ALXO

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 Lettmann, 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 gonna 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 dataset that was presented yesterday in Munich at ESMO Breast Cancer 2026 from the analysis of our trial evaluating evorpacept and zanidatamab, which clearly showed again that CD47 expression is a key predictive biomarker for increasing durable clinical response in heavily pre-treated HER2-positive patients.

This further validates the results we saw with evo and HER2-positive gastric cancer from our ASPEN-06 trial. We are also very excited today to be joined by Dr. Sara Hurvitz 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 Cancer data in detail and also share her views on evorpacept's significant potential within the current treatment paradigm for HER2-positive metastatic breast cancer. Our CMO, Barbara Klencke, will 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-09 breast cancer phase II trial. Barb will then provide an update from our ongoing phase I trial with our novel EGFR-targeted ADC, ALX2004, which also continues to track to plan. We are enthusiastic about its potential to also change care in EGFR-expressing cancers. On slide four, we continue to advance both our programs, evo and ALX2004, 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 12-18 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 5 different datasets, including randomized data. 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 ALX2004, 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 ALX2004 was designed to address this with a novel epitope and linker payload construct.

We have been pleased to see the strong pre-clinical data to date translate to the clinic and with the continued strong progress in dose escalation, where we have been able to further increase 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 observed 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 dataset with evo, ALX2004 is also progressing through dose escalation very well and remains on track for initial safety readout in 2nd 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. 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 that are staged 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 evorpacept 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. ALX2004, as I mentioned, is also progressing well with enrollment and dose escalation ramping and are on track there for an initial safety readout 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 and 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.

Again, ASPEN-09 is on track, and we continue to also be encouraged by our ongoing study with our partner Sanofi, testing evo in multiple myeloma. Our two studies in HER2-positive cancers have now been completed, as we'll focus on today, and ALX2004 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. We'll then turn the call over to Dr. Hurvitz to review the new data. Barb?

Thank you, Jason. These next few slides describe evorpacept'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. Let me just go through this. Cancer cells commonly upregulate CD47 expression to evade immune detection. Evorpacept blocks the CD47 signaling, but it does so without an active Fc domain. Evorpacept by itself does not engage the phagocytic activity of a macrophage. We need to combine evorpacept with an anticancer 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 evorpacept inhibits the don't eat me signal.

Therefore, the combinations of evorpacept 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 evorpacept-treated patients. It also, the clinical safety data is also entirely consistent with this mechanism of action that we show here. Evorpacept was designed again without an active Fc domain. That's shown on the right side of this slide. 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. With that description of evorpacept, its mechanism of action, and its differentiation, let me now turn the conversation over to Dr. Sara Hurvitz. On slide 12, you can see her background here. She is a steering committee member for our ASPEN-09 phase II study of evorpacept in HER2-positive breast cancer patients.

She was an investigator on the evorpacept and zanidatamab trial that we'll discuss today. 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. Sara?

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 deruxtecan and tucatinib demonstrating benefits in pretreated disease. With the results of DESTINY-Breast09 showing benefits with T-DXd 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 ENHERTU. 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 ENHERTU 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 T-DXd, but observational and retrospective datasets are fairly consistent, showing that PFS rates of under six months is what patients experience post-T-DXd. 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. 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. 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. HER2-positive breast cancer cells appear to have a lot more CD47 expressed than HER2-negative breast cancer cells. 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. These data provide strong rationale for us to be evaluating evorpacept in HER2-positive recurrent or metastatic pretreated disease.

On slide 19, you can see some elegant data demonstrating that T-DXd treatment may actually upregulate expression of CD47, again providing strong rationale to treat HER2-positive recurrent T-DXd pretreated breast cancer with evorpacept. 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 I-B/II trial of zanidatamab, a HER2-targeted bispecific in combination with evorpacept in patients with HER2-positive metastatic disease. Slide 21 gives you an overview of the study design. This is a phase I-B/II study, and we presented the safety dose escalation cohort data from three patients with HER2-positive breast cancer enrolled and data from cohort one, 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 T-DXd and a median of five prior lines of HER2-targeted therapies. This is extremely heavily pretreated 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. 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 zanidatamab at 1,200 mg for those patients weighing less than 70 kg and at 1,600 mg for patients 70 kg or greater. The evorpacept was given at 20 mg per kg for these three patients enrolled in the phase I-A 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 T-DXd.

As 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 centrally 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 T-DXd have a median PFS of less than six months. 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. 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.

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%, 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 phase I-B/II study. Evorpacept and zanidatamab showed promising antitumor activity in patients with heavily pre-treated HER2-positive metastatic breast cancer, median of five prior lines of therapy, all of whom received prior T-DXd. Greater antitumor 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 T-DXd, supporting the continued use of HER2-targeted therapies. A biomarker-driven approach incorporating CD47 may optimize patient selection for this combination regimen and warrants further study. With that, I will turn it back over to Barb.

Thank you, Sara, 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 evorpacept plus zanidatamab. 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 evorpacept and zanidatamab combination. In the last row in this table is a patient who was unevaluable for either response or CD47 expression level. On slide 28, I wanna highlight the consistency that we see between the results of the evorpacept-zanidatamab 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 for 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. 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 II study of evorpacept, trastuzumab, paclitaxel, and ramucirumab 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 evorpacept 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.

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 evorpacept when combined with a HER2-targeted antibody. On slide 29, I'm again showing the results of the evo-zani 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 both 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 evorpacept-zanidatamab study of 22.1 months. While the median PFS for those without CD47 expression was only 3.4 months. In the gastric study shown on the right, the median PFS was 18.4 months for the patients in the evorpacept arm, and the hazard ratio in this subset in the randomized trial was 0.39. These data are really why we're so excited about moving forward with the development of evorpacept in HER2-positive breast cancer. Slide 31 shows our ongoing ASPEN-09 study in the HER2-positive breast cancer setting.

Like the zanidatamab-evorpacept study population, all of these patients will have had to have had prior ENHERTU. 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 overexpress CD47, representing a $2 billion-$4 billion market opportunity in the United States, the five major European markets and Japan.

I'm now gonna turn for the last few minutes of this talk to our second molecule. Slide 34 shows ALX2004, our EGFR antibody drug conjugate. This is actually a very unique molecule. It was designed by protein engineers and cancer biologists 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 matuzumab-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 deruxtecan ADCs, but the stability of the linker antibody has been enhanced to minimize systemic payload release.

The molecule also contains a proprietary TOPO1 inhibitor payload. It has an antibody-drug ratio of eight, and the payload has similar direct cytotoxic potency, but it has enhanced bystander activity compared to deruxtecan. On slide 35, we show the phase I design. This is an ongoing study. 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. 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 1 mg.

We said we escalated to 2 mg, then we announced that we had escalated to 4 mg per kg dose cohort. As we advance 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. I'll now turn the presentation back to Jason.

Thanks, Barb. Also a big thank you to Dr. Hurvitz 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. With this new data today, we have now demonstrated in two studies in two HER2-positive cancers that evo is a very active drug and that a CD47-targeted approach can drive transformational benefit to patients. 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 one year to two years, 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. 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. 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 may be necessary to pick up your handset before pressing the star keys. Again, that is star one to ask a question. 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. Congrats on the data today. 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? Do you plan to put out data on mPFS? What would be good data for mPFS? The 2nd question for Dr. Hurvitz. 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.

Great. Thanks, Kyle. Appreciate the question. 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. I think as Barb highlighted well in her comments, feel very good about our timelines and delivering really meaningful data mid-2027. Barb, do you wanna weigh in more on just, you know, what we hope in terms of durability and PFS-

Yeah

at that time?

Yeah, absolutely. Well, as Dr. Hurvitz said, most of the available therapies are not producing very good outcomes for patients after ENHERTU. Much of the data suggests that the response rate may be 15%, if you were to receive a trastuzumab chemotherapy treatment alone without evorpacept. A 30% response rate would be a doubling of what we would expect to see without the evorpacept. 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 evorpacept 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. 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. I would think that PFS might be too immature to report, but it really depends on the continued progress. We'll have to see. Yeah, Dr. Hurvitz, whether you have comments on your expectations for the ASPEN-09 data, or in particular, the 2nd part of the question about the role of CD47 testing in the clinical practice, if evorpacept is able to get to market.

Yeah. Thank you, Barb. I fully agree with your 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 pre-treated. 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. The ASPEN-09 study is gonna allow patients, as Barb stated, with both CD47 low and high tumor expression 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.

If CD47 is validated as being a predictive marker for benefit from evorpacept, 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 doing it, using it. You know, I've been treating breast cancer patients for over 20 years, 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-T-DXd now. Their progression-free survival, their duration of response to the next line of therapy is pretty short.

These data provide patients a lot of hope. 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.

Our next question will come from Derek Archila with Wells Fargo.

Hey, good morning, congrats on the update here. Just a few questions from us. I think, you know, first, you alluded in the prepared remarks, just remind us, you know, the population in ASPEN-09 and then how it compares to some of the patients from the update today. That would be helpful. Then, just two quick ones. I think you mentioned the 20,000 patients CD47-high post in HER2. Does that assume, you know, greater than 20% CD47 expression? I just wanna make sure the cutoff is the same. 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? Thank you.

Yeah, sure. Those are great questions. Thanks, Derek. 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 ENHERTU. You know, on average, it's seen five prior lines of HER2-directed therapy, et cetera. You know, I think the beauty of this design that we're pursuing now is it's effectively the same. I do think that definitely contributes to our confidence in this study.

On the 2nd question, and I can have Barb weigh in on this, you know, I think we do know, and 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. 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. Barb, do you wanna speak to that a little more?

Yeah. I think one of the most important things about what we will understand with data from ASPEN-09 is what's the optimal cut point? Where on the total membrane staining scale would we see the greatest differential between high response rates in the CD47 positive versus CD47 low? It's likely to be a continuum, and we're likely to be able to not see, you know, 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 SITC in the fall of 2025, a variety of different cut points that ranged from 45-57%. Gastric may be different than breast, though.

With the ZANI data, we have just such a small number of patients. 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. ASPEN-09 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 gets, of course, are the two slides that Dr. Hurvitz 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. It could even be higher than 50%. We'll, you know, we'll learn a lot from the ASPEN-09 on that exact question.

I think your last question, Derek, just on zani, you know, a couple comments there. I think one, really pleased with the partnership with Jazz Pharmaceuticals and what we're seeing here, for patients. I think, you know, no question that 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. I think what's really promising about the totality of the data is whether we're combining evo with trast, with zani, with RITUXAN, with an anti-CD38 like SARCLISA. You know, we see activity, and I think that's right on mechanism. For us, taking the combination of evorpacept plus trastuzumab going forward makes sense.

Again, it's the exact same combination that we utilized in our ASPEN-06 study, which is a randomized study, as you know. I do think that gives us a lot of conviction here going forward.

Incredibly helpful. Thanks again.

Thanks, Derek.

Moving next to Allison Bratzel with Piper Sandler.

Good morning, team. This is Ashley on for Ally. Just two questions from us. 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. Just looking for some updated thoughts there. 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. Does this impact the statistical powering at all for ASPEN-09?

Sure.

Um-

Yeah. Great question. Do you wanna go on the CDX front, Barb?

Sorry, Jason. 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 ASPEN-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 preselected patients. We will have an assay available, and then if that phase III study is positive, then we would work with our Ventana partner to not only bring evorpacept to market, but to ensure that the companion diagnostic were then commercially available.

And I know-

Statistical powering oh, go ahead. Go ahead, Jason.

No, go ahead, Barb. I mean, to kick that off.

Okay

I mean, I think, of course, we're not gonna power the study at 100% ORR, and that's not what we're going to do. I think 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 III, where we can run a tighter registrational study with assumptions that I think are reflective of what we've seen, which has been a really strong spread, if you will, both in terms of ORR as well as DOR and PFS. Go ahead, Barb. I know I cut you off there.

No, no. That's exactly right. I think with a single arm trial, ASPEN-09, the statistics are really around estimating the point estimate of a response rate, and narrowing the confidence intervals with a larger sample size. What ASPEN-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 phase III subsequently, and really understanding the treatment effect in patients based on their CD47 status.

Got it. This is really helpful. Thank you.

Moving next to Li Watsek with Cantor.

Hey, this is Daniel Bronder on for Li Watsek. 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 Breast, you have the concordance of HER2 amplification by ctDNA and FISH. I was just curious how that translates into HER2-positivity in IHC. On the regulatory front, you mentioned registrational trials a few times in your opening remarks and in the previous response as well. Does that mean you're ruling out a potential accelerated approval based on ASPEN-09, or are you keeping optionality here? Thank you.

[crosstalk] Yeah, sure. Those are great questions. Thanks. Go ahead.

I'm sorry. I should stop doing that. Dr. Hurvitz, I'll have you make some comments after I'll address the regulatory one first, give you a chance. I'll have you talk a little bit to the HER2 data that was in the poster. The regulatory strategy, Jason said a few minutes ago that we do not have an expectation that we could replicate a 100% response rate. That would be fabulous if we could, and if we do, I think absolutely we would talk to the health authorities, U.S. 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%.

We'll just have to wait and see what the response rate is in ASPEN-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. There are a lot of regulatory considerations. I think, you know, that is not our base case. Our base case is that a phase III 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 100%, you know, it's gonna be a, an uphill battle, but obviously that would benefit patients if we could bring it to market sooner. We'll wait and see. Maybe I'll flip it back to Dr. Hurvitz 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. 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. I would just call out that, you know, this is not uncommon. It's been reported in other studies that there's discordance. It may not necessarily mean that there's been HER2 loss that's occurred over time. It may actually be related to artifact 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.

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. The testing changed from local to central and also from archival tissue to fresh tissue after ENHERTU for the vast majority of subjects. Either of those factors could have contributed to the differences between local HER- positive results and central positive results. Another point, it was in the poster in table two, there was some data presented looking at concordance between HER2 amplification status by the central tissue-based FISH as well as plasma ctDNA Next-generation sequencing.

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. It was below the threshold of expression. Those that were negative essentially by FISH were also negative by ctDNA. 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 Jefferies.

Hey, team. Congrats on the positive data and excited about the momentum going into ASPEN-09. Maybe two from us. You previously mentioned we're seeing roughly half of HER2-positive patients being CD47-high. As we're into the early ASPEN-09 screening, is the observation you're seeing consistent with that half of HER2-positive patients being CD47-high? You know, is tissue adequacy and turnaround time any potential gaining factor here for enrollment? Thank you.

Yeah, sure. Good question. I think on the ASPEN-09 front, of course, we're gonna, you know, monitor that closely. Then in terms of a disclosure- You know, we'll weigh it and disclose that when we get to the data readout on 80 patients. Obviously, I think it's something that's important and, you know, 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. Barb, do you wanna add anything there?

Only that, the ASPEN-09 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 III, assuming that that future phase III requires CD47 overexpression for entry. This study does not, so the urgency is not there. 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 20 of 2027.

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

Thanks.

Moving next to Sam Slutsky with LifeSci Capital.

Hi, this is Oliver McCammon for Sam Slutsky. Thanks for taking our questions. In the phase I-B/II 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 IHC 3+ as being a cutoff for CD47 high. Can you just discuss the nuances of the two cutoffs used and the selection process? Thanks again.

Sure. 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 HER2-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. 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. Barb, do you wanna expand on that?

Just in terms of total membrane staining and how that's calculated, so the proportion of cells that are one plus are multiplied by one, the proportion of cells that are two plus IHC stained, staining intensity would be multiplied by two and so forth. IHC three, multiply the proportion of cells that are IHC three plus by. You add those, so it's a cumulative total. If I were to look at the threshold for gastric, 10% or more of cells being three plus, 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 a cut point was a little bit lower in the zanidatamab trial.

It was zanidatamab, evorpacept was a very small trial, so we will look again once we have data from ASPEN-09 and optimize that. It may change. In fact, I would imagine likely change with a much larger sample size, but technically are doing it. We modify the tech bit once we start to work towards development and hanging diagnose our partners at Ventana.

Very helpful. Thank you.

Thanks, Oliver.

This now concludes our question and answer session. I would like to turn the floor back over to Jason Lettmann 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. 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.

Greetings, and welcome to the ALX Oncology Holdings Inc. Fourth Quarter 2025 Financial Results Call and Webcast. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. As a reminder, this conference is being recorded. I would now like to turn the call over to your host, Jason Lettmann, Chief Executive Officer. Thank you. You may begin.

Thank you, and welcome to our Q4 and fiscal year 2025 results call. We appreciate you all spending some time with us this morning. As usual, we will be making forward-looking statements during the call, so please refer to our FOS slide in our corporate deck. With me today, we have Harish Shantharam, our CFO, as well as our CMO, Dr. Barbara Klencke. And in terms of the first bit of news, we are delighted to announce today that Barbara will continue leading our clinical efforts as our permanent Chief Medical Officer. Welcome, Barbara. As many of you know, after joining in an interim capacity in September 2025, Barbara has been absolutely instrumental in driving our development programs forward over the last five months. Barbara, as many of you also know, is an incredibly experienced oncologist and drug developer, having served as CMO at Sierra Oncology and having senior roles at both Onyx and Genentech before that. We are beyond fortunate to add Barbara during this critical inflection for the company and thrilled to welcome her permanently. I will turn the call over to her later today to walk through some of our clinical updates. In terms of the agenda and the goals for today, we will review our key Q4 2025 and year-to-date accomplishments referencing our press release and corporate deck available on our website. Then, at the end, we plan to open it up for any questions you may have. In general, our focus at ALX Oncology Holdings Inc. remains on execution. We have made great progress on both of our programs of vorpercept and ALX 2004 in 2025 and positioned ourselves to achieve significant catalysts from these programs in the coming 12 to 18 months. Our goal and vision for each is to advance both programs to a stage where they are ready for pivotal studies by the end of next year. Execution has been strong over the last quarter, and I am very pleased to report that our clinical development progress and timelines remain on track. In terms of evorpicept, or EVO, in 2025, we are coming off a year of massive amounts of data really demonstrating the potential for evorpocept across a variety of combos and tumor types, which well informed our development strategy for EVO today. We have treated over 750 patients with EVO to date and are now highly confident where the drug works and, most importantly, where it works best. The MOA of combining EVO with antibodies and bispecifics has been well validated in the clinic and will pave the way for us going forward. Importantly, CD47’s key role as a biomarker for increasing durable response with avoricept in HER2-positive gastric cancer patients was further strengthened and validated by additional data in November at the SITC meeting. Here, we shared further data from our gastric study demonstrating a transformative benefit for patients both in terms of durability and PFS. In addition, we recently shared top-line data from the phase 1 of vorprecept and zanidatumab breast cancer trial, which is now a second dataset validating the role of CD47 and its importance as a biomarker. The follow-up analysis of this trial from the HER2-positive cohort showed that the responders to this combination treatment in a post-in-HER2 setting were largely restricted to CD47 overexpressors, which is a similar finding that we had in our gastric study. Full biomarker analysis from this trial is expected to be presented at a medical conference in Q2 of this year. These findings taken together strengthen our confidence in the ongoing phase 2 ASPEN-9 breast trial, where we will evaluate patient responses by CD47 level to further define the predictive potential of this biomarker among patients with HER2-positive disease that have progressed following in-HER2. We launched the study last year and continue with site activation globally at a strong pace. We remain on track with our clinical timelines here and expect to provide top-line data for 80 patients from this study in mid-2027. As shifts to the treatment landscape occur in breast cancer, EVO has the potential to provide both a best and first-in-class option for the 50,000 patients in the second-line-plus breast cancer setting. EVO is also poised to be the only therapy that can address CD47 expression in this large patient population. Overall, the results for EVO from these two HER2-positive cancer trials support the potential for us to pursue a targeted oncology approach to additional tumor types with EVO. And given the broad over CD47 in both solid tumors and heme malignancies, it gives us a real opportunity to pursue a focused development strategy for EVO in combination with anticancer antibodies and bispecifics. We are excited about our study in breast and also excited about the NHL data, which we recently shared in December, which furthers the findings of EVO into heme malignancies. We are also ongoing partnering with Sanofi and we are excited about what we are seeing across both of those studies, and Barbara will go into both in more detail. In terms of 2004, turning to our ADC now, we are also very pleased with the clinical progress of ALX 2004, which, as you know, is our novel and potentially best-in-class EGFR-targeted ADC. We cleared the first two dose cohorts and continued to progress development per plan with the 4 mg/kg dose now in the phase 1 trial. We are now expecting full ALX 2004 safety data from the dose-escalation cohort later this year in the second half of 2026. The potential of these two novel therapies, coupled with our substantial progress on their respective clinical programs, contributed to the successful completion of our recent financing of $150,000,000, which we closed a few weeks ago. With our newly strengthened balance sheet, we now have the opportunity to deliver more robust and meaningful data readouts in both of our ongoing clinical programs as reflected in our milestone updates here. Our mission again is to have these two programs ready for a pivotal phase study by the end of next year, and we believe we can do so with continued focus on execution. I will now turn it over to Barbara to walk through some clinical data and findings and plans in more depth. Barbara?

Thank you, Jason. Let me start with some quick highlights of the strong results that we have seen with avorpicep in two HER2-positive breast cancer indications that we have reported on within the past three months. I am referring now to slides 14 to 18 in our corporate deck. In the randomized phase 2 HER2-positive gastric cancer study, we saw impressive response rates with the vorapicep when combined with a trastuzumab-based regimen in the subset of patients with CD47 tumors. We reported this data at the SITC conference in November 2025. In this subset, the response rate was 65% in second- and third-line gastric cancer patients compared to 26% in the control arm. This is a delta of nearly 40%. The median duration of response was also quite impressive. It was more than two years, and more than three times longer than that seen in the control arm. The median PFS was 18.4 months in the avorpecep arm and seven months in the control arm, with a hazard ratio of 0.39. And finally, the median overall survival was 17 months with evorpazep versus approximately 10 months in the control arm, with a hazard ratio of 0.7 in this subset. In summary, this randomized study established the potential for CD47 to become an important predictive biomarker. In parallel, we worked with our partners at Jazz to evaluate the CD47 expression in patients enrolled in the phase 2 study of aborpicep in combination with zanidatinib. As a reminder, this study enrolled HER2-positive breast cancer patients who had progressed on prior HER2-directed therapies, all of whom had received prior in-HER2. We first reported data from the study at the San Antonio Breast Conference back in December 2024. As you can see on slide 22 in our corporate deck, at that time, we reported that in the nine late-line patients with confirmed HER2 expression by central assessment, the response rate with the vorpocept plus anadaptinib was a remarkable 56%. The duration of response at that time ranged from 5.5 to nearly 26 months, and the median PFS was 7.4 months. These data compared very favorably to benchmark data such as the data from the SOFIA trial, a predominantly second- and third-line HER2-positive breast cancer trial, which produced a response rate of 22% for margetuximab, whereas this data was obtained in patients who had a median of six prior lines of therapy. Now recently, in January, we concluded the CD47 biomarker analysis from these patients. We recently announced that the responders were predominantly restricted to the patients who overexpressed CD47. Full biomarker analyses from this trial will be presented at the ESMO Breast Cancer Conference in 2026. The data from these two independent studies show the potential of avorpicept to drive very substantial benefit for patients with high CD47 expression. These extraordinary outcomes clearly validate avoricep’s mechanism of action and provide increased confidence for our ongoing phase 2 breast cancer study. Before I provide an update on our ongoing phase 2 breast cancer study, I also want to highlight the results that we have seen so far in the hematologic malignancy setting. These data are summarized on slide 13 in our corporate deck. In three separate cohorts of indolent non-Hodgkin’s lymphoma patients, we see very high complete response rates relative to published CR rates in relevant benchmark studies. The most recent study was presented at ASH in December. These were in treatment-naive, first-line indolent lymphoma settings. These patients received evorbicep combined with Rituxan and Revlimid, known as the R-squared regimen. They achieved a complete response rate of 92%, which is almost double that seen with R-squared alone. These data are entirely consistent with the two studies of evorpocept with Rituxan or R-squared in previously treated indolent lymphoma patients where the CR rates were also extremely robust and more than double the CR rates enveloped in relevant benchmark studies, as you can see on the slide. Together, these five datasets strongly support the potential of a vorpa set to enhance macrophage-driven ADCP when combined with an Fc-active anticancer antibody. These data give us high confidence for our ongoing study in HER2-positive breast cancer. Let me now provide some quick updates on that study. The design of the study is provided on slide 23 of our corporate deck. As a reminder, in this study, we evaluate avoricep in combination with trastuzumab and single-agent chemotherapy in a single-arm design enrolling HER2-positive metastatic breast cancer patients who have progressed on in-HER2. Following the strong validation of CD47 as a predictive biomarker of benefit with avoracep plus anadaptinib, we have now decided to enlarge the current phase 2 study to up to 120 patients from 80 to increase the number of HER2-positive patients with CD47 overexpression. In addition, we are updating the primary endpoint to response rate in patients who have high CD47 expression. A key secondary endpoint will track response rate by HER2 status informed by ctDNA. This way, we will be able to track response rates both by CD47 expression on its own as well as in double-positive patients informed by high CD47 expression and HER2-positive status. As in-HER2 has now been approved as first-line therapy, the treatment landscape for the second line and subsequent therapies has entered uncharted territory. The optimal sequencing of subsequent therapies is unknown. Several real-world evidence studies suggest that response rates and PFS or time to next treatment might actually be lower than expected with available regimens in patients who have failed in-HER2 therapy. So we see a notable gap in the understanding of the optimal sequencing of available therapies and really a large unmet need for effective treatment options in this post–in-HER2 setting. Based on the activity that I have described to you for the avorpus app across a number of settings when combined with an anticancer antibody, we believe that avoricep has substantial potential for benefit in metastatic breast cancer patients in this setting. Furthermore, a CD47 biomarker-driven approach in HER2-positive patients could enable a highly targeted patient selection strategy. To be ready for a prospective selected registration study in the future, we have initiated work on developing a companion diagnostic for CD47 expression. With respect to enrollment in the ongoing phase 2 trial, we are making good progress. While we are still early in the enrollment curve, the site activations remain globally on track. We are pleased to see that investigator interest in the study remains strong. We project being able to share meaningful efficacy and safety data, including response rate, biomarker results, and early durability trends by mid-2027. Now let me turn our attention to the second clinical program, ALX 2000 and 4, our EGFR-targeted antibody-drug conjugate. While EGFR is a validated target, developing an effective ADC has remained a significant challenge due to the narrow therapeutic window. We have leveraged historic learnings to develop ALX 2000 and 4, our EGFR-targeted ADC, which was designed by our internal team of world-class protein engineer experts. The preclinical dataset is particularly exciting as it demonstrates potent, dose-dependent antitumor activity in numerous models across a broad range of EGFR expression levels and relevant mutations such as those in p53, KRAS, BRAF, and others. EGFR-related skin toxicity and interstitial lung disease were notably absent in our GLP tox studies in nonhuman primates. The antibody, metuzumab, has a unique affinity-tuned epitope whose binding to EGFR is not by mutations in the binding domain for the other approved EGFR antibodies. In creating this ADC, we combined this antibody, the metuzumab antibody, with our proprietary topoisomerase I inhibitor linker-payload, which was selected for linker stability and for its robust bystander effect. Given the attention paid to both efficacy and safety in the design of this molecule, we believe that ALX 2000 and 4 is uniquely positioned to break new ground as a potential first-in-class therapy for EGFR-expressing solid tumors. Additional preclinical highlights can be found on slides 26 to 33 in our corporate deck. I would also refer to the comprehensive preclinical data that was presented at the triple meeting conference in October 2025 and more recently at the 2026 World ADC Conference. Finally, in terms of progress in the clinic, we are currently enrolling patients in our third dose cohort, having initiated dosing initially at a robust dose of 1 mg/kg, then escalating to 2 mg/kg, and subsequently to 4 mg/kg based on seeing no DLTs at the prior dose levels. We believe that the 4 mg/kg dose, our current dose level, could potentially now be at the lower end of the therapeutic dose range. As a reminder, we are enrolling only patients who have non-small cell lung cancer, colorectal cancer, head and neck cancer, or esophageal squamous cell cancer, as these are EGFR-expressing tumor indications. In this phase 1 trial, we will perform both the dose-escalation as well as the dose-expansion component. These data will then ultimately set the program up to advance into a registration study. We plan to provide data from the dose-escalation portion of the ongoing phase 1 study in the second half of this year. With that, let me hand this over to Harish.

Thank you, Barbara, and good morning, everyone. 2025 was a year of strategic prioritization and clinical validation for ALX Oncology Holdings Inc., highlighted by the progress we made on our lead program evaporposet, and the clinical entry of our first ADC, ALX 2004. In terms of financials, we finished the fourth quarter of 2025 with cash, cash equivalents, and investments totaling $48,300,000 before strengthening the balance sheet from our equity financing we closed earlier this month in February. The net proceeds from the offering were $140,400,000 after deducting for the underwriting discount and other offering expenses. Following the cash inflow from this offering, we believe the cash and investments on hand are sufficient to fund ALX Oncology Holdings Inc. operating expenses through 2028. With our newly strengthened balance sheet, we now have the opportunity to deliver more robust and meaningful data readouts in both of our ongoing clinical programs over the next 12 to 18 months. The key milestones we currently guide to include: number one, the full biomarker analysis readout from our phase 1/2 trial evaluating evorpocept in combination with danitatumab in advanced HER2-positive breast cancer patients will be presented at the ESMO Breast Conference in May 2026; number two, the ALX 2000 and 4 safety data from the dose-escalation phase of the trial is anticipated in 2026; number three, the readout on evorposet top-line data from 80 patients from the ongoing phase 2 ASPEN breast cancer trial is anticipated in 2027. With respect to the latest quarterly financials, the GAAP net loss was $22,800,000 for the three months ended 12/31/2025, or $0.42 per basic and diluted share, as compared to a GAAP net loss of $29,200,000 for the three months ended 12/31/2024, or $0.55 per basic and diluted share. The decrease in year-over-year spend can be primarily attributed to lower stock compensation, lower personnel and related costs, as well as lower preclinical costs following pipeline prioritization. Please refer to the press release for the detailed breakdown on the R&D and G&A operating expenses for the quarter. Operationally, our team is now singularly focused on executing the ongoing phase 2 trial in breast cancer for evorpoced and the phase 1 trial for ALX 2004. Moving forward, the clinical spend will be largely driven by these two trials, partially offset by reduced spend in evaporizat legacy trials that are winding down. With that, let me hand the call back to Jason.

Jason?

Thanks, Harish. As we discussed, we are coming off a very strong 2025 where we had an incredible amount of data with evorbicept really demonstrating our path forward. We are also very pleased with the progress on ALX 2004. We continue to advance through dose escalation and are looking forward to significant catalysts across both programs over the next 12 to 18 months. Our focus internally remains on execution, and that is what we will plan to do going forward. We are very happy to remain on track in terms of the execution across both studies. We will now open for questions.

Thank you. If you would like to ask a question, please press 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question comes from the line of Allison Marie Bratzel with Piper Sandler. Please proceed with your question.

Hi, good morning, and thanks for all the updates, and thanks for taking the questions. Just some follow-ups from me on EVO. So I think initially, we were expecting an interim look at 80-patient readout this year. So could you just confirm, is that correct? And Barbara, I know you covered this in the prepared remarks, but just hoping you could talk some more to the rationale behind the upsizing to 120 patients, the change in the primary endpoint, and just talk to how that informs on the regulatory strategy. Then maybe just secondarily, what kind of feedback are you getting from investigators on the biomarker approach, and what do you expect to see on enrollment trends in ASPEN breast? Thank you.

Great. Thanks, Allison. I appreciate the question. I will let Barbara take the second question. On the first question, that is correct. We are guiding towards 80-patient full data from those 80 patients in mid next year. From our perspective, our goal internally and externally as well is to communicate full, robust data. At that point, we should have enough patients to really understand where the study is headed. We certainly are trying to guide to ensure we have enough CD47-positive patients in this study. As you know, the enrollment is essentially all comers. So guiding to the 80, we think, makes the most sense because we are confident at that point we will have real, fulsome data across both the CD47-high population as well as the other buckets that we will be looking at as well. That is the plan. Certainly, it is an open-label study. We have an opportunity to share earlier if we think it makes sense, as well as talk to regulators earlier, but the current plan is mid-2027. On your second question, Barbara, do you want to take that?

Yes. Addressing the interim, Jason just did that. Upsizing, again, Jason hinted at that, really just wanting to ensure robust numbers of patients in various segments and various subpopulations. We will have patients who can be confirmed HER2-positive in this setting by ctDNA or not. We will have patients whose tissue has evidence of overexpression of CD47 or not. We just want to make sure that we have robust numbers. I think the most important thing for this study could really be the optimal cut point. We have to be able to have data that drives the proposed cut point. FDA will be very interested in that. We just wanted to make sure that we had enough patients who were CD47 overexpressing that we can do that. In terms of a primary endpoint, it has always been a response-rate endpoint trial. In the two studies that we talk about, the gastric and the adaptinib combination, it has been pretty remarkable just how powerful CD47 is as a predictive biomarker. So I have moved that up to the primary endpoint, and response by HER2 status will still be an important key secondary endpoint, but we feel like the CD47 is going to be the most powerful predictor of response. That is the justification for changing the primary endpoint. You asked about the investigators’ perception of the study with a biomarker selection strategy. I think they are very excited about it. To have the ability to find a population for whom the therapy is going to provide substantial benefit, and what we have seen in all of our prior studies that I talked about today—lymphoma, gastric, breast cancer—we are seeing these remarkable response rates and we are also seeing durability. The two endpoints together are really providing transformational benefit. The ability to find the selected patient population where the treatment outcome can be so robust, I think—

Our next question comes from the line of Li Wang Watsek with Cantor Fitzgerald. Please proceed with your question.

Sure. Happy to do. Thanks, Daniel. As Barbara mentioned and we highlighted in our comments, both studies remain on track, and the execution has been strong. The change post financing here has been to ensure that we are communicating robust data. If you look at what we would have this quarter or next quarter versus towards the end of the year in 2004, it is really a step change in data. We should have, towards the end of the year, really fulsome data from the dose-escalation phase, and I think that will allow us to be much more clear about what we are seeing. Ideally, we will be able to communicate where we think the expected dose or two doses will shake out and allow us to communicate that externally. The goal is to make updates meaningful and full, and that is the thinking behind that guidance.

If I may follow up on this, is it safe to expect up to four dose levels to have been tested at the point when you make the disclosure?

I think that is reasonable. As you know, we went from one to two to four, so we have doubled now twice. We do think we are at the low end of the therapeutic window and continue to progress that study very well. The fact that we have cleared one and two so rapidly without seeing DLTs is encouraging. Certainly now in the four, things continue to go well, and I do think getting to four doses as part of that cohort is definitely a reasonable expectation.

Great. Thank you so much, and congrats on the update.

Thank you. Our next question comes from the line of Samuel Evan Slutsky with LifeSci Capital. Please proceed with your question.

Good morning, everyone. I appreciate the questions. Two for me. One is that for the 80 patients in ASPEN-9, remind me what is the expected ratio of those with CD47 high versus low expression? And then on 2004, on 4 mg/kg being at the lower end of the therapeutic dose range, looking at some of the other EGFR ADCs that are using topo 1, it seems like they are at either 4.8 mg/kg Q3W or less in terms of dose. Curious on what is driving this difference in where the therapeutic range starts with your drug, or is it that you would just consider that you have a wider therapeutic window, which hopefully leads to better efficacy versus others?

Thanks, Sam. I will take the first one, and Barbara can handle the second one on the range. In terms of the percentages, what is nice about CD47 is it is really well studied in the literature, and this specific question around CD47 expression has been well documented. We know in our gastric study that about half of those patients that were confirmed HER2-positive were CD47-high, and we looked, as you recall, across four different cutoffs and showed that range to be roughly 40% up to around 57% of the population. So a really substantial percentage. We also know from the literature that percentage is relatively consistent in breast. Again, we expect the cutoff and the expression profile to be different, but the patients that have CD47 high we expect it to be around half, and the literature would support that. It is important to run the study to see how that shakes out, but we are expecting to see a significant number of this population be CD47 overexpressors. Barbara, do you want to take the question on the therapeutic range with 2004?

Exactly. The highest nonseverely toxic dose in primates was 1 b, which is potentially around 6.5 mg/kg in patients. There is definitely variability on that, but that was one way for us to think about where we might be able to get the dose to. I think it will be data driven. I would never think that we would double again. We are now in a range where smaller incremental increases will be pursued. We will have to see how things go in terms of the tolerability and toxicity that we see in patients. We think somewhere in the range of the fours, five, six mg, maybe a bit higher, because, as you know, in the nonhuman primate data, there really was not any severe toxicity, so maybe we can go just a little bit above the six to seven range, but we will see. We will provide further updates later in the year, but that is the allometric scaling in terms of where we think we might start to see some toxicity.

Okay. Thanks.

Thank you. Our next question comes from the line of RK with H.C. Wainwright. Please proceed with your question. Thank you. Good morning, Jason and Barbara.

A couple of questions on ASPEN-09 and one on 2004. On ASPEN-09, as you are expanding the trial to 120 patients, trying to understand the logic behind it. Can you discuss what is the prevalence of CD47 high in post–in-HER2 patients, especially if you are defining CD47 high as IHC 3+ greater than 10%? Is this expansion driven more by statistical power, or are you concerned about lower-than-expected prevalence of the biomarkers? On the second one, when we start thinking about physicians’ choice of chemotherapy, should we be concerned about subsequent ADC use in this post-trastuzumab setting that it can impact the CD47 expression? And then on 2004, with the safety data expected in the second half, how are you monitoring the interstitial lung disease and the skin tox?

Those are great questions. Thanks, RK. On ASPEN-09 and CD47 expression post in-HER2, we think that the percentages should hold that I mentioned before. Roughly half of the population should be CD47 high. We did highlight in the past on our calls our recent study last year that showed that patients who are exposed to in-HER2 overexpress CD47. We think it is certainly possible that those numbers are higher in this population. We know that CD47 is a key mode of evasion post in-HER2, so we do think that is possible. Barbara, do you want to take the next one on the various chemo options and how that may impact things?

What we know in terms of CD47 expression, there is data in the literature that it rises in patients post in-HER2. We do not have a lot of other data. Most of the data on CD47 comes from survival tissue from the time of diagnosis. The literature does support higher rates of overexpression post in-HER2, which is absolutely perfect as our patient population. It is where there is an unmet need, and it is clearly the clinical setting that is the most wide open at this point in time. I am not sure that I have any concern that different chemotherapy drugs will perform differently in patients who have CD47 expression when they are combined with trastuzumab. Our main focus on mechanism of action is the combination of trastuzumab or some such antibody with an active Fc plus avorpazep. We certainly will look at the five different chemotherapy options across the different subsets if there are any major differences, but I am not expecting to see much variability there. In terms of ALX 2004, you asked about how we might be monitoring for both ILD and skin toxicity. Patients go through CT scans on a regular basis as per protocol, and a lot of times, that is where initial phases of interstitial lung disease may be detected. You do want to detect it before it gets too symptomatic, and having scans to watch for their cancer progression or response, that should be picked up. There are guidelines in the protocol. They are all very cautionary, just because this class of agents has in the past caused—you know, the payload itself has been associated with ILD—but we did not see any evidence of that in our nonhuman primate toxicology studies. We will monitor for it, but we have a low likelihood based on our NHP work. In terms of skin toxicity, certainly metuzumab was the antibody that we selected for the lower skin tox that has been shown clinically in the early investigational use of that metuzumab antibody. Every time a patient is seen in clinic, they will be examined and can report that, so that will be an early thing that we could pick up once we get into the various dose ranges. Our prediction is that we are not going to see skin toxicity at the lower doses. Certainly, cetuximab and panitumumab are known to have quite a bit more skin toxicity. If you were to do a cross-trial comparison of safety data from the approved antibodies versus metuzumab’s safety profile, that gives us a wider therapeutic window. We do not expect to be too limited by skin tox. It allows us to move up higher into the dose range, similar to the question that maybe Sam asked earlier about maybe having a wider therapeutic window for this agent based on the protein design that we have with this agent.

Thank you. Just on the sample size, there was no change in the assumptions in terms of the percentages or efficacy. There has been no change there. The driver is really to ensure that we have a very robust phase 2 and are in a position to de-risk the phase 3 as much as possible. The ability to flex up to 120 allows us to do that. Of course, as we mentioned, it is an open-label study. If we see data that is even in the ballpark of the 56% we saw and the 60% we saw in the breast and gastric studies respectively, I think we will have plenty of room to clear the hurdle. The goal of this is to inform the phase 3. Once we see a sufficient signal, that will then spur into action conversations with the regulators, moving quickly to a phase 3.

Fantastic. Thank you very much. Thanks to both of you for answering in detail.

Thank you. Our next question comes from the line of Roger Song with Jefferies.

Good morning, team. Thanks for taking our questions, and congrats on the updates. This is Nabil on for Roger. Question on the CD47 cut point. Maybe this was asked, but wanted to ask again: Is that IHC cutoff for ASPEN-9 primary endpoint already locked in, or could you talk about those prespecified decision rules you are using to select that cut point? And then on the IHC availability, how do you handle borderline cases with maybe some insufficient tissue? Is that ever a thing that comes up? Thank you.

Thanks, Nabil. On the CD47 expression, I would say what we know is that we would anticipate it to be different across different tumor types. We know gastric, as a baseline tissue type, expresses CD47 more highly than breast. With gastric, it effectively did not matter, meaning we could pick IHC 3, IHC 2/3, and continue to see a good response. The pre-Eval-plus-any study in breast informs that. We have a good estimate of how it could look, and going forward, it will be critical for us to run this study to really understand exactly where to set the cutoff. That is part of the goals of this current study that we are in the midst of, and I think that will be informative. In terms of the missing tissue or different tissue types, we do not anticipate that to be a significant issue, just because we are using tissue at time of diagnosis to base CD47. We expect CD47 to be relatively stable, and I think that should be pretty straightforward. Barbara, anything else to add on that?

No. I think everybody will be required to submit tissue. There is always an estimate in most trials that you might have some missing data. I would not expect it to be unusual. So 10% or less. We anticipate being able to have measurable CD47 in nearly all patients. It could be 100%, but I would not be surprised if we ended up with a rare patient for whom the tissue just was not sufficient, but that should not be a problem. IHC is a very standard assay methodology, so it is easy to perform, etc. So no major risks there.

Thank you. Ladies and gentlemen, that concludes our question-and-answer session. I will turn the floor back to Mr. Lettmann for any final comments.

Thanks, everybody. We appreciate the good engagement and questions this morning. It is an exciting time at ALX Oncology Holdings Inc. out in front of us, and we continue to execute well. We are looking forward to the next quarter and the next year where we have a lot of important milestones to lay out. We appreciate all the interest and support. Thank you.

Thank you. This concludes today’s conference. You may disconnect your lines at this time. Thank you for your participation.