All right. Welcome everyone to our Jefferies 2026 Global Healthcare Conference. My name is Roger Song, Senior Analyst covers mid-cap biotech. It is my pleasure to have a next fireside chat with ALX Oncology. Welcome, Jason and Barbara.
Thanks for having us. We appreciate it. Right before happy hour no less.
Yeah, here we go.
Thank you.
Yeah. Okay, awesome. Last but not least, and then maybe the best. All right. Jason, do you want to give yourself and ALX two minutes of s tate of art? Yep.
Again, thanks, Roger, to you and the Jefferies team for hosting us. Really appreciate it. It's been a great meeting for us. ALX really coming off of a strong ASCO and a lot of momentum over the last few months. As a reminder, we're advancing two programs, both in the clinic. First is evorpacept, which is our lead program in CD47. We've been working on CD47 for now close to a decade, and really have been pleased over the last year to see the original thesis, the original vision, of evorpacept pan out in the clinic. Dating back to the company's inception, we took a different approach to the target. CD47, of course, is utilized by cancer, frankly, all cancers to evade the immune system. There's no question about the importance of its biology.
What has been challenging is that it's literally expressed everywhere, and that has made for a difficult target. Our approach, again, dating back to the beginning, was separating the "don't eat me" signal from the "eat me" signal. evo blocks the "don't eat me" signal, utilizes an Fc active antibody to drive the "eat me" signal. Taken together, that drives targeted phagocytosis against tumor. That has played out. It's played out now in five different clinical data sets. The other thing that's become very clear is that CD47 is also a very strong and predictive biomarker. That's been news for us over the last year, again, supported by data both in HER2 positive breast as well as HER2 positive gastric cancer.
That really has been an important transition for the company as we're truly a targeted oncology play now, and we believe CD47 is an incredibly big opportunity. We have an opportunity to be the answer, we think, for those patients that overexpress CD47. Our second program, which we'll get into, ALX2004, is a novel EGFR-targeted ADC. I think in validated targets, in oncology, EGFR is still not yet cracked. It's been a difficult target for an antibody-drug conjugate. We spent a lot of time internally developing ALX2004 to address this. We have a unique antibody. We are the only ADC in development using matuzumab as our epitope. That provides some really unique differentiation. We also spent a lot of time optimizing the linker payload construct.
That program is also really doing quite well in dose escalation, we continue to escalate dose and are really encouraged by what we're seeing. All of that taken together is what led us to raise $150 million back in February, brought in a really strong group of new investors as part of that. I think our conviction in both programs, frankly, is higher than it was when we closed the financing. A lot of things to be excited about right now.
Excellent. All right. I know it's interesting, I think we just caught up earlier before the talk is that folks are interested in either evo or the two and the four programs. Seems people have a different focus. Today conversation, let's evenly distribute it all, just touch on both, and maybe we focus on the evo for a moment right now. The recent data in terms of the biomarker-driven CD47 positive, in both you said gastric and breast is very impressive, right? You see the clear difference between expressor versus non-expressor. Now you're doing the phase II ASPEN-09. I think at this point you're guiding towards the mid-year next year for the initial data. What is the profile you're looking for on both efficacy and safety?
Yeah, sure. I'll let Barb talk about where we see the bar. I think what, again, is most encouraging is in two positive, HER2-positive tumor types with breast and cancer. We've seen a really strong overall response rate. In our randomized setting in gastric, we had a roughly 40% delta in ORR versus control. In the new data we shared at ESMO Breast just a few weeks ago, we showed that all patients, five out of five patients in our combination with zanidatamab responded with one CR. I think in terms of response data, we're really excited by what we're seeing, but perhaps most encouraging is the durability and where we're seeing DOR of 20 months roughly in PFS, in the case of our gastric study, over two years.
That's the type of durability you hope to deliver with an IO mechanism like CD47, and I think we're seeing that in the data. Barb, do you want to speak to where we see the bar?
Yeah. Thanks. Yeah, with the focus being really what's the bar for the ASPEN-09 study? Maybe I'll take a step back. ASPEN-09 is a single arm trial. It enrolls HER2 positive breast cancer patients who have all received prior ENHERTU. The reason for that is that's where the unmet need is. ENHERTU is quite an active agent, the most active agent seen to date in HER2 positive breast cancer, and it's moved up and solidly first line therapy now. Unfortunately, afterwards what had been first described anecdotally is that available therapies just are not producing the outcomes that were expected. Now we've seen several large real world data sets confirm that with response rates post ENHERTU 15% in a couple of studies, PFS about four months.
The two studies, real world studies, I'm thinking about a Japanese study of over 600 patients by Nozawa and then BostonGene, Tarantino, both in manuscript form. What do we need to see in ASPEN-09 single arm study post ENHERTU? First of all, I want to make sure that I'm well above the comparator. Like I said, the comparator is not very good. That's one thing. In terms of what have we actually seen when you combine evorpacept with trastuzumab or zanidatamab, two various HER2 antibodies. Jason just talked about some of those data. In gastric cancer, HER2 positive gastric cancer, in second and third line, patients had all seen at least trastuzumab or maybe other HER2 agents, 65% response rate. In zanidatamab, that is in patients who express CD47 high overexpression.
In that similar subset, confirmed HER2-positive status still in those patients, CD47-high, we had five of five CD47-overexpressing HER2-positive patients respond. That was the data just at ESMO Breast just a couple of weeks ago. We're seeing fabulous outcome, but I think what we really only need to see, and this is the bottom line, what we need to see is somewhere in the range of about 30% response rate and a PFS of about six months. That gives us quite a buffer in a future phase III, thinking that we could double a response rate or better, and we could enhance PFS by 50% or more, and that would be a real win for patients with those outcome.
Got it. Great. The other thing is, one of the very important component is the CD47 cutoff or the expression level. The good thing is so far, if they are expressing, it's not that sensitive to the level of the expression, maybe it's a good thing. On the other side is the ASPEN-09, you will refine the cutoff how we should make the decision on the cutoff as you design the phase III.
Thanks. Yeah, exactly. ASPEN-09, we have great data. Why do we need to do another phase II study before moving on to phase III? Well, one of the questions that we want to address is have we identified the optimal cut point? We would envision a phase III being a selected patient population only enrolling the CD47 high. We need to really understand how to define that. We are enrolling all comers in the ASPEN-09, meaning we are testing retrospectively for CD47 levels, and we will look to see where a threshold segregates patients who have a very high response rate from those who have a lower response rate. If it's anything like our prior data, as you said, it could be more or less an on/off.
For gastric, we presented a data table where we showed a variety of different cut points, and as long as you had any expression of two or three plus IHC for CD47, essentially, there was a near 40% enhancement of response rate and a PFS hazard in a randomized phase II with a hazard for PFS of around 0.4. Really extraordinarily good results. It wasn't a cherry-picked cut point. We saw similar results across a whole range of levels. In breast cancer, we also saw in the zanidatamab trial a cut point. The patients who were considered low in that trial had either zero or 5% total membrane staining. The patients who were considered high were 20% or more. It was a small data set. Those were across nine or 10 patients.
Now we have the opportunity to run a larger study, up to 127 patients, really get this cut point right, and then be able to utilize that applied to a phase III. We're moving down. The other thing I'll say is that this will be a companion diagnostic. We're working with Ventana, Roche Diagnostics to be ready for a phase III with all of the companion diagnostic work that needs to be done.
How far away of developing the companion diagnostic, and then before you decide the cutoff, can you start to work on it, and then once you get that, you can quickly slip in the numbers?
Absolutely. ASPEN-09 is a rather large trial for a Phase II at 120 patients. It is open label, there might be opportunity. We've talked about having patient data on 80 patients, for example, by middle of 2027, we can apply some of the learnings to fine-tune it. Anyway, I do think the process will move us from a research prototype assay to a locked formulation assay. There's a process that we go through, that is what is occurring during the ASPEN-09 Phase II.
Excellent. Okay, great. Fast-forward, interim data looks supportive. Can you use that data set to talk with the FDA, discussing the potential pivotal program at that point?
Yeah, absolutely. I think the plan, again, we've guided to mid-year next year for 80 patients of data from this study. I think we feel really quite confident in that guidance. At that point, we'll go to the FDA. We'll have certainly a lot more data to share, both on the cut point as well as overall efficacy with, I think, some encouraging durability is what we would aim for. At that point, we'll be able to lay out the phase III, which should be very similar to what we're running right now. It'd be evo plus tras plus chemo versus a tras chemo comparator, and anticipate having those conversations next year.
Okay, good. How much the treatment landscape is going to change in the coming years? Because I think Barbara referred is right now the standard of care is pretty bad. 15% and four months PFS. How we think about the future posting HER2, the breast cancer, what else is coming, and what's on your radar to benchmark?
Yeah, I think right now, unfortunately, the unmet need is really quite high. If you look at patients that progress, as Barb mentioned, what the real-world evidence has highlighted is irrespective of what they receive, whether it's tras, various chemo, the TKIs, the response rate consistently is around 15% with a few months of PFS. We see a lot of opportunity there. Perhaps one of the most exciting and interesting things for us with this focus on CD47 is that we, in essence, are the only CD47 therapeutic in development, certainly at this stage, at this point. It's due to how this played out with our competitors, with Fc active antibodies. That approach largely didn't work. It took two very large acquisitions and randomized data to prove that.
The result of it all is this program essentially standing on its own and not having a ton of competition. Our goal is to focus on CD47 high, and whether it's breast or gastric or heme malignancies, we do not see competition in that segment. Again, we know that patients that overexpress CD47 do even worse, and that's what we're focused on, is really being the answer ultimately in the CD47 high population.
Excellent. Yeah. We really look forward to that data set, and then they can change the treatment criteria for the post ENHERTU population. Okay. I deliver my promise, we're going to spend nearly half of the time.
Right
2004, which I think I got quite a few investors ask about this program, and some of them are very excited about it. Tell me why you think EGFR ADC, your program, can be different from the past, because in the past, we have a couple company tried, but it was not that successful.
Yeah, sure. EGFR is an incredibly well-validated target, and I think what we saw in the space when we first embarked on this effort was a real need to approach it differently. If you look at the top targets that are validated on oncology, there's no question that ADC or EGFR is in the top five, but yet there is no approved EGFR ADC, and there's really open field even in terms of late-stage development. What we tried to do, and again, this was an effort in-house back in 2021. We pulled together a very strong team in Palo Alto led by Jaume Pons and Marija Vrljic, who are just incredible ADC researchers and scientists to work on this. One of the things they did was go back through the history of EGFR development to understand what has been done on the antibody front.
Through that work, we identified an antibody called matuzumab, which was developed by Merck Serono, specifically with unique binding to EGFR to avoid the on-target toxicities associated with cetuximab and panitumumab. That is a very key difference. Not only do we think it will result in improved toxicity, but almost all of the bispecifics and ADCs in development utilize cetuximab as their epitope. If you think about an escape mechanism post cetuximab, it's very likely that the tumor has mutated off of that. By applying a different epitope, we believe we're going to have a unique advantage there. That's part of what we're working on. I think the linker payload construct also really goes back through the history of ADC development. We know Topo1 has been the best payload for ADCs. HER2 is perhaps the best example.
We're utilizing that as our payload and spent a lot of time optimizing the linker payload to maximize the bystander effect and really nail the on-target delivery. I think that design is what we've now seen translate. We've seen it translate into the in vivo work. We saw it translate into the NHP work where we did not see a lot of the traditional skin-related issues. We did not see ILD associated with the payload and really had a clean signal, which then led us to the clinic. As I mentioned, we've continued to dose escalate in the clinic. We started at one, doubled to two, then doubled again to four, and have been able to escalate beyond four. Again, I think there is a lot of opportunity for an EGFR-targeted ADC.
In these spaces that we're looking at, for example, head and neck, we think we have a really good opportunity to be the first Topo1-based ADC in that space. Yeah, excited about that program as well.
Great. Just clarify, you say you starting with one and double to two, four. Now you are in eight or you're cleared of four?
We've gone double to two, double to four. We've gone beyond four now.
Go beyond four. Okay.
I think we look to the other ADCs in terms of therapeutic window, and we'd expect four and above would be now entering the therapeutic window. That's what we continue to target.
Got it. Okay, good. In terms of the skin and then the ILD, you don't see that signal in NHP? You didn't say that's in the clinical yet in here.
Yeah, I would just say so far so good. We've been able to escalate really quite rapidly. We started dosing patients back in August and have continued to be able to move forward really quickly with that program. We're planning an additional safety update later this year. Continue to have a lot of confidence in that guidance and looking forward to sharing more at that point.
Got it. What kind of a tumor type you are enrolling and then prioritizing considering the expression level? Also, it's a phase I.
Yeah. Sure. You want to take that, Barb?
Yeah. We have a restriction in the phase I even of four tumor types that all have high expression of EGFR. That would be head and neck, esophageal squamous cell cancers, non-small cell lung cancer, and colorectal cancer. From the very start, we are targeting a patient subgroup by indication that has a higher likelihood of responding because of their EGFR expression levels.
Okay, got it. Then in terms of the data we're going to see later this year, how meaningful the data set will be? I know you're focusing on the safety, which is right, because we know the limitation for the past ADC EGFR is the safety. Then outside of safety, and how big the data set you will feel it's meaningful to show the safety, and then also how likely are we going to start to see early activity you see above four usual therapeutic dose?
Yeah. I think this is dose escalation characterized by relatively late line patients across the four tumor types that Barb mentioned. Certainly tough patients that we're enrolling in the study. What we want to see and want to share with investors is answers to some of the safety questions, right? Can we dose into therapeutic range without seeing a high rate of ILD? Can we avoid significant diarrhea and GI tox? Can we avoid skin and rash and some of the EGFR-related tox? Is the rest of the safety profile manageable? That's the goal. I think that is very important if you're able to do that at a therapeutic range, call it four and better. It's an important milestone for an ADC.
I don't think it's lost on us that activity is also important, and so hopeful about sharing some signs of activity as well when we get to that point.
Got it. In terms of those tumor types, how do you look at the distribution? Because it's a phase I unit, right? Non-small cell lung, you have a lot of options. Maybe esophageal is less so. Tell us how you balance that.
Yeah, I think we've taken a pretty thoughtful, proactive approach to that. Of course, late line CRC patients are easier to enroll just given the high unmet need there. As Barb alluded to, it's very important for us to have data across all four tumor types with a particular emphasis on head and neck and lung. I think we see real opportunity in those spaces for an EGFR-targeted ADC. As we've gone through this, and again, I think Barb and the team has done a great job of this, is just ensuring we have a good balance. In terms of expectations, I would expect to see a good mix of those different tumor types later this year.
Okay. At this point, do you want to guide how many patients potentially you're going to show us on the safety-
It's going to be a good number.
Efficacy? Yeah.
No, I think we want to get 10, 15 or more. I think enrollment has gone quite well. We had a great ASCO on both programs. We spent time meeting with investigators that focus on all four of these different tumor types. I think the enthusiasm is high and building. I think we'll be able to provide some good insights as to where we are on these different cancers as well as at the right doses, if you will.
Okay, great. As I said, I think EGFR ADC is highly interesting. I think you're now going to give us the first data set. How you think this first data set going to guide you next, or you will start to backfill or think about the expansion? You mentioned the head and neck and then the non-small cell lung, are there other? You say that for a reason based on the data, or that's your strategy?
No, I think our strategy with this program is getting to the right dose and then speed. I think in ADC development, it's really important that execution is tight. From our perspective, once we get through this phase, it'll be quickly into backfill, into expansion, and doing so in settings that are going to be relevant for our phase III. Second line head and neck, second line lung is very important. I think we would, and will, very quickly pivot to that. That'll enable us going into next year to have a data set that's in the right patient population and we think provide a real clear look as to what the activity is for the drug.
Awesome. Right. Look forward to that. Maybe just the last minute, what else do you want to highlight? Also the cash and the runway, and then cover the catalyst upcoming.
Yeah, sure. I think we're well capitalized at this point coming off the raise. We have about $170 million as of the last quarter. That'll fund us well into mid 2028, which will get us through most, if not all, of what we just talked about. We're going to have really robust data in ASPEN breast. We see incredible opportunity to be the first CD47-directed therapeutic. With ALX2004, we're certainly focused on safety. That's what's most near term. The cash will get us well through a lot more than that. Again, I think next year we're looking to have true proof of concept in indications that matter with 2004. Ideally, our internal goal is to have two programs that are ready for randomized registrational grade trials by the end of next year. That's what we're shooting for.
Excellent. Thank you, Jason. Thank you, Barb. Thank you, everyone.
Thank you. Appreciate it.