Good morning. Thanks for joining us for another session at the 42nd JP Morgan Healthcare Conference. I'm Brian Cheng. I'm one of the senior biotech analysts here. I'm joined by my associate, Sean Kim, who is in the audience today. On stage, we have the whole team from BioAtla, which is also in the audience. So we're gonna start, kick off with a fireside chat style, to, to kind of walk through, your entire portfolio and get the latest on, and the greatest. Maybe it would be great to kind of, you know, get a recap of the, the latest development. You know, December had been a particularly, busy, time for you across a number of assets, in your portfolio.
So maybe, Jay, maybe you can kick us off with just, you know, what we got in 2023. You know, what were the key milestones that you achieved back last year, specifically around December? And as we look into 2024, what are the key goals across each of the program?
Okay. Well, thanks for inviting us here, Brian, and it's a pleasure to join everyone. 2023 was a very productive year for BioAtla, as Brian just alluded. And in fact, let me highlight three key accomplishments. 1 is that we had very exciting CTLA-4 data, both from efficacy and a safety standpoint, which is a very significant need out there in the marketplace, and that's been illustrated both by obtaining partial and complete responses with our initial readout there. Number 2, we had 33% partial responses in a very difficult-to-treat AXL-positive fourth-line non-small cell lung cancer patients. And number 3, we've had durable complete and partial responses in ROR2 in both melanoma and head and neck cancer.
In addition, last year, we prioritized our portfolio, which allows us to deliver on our near-term key data sets and value inflection points later on this year. Our current cash runway takes us into the second half of 2025, and we would expect to see some of those impacts of that prioritizations really in the second quarter this year. But onward to what's happening in 2024, more specifically, we will see readouts, additional readouts of CTLA-4 phase II readouts, in the first and second half of this year, as well as additional exploration of higher doses, and that will be completed in the first half.
We also expect final readouts on the target-agnostic data for both AXL and ROR2 ADC assets, for both of these CAB antibodies, and those will both occur in the first half of this year. And this data that will be coming out will allow us to file registrational study in either AXL and/or CTLA-4, either independently or together with partners.
Great. So we can do it sequentially. Maybe we'll start off with CTLA-4. That's your earlier program, but, you know, we've gotten, you know, early signs of efficacy here. To remind me here, you know, your CTLA-4 approach, how does that differ from, you know, what we're seeing, you know, with the currently approved agents and, you know, the dosing work that you have done? Can you just kind of tell us how that compares to the dosing that we've seen with the currently approved CTLA-4 agents?
Eric, do you want to grab that one?
Sure, I'm happy to take that. Thank you for the question. You know, we're super encouraged with what we're seeing. With Jay just mentioning, we have a complete response that's confirmed in a patient with metastatic cervical cancer, and then a patient with metastatic gastric cancer now in a confirmed partial response. Your question is about the currently approved agents, tremelimumab can be given as a single dose, ipilimumab can be given at 1 per kilo, every 6 weeks. Sometimes there's a dose limitation at the 3-per-kilo dose level. And, you know, with 25 years of experience with CTLA-4 blockade, investigators love what they're seeing in long-term survival benefits from randomized trials, but they're very hesitant to use higher doses, and that's the real challenge.
What we've done is we've recently cleared the 5 mg/kg dose with acceptable tolerability, and now we're testing 10 mg/kg.
I'd add, that's in combination with PD-1, so it's, I think, a significant safety bar.
Mm-hmm. So when you think about the 10 mg/kg dose, how does that compare to, you know, the PK/PD profile that you're seeing? And how comfortable are you that you can potentially dose higher and, you know, assuming that you can, d osing higher means that you can translate to a better efficacy.
Exactly. That's our thesis, is dosing higher would translate to better efficacy, and, we're quite confident that the 10 mg/kg dose will be acceptably tolerated. And we'd like to be able to continue dosing. That's an important point to make, is that often, with the currently approved drugs, investigators need to stop dosing, because of immune-related adverse events, and we'd like to continue that exposure over time. And our PK findings are really normal and expected.
Mm-hmm. And maybe just on the, you know, the combination approach, right? You know, you see how do you view it as a monotherapy agent, you know, in terms of potential? And then, as you think about the optimal combination for dosage for to combine it with, for nivo, for PD-1. Do you have a sense of what the target dose is, so that, you know, you can build on what you already know about the agent?
Yeah, great question. We believe fundamentally that the highest acceptably tolerated dose is the dose we'd like to use in combination. We'd like to use it both as monotherapy and in combination with PD-1 blockade.
Overall, how do you think about the market that you can penetrate with this asset? You know, given that, you know, doctors that are in the space are already—I mean, they know a PD-1 CTLA-4 is really in their playbook already, right? So, how do you view your CTLA-4 CAB, right?
Sure.
I n the overall market? And, you know, when you think about this asset specifically, too, when let's say, you know, you go out there, you're a sales rep. Let's say, you know, 3-5 years down the line, are they gonna pitch it as this asset, 3071 specifically? Is this gonna be a pitch for better safety profile or better efficacy?
Yeah, I can take that, and I would say both. You know, we view, based on our phase I data, that our CAB CTLA-4 has the potential to be a best-in-class CTLA-4, and also holds the promise to be used as often as a PD-1. Our overarching thesis is that the CAB technology enables CTLA-4 blockade in the tumor microenvironment, which results in clinical benefit consistent with, or even better than, the approved agents, and also enables the drug to be given for a longer period of time, and thus, enables the patient to really experience the full clinical benefit of the therapy.
You know, we already have seen compelling profile at the current dose in combination with PD-1, and we're studying higher doses, like, you know, and excited to see what those results will look like, both as a monotherapy and in combination with a PD-1.
So just going back to the December updates, you know, you aside from the efficacy, which, you know, Jay, you kind of mentioned, you know, in your, in your, the first question that I asked. You laid out two specific paths for, right, for this, for the phase II. One is for treatment refractory, and then the other one is for treatment naive. How are you thinking about just the plusses and minuses to go into the later stage? 'Cause, I mean, there are certainly risks, you know, going for one or the other, right? And, you know, there is a higher bar to go into the treatment-naive setting. So what are you considering? What are the key factors that would make you want to go one way or the other?
Sure. Sure, I'm happy to step into that. So again, both. We're looking at both the treatment naive and the patients that are treatment refractory, and we're really allowing our data to guide us here. So we're exploring not only higher exposures of CTLA-4, but we're also exploring the CTLA-4 monotherapy and in combination in treatment-refractory tumors. We'll have the data guide us there for next steps. And very importantly, we're also studying patients that have newly diagnosed metastatic melanoma and metastatic non-small cell lung cancer to obtain data there to guide us for that next steps for the randomized pivotal studies.
Mm-hmm. So how should we think about, you know, what we should... What's the bar to achieve, right?
Yeah.
And what do you need to see to get confident around the individual settings? And maybe can you kind of frame how we should think about, you know, what, what's the green light or go, no-go decision, right? I mean, when you look at the sarcoma work that you have done, it's very clear-cut, right? So, as you think about this program, which is still relatively early stage, so what, what is the bar here to move into the individual, settings?
Sure. I think the bar is to obviously be meaningfully better than the marketed CTLA-4 antibodies, both in terms of safety and efficacy, and the ability to deliver it over a longer period of time. Ultimately, the bar in a randomized registration study would likely be progression-free survival in a randomized setting.
Okay. Maybe turning to AXL 3011. Maybe touch on the first indication first, in UPS. What's the latest progress in the ongoing study? You know, maybe a quick update on just where, how we should think about the study and also the near-term milestones.
Yeah. So there's first there's the UPS study, and then there's the non-small cell lung cancer study. So the UPS, we updated in November that we had focused on one of the two doses we were taking forward in the first 40 patients. Because we focused on a dose, now we've narrowed that to needing 20 patients. We've also are looking at target-agnostic patients outside of that study just to see if there would be another way to increase the pace. So we are going to update the pace of that study and where we're headed with that in the first half, potentially in our fourth quarter earnings call at the end of March, and that would be a hope that we can do that and have enough insight on it.
But, but that's kind of where that's at, at the moment. You'll hear-
On the target?
Y eah, on the target, w ell, we're gonna update on the pace of the UPS and how that goes forward.
Okay.
Whether we'll have all of the data on the target agnostic, I don't know, 'cause I don't see that coming into play until the second portion of that, UPS study, 'cause the initial portion is 20, the second portion was 40. So it's, it's something that would be brought to bear if it, if it, made sense-
Mm-hmm.
B ased on the data. And then, of course, with the non-small cell lung cancer data, we are in the midst of—we have almost completed enrolling the target agnostic data set, at least at the 2 Q, 3 W level, and we'll, we'll subsequently finish the every other week dosing. So long story short, both of those are going to read out target agnostic in the first half, so we'll have completed that entire analysis, and we're, we believe that we will be able to go forward in non-small cell lung cancer in target agnostic, just like we already have demonstrated in ROR2 and are moving forward target agnostic there.
Mm-hmm.
So this is a good segue to get into that specific angle, right? So, you know, how confident are you that you can get into the target agnostic population? And maybe you can also talk about just, you know, your work to kind of make sure that this is the case, you know, and in NSCLC and also potentially in UPS as well.
Yeah. I'll just start off by saying that, when we moved to target agnostic for ROR2, and the reason was, and I'll just back up for a second, we were using a biomarker. We were getting 10% positivity rate for ROR2, but it's immunohistochemical assay, and it's relatively insensitive. So the level you need for that biomarker is much higher than you need for the action of the drug. So when we moved to target agnostic, we immediately got two PRs at a TmPS equals zero based on that arbitrary detection of that assay. So you realize the companion diagnostic isn't contributing, it's slowing down the process. You're not able to help as many patients, so we moved there. We also saw, likewise, in head and neck cancer, TmPS zero there.
So then when you come back to AXL, which I think is more along your lines of the question, we've seen responses at 100% TmPS score, and we've seen responses at 0% TmPS score, excuse me, at 1%. So it's clear that you can get responses across that entire range. So basically, what we're doing is simply testing some additional patients at TmPS 0 and demonstrating some clinical benefit, and that will be the green light that to move to this lung study to the registrational trial. And so that will read out in the first half, and that's that. We feel like it's very high probability.
Got it. So, additional target agnostic patients data-
You got it.
... in TPS 0.
Just showing clinical benefit-
In-
Then move from there.
And then move into figuring out the next pivotal study.
And by the way, I just should add that I think in general, the vast majority of ADCs that are out there, also are target agnostic, and I think it just simply reflects on the fact that, these drugs are very potent.
Mm-hmm.
They need less of the receptor on the cancer cell to get an effect than what these biomarkers show. And I think on top of that, with the CABs, you're able to really push dose and keep patients on longer. So it's a win-win scenario to move this direction.
Maybe going back to UPS. I know that we're kind of jumping back and forth, but just going back to UPS.
Mm-hmm.
You know, how do you think about the market opportunity here? You know, this is a small indication, and so you know, you can definitely go on it, you know, commercially by yourself versus you know, and also partnership as well. So what's the latest thoughts around potential partnership for AXL, specifically for UPS? I know that there's potential partnership discussion currently ongoing, but how do you think about that specific UPS piece, you know, in a broader context of, you know, since this is your lead program.
Mm-hmm.
Y ou know, late, you know, late stage?
Yeah. I'll first start with sort of how we're viewing the opportunity. So UPS represents one of the largest subtypes of sarcoma, and there's a significant unmet need because of the limited therapeutic options. So when we think about the market and the potential here, we believe that our CAB-AXL ADC can achieve peak of over $500 million worldwide, and with a relatively small commercial infrastructure, as you noted, Brian. So making it an attractive indication for us to potentially commercialize ourselves. Just to comment on the partner on the partnering aspect of the question, it's very difficult to partner an asset by an indication.
And so when we look for a potential strategic collaboration for our AXL ADC, we would be focused on the asset as a whole, partnering in both UPS and non-small cell lung.
Great. Within third-line plus non-small cell, how do you think about the bar in terms of the response profile? You know, how should we think of the regulatory path moving forward, you know, just based on your interactions with the regulatory agency?
Yeah. Thank you for the question. As we reported on our day with Dr. Carl Gay, we spoke about our regulatory interactions that charted two paths forward, potentially. And regarding the third-line plus, we received agreement from the FDA that an approval would be based on demonstrating improved overall survival in a blinded, randomized study versus single-agent chemotherapy. And that was really a gratifying response that enables us both to consider a second-line indication against docetaxel or the third-line indication that we just described.
Great. And then, in the overall potential opportunity within NSCLC, how should we think about the, the market opportunity here?
Mm-hmm.
Can you just kind of help us conceptualize the potential commercial opportunity, you know, in the key markets?
Sure. So if you, if you look at specifically, and extrapolate the population from our phase II study, right? So PD-1 failure, EGFR wild type, and you, and you extract that population to estimate market potential, both the second and the third line each represent large billion-dollar-plus opportunities worldwide for us. So, so both second line and third line would be, you know, a substantial commercial opportunity for BioAtla.
Maybe switching gear to ROR2, 3021. There are multiple paths here for ROR2. You know, where are you in ROR2? Maybe just a quick recap on the indications that you're working on, and you know, what could be the next near-term inflection points in terms of data flow?
Sure. So the key indications that we're looking at are patients that have treatment-refractory metastatic melanoma, and we're also looking at treatment-refractory head and neck cancer. Importantly, a patient who's had treatment-refractory metastatic melanoma continues in a complete response that's lasted over two years, and we now have announced several additional patients that have achieved partial responses, one lasting quite a long time as well. So these studies are now fully enrolled, and we anticipate readouts of both of the data sets in the first half of this year for both head and neck and the melanoma.
Okay. Can you talk about just the opportunities for you with ROR2 and within melanoma, and SCCHN as well, too? How should we... You know, as you know, are these big markets for you, and are they commercially attractive to move forward?
Yeah, I mean, there's a profound unmet need in treatment-refractory melanoma as well as treatment-refractory head and neck cancer. And so, you know, we believe that an effective, off-the-shelf ADC with a manageable tolerability profile would have considerable commercial potential in both treatment-refractory melanoma as well as in treatment-refractory head and neck cancer.
Maybe going back to Eric, to the readout that you have in both of the lead indications, right? How should we think about the signal that you're looking for to make sure that, you know, these indications are good to go, these are, you know, de-risk indications that you can move forward with? How should we think about the, you know, the response that you're looking for in the first half?
Sure, sure. In refractory melanoma and head and neck cancer and/or are an overall response rate of about 25%-30% with an antibody drug conjugate, I think is about the bar. Yep.
What about for, you know, SCCHN as well?
It might be a little bit lower.
Mm-hmm.
B ut in that range.
Okay. How many patients could we potentially see in the upcoming readout?
Mm-hmm.
I'll just say that we do have a corporate deck on our website that gives this and the goals for 2024 that just went up this week, and but we're estimating about 25 patients in melanoma and 20 patients in head and neck for ROR2.
Great.
I mean, maybe moving on to EpCAM, how do you think about the potential for the phase I? And, maybe just also kind of backtrack a little bit as to, you know, talk about the, the mechanism of action, too. We have seen some signals with EpCAM before. Maybe just kind of backtrack us to your, your EpCAM CD3 approach, and then we can talk about, you know, the potential of this phase I study.
Maybe Eric can share this one with me, and I'll just start off by saying this is a dual CAB antibody, so it has a CAB on the T-cell recruiting CD3 arm. It also has a CAB on the tumor-targeting arm, which is the EpCAM. This is a target that is on a tremendous number of cancers, and we can consider it a pan-cancer type drug, which I'd almost consider CTLA-4 in a similar category. But it, because it's also in normal cells, you really need that CAB selectivity that's driven by the pH selectivity that's naturally occurring with the cancer cells. And so, in the preclinical work, very exciting, over 100-fold improvement in the therapeutic index, which is really unheard of.
I, just to frame this, I think in the old days, if you saw a 2- to 3-fold improvement in therapeutic index, you'd be quite thrilled. To see a 100-fold is unprecedented. So, I think that gives you a little sense maybe of the molecule itself, and we're doing a dose escalation, and maybe, Eric, allow you to add to that.
Sure, I'm happy to, Jay. So several years ago, Amgen tested an agent called solitomab. It's an EpCAM CD3 bispecific T-cell engager that's obviously not conditionally binding. They through a phase I study, they ran into gastrointestinal toxicity, hepatic transaminase elevations. But there were some inklings of clinical benefit in that study, and they really, really tried to push the dose, but because of those toxicities, were not able to go forward. So our strategy is with the conditional binding arms, both, as Jay mentioned, on the EpCAM side and the CD3, that we're really further amplifying the therapeutic window. And we see multiple other sponsors interested in EpCAM as well. So it's so widely expressed on adenocarcinomas, and we're very enthusiastic.
We have a committed set of investigators that are actively enrolling patients on that trial.
We anticipate finishing the phase I this year and reporting out on it, and hopeful that we can advance it into phase II later in the year.
Okay, and then, how should we think about the bar here in adenocarcinoma?
Yeah.
For the phase I? And just to remind me, is this a dose escalation study for phase I? And, you know, how many doses are you testing? And, yeah.
Yes, and as Jay mentioned earlier, we have a slide in our corporate deck that is quite detailed on illustrating our dose escalation, the dosing groups, an accelerated titration pathway, as well as the potential, if we needed to go to it, to give a prime dose. We really built all of that into the protocol. And you asked about the bar, and it's really an interesting question. So if you think about it, this is all adenocarcinomas, so all cancers that, you know, from glandular tissue, which, you know, would include all the gastrointestinal malignancies, breast, prostate, lung, others.
Colorectal.
Quite a few.
Mm-hmm.
So it's hard to really establish a bar, but in treatment refractory setting, if we were to see multiple confirmed responses per RECIST, I think that would give us indication that we have a very promising agent. And then, we would look to the market potential of these different opportunities, the competition, and then guide for which indication we would pursue.
Okay.
We did clear the second dose on that dose escalation chart that you'll see on the corporate deck, and it's labeled Clear, so cleared, so you'll know exactly where we're at.
Any early thoughts about the safety?
So far so good, but I would say that it seems, you know, like it's gonna be potent, so we're gonna... And so far, so good on safety.
Mm-hmm.
We'll keep watching.
Just to kind of go back to your point about the multiple indications within this broad indication, can you talk about just, you know, what is the lowest hanging fruits here, just based on, you know, what we have seen in the past from other EpCAM CD3 approach? How do you think about the lowest, you know, indication subset of indications to grab, as we look into potential updates, you know, sometime this year?
Hmm.
Well.
I'll just say colorectal cancer is certainly one of the ones we talk about. I would stop short of saying that's a decision, but I just wanna point, highlight that one area. It's a huge unmet need, and this is a drug that could really make some impact there. So anything else you guys would like.
Yeah, I was just going to say, of course, you know, we're, we'll let the data help to guide our decision in terms of what to pursue, but I was going to also reiterate that colorectal cancer certainly is a significant unmet need and one with, with, I think, very large potential.
Maybe, Jay, so maybe just taking a step back now. Now, I think we did a you know discussion on each of your assets. Maybe taking a step back onto your entire platform, right? You know, we've seen a number of ADC deals in the last couple of months.
Mm-hmm.
It's been an interesting thought, you know, that, you know, how different are these ADC platforms overall? In your approach, your CAB-ADC approach, can you just talk about just how different is your CAB approach and how, you know, potentially, you know, applicable to other indications, to a set of indications, compared to other ADCs, companies that we have seen out there?
Yeah. So, the CAB platform can work in any cancer indication across the board. There's no limitation from that standpoint. And I would also say that CABs can improve any ADC system because it really eliminates on-target binding. So what does that mean? That means if there's a receptor on your normal cells where you don't want the ADC to attack, our CAB, using the CAB technology, it won't go after those receptors on normal cells. It will only go after those cancer cells that have that receptor, and that's based on this pH mechanism that we developed--we identified and then further developed the CAB antibodies to. So it's very interesting.
So in our initial two CABs, we're using, you know, the MMAE and peptide linker, but as we have newer generations, we've also moved to the sugar linker downstream, and expect an IND in the first half of this year for that. But I have to say, we're mostly focused on our clinical assets at the moment, for obvious reasons. But nonetheless, I think the CAB technology brings to bear a therapeutic index improvement that's very, really quite difficult to attain with any other ADC technology that I'm aware of. I mean, the closest you might say is if somebody tries to target two receptors on the same cancer, so they're trying to get there, but this is a very clean play and doesn't require that dual receptor requirement. But the technology would actually improve that system as well.
So, I think it's a good segue getting into your, you know, the partnership question, right? So, you know, when I think late last year, we talked about the, your interest in potentially partnering off one or two of the assets. What is the specific characteristic of these partnership interactions that you're looking for, you know, to make sure that, you know, the baby that you have grown are in the right hands?
Yeah.
Mm-hmm.
Sheri, you wanna?
Yeah. I'll just start off by saying that, you know, with the recent as well as the emerging data, we think that this is the optimal time for BioAtla to really seek strategic collaborations. And we're looking for, you know, partners who can, who are able to support robust, pivotal clinical development paths. And, you know, when we look at CTLA-4 specifically, you know, there are so many indications that can be pursued with this particular asset. So, you know, looking for a, I think the ideal partner would be a larger pharmaceutical company, who has a PD-1 on market, or a PD-1 in late-stage clinical development.
I would also say that, you know, partners that are able to, like I said, support pivotal development paths that will, actually expand the market potential, and help us maximize the value of these assets, given the broad applicability of these ADCs and CTLA-4.
So let's say, you know, we have the same conversation related to portfolio, right? Let's say two years from now, you know, 2026, at this conference, what, what do you think we'll be looking for? You know, how, how do you think your pipeline chart is going to look like? And, I think this gets back to your question of, you know, what, what do you, what do you wanna keep? What do you want to partner on?
Yeah. I think, first off, you know, I talk a fair bit about technology 'cause I know the power of it, but, you know, really, what is our mission? Our mission is to bring life-saving cures to cancer patients. And, you know, what I'm very encouraged about is that and excited about, actually, is we're already seeing durable complete responses and partial responses in patients, so that's fundamental. And we're seeing it in each of our three phase II clinical assets, all of them. And so at a minimum, in a couple of years, you know, let's call it 2026, like you said, Brian, you know, I'd expect to see two assets in late-stage phase III development in collaboration with partners preparing for commercialization.
In addition, we would like to advance at least one of our existing clinical assets into phase III clinical development, where we can develop it on our own. Then, in addition, of course, we would like to outlicense multiple preclinical assets with partners as well, so we can further leverage our platform.
Great. In terms of just the, I guess, you know, just to kind of wrap up the, what, what we discussed today, can you talk about, you know, what, what we could expect beyond the, the set of assets that you have, you know, in the preclinical work, the discovery work that you have done? You know, can you give us some insights on what, you know, potentially what you're looking at? And then just to kind of wrap up is, you know, what are the near-term data catalysts, you know, for, for the rest of 2024?
Well, let Sheri do the near-term data catalysts, but I think in terms of preclinical assets, and obviously, we did a portfolio prioritization to make sure that we can extend the runway into the second half of 2025, so we really hit these key milestones. But, you know, I think that we have a blend of CAB ADCs and CAB T-cell engagers as our primary group of preclinical compounds, and a next-generation ADC CAB system will be out. So when we look at how we're reviewing this portfolio, we're really looking for partners in that area that can really take some of these novel assets and push them forward. So, but the other part of the question, I'll let Sheri touch on.
Yeah, data flow for the rest of 2024. What, what should we look for?
Yep, absolutely. So 2024 is a very exciting year for BioAtla. There are a couple of important catalysts that I'll highlight and leave you with. The first is safety and efficacy data of our CAB-CTLA-4 at higher doses, potentially even up to 14.2 mg/kg, as well as phase II data in combination with a PD-1 in refractory solid tumors. That's the first one. The second one are those datasets in target-agnostic populations for both our CAB-AXL-ADC and our CAB-ROR2-ADC. The third is initiation of potentially registrational study with either our CAB-AXL-ADC in non-small cell lung cancer and/or our CTLA-4 in a refractory tumor. And finally, completion of a strategic collaboration transaction for our CAB-CTLA-4 and/or one of our CAB-ADCs.
Great. Yeah, go ahead.
I'll just say, Brian, thank you for having us here today. It's been an exciting year, and we're focused on execution and delivering these at key value inflection points throughout the year.
Great. It's always a pleasure to have you. Thanks for joining us, and looking forward to seeing the number of data catalysts that you have for the rest of the year. Thank you.
Great.
Thank you.
Thank you.
Thank you.