Conference Transcript - ALXO 2026-06-03

Roger Song, Analyst — Smica Biotech

All right. Welcome, everyone, to Jeffrey's 2026 Global Healthcare Conference. My name is Roger Song, senior, and I cover Smica Biotech. It is my pleasure to have a next fireside chat with ALX Oncology. So welcome, Jason and Barbara.

Jason Lettmann, CEO

Thanks for having us. We appreciate you.

Roger Song, Analyst — Smica Biotech

Thank you. Yeah. Okay. Awesome. Last but not least, and then maybe the best. So, all right. So, Jason, do you want to give yourself and ALX a two-minute state of art?

Jason Lettmann, CEO

Again, thanks for us. And ALX really comes to a decade and really have been pleased over the last year to see, you know, the original thesis, the original vision of Vorpicep 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 and there's no question about the importance of its biology. What has been challenging is that it's literally expressed everywhere and that is made for a difficult target. And our approach, again, dating back to the beginning, was separating the don't eat me signal from the eat me signal. So EVO blocks the don't-eat-me signal, utilizes an FCA-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. And the other thing that's become very clear is that CD47 is also a very strong and predictive biomarker. so 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 and 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 and we have an opportunity to be you know the answer we think for those patients that over expressed CD47. Our second program, which we'll get into, ALX2004, is a novel EGFR targeted ADC. I think invalidated targets in oncology, EGFR is still not yet cracked. It's been a difficult target for an antibody drug conjugate, and we spent a lot of time internally developing ALX2004 to address this. So we have a unique antibody. We are the only ADC in development using metuzumab as our epitope. That provides some really unique differentiation. We also spend a lot of time optimizing the linker payload construct. That program is also really doing quite well in dose escalation, and we continue to escalate dose and are really encouraged by what we're seeing. So So 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. And I think our conviction in both programs, frankly, is higher than it was when we closed the financing. So a lot of things to be excited about right now.

Roger Song, Analyst — Smica Biotech

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 2004 programs and then seems that people have a different focus but today conversation let's get it get you know evenly distributed all you know just touch on both and maybe we'll focus on the EVO for a moment right now the recent data in terms of the biomarker driven cd47 positive and then in both you you said you know gastric and breast is very impressive, right? You see the clear difference between expressor versus non-expressor. And then now you're doing the phase two, as the nine, and then you, I think at this point, you're guiding towards the mid-year next year for the initial data. So what is the profile you are looking for on both efficacy and safety?

Jason Lettmann, CEO

Yeah, sure. I'll let Barb talk about where we see the bar. I think what, again, is most encouraging gene 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. And then in the new data we shared at Esmobrest just a few weeks ago, we showed that all patients, five out of five patients in our combination with zanidatumab, responded with one CR. So 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 and 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. And yeah,

Barbara Klencke, Analyst — Other

with the focus being really, what's the bar for the Aspen 09 study? So maybe I'll stop, take a step back. Aspen 09 is a single arm trial. It enrolls HER2 positive breast cancer patients who have all received prior in HER2. The reason for that is that's where the unmet need is. In HER2 is quite an active agent, the most active agent seen to date in HER2-positive breast cancer, and it's moved up in 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. And now we've seen several large real-world data sets confirm that with response rates post and HER2, 15%, and 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 Boston group, Tarantino, both in manuscript form. and and so what do we need to see in Aspen 09 single arm study post in HER2 first of all I want to make sure that I'm well above the comparator and like I said the comparator is not very good so that's that's one thing in terms of what have we actually seen when you combine of orpicep with trastuzumab or Zanidatinib, two various HER2 antibodies. Jason just talked about some of those data. So in gastric cancer, HER2 positive gastric cancer, in second and third line, patients that all seen at least trastuzumab or maybe other HER2 agents, 65% response rate. And then in Zanidatinib, and that 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. So 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. And that gives us quite a buffer in a future phase three, thinking that we could double response rate or better, and we could enhance PFS by 50% or more, and that would be a real win for patients with those outcomes.

Roger Song, Analyst — Smica Biotech

Got it. And then the other thing is one of the very important components is the CD47 cutoff or the expression level. The good thing is, so far, as long as they are expressing, and then it's not that sensitive to the level of the expression. maybe it's a good thing but on the other side is the aspen 09 you will you know find you know refine the the cutoff and then how we should you know make the decision on the cutoff and then

Barbara Klencke, Analyst — Other

what as you design the phase three thanks yeah exactly oh aspen 09 we have great data why do we need to do another phase two study before moving on to phase three well one of the questions that we want to address is have we identified the optimal cut point because we would envision a phase three being a selected patient population only enrolling the cd47 high so we need to really understand how to define that we are enrolling all comers in the aspen 09 meaning we are testing retrospectively for CD 47 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 and if it's anything like our prior data as you said it's it's it could be more or less than 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 two with a hazard for PFS of around 0.4 so really extraordinarily good results And 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 zanidatinib trial a cut point. The patients who were considered low in that trial had either 0 or 5% total membrane staining. The patients who were considered high were 20% or more. But it was a small data set. Those were across 9 or 10 patients. So 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. So 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 Phase III with all of the companion diagnostic work that needs to be done.

Roger Song, Analyst — Smica Biotech

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?

Barbara Klencke, Analyst — Other

Absolutely. ASPIN-09 is a rather large trial for Phase II at 120 patients. It is open-label, so there might be opportunities. We've talked about having patient data on 80 patients, for example, and then, you know, by middle of 2027, and we can apply some of the learnings to fine-tune it. So 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, and that is what is occurring during the ASPIN-09 phase, too.

Roger Song, Analyst — Smica Biotech

Okay, great. And then fast forward, the intern data looks supportive. Can you use that data set to talk with the FDA, you know, discussing the potential pivotal program at that point?

Jason Lettmann, CEO

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, and 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, you know, I think some encouraging durability is what we would aim for. And at that point, you know, we'll be able to lay out the phase three, which should be very similar to what we're running right now. So it would be EVO plus TRAS plus chemo versus a TRAS chemo comparator and anticipate having those conversations next year.

Roger Song, Analyst — Smica Biotech

Okay, good. And then how much the treatment landscape is going to change in the coming years? Because I think Barbara III is right now the standard care is pretty bad, right? So 15% and four months PFS. But how do we think about the future post in her to the breast cancer? And then what else is coming and what's on your radar to benchmark?

Jason Lettmann, CEO

Yeah, I mean, I think right now, unfortunately, the unmet need is really quite high. I mean, 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 PFS. So therefore, 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. You know, it took two very large acquisitions and randomized data to prove that. But the result of it all is this program essentially standing on its own and not having a ton of competition. So 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. And, 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.

Roger Song, Analyst — Smica Biotech

Excellent. Yeah, we really look forward to that data set, and then they can change the treatment, particularly for the post-inhertia population. Okay, I gave you my promise that we're going to spend nearly half of the time talking about the 2004, which I think I got, you know, quite a few investors asked about this program and some of them are very excited about it. So tell me why you think EGFR ADC, you know, your program can be different from the past because in the past we have a couple companies tried, but it was not that successful.

Jason Lettmann, CEO

Yeah, sure. So 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. And 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 Jama Pons and Maria Vergic, who are just incredible ADC researchers and scientists, to work on this. And 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. And through that work, we identified an antibody called metuzumab, which was developed by Merck-Sorono, specifically with unique binding to EGFR, to avoid the on-target toxicities associated with cetuximab and panatumumab. 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. So if you think about an escape mechanism post-cetuximab, it's very likely that the tumor has mutated off of that and by applying a different epitope we believe we're gonna have a unique advantage there so that's part of what we're working on and then again I think the linker payload construct also really goes back through the history of ADC development we know Topo has been the best payload for ABCs there's in HER2 is perhaps the best example so 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. And 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, you know, a lot of the traditional skin-related issues. We did not c ild associated with the payload and really had a clean signal which then led us to the to the clinic and 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 so again i think there is a lot of opportunity for an egfr targeted adc and in these spaces that we're looking at for For example, Head and Neck, we think we have a really good opportunity to be the first topo-based ADC in that space. So, yeah, excited about that program as well.

Roger Song, Analyst — Smica Biotech

Great. Just to clarify, you say you're starting with one and double to two, four. Now you are in eight, or you're clear to four?

Jason Lettmann, CEO

We've gone double to two, double to four. We've gone beyond four.

Roger Song, Analyst — Smica Biotech

Go beyond four.

Jason Lettmann, CEO

So, you know, I think we look to the other ADCs in terms of therapeutic window. We'd expect four and above would be now entering the therapeutic window. And that's what we continue to target.

Roger Song, Analyst — Smica Biotech

Got it. Okay, good. And then 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?

Jason Lettmann, CEO

Yeah, I would just say so far so good. I mean, we've been able to escalate really quite rapidly. We started dosing patients back in August and have continued to be able to, yeah, move forward really quickly with that program. We're planning an additional safety update later this year. You know, continue to have a lot of confidence in that guidance and looking forward to sharing more at that point.

Roger Song, Analyst — Smica Biotech

Got it. And then what kind of a tumor type you are enrolling and prioritizing considering the expression level, also it's a phase one.

Jason Lettmann, CEO

So it's just, yeah.

Barbara Klencke, Analyst — Other

Yeah, we have a restriction in the phase one even of four tumor types that all have high expression of EGFR. So that would be head and neck, esophageal squamous cell cancers, non-small cell lung cancer, and colorectal cancer. So 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.

Roger Song, Analyst — Smica Biotech

Okay, got it. And 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 limitations for the past ADC EGFR is the safety. and 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 we're going to start to see early activity you see above four

Jason Lettmann, CEO

usually yeah i mean i think you know this is uh dose escalation characterized by relatively late line patients across the four tumor types that that barb mentioned so certainly tough patients that we're enrolling in the study what we want to see and and want to share with investors is is answers to some of the safety questions right can we dose into therapeutic range without seeing a high rate of ilt can we avoid significant diarrhea and gi tox can we avoid skin and rash and some of the egfr related talks and is the rest of the you know safety profile manageable That's the goal. I think that is very important. If you're able to do that at 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, you know, some signs of activity as well when we get to that point.

Roger Song, Analyst — Smica Biotech

Got it. And then in terms of those tumor types, how do you look at the distribution? Because it's a phase one unit, right? And then, you know, you have a lot of options, maybe esophageal is less. So tell us.

Jason Lettmann, CEO

Yeah, I mean, I think we've taken a pretty thoughtful, proactive approach to that. Of course, you know, late-line CRC patients are easier to enroll just given the high unmet need there. But 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. So 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. So in terms of expectations, I would expect to see a good mix of those different tumor types later this year.

Roger Song, Analyst — Smica Biotech

Okay. At this point, do you want to guide how many patients potentially you're going to show us on the safety? And then efficacy, yeah.

Jason Lettmann, CEO

No, I mean, I think we, you know, we want to get 10, 15 or more. You know, I think enrollment has gone quite well. We had a great ASCO on both programs. We spent time meeting with investigators and focus on all four of these different tumor types. And, you know, I think the enthusiasm is high in building. So I think we'll be able to, you know, provide some good insights as to where we are on these different cancers as well as at the right, you know, doses, if you will.

Roger Song, Analyst — Smica Biotech

Okay, great. As I said, I think EGFR, ADC is highly interesting. And then I think you're not going to give us the first data set. And then how do you think this first data set is going to guide you next? or you will start to backfill or think about the expansion? You mentioned the head neck and then the non-small cell lung. Is that the, you know, you say that for a reason based on the data or that's your strategy?

Jason Lettmann, CEO

No, I think our strategy with this program is getting to the right dose and then speed. I mean, I think in ADC development, it's really important that execution is tight. And so 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 three. So second line head and neck, second line lung is very important. And I think we would and will very quickly pivot to that. And that will 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.

Roger Song, Analyst — Smica Biotech

Awesome. Right. Look forward to that. Maybe just the last minutes, you know, what else do you want to highlight? And then also the cash and the runway and then cover the catalyst upcoming?

Jason Lettmann, CEO

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 28 which will get us through um you know most if not all of what we just talked about we're going to have really robust data and aspen breast again we see incredible opportunity to be the first cd47 directed therapeutic um and then with alx 2004 i mean we're certainly focused on safety that's what's most near term the cash will get us well through um a lot more than that so again i think next year we're looking to have true proof of concepts in indications that matter with 2004 and ideally our internal goal is to have two programs that are ready for randomized um you know registrational grade trials by the end of of next year uh and that's what we're uh we're

Roger Song, Analyst — Smica Biotech

shooting for. Excellent. Thank you Jason. Thank you Barr. Thank you everyone. Thank you. Appreciate it.