelines and delivering really meaningful data mid-27. But Barb, do you want to weigh in more on just, you know, what we hope in terms of durability and PFS at

that time. Yeah, absolutely. Well, as Dr. Hurwitz said, most of the available therapies are not producing very good outcomes for patients after Inher2. Much of the data suggests that the response rate may be 15% if you were to receive a trastuzumab chemotherapy treatment alone without Avorpicep. So, a 30% percent response rate would be a doubling of what we would expect to see without the Avorpicep. So, I think anything north of 30% would be a very, very good outcome with a duration of six months plus. As you've seen in the data that we reported previously, one of the things that's so compelling about Vorpicep is that when we see a response, we see a very good duration of response. By middle of 2027, I think the duration of response will be pretty preliminary. So, I'm expecting that with 80 patients' worth of data, that we can assess response rate pretty well. Duration of response may be somewhat truncated, but I would hope to see somewhere in the range of six months plus with immature data. And I would think that PFS might be too immature to report, but it really depends on the continued progress. So, we'll have to see. Yeah, and Dr. Hurwitz, whether you have comments on your expectations for the ASPEN-9 data or in particular the second part of the question about the role of CD47 testing in the clinical practice if a Vorpicep is able to get to market. Yeah, thank you, Barb. I fully agree

with what you stated about the ASPEN-09 study. I mean, I think seeing anything around 30% objective response rate and a PFS of six months would be pretty important in patients this heavily pretreated. So, I echo your comments. In terms of the additional question regarding how we would use CD47 expression, you know, I think this is something that's really very compelling and interesting, and the OSPEN-09 study is going to allow patients, as Barb stated, with both CD47 low and high tumor expressions so that we can validate these data. We have to keep in mind it was a small number of patients, but the data were really pretty interesting and compelling. So So if CD47 is validated as being a predictive marker for benefit from a Vorpicep, then I do think we will be probably seeing it developed as a companion diagnostic. But it's too little data at this point to see, you know, to make that statement definitively that that's how we'll be using it. I've been treating breast cancer patients for over 20 years, and the data within HER2 were really exciting when we first saw them come out in 2019. I feel that same flurry of excitement seeing these data because it's pretty tough to treat patients post-TDXD now, Their progression-free survival, their duration of response to the next line of therapy is pretty short. And so, these data provide patients a lot of hope. So, I'm excited to see the data validated, just taking into consideration that it is a small number of patients.

Really helpful. Thank you, guys. Thanks, Kyle.

And our next question will come from Derek Archillo with Wells Fargo.

Hey, good morning, and congrats on the update here. Just a few questions from us. I think, you know, first, you alluded in the prepared remarks, but just remind us, you know, the population in Aspen09 and then how it compares to some of the patients from the update today. That would be helpful. And then just two quick ones. So, I think you mentioned the 20,000 patients CD47 high post and HER2. So, does that assume, you know, greater than 20% CD47 expression? or I just want to make sure the cutoff is the same? And then with the data here and the proof of concept with the ZANI combo, I guess, you know, how do you think about further developing this?

Yeah, sure. Those are great questions. Thanks, Derek. So I think, you know, in terms of the population that we're studying now, you know, it is this population. That's what I think really de-risks, if you will, this current study. You know, I think as we walk through today, this is a late-line breast population. 100% of the patients in this cohort had seen prior in HER2, you know, on average had seen five prior lines of HER2-directed therapy, et cetera. So, you know, I think the beauty of this design that we're pursuing now is it's effectively the same. So I do think that definitely contributes to our confidence in this study. Then on the second question, and I can have Barb weigh in on this, you know, I think we do know from the literature, we expect that the expression profiles will be different across different tumor types. That's certainly what we've seen when we look at breast and gastric. But again, I think what's so encouraging is that, you know, there's just a lot of room here in terms of choosing a cutoff, if you will. So, Barb, do you want to speak to that a little more?

Yeah, I think one of the most important things about what we will understand with data from Aspen09 is what's the optimal cut point? Where on the total membrane staining scale would we see the greatest differential between high response rate and the CD47 positive versus CD47 low? And it's likely to be a continuum, and we're likely to be able to not see a cliff where it's crystal clear. What we've seen in both the gastric and the breast study, though, is we're seeing about half of patients overexpress CD47, at least in our gastric study with a larger sample size we shared at CITSI in the fall of 2025, a variety of different cut points that ranged from 45 to 57%. Gastric may be different than breast, though. And so with the ZANI data, we have just such a small number of patients. So, but what we saw in the ZANI trial, again, about 50% were CD47 high. One of the biggest reasons we increased the sample size from 80 to 100 is just so that we could get more data because this point exactly, what is the cut point? How does it differentiate response rates? And what does it do to the population in terms of potential commercial opportunity balanced against, you know, finding the best treatment effect for patients is a really important question. So Aspen09 will help us optimize the cut point. My best guess today is it'll be somewhere in the range of 50, 60, 70% of patients could be CD47 overexpressing, but we'll see. What also, of course, are the two slides that Dr. Hurwitz showed where the rates are higher in patients who have more advanced disease. They are higher in the cell lines post in HER2, and they are higher in patients who are HER2 positive. So it could even be higher than 50%. We'll, you know, we'll learn a lot from the Aspen09 on that

exact question. And I think your last question, Derek, just on Zannie, you know, a couple comments there. I think one, really pleased with the partnership with JAS and what we're seeing here for patients. I think, you know, no question, the very strong activity with this combination. You know, the second thing, and I think why it's important to look back at our mechanism is Evo works in combination with an FC active antibody, and it was designed to do so. And so I think what's really promising about the totality of the data is whether we're combining Evo with TRAS, with ZANI, with Rituxan, with an anti-CD38 like CERCLEZA, you know, we see activity. And I think that's right on mechanism. And so for us, taking the combination of EVO plus TRAS going forward makes sense. Again, it's the exact same combination that we utilized in our Aspen 6 study, which is a randomized study, as you know. So I do think that gives us a lot of conviction here going forward.

Incredibly helpful.

Thanks again.

Thanks, Derek.

Moving next to Allison Bretzel with Piper Sandler.

Good morning, team. This is Ashley on for Allie. Just two questions from us. So just curious to learn what's the latest on the companion diagnostic development. I know you guys have talked about this on previous earnings calls. So just looking for some updated thoughts there. And also, you know, just based on the data today and this data set, you know, it looks like the CD47 biomarker strategy, you know, is being further validated. So does this impact the statistical powering at all for ASPIN 09?

Sure. Yeah, that's a great question. Do you want to go on the CDX front, Barb?

Yeah. Sorry, Jason. Yes, the Ventana Laboratory is our partner. We are working right now on developing a companion diagnostic. What we want is by the time we are finishing the full data set of ASPIN-09, as I alluded to earlier, setting a cut point that could then be available for pre-selection of patients potentially in a Phase III trial. That's our base case assumption is that our Phase III would be in pre-selected patients. So, we will have an assay available, and then if that FEZ-3 study is positive, of course, then we would work with our Ventana partner to not only bring the Vorpicep to market, but to ensure that the companion diagnostic were then commercially available. In terms of statistical powering, go ahead, Jason.

No, go ahead, Bob. I just, I mean, to kick that off, I mean, I think, you know, of course, we're not going to power the study at 100% ORR, and that's not what we're going to do. And I think, you know, but if you look at the beauty of a targeted approach, I think it allows and our hope is it'll allow a much more targeted phase three where we can run a tighter registrational study with assumptions that, you know, I think are reflective of what we've seen, which has been a really strong, you know, spread, if you will, both in terms of ORR as well as DOR and PFS. But go ahead, Barb. I know I cut you off there.

No, no, that's exactly right. I think with a single-arm trial, ASPIN-09, the statistics are really around estimating the point estimate of a response rate and narrowing the confidence intervals with a larger sample size. But what ASPIN-09 does is it allows us potentially greater precision with this larger trial of 120 patients such that we can then have a lot of confidence walking into a FEZ-3 subsequently and really understanding the treatment effect in patients based on their CD47 status.

That was really helpful. Thank you. Moving next to Lee Watzek with Banter.

Hey, this is Daniel Branderon for Lee Watzek. Thank you for taking our questions. We have a couple, one more technical and then one regulatory. We'll start with the technical one. On the poster from ESMO breath, you have the concordance of HER2 amplification by CTDNA and FISH. I was just curious how that translates into HER2-positivity in IHC. And then on the regulatory front, you mentioned registrational trials a few times in your opening remarks and the previous response as well. Does that mean you're ruling out a potential accelerated approval based on ASPIN 09, or are you keeping optionality here? Thank you.

Yeah, sure. Those are great questions. Thanks. Go ahead.

I'm sorry. I should stop doing that. And Dr. Hurwitz, I'll have you make some comments after I'll address the regulatory one first, give you a chance. But I'll have you talk a little bit to the HER2 data that was in the poster. So the regulatory strategy, Jason said a few minutes ago that we do not have an expectation that we could replicate 100% response rate. That would be fabulous if we could, and if we do, I think absolutely we would talk to the health authorities, US FDA, about an accelerated approval strategy. I just think that that is such a high bar, and we're also very, very aware that an advantage for patients would be anything north of, say, 30%. So we'll just have to wait and see what the response rate is in ASPIN-09. I think regulatory approvals for single-arm trials, when you have a combination of two agents, very difficult to get an accelerated approval. It's also true that it's very difficult to get an accelerated approval with retrospective application of a companion diagnostic. We would need at least some additional prospectively selected patients. So there are a lot of regulatory considerations. But I think, you know, at this case, that is not our base case. Our base case is that a phase three trial will be required because the bar is high for accelerated approval, but we'll just have to wait and see what the response rate is. If it's extraordinary, we'll talk about it. If it's somewhere north of 30%, but less than a hundred percent, you know, it's going to be an uphill battle, but obviously that would benefit patients if we could bring it to market sooner, but we'll wait and see. So maybe I'll flip it back to Dr. Hurwitz to talk

a little bit about some of this HER2 data in the poster? Yeah, thank you, Barb. The HER2 data is actually kind of interesting. So, there are two aspects. First, there was the difference in the central confirmation of HER2 positive disease that was shown in the poster where 10 of the patients out of the 24 were noted to have centrally confirmed HER2 positive disease and 14 were not. And I would just call out that, you know, this is not uncommon. It's been reported in other studies that there's discordance. And it may not necessarily mean that there's been HER2 loss that's occurred over time. It may actually be related to artifacts from testing older tissue. It's important to keep in mind that in order for patients to enroll in the study, HER2 status was based on archival tissue that was read locally, but once they got on the study, the assays that were done were done on fresh biopsy samples obtained at the start of the study from most patients, and those were tested centrally. And so the testing changed from local to central and also from archival tissue to fresh tissue after in HER2 for the vast majority of subjects. So, either of those factors could have contributed to the differences between local HER2 positive results and central positive results. Another point was in the poster in Table 2, there was some data presented looking at concordance between HER2 amplification status by the central tissue-based fish, as well is plasma ctDNA next generation sequencing, and it's important to call out that of the six patients with HER2 amplification by FISH, or excuse me, the seven patients, six of them were also noted to have amplification by ctDNA. Just one of the patients there did not, and that may have just been due to the fact that there wasn't enough circulating, there was a low tumor fraction that was below the threshold of expression. But those that were negative centrally by FISH were also negative by CT DNA. And so that's reassuring and provides sort of validation that the central HER2 amplification is correlating well with circulating tumor DNA.

We'll go to our next question from Roger Song with Jeffries.

Hey, team. Congrats on the positive data and excited about the momentum going into Aspen09. Maybe two from us. So you previously mentioned we're seeing roughly half of HER2 positive patients being CD47 high. As we're into the early Aspen09 screening, is the observation you're seeing consistent with that? half of HER2 positive patients being CD47 high. And then, you know, is tissue adequacy and turnaround time any potential gaining factor here for enrollment? Thank you.

Yeah, sure. Good question. So, I think on the Aspen 9 front, of course, we're going to, you know, monitor that closely. And then in terms of a disclosure, you know, we'll wait and disclose that when we get to the data readout on 80 patients. Obviously, I think it's something that's important, and we're able to monitor really quite quickly. So the lag has not been a concern, and, of course, I think our team is focused on that. But, Barb, do you want to add anything there?

Only that the ASPEN09 study enrolls patients irrespective of CD47, so there is no urgency in terms of the turnaround. You're absolutely right that it would be something that we need to ensure that we work through those processes for a future phase 3, assuming that that future phase 3 requires CD47 overexpression for entry. But this study does not, so the urgency is not there. But as Jason says, we're not going to disclose prevalence rates or any of the biomarker data until we come out with data in the middle 2027.

All right. Thank you. I'll go back to the queue.

Moving next to Sam Slutsky with LifeSci Capital.

Hi, this is Oliver McCammon on for Sam Slutsky. Thanks for taking our questions. So in the Phase I B2 breast cancer study, you defined CD47 high as total membrane staining of 20% or greater. And in the past, you talked about 10% or greater IHC3 plus as being a cutoff for CD47 high. Can you just discuss the nuances of the two cutoffs used and the selection process? Thanks again.

Thanks, Oliver. Again, I think Barb hit on this, but we fully anticipated, even ahead of this data, that the expression profiles would be different. There's, of course, a lot of similarities between her two positive tumor types, insofar as typically a drug that works in one will work in the other. That said, I think there will be a difference in expression, and we're seeing that here. And again, I would just highlight that, you know, if you think about defining a cutoff when you see ORR as high as we're seeing across both of those studies, you know, it suggests there's probably many different right answers, if you will, in terms of the cutoff we could use. But Barb, do you want to expand on that?

Just in terms of total membrane staining and how that's calculated, so the proportion of cells that are 1 plus or multiplied by 1, the proportion of cells that are 2 plus IHC staining intensity would be multiplied by 2 and so forth. So IHC3, multiply the proportion of cells that are IHC3+, and then you add those. So it's a cumulative total. So if I were to look at the threshold for gastric, 10% or more of cells being 3+, that would potentially be about a score of 30. It may be that different labs and slightly different methods. But to put it in context, it's similar, but the cut point was a little bit lower in the zanidatinib trial. It was a zanidatinib, Vorpicep was a very small trial. So we will look again once we have data from Aspen09 and optimize that. So it may change. In fact, that would likely change much, much for the sample size, but technically they're doing it. And then we modified the tech bit once we start to work towards development, hang and diagnose with our partners at Ventana.

Very helpful. Thanks, Oliver.

And this now concludes our question and answer session. I would like to turn the floor back over to Jason Leppman for closing comments.

Great. Thanks, everybody. It was a strong quarter for us. Appreciate all the engagement here today. Both programs, as we mentioned, are on track and super excited about what we're seeing in both. So, again, appreciate the questions and support. Looking forward to future updates. Enjoy your Friday and your weekend. Thanks so much.

Ladies and gentlemen, thank you for your participation. This does conclude today's teleconference. You may disconnect your lines and have a wonderful day.