Good afternoon. Welcome to the J.P. Morgan Healthcare Conference. My name is Raji Gunasekera. I'm with the Healthcare Investment Banking team at JPM, and today I'm pleased to introduce the ALX Oncology team and their CEO, Jason Lettmann.
Great! Thanks for having me, Raji, and thanks to J.P. Morgan for having us. Dangerously close to happy hour here, so appreciate you guys tuning in. Forward-looking statements, and here we go. So we are ALX Oncology. We're in the CD47 space. We believe we're the leader in the space, and we'll go through some of the history, but very excited about the last year coming off a great 2023, and looking forward to an outstanding year here in 2024. So a few highlights. Last year, we shared the results from ASPEN-06, which is the first randomized study in the solid tumor space to show activity, and in this case, in gastric cancer.
And what we showed is, relative to standard of care, a 30% delta versus control, so 52 versus 22% on control. And again, first time that a randomized study in CD47 is read out positively. This was encouraging, but for us, just further confirmation and building off of what we've seen in the past, where we've had multiple studies that have highlighted both a differentiated safety and efficacy profile. We are gonna talk about two mechanisms of action today, one, in combination with anti-cancer antibodies, and two, in combination with checkpoint inhibitors. And we have encouraging data across both mechanisms. As I mentioned, if you look out to this year, we have several data readouts coming, first of which is full data on ASPEN-06, which will happen next quarter, Q2.
In the back half of the year, we're gonna share data from two randomized studies in head and neck cancer, also first in class. It'll be the first randomized data to read out in CD47 in combination with a checkpoint. Beyond that, we are encouraged by where we can go from here. We have ongoing studies in breast, bladder, ovarian, as well as heme. We do not believe this is a heme versus solid story. We think with the right mechanism and the right combination, we'll continue to show activity. And last, but certainly not least in this environment, we have a strong balance sheet and are well-funded through early 2026. So, as a reminder, CD47 is the ultimate marker of self. It's how healthy cells evade destruction by the immune system.
And so therefore, it's been a pretty challenging area to target. CD47 is the "don't eat me" signal, and I'm sure many of you have read about it. And what we're developing is evorpacept, which has an inactive Fc domain and is the only CD47 blocker in development that has an inactive Fc. So on the next slide, on the left, you can see how evorpacept works. Evorpacept achieves near complete CD47 blockade, without targeting blood cells, and then this is a very important differentiator. As you'd imagine, when you're trying to target something like CD47, it's very important to target just cancer. So when you combine evorpacept with an anti-cancer antibody, which in essence provides the "eat me" signal or the positive signaling, we get what you see on the right, which is a very targeted destruction of cancer.
This is markedly different than how conventional CD47 agents have attacked the problem. In trying to develop a drug with single agent activity, they've combined both the positive signal, as well as blocking the "don't eat me" signal. And what you see is, by indiscriminately blocking CD47, you're both going to target healthy cells and in this case, red blood cells, which has been an interesting fact that's affected many of our competitors in the space. And that's what this slide highlights. Again, on the top is evorpacept with an inactive Fc domain. And throughout our clinical studies with combinations, whether it's Keytruda, Herceptin, Rituxan, we've seen a very consistent efficacy signal, and the only randomized data to date that has read out positively.
This is very different than what others have seen, whether that's Trillium, Forty Seven, I-Mab, that have been limited by heme-related tox, and ultimately with magrolimab led to the failure in MDS and AML last year. The good news here is that, you know, we've saw a very predictive signal from the early days. And what you see on the left here is evorpacept and demonstrated superior phagocytosis versus both magrolimab and Trillium. And what this is then translated to in the clinic in over 400 patients is a differentiated profile. And, you know, I think lately, particularly following the randomized data, we've had a lot of questions as to why, right? There's certainly an aptitude and a willingness to try to think about this as a class effect, but evorpacept is fundamentally different.
You know, on the left here, we see how we're different. A higher affinity CD47 binding, which results in more potent activity. We have an inactive Fc domain, which causes less sink effect, both in terms of sync to healthy cells, but also in terms of directing macrophages to the right place, and we have a lower molecular weight, which we think is particularly important in solid tumors. And last, we have antibody-like PK, which allows us to dose right aside, right alongside the backbone regimen. And this is what's translated in robust clinical activity, best-in-class safety, strong solid tumor activity, and broad combo potential. So with that, we're really pursuing testing two mechanisms, as I mentioned on the top, in combination with anti-cancer antibodies, and importantly, ADCs, which I'm sure everyone's heard of at this point, and then with checkpoint inhibitors.
So we're gonna talk about the combination with Herceptin and RamPac and gastric. Talk about as well as what we're doing in bladder with Padcev. And then on the breast front, we are running a study with our partner Jazz to look at zanidatamab as well as Enhertu. We believe we can both be used in combination with Enhertu, as well as in many of the spaces that they're currently playing. And then on the bottom is what we're doing on the checkpoint front. Again, different mechanism, but also very relevant, and we are running the what will be the first studies to read out in combination with a checkpoint inhibitor, and that's ASPEN-03 and ASPEN-04. So we'll start with gastric.
The ASPEN-06 study is looking at evorpacept plus Herceptin, and as a reminder, this is how ALX-148 or evorpacept works. We block the "don't eat me" signal, and then we use Herceptin to provide the positive signaling, which increases ADCP in combination with trastuzumab or Herceptin. This is the registration strategy we're pursuing. On the left, the first study done was our phase I study. Again, saw a very strong response rate there, which led to ASPEN-06, which we're gonna talk about, and then ultimately into our randomized study, which will be our phase III. The phase II design... Wait, can I go back? Here we go.
The phase II design looks at evorpacept plus Tras or Herceptin, and then RamPac or the chemo backbone versus Traz plus, plus RamPac. And that, that is a little different than the registration study, which will be comparing versus RamPac, because RamPac alone is the global standard of care in the second line. This highlights what the current benchmarks are. So on the top is the RAINBOW study, which was RamPac versus Pac. Again, I think the highlight here is, 28% versus 16% overall response rate with pretty modest survival gains. And then there is the DESTINY-Gastric01 study, which is an Enhertu study, which looked at Enhertu versus, physician's choice chemo. Again,41% versus 11% , 11% overall response rate. So both large randomized studies, but demonstrate relatively modest response rates and survival benefits that certainly need improvement.
So, as we mentioned, the design of ASPEN-06 was to really isolate the contribution of evorpacept. So the only difference between the two arms here was the addition of evorpacept, and importantly, we did not limit what prior treatments were used in the first line. So whether that's Enhertu or checkpoint, we truly ran a second and third line study to test the power of evorpacept. This was an interim pre-specified analysis of 54 patients, and the goal was to see, you know, a 10% delta versus response, versus control, excuse me. The study was well-balanced. Again, this was a global study. We had over 40 sites participating across 19 countries, and the arms were balanced in terms of age, stage of disease, et cetera. Turning to safety, I think this has been very encouraging and perhaps underappreciated.
We've seen a really consistent tolerability of evorpacept across a number of studies. And what you can see here is with the Evo arm on the left versus control, a very balanced safety profile, which is consistent with the backbone therapy. And we do not see evorpacept adding any additional tox on top of backbone. So in terms of the punchline, what we demonstrated was a 52% versus 22% overall response rate. Again, we were shooting for a 10% delta, which from a clinical perspective, is the minimal difference that we needed to see. So we're very pleased to see nearly triple that. Again, first randomized study to read out in solid tumors in the space. Also encouraged to see 1 CR, which are few and far between in gastric.
Although early, I think encouraging durability as well, as we were not reached on the treatment arm, but yet had 7.4 months on the control. So again, this compares well with both DESTINY studies as well as the RAINBOW study. So in terms of the waterfall, again, I think what we see here is substantial, consistent tumor shrinkage on the left versus control on the right. And I think what was most exciting for us as a company is if you were to overlay the ASPEN-06 data with the ASPEN-01 data on the right, a very consistent effect. So what we saw in phase II was remarkably similar to what we saw in phase Ib study. Again, as context, the RAINBOW study-...
with RamPac as the global standard of care, you know, we showed a pretty substantial benefit over that and, you know, are encouraged by that as we think about next steps. So in some robust clinical activity, we had ORR of 52% in a patient that's in desperately desperate need of other options, and we think we compare well versus the standard of care out there. Again, well tolerated. We are not seeing the heme-related tox that others in the space have seen, and it's been consistent across what we saw in the phase I and now have seen in the phase II.
So with that, I'm gonna turn to the second mechanism, which is really looking at using the same "don't eat me," blocking "don't eat me" signal, but this time doing so to better activate T cells. So in the head and neck study we're running, we're looking at evorpacept plus Keytruda. And in essence, you know, by blocking the "don't eat me" signal, we are able to better activate T cells. And through activating the dendritic cells, we're able to cross-prime T cells to better target cancers like head and neck. So historically, if you look at the space, head and neck is interesting in that overall response rate has not necessarily been predictive to survival.
The definitive studies in the space, KEYNOTE-048 and KEYNOTE-040, demonstrate this, where they showed roughly equivalent overall response rates, both in first and second line, and then they demonstrated gains, relatively modest gains, but gains in overall survival. Which I think is really important, because if you look at our data, we've now tested over 20 patients in a phase 1b, and what we were able to demonstrate was consistent survival benefit. So if you look at our overall survival rate at 12 months, which is in the green, you know, in both first and second line, we showed north of 80%, which we believe is a very strong, although early signal in head and neck, and helps validate what we think is a second very interesting mechanism. So what are we doing now?
We're running two large phase 2 studies, ASPEN-03 and ASPEN-04. These are first-line head and neck studies and will be definitive studies in the space. Again, first randomized studies to read out in CD47, which we're planning on later this year. And the study design reflects the current Keytruda label. So one is Keytruda alone, so evorpacept plus Keytruda versus Keytruda, and ASPEN-04 is evorpacept plus Keytruda plus chemo versus Keytruda and chemo. Again, directly reflective of the label. It's a co-primary endpoint, so looking at OS at 12 months as well as response rates. And that's gonna also read out later this year. So what we're excited about is, again, two potential first-in-class mechanisms.
We don't have the third mechanism on here, which many of you are aware of, but magrolimab and others were testing a different mechanism other than these two. We believe that the responses and the activity that we've seen across these mechanisms have been differentiated and consistent, and that's what you see in the middle panel here. Again, the gastric data was the first to read out in solid, but it builds on both data we've seen in heme with our phase Ib in NHL, as well as our phase Ib in gastric, which was also positive. And again, similar for the checkpoint story. We had positive phase Ib data, which drove our strategy in terms of phase II. So from here, we're now testing nine. We have nine ongoing studies, so a very robust development plan.
On the anticancer antibody front, we are testing with trastuzumab, as I mentioned, but we also believe that this, this effect with an anticancer antibody should apply to heme. And so we're running a study in collaboration with Sanofi to test evorpacept in combination with Sarclisa, and we also are soon gonna read out data in NHL. On the ADC front, which, again, mechanistically, we think makes sense, we are testing evorpacept in combination with two of the most prominent ADCs out there, with Padcev and bladder, as well as in HER2. And again, mechanistically, we believe we should be synergistic and additive to an ADC.
And then last, as I mentioned, we're going to read out over 300 patients randomized later this year, testing the theory with Keytruda, which we believe will be a seminal moment for the CD47 space. So, in terms of milestones, how does this set up for upcoming catalysts? Of course, we have a really busy year, but we have gastric data, full gastric data coming Q2. As I mentioned, we're gonna report NHL data, Q1, Q2, which we're excited about to help broaden the story beyond solid here. And then in the back half of 2024, of course, we have the 2 big readouts with ASPEN-03 and ASPEN-04. And then, you know, we'll also have additional readouts with ADCs, Padcev and HER2. Behind that, we have a really exciting pipeline.
We've been working on ADCs for the last, I'd say 3 years. We've been very quiet about that, but are also planning to share more, over the next six months as to what we're doing.... with novel ADCs and are actually, planning to have one of the ADCs in the clinic over the next year. So in terms of financials, we've raised over $600 million to date, off of the gastric data. In the fall, we raised, roughly $60 million, which was a strong financing, very much oversubscribed. But that leaves us well set up going into the year. We also have a $100 million loan facility with Oxford and SVB.
We've pulled 10 of the 100, and so we now are in a place where we can we can get through all the milestones this year with no financing overhang and have cash into early 2026. So that's us. Again, very excited about what we what we have. Very excited about what we've shown, which is differentiated in this space, and looking forward to a big year. So questions? Sure.
Thank you very much, Jason, and the ALX team. Are there any questions from the audience?
Start happy hour early, I think.
All right. That being said, we do have some questions from our end. As you noted, obviously, you have a lot of exciting milestones and data coming out. So I wanted to talk about evorpacept, specifically for ASPEN-06 in your phase II trials. So you're expecting final analysis from the phase II study, which will include about 122 patients, to be disclosed in Q2 of this year. How does this interim data give you confidence for the full dataset next year? And what is your-- what's your bar or expectation for full data, appreciating that investors might be expecting ORR to come down with a few more points? And how should we think about the disclosure of the data as well?
Thanks. Yeah, I think, you know, what's important to note is that this isn't a phase 1b going into a phase II. This is a phase II pre-specified interim readout going to final. So again, you know, this was a global study enrolling over 40 sites, and we've shared, you know, I think, the data to date. So what is the risk when from going from what we have now to final with 122? You know, it's hard for me to handicap. That's what you all do. But again, I think we see the enrollment and the sites, et cetera, being all consistent and, you know, I think as we tried to highlight in the slides, the efficacy and safety is both very consistent between the phase II and phase 1b.
So we're confident, and we've had a lot of enthusiasm and interest in the study, which helps drive us forward and, you know, we're feeling optimistic about the data. Mm-hmm.
Nice. Thank you. On that topic, is that something that you would release on your own or maybe hold for a medical conference?
We're still working toward the exact plan there, but I, again, feel confident around Q2 and the, and the timing and where we are.
Thank you. How do the encouraging early results in gastric cancer de-risk your other programs?
Yeah, I think that's one of the most exciting things for us. If you go back a few years, the reason to choose gastric was because it was a great place to test the theory, if you will, to test what the drug could do in combination with anticancer antibodies. So I'd say we're excited about the future in gastric, but what is as exciting is where else we can go. And that's the beauty of this mechanism, is that the combinations with other anticancer antibodies in other spaces make logical sense, and we feel are very, very much de-risked. So you could think about HER2 positive breast, you could think about colorectal in combination with EGFR. You know, you just tick through the list of where anticancer antibodies have built franchises, and those are places we can play.
So that's what we're doing right now.
Thank you. Speaking of where else you can go, wanted to touch on your ex-U.S. strategy. So Asia has a disproportionately higher disease incidence and prevalence of gastric cancer than U.S. or Europe. Can you talk about your geographic development strategy for evorpacept in gastric or GEJ cancer, as well as your potential commercialization strategy outside of the U.S.?
Sure. Well, we have all zero employees in our Asia offices, so it's, you know, I think it is on us to figure out how best we get this drug to the world, if you will. And I think gastric, as you know, is largely a Asia-based disease, and so we need to think about how we best do that. And I think one of the great parts about having interim data as strong as it is, is it allows us to talk to partners now and explore that. And so, you know, we'll see. I think the good news here is that we have not done any deals around evorpacept. It's a completely wholly owned asset.
It's unencumbered, and so we, as a company and a board, have a lot of flexibility as to how we'd go forward, and, you know, we're gonna explore that, and if a deal makes sense, we'll do one. But I think we also, you know, have a lot of options in front of us here.
That's awesome. Yeah, two-year cash runway definitely helps for that as well.
That helps.
And just shifting gears a little bit to head and neck cancer and talking about your ASPEN 3 and ASPEN 4 updates. So wanted to talk about accelerated approval. So ASPEN 3 and ASPEN 4 were designed to potentially support registration. Is that still the case, and is accelerated approval still on the table for you?
Yeah, I think the way it was designed, if you look at combining 12-month OS and ORR as co-primaries, was to support that. Again, the cost you pay as a small company is it takes a long time to get there. But the good news is we're on the cusp of that now.... And that's what we're planning to share towards the end of this year. So, you know, I don't wanna play FDA. I'd be terrible at that if I tried. But of course, with a strong package in a space like head and neck, that has a really significant unmet need, you know, we're gonna present our story and see where it goes.
But certainly, the design of the study, when you think about over 300 patients randomized, is robust enough to support it from, from our perspective.
Yep, that makes sense. And speaking of design and stats, so in the phase II studies, you have co-primary endpoints of 12 months, OS rate and ORR. Can you clarify, do both 12-month OS and ORR need to be statistically significant to be considered a win in the phase II studies?
Yes. Yeah, that's correct.
And then-
I don't wanna play statistician either.
Fair. And then for the other indications that are attractive with the pembro combination, what indications are you thinking about for the future? And would these be programs that you would think about partnering to bring forward?
Partnering which programs? The pipeline programs?
Yeah, that's correct. You're-
Yeah, I think, I think that's certainly possible. Again, you know, we... I think quietly have been building a really strong pipeline, thanks to Jaume and the R&D team. And certainly with the space, you know, the hotness, if you will, of ADCs, I think it puts us in a position to talk about partnering there as well. So it's something we're also interested in exploring.
Perfect. And then, just to touch on some of your other programs, besides evorpacept, you have another program named ALTA-002. Can you talk about that a little bit for us as well?
Yeah, sure. So that's a combination. It's a joint effort with a company called Tallac that we're working on. Again, you know, we're excited about the program and, you know, hoping to get that in the clinic this year as well. More to come there. We've intentionally not said much, but plan to share more later this year.
Awesome. Thank you. That's all from our side. Are there any other questions from the audience? No? If not, we can wrap up early. Thanks again. Appreciate you all.
Thanks, everybody.