ALX Oncology Holdings Inc. (NASDAQ:ALXO) Q2 2025 Earnings Call Transcript

ALX Oncology Holdings Inc. (NASDAQ:ALXO) Q2 2025 Earnings Call Transcript August 12, 2025

ALX Oncology Holdings Inc. misses on earnings expectations. Reported EPS is $-0.49 EPS, expectations were $-0.46.

Jason W. Lettmann: Thanks, everyone, and welcome to our Q2 2025 results. I appreciate everybody spending some time this afternoon with us and looking forward to this update. On Slide 2, before we start our presentation, as housekeeping, here are our forward-looking statements for your review. So, in terms of Slide 3, this is the agenda and plan for today. We’re going to be providing an update on our key accomplishments in the second quarter of 2025. Most notably, we are very excited to share with you new data from our analysis of ASPEN — our ASPEN-06 trial that showed CD47 expression as a key predictive biomarker for increasing clinical response with evorpacept. So our goals for today are, most importantly, to share this new data with you all, then give you a sense of how this data now impacts our development strategy for Evo, then provide a quick update on our novel EGFR-targeted ADC, ALX2004, which is set to enter the clinic imminently as well as share revised guidance on our financials and cash position.

Som in terms of the agenda, our CMO, Alan, will first present these top line results and also provide an update of our clinical programs with Evo. Harish will then conclude by an update on our cash runway as well as our near-term key milestones. And last, we’ll open it up to you all for Q&A. On the next slide, on Slide 4, in the second quarter, we made significant advances in both our evorpacept and ALX2004 clinical programs. On the Evo front, we, again, are excited to share data that is demonstrating the potential of CD47 expression as a predictive biomarker and highlight a clear opportunity to now identify patients who are most likely to achieve the greatest benefit from evorpacept. As Alan will present in detail in his clinical section, in this analysis, we saw that patients with high CD47 expression derive the greatest benefit from evorpacept versus those with low expression.

And as a result of these findings, we have modified our Phase II clinical trial in breast cancer to enable pursuing a CD47 and HER2 biomarker-driven strategy in this study. These results support the potential to pursue targeted oncology approaches in additional tumor types with Evo. And given the broad overexpression of CD47 in both solid tumors and hematologic malignancies, gives us an opportunity to really focus Evo as a targeted IO therapy. In terms of process and progress, we remain on track to dose our first patient with our second pipeline product, our novel EGFR antibody ALX2004, which is a highly differentiated ADC, and we’re very excited to be in the clinic this month. We are also excited about the progress made in our partnered randomized Phase I/II UMBRELLA study with our partner, Sanofi, which is evaluating evorpacept with SARCLISA and dexamethasone in patients with previously treated multiple myeloma.

That phase of the study is now complete, which we’re excited to announce. And Sanofi will now begin the dose optimization portion of the study and be moving forward with that combination. Turning to our financials. The prioritization of our efforts in evorpacept in breast cancer and ALX2004 has now enabled us to further extend our cash runway guidance into the first quarter of 2027, which solidly positions us to achieve multiple value-enhancing data milestones that we have ahead of us this year and next year. Turning to Slide 5, in terms of the punchline on our CD47 expression analysis. As I mentioned, we now have clear data to support that CD47 overexpression is a clear predictive biomarker for patients. As a reminder, we’ve shared top line results previously for ASPEN-06, at ASCO GI earlier this year in January.

And today, we are sharing new data of a preplanned analysis of that same data set. In this analysis, we analyzed CD47 expression levels using IHC, and we found that patients with both confirmed HER2 positivity and CD47-high expression had a dramatic response to evorpacept as compared to those in the control group. As you can see here, on an ITT — on the ITT, we saw 41% versus 27% ORR. And if you look at the data now in patients that clearly have CD47-high expression, we showed a significant magnitude of benefit for those patients, where we had an ORR of 65% versus 26% in the control arm with a nominal p-value of less than 0.05. This strong magnitude of benefit for Evo in combination, in this case, with TRP in CD47-high patients was also reflected in both DOR, PFS as well as survival.

And we are planning to present the full data set at an upcoming medical conference in the fourth quarter of this year. Turning to Slide 6. As a reminder, Evo is a unique CD47 blocker that sets it apart from CD47 inhibitors that have been developed in the past with its differentiated safety profile and clinical activity. With its inactive Fc domain, which delivers best-in-class safety and combination potential across a wide range of biologics and targets, it’s truly a different CD47, and we’re now seeing that in the clinic. And following the encouraging results that we have shared today and are looking forward to sharing more later this year, we clearly see that CD47 is a biomarker. And this biomarker-driven enhanced efficacy from Evo and HER2-positive gastric is a clear demonstration of the drug’s potential to be a first-in-class and best-in-class targeted IO therapeutic and to drive superior outcomes for patients with CD47 overexpressing cancers.

Turning to Slide 7. CD47 is overexpressed across a wide range of both solid and liquid tumors. This has been well, well published in the literature, and it’s clear that CD47 is a marker that both solid and liquid tumors use to evade the immune system. And as you can see in this slide, CD47 is overexpressed across a very wide range of solid and heme malignancies, making it a very compelling target, not only where we’re focused, but beyond. Now turning to Slide 8. It is also clear that this overexpression matters. And when you look at research in CD47 over the last decade plus, it’s a very strong foundation that CD47 is a negative prognostic biomarker. What you can see here is in the meta-analysis of 38 cohorts across 17 publications, which includes over 7,000 patients, CD47 is clearly associated with shorter survival and worse outcomes.

And you can see on the right, the wide range of tumor types where this has been documented. So, turning to Slide 9. This sums up what we’re most excited about now, which is really driving a targeted IO breakthrough and a first- in-class drug with Evo. So, what does this mean for our program? What does this mean in terms of future development? Well, as you know, our CD47 blocker has been successful where no other has in terms of its manageable toxicity profile. In addition, we’ve now demonstrated efficacy in a randomized study, and we’ve identified an actionable and predictive biomarker for response to Evo in our gastric cancer study. And again, this biomarker is on mechanism. We are developing a CD47 biomarker, and therefore, it is really no surprise to see CD47 overexpression showing such a strong impact to our data.

So, what this allows is us to use CD47 to select for patients in both current and future trials with the goal of replicating the results we have seen here with gastric cancer and demonstrating the same significant and transformational benefit for patients. As you know, a predictive biomarker could also facilitate smaller and faster future studies given the potential for a wide magnitude of benefit. And importantly, we estimate that CD47 overexpression is in roughly 50% to 70% of HER2-positive breast patients, which opens the door to a very significant commercial opportunity, and more importantly, a significant patient population to benefit. And finally, we also know from existing data that CD47 expression, again, is found to be high across multiple tumor types, which enables us to go in many directions following this breast study.

So now, next, Alan will take over and provide more details both on this data as well as how it impacts our plans going forward in breast. Alan?

Alan Bart Sandler: Thank you, Jason. Good afternoon, everyone. I’m excited to be able to share with you some updated data from ASPEN-06 on CD47 expression as a predictive biomarker for evorpacept. We’ll go to the next slide. And this slide is a quick highlight again to review the evorpacept’s mechanism of action with anticancer antibodies and specifically with HERCEPTIN on this slide. Again, the mechanism is relatively simple and the concept being that due to CD47 expression in healthy cells driving on-target toxicity, the conventional approaches with an active Fc were fraught with significant challenges related to toxicity. As a result, evorpacept was designed to have a silent Fc and utilize the companion cancer antigen directed antibody as a means to direct the activated macrophages to the cancer target.

Next slide. So, again, what I’d like to show you today is, go back over some of the data that we have with respect to our ASPEN-06 data and will highlight the impact of CD47 expression as a key predictive biomarker to enhance that of the evorpacept activity we previously discussed in the gastric GE junction space. This slide, again, reminds you all that patients were eligible based on the archival tissue for HER2 levels of expression, and there were 127 patients on study. Next slide. So, to remind you, the addition of evorpacept drove a 41% response rate as compared to 27% in the control arm. Additionally, as noted in the swim lanes, both qualitatively and quantitatively, there was an improvement in the duration of response. The median going from 9.1 months in the control arm to 15.7 months in the experimental arm.

Now, the next slide and an important point here is, these are now patients that had a confirmed HER2 positivity as noted by fresh biopsy or ctDNA. This resulted in a further increase in the response rate to 49% on the experimental arm as compared to 24.5% in the control arm and still maintaining an excellent duration of response of 9.1 months in the control, 15.7 months in the experimental arm. I’ll also comment on the fact that you see despite the fact of confirmed HER2 expression, there was no difference in response rate or DOR on the control arm. Moving to Slide 15. Patients in ASPEN-06, as noted previously, were tested for both HER2 and for CD47 expression. Let me now show you how we got there. So, the ITT population are patients enrolled with either HER2 fresh or archival tissue and it totaled 127 patients.

We then attempted to confirm those patients that were truly HER2 positive closest to starting on study. These patients were defined by a fresh biopsy or by ctDNA that was collected at the time of entrance into study. This resulted in 96 patients confirmed to be HER2 positive. Of those 96 patients, 90 patients had tissue evaluable for CD47 assessment by IHC. 43 of those patients were defined as CD47-high, as defined by greater than or equal to 10% of the cells being IHC 3+. 47 patients were CD47 low. So now, let’s take a look at the results on Slide 16 for CD47 expression as a predictive biomarker. You’ll note in the ITT population, as a reminder, the response rate was 41% versus 27%. Now when we combine CD47-high along with the confirmed HER2 positivity, the response rate is up to 65%, and you’ll note no difference in the control arm with a response rate of around 26%.

We’ll also note that DOR, PFS and OS showed a strong magnitude of benefit as well in this population. The results were also consistent across multiple CD47 expression cutoffs and the full data set will be presented at an upcoming medical conference in the fourth quarter of this year. Let’s move to Slide 17. The magnitude of benefit that we’ve seen in patients with high CD47 expression in HER2-positive gastric cancer enables us to pursue a targeted development strategy for evorpacept in breast cancer and other tumors that overexpress CD47. Moving to the next slide. So, I’ll now discuss our clinical program for evorpacept in breast cancer, emphasizing the CD47 biomarker strategy. So, our opportunity in breast cancer now has a high probability of success, having been derisked by positive data in 2 different HER2-positive cancers.

In addition, this represents a very high unmet need as the changing frontline standard of care drives opportunity in those patients who have progressed on ENHERTU and/or other HER2-directed therapies. In addition, it remains a highly targeted approach now using both HER2 as well as CD47 in a biomarker-driven approach. Next slide is Slide 20, where we’ll discuss our prior data in zanidatamab in combination with evorpacept in patients with metastatic breast cancer progressing on prior HER2-directed therapy. The key eligibility criteria are shown on the left, and it required at least 3 prior regimens, including HER2-directed therapy. There were 21 patients who are HER2 positive in this clinical trial, which we’ll emphasize, and I’ll discuss in the next slide or 2.

The summary of the baseline characteristics for this cohort are noted on the right. Again, a heavily pretreated population with a median of 6 prior therapy. Notably also, 100% of the patients had received prior in ENHERTU . Next slide, 21. Now looking at these 21 patients, if you look at the overall response rate, it was 33% or 7 out of 21. But importantly, given the mechanism of evorpacept and requiring HER2 expression, you’ll note in the 9 patients who were confirmed to be HER2 positive, there were responses in 5 of those patients for a 56% response rate. The median DOR was not reached and the median PFS was 7.4 months. And this compares favorably to the Phase III SOPHIA study that looked at margetuximab in single-agent chemotherapy or trastuzumab and single-agent chemotherapy.

Now, let’s discuss the importance of CD47 with respect to HER2-positive breast cancer. Slide 22 shows that several studies have now shown that CD47 protein expression in HER2-positive breast cancer is overexpressed at the time of initial diagnosis, somewhere in the range of slightly over 50%. Slide 23 looks at CD47 and it’s being upregulated in response to prior ENHERTU therapy in this HER2-positive setting, looking at breast cancer cell lines shown here. This is, of course, important for our upcoming breast cancer study that is going to be targeting post ENHERTU patients. Slide 24 has 2 key elements of importance. First, CD47 expression is higher in HER2-positive breast cancer cells as compared to HER2-negative, shown on the left. In addition, CD47-high cells are more common in recurrent and previously treated HER2-positive breast cancer.

Slide 25 is the schema of our proposed breast cancer study. Based on the magnitude of benefit for evorpacept in CD47-high patients in ASPEN-06, we have amended the design of our Phase II ASPEN breast cancer study in HER2-positive patients now evaluating evorpacept in combination with trastuzumab and single-agent chemotherapy. This updated trial will now be a single-arm design, enrolling HER2-positive patients by archival biopsy and will be evaluated with CD47 expression. With this new design, we expect to accelerate enrollment into the study and provide interim data in Q3 of next year. Evaluation of CD47 expression or evorpacept’s benefit is expected to provide results that could support a biomarker-driven registrational study in this indication.

I will now turn the call back to Jason, who will discuss this commercial opportunity and our novel EGFR ADC, ALX2004.

Jason W. Lettmann: Thanks, Alan. Now turning to the commercial impacts and the breakdown of the market in terms of CD47-high in HER2-positive breast patients. As you can see in the slide, in the big bubble, there are roughly 48,000 patients in the second line plus setting who are HER2 positive. Of that, there are approximately 60% to 80% of patients that retain HER2 positivity, if you will. And of that, there are — 50% to 70% of those patients are CD47-high. As Alan highlighted, there was a number of publications to support CD47 overexpression in HER2-positive breast. And we believe this represents roughly 20,000 addressable patients who are both HER2-positive as well as CD47-high. If you boil this down and use conventional estimates on pricing, you get to roughly a $2 billion to $4 billion market opportunity, again, just in patients that are CD47-high and HER2 positive.

This represents a significant opportunity for Evo. And again, this is one of the aspects that we’re excited about as we think about Evo as a targeted IO approach. So, turning to the next few slides, I wanted to quickly just give a quick update on ALX2004. We’re very excited about advancing our second pipeline program here. As you remember, it is a novel ADC that is targeting EGFR. On Slide 28, highlights the development approach and how we got here. As you may recall, ALX2004 was developed by a world-class team in our Palo Alto labs with a vision starting back in 2021 to create a best and potentially first-in-class drug designed to maximize the therapeutic window and overcome the historical tox challenges that others have encountered in targeting EGFR with an ADC.

ALX2004 has been optimized on all 3 components to do this; the payload, the linker, the antibody have all been optimized to create a truly novel molecule against a validated target. On the antibody front, its affinity was tuned to maximize the therapeutic window with EGFR binding epitope that is distinct from the approved EGFR antibodies. The linker payload construct was also optimized to be similar to ENHERTU in many ways yet offer enhanced bystander effect with improved linker stability for on-target delivery of payload. And as this then translated to preclinical experiments, the preclinical data, both in vitro and in animal models support dose-dependent activity and a differentiated safety profile that supports our conviction that this molecule could potentially demonstrate efficacy with, importantly, a manageable safety profile in patients.

So, turning to Slide 29, quickly. This, again, highlights our development plan. Again, we are on track and continue to execute on our timelines that we communicated before as we are very close to dosing our first patient and expect that to happen later this month. We will then go through dose escalation and to dose exploration and ultimately, dose expansion, and the goal of really nailing the dose here that is safe as well as demonstrating efficacy across 4 different tumor types that are known to be EGFR expressing. This will then set up the program well to advance into a registrational study after this. So, that’s the plan with ALX2004. Again, very excited that we remain on track and looking forward to dosing our patients — our first patient very, very soon.

I will now turn the call over to our CFO, Harish, who will walk through upcoming milestones as well as revised guidance on our financials. Harish?

Harish Shantharam: Thank you, Jason. Now, turning to Page 31. Here’s a snapshot of our clinical pipeline. As we have communicated previously, we are pursuing a focused development strategy for evorpacept in combination with anticancer antibodies, given the consistent proof of concept that we have seen in various clinical studies with different monoclonal antibodies. Our priority is to advance our HER2- positive breast cancer program with a CD47 biomarker-driven approach. From our partner program with Sanofi’s SARCLISA in multiple myeloma, dose escalation has now been completed, and we are excited to see the trial moving into dose optimization phase. ALX2004, our EGFR ADC program, remains on track to dose the first patient this month.

Now, turning to the next slide, 32. You can see the major data readouts from our clinical pipeline and potential inflection points we have over the next year. As we mentioned multiple times during this call, we are very excited about the CD47 biomarker data from ASPEN-06, and we’ll be initiating our amended breast cancer trial, which will include a CD47 expression analysis. We expect to start dosing patients in Q4 this year and expect interim data readout from this trial in Q3 2026. On ALX2004 front, we’re about to dose first patient this month, as I mentioned, and anticipate providing initial safety data first half of next year. With the prioritization of our capital to focus only on evorpacept trial in breast cancer and on ALX2004 and halting our previously announced evorpacept colon cancer program, we have been able to extend our cash runway guidance into the first quarter of 2027.

Also, please note that the cash runway guidance here reflects significant decline in clinical trial spend in future quarters as we close out multiple legacy evorpacept trials, including ASPEN-03, -04, ASPEN-06 and ASPEN-07 following the final data readout in these trials. You can refer to our Q2 ’25 results press release for a review of our detailed financial statements for the quarter. With this, I’d like to turn the call back to Jason for any closing comments before opening the line for Q&A. Jason?

Jason W. Lettmann: Thanks, Harish. Appreciate it. And in summary, again, really strong quarter in terms of our execution, continued tight discipline around our capital and I think a number of milestones that we’ve achieved. Of course, great to have validation with Sanofi and our study with SARCLISA, and excited about next steps there, continue to execute on ALX2004, and as we mentioned, very close to FPI. And then last, as Harish mentioned, continue to be very mindful of cash and pleased to have now extended our cash runway to Q1 of ’27. Overall, though, I’d say we’re most excited about what we’re seeing with CD47, again, as a predictive biomarker. As many of you know, IO has been a tough space for some as it’s been difficult to target the right patients and to know where and how to best deliver those drugs.

And I think what we see here with Evo and with CD47-high is, we know we have a biomarker that negatively impacts patients. And so, to be able to select those patients, treat them with Evo, again, very much on mechanism when we think about CD47, really offers us the potential to deliver a transformational benefit in our study in breast. So, excited about that, excited about presenting the data in Q4 at a medical meeting, and we’re looking forward to any questions from you all. So, with that, I’ll open up the floor to Q&A. Thank you.

Q&A Session

Operator: [Operator Instructions] Our first question comes from the line of Allison Bratzel with Piper Sandler.

Allison Marie Bratzel: Really just a couple of clarifications. First, do you need to meet with FDA to finalize trial design changes for ASPEN-Breast? Or are there any other barriers to implementing the biomarker strategy in the trial? Secondly, could you just frame for us investigator feedback on the CD47 biomarker approach? How you think that it could affect enrollment trends? And then lastly, just on the interim look for ASPEN-Breast in Q3 next year. Maybe just frame for us what kind of data you would need to see to give you confidence to continue pursuing that biomarker approach in breast or other tumor types?

Jason W. Lettmann: Great. Thank you. Appreciate the great questions, Ally. So, on the first one in terms of FDA feedback and interaction, we did submit the amendment for the ASPEN-Breast study to FDA and are ready to go there. So, I think it was important for us to revise the protocol, given this new data to make sure we’re really focused on CD47 as a biomarker there. So, there’s no holdup from FDA, and we’re all set to move forward, which I think is good news. So then, on the second question on investigator feedback, I’d say it’s been great. I think even before this, there was a lot of enthusiasm for Evo and for CD47. Again, there’s good reason why CD47 was such a hot target for so long, and that’s because there’s a lot of fundamental biology here.

And so, when you think about the future of breast cancer, understanding why patients progress on ENHERTU and identifying evasion modes is really important for clinicians and of course, for patients. And I think that’s what this represents. For patients that progress on ENHERTU, there is a big open question as to what’s next. And so, for us to be able to deliver this as a biomarker, I think, is really exciting. So, we’ve had phenomenal feedback. And again, we are cautious about how that will translate to enrollment. But again, I think it’s a unique story we’re going to be able to tell. And as I’m sure you know, there’s competition. A lot of it is just other ways to go after HER2 with ADCs. And I do think due to the competitive framework and shakeout here, we’re pretty much the only answer for patients that are CD47-high.

So, I think it’s — yes, I think the clinician feedback has been great. And then on the last, on the interim, I’ll let Alan weigh in on the bar and what we’re hoping to see. But we’re laser-focused on this study from an execution perspective, going to enroll it as quickly as we can and deliver data Q3 that’s meaningful. But Alan, do you want to talk more about specifics around what we’re hoping to see?

Alan Bart Sandler: Yes, sure. Thanks, Jason, and thanks for the question. So, historically, the data that is generally accepted to be the current standard of care with HERCEPTIN and single-agent chemotherapy is roughly around 20%, give or take, 1% or 2% on either side. So, what we’re looking for is something that we think would be fundamentally changing. And that would probably be something in at least the high 30s and preferably 40% or greater, which would give us an opportunity that we think would be both statistically noteworthy and certainly, clinically compelling as well. And of course, we would anticipate those response rates to be associated with durability as well.

Jason W. Lettmann: Great. Did that answer the questions? I think I got it.

Allison Marie Bratzel: Yes.

Operator: Our next question comes from the line of Li Watsek from Cantor.

Li Wang Watsek: Thanks for Sharing the new data. I have a couple on the ASPEN-Breast study as well. Can you clarify if you intend to pursue a registrational path with the current Phase II study or you will need to run a separate study to support registration? And then, how do you address contribution of components question for the study?

Jason W. Lettmann: Sure. Thanks, Li. Those are both great questions. I’ll let Alan offer some thoughts on whether or not this could be registrational, I think it really would require an accelerated approval path, but we can talk more about that. I think at a high level, the goal of this study is really for decision-making purposes around all these things we’ve been talking about. So, we have very exciting data with CD47. I think, importantly and hopefully not lost, this wasn’t cherry-picking in that we saw the same effect across a number of different cutoffs of expression. So, the data is really robust. But of course, to go into Phase III, you need to be able to pick your cutoff. And so, I think this will be informative for us to be able to do that and then truly be able to run a biomarker-driven registrational study. But maybe I’ll let Alan add some color on the AA potential here and what we could see in an upside.

Alan Bart Sandler: Right. Sure. So basically, the — it all is going to depend upon the data. But as I mentioned, looking at response rates that are in the 40% or higher range, that would certainly leave a door open for discussion. However, the study that we have currently is for 80 patients and using a percentage of those would be both HER2 positive as well as CD47-high. So, as we look at the data and one of the advantages of this single-arm study is there’s no defined interim analysis. It’s an open-label study. So, if we’re looking at data that seems super compelling and maybe we have some discussions with the FDA, we could add patients to this so that it might have an opportunity for accelerated approval. But that, of course, will depend on the data, as I’ve mentioned.

Your other question relates to contribution of components. And so, the study is HERCEPTIN and single-agent chemotherapy of dealers’ choice. There is about 4 or 5 choices that the investigator can have. So, the difference would be Evo over what has been utilized as standard of care. So, we think that the contribution of components would be fairly well established with this study. Did I address both of your questions?

Li Wang Watsek: Yes.

Operator: Our next question comes from the line of Roger Song from Jefferies.

Roger Song: Congrats for the data. I just have a question related to the CD47, this cutoff, 10%. Since you mentioned you look at different expression levels, see pretty consistent data. Just curious how those data look like? And then also, would you expect this 10% cutoff going to apply to other Evo programs, including different combo and different line of therapy? And then, just last part of the question, any biology reason for higher or lower expression level as the cutoff?

Jason W. Lettmann: Yes. Great. Well, thanks, Roger. Those are great questions. Again, I think what was really important for us was looking at different cutoffs because it’s an open question as to how much is enough. And again, this will be presented in Q4 at a medical meeting. But the key point that Alan made, to just reiterate, is across a number of cutoffs, we’re seeing it stack up. And I think, again, we see what we shared today across ORR. But the second key point, again, is that we’re seeing very, very encouraging data across DOR, PFS and OS, even in a scenario where you’re dramatically underpowered to show a benefit, particularly on PFS and OS. So, I’d say more to come on that question. But again, I think it wasn’t — we could have picked a range of different cutoffs, and I think the answer looks similar.

So, I think that’s really encouraging. And I do think as you — to your second part of your question on what cutoff to use when we think about other studies, I think it’s TBD. But again, for us and most important is, so far, it seems like there’s not a lot of magic to what cutoff would be chosen. And then on the biology front, I think Alan walked through this again, it’s great to have a target that is so well studied with CD47. We shared those 5 studies in the deck, looking at this question of CD47 expression in breast. And again, I think it — again, it showed it was roughly half of those patients were CD47-high, and they used a range of different levels and staining, et cetera. So, we think it’s pretty robust. Again, we’re — we have more to learn here.

That’s what we’re going to do in the breast study, but I think we have a pretty strong signal here. Does that answer your question?

Roger Song: Yes, it does.

Operator: Our next question comes from the line of Sam Slutsky from LifeSci Capital.

Samuel Evan Slutsky: I guess, first, did you look at this correlation between CD47 expression and response in any of the other studies with evorpacept? And then if so, did the data replicate? And then maybe I missed this, but how many patients do you expect in the interim with ASPEN- Breast?

Jason W. Lettmann: Yes, sure. So, we can take the second one first. I think what we’re hoping to do is show, it gets to meaningful data. So, I don’t think it’s a handful of patients. I don’t think it’s going to be the full data set either. But I think, again, if you look at how many patients that we shared here, we’re seeing a strong signal in a relatively small data set. So, this is not a formal predefined interim analysis. I think it’s going to be driven by the data itself. And then, on the second question, we are actively looking at this question of how CD47 plays in our other data sets. As you know, Sam, we’ve been testing different mechanisms here; one with an antibody, two with a checkpoint, three with an ADC. So, I think we need to be cautious about making too many conclusions across different mechanisms.

But certainly, when we think about the work with Sanofi or Jazz, et cetera, looking at CD47 there is very important. And I think there’s more to come. Alan, anything on that last one that I missed or that you want to add.

Alan Bart Sandler: No, Jason, I think you covered it well. Sam, have we addressed your questions?

Samuel Evan Slutsky: Yes. So, might we see that then at a future update if any other studies saw any correlation?

Jason W. Lettmann: Yes. No, absolutely. I mean I think that — yes, it’s an important question and something we’re actively on top of. So, it’s a great thought.

Operator: Our next question comes from the line of Arthur He with H.C. Wainwright.

Yu He: This is Arthur on for RK. So, obviously, very encouraging and intriguing data point for the CD47-high. So, I’m just curious, one question regarding the data analysis. How is the baseline characteristic between the CD47-high and low patient group?

Jason W. Lettmann: So, the baseline characteristics, we’ll share more at a medical meeting as well. I’d say they’re generally well balanced. And again, when we cut this analysis a number of different ways, I think it stands up, right? If you think about expression levels and different cutoffs, as you widen the aperture, so to speak, you’re going to include more patients. And so, when we do that, again, that’s why looking at different cutoffs is important because it’s robust. So, I think we’ll have more to say on the baseline front, but at a medical meeting, we didn’t disclose that here. But again, I think the data holds up.

Yu He: Got you. And my second question is regarding the Slide 23. It’s obviously very interesting for the upregulation of CD47 expression upon the ENHERTU treatment. So, I was just curious, do you guys have any — know or be aware of any patient biopsy data up on the — regarding the CD47 expression up on the treatment?

Jason W. Lettmann: So, I think your question is patient biopsy data post ENHERTU?

Yu He: Yes.

Jason W. Lettmann: Yes. It’s a great question. I don’t know the answer to that. I don’t know if we’ve seen anything on that in the literature. But Alan, maybe you’re aware of something.

Alan Bart Sandler: Well, I think if the question is related to CD47 increasing and being higher after initial diagnosis, there is evidence for that, not from our studies, but there is evidence that the CD47 levels of expression go higher with subsequent lines of therapy, potentially as a means of resistance.

Jason W. Lettmann: Yes. And I think that’s a great point. Yes.

Alan Bart Sandler: Which I was just going to say bodes well for the clinical trial that we’re going to be conducting post ENHERTU and in previously treated patients.

Jason W. Lettmann: And I will — the only thing I’d add to that is that we’re going to also encourage repeat biopsies when we can. Of course, that can be a pain for patients and clinicians. But if we can get data here that both is biopsy at time of diagnosis, which, of course, we’ll have, but also when they enter the study, I think that will be a really helpful tool to look at. But again, I think that’s why this 50% number that’s across the 5 studies, I think that’s a fair assumption. And if you assume that it’s, in fact, the resistance mechanism and it’s actually higher; then in the overall population, we could see as high as 70% of the patients, but that’s a TBD.

Operator: Our next question comes from the line of Ting Liu with UBS.

Ting Liu: So, I have a quick follow-up on the 10% IHC3 cutoff. Sounded like this biomarker analysis was prespecified, but this threshold wasn’t. If you could clarify quickly, am I understanding this correctly? And when you make the protocol change to the breast cancer study, would you prespecify a threshold? Or will that be dependent on the data analysis?

Jason W. Lettmann: Yes. No, that’s great. Those are great questions. Thanks. So, yes, it was preplanned to look at this. I think stating the obvious when you’re developing a CD47, looking at CD47 expression is important. We did not specify a cutoff. I think typically and you think about targeted oncology, you need to do the all-comer work, if you will, to understand what specific cutoff is the right one. So, we did not prespecify 10%. And again, that was — that’s why it was really important to look at a bunch of different cutoffs to see what was robust. And frankly, they — it worked across multiple different cuts. And to your second point on the breast study, we have not predefined the right cutoff. Again, we need to run the same experiment, right, to see what is — what makes sense.

And I think there’s commercial implications and clinical implications to picking and you just really, really want to make sure you’re picking well before heading into a registrational study. And so, the breast study also does not predefine 10% is the right answer, so to speak. We want to get more data on that before we pick.

Operator: There are no additional questions at this time. This now concludes our question-and-answer session. I would like to turn the floor back over to Jason Lettmann for closing comments.

Jason W. Lettmann: Great. Well, thanks, everybody. Appreciate the engagement, as always, and good questions, and we’re looking forward to future updates on this data as well as others over the next few months. So, thanks again for the time this afternoon. Really appreciate it.

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