Well, welcome to everyone. This is the annual Citizens JMP Life Sciences Conference. It's my pleasure to introduce BioAtla. Presenting for the company is the team here, Jay Short, CEO of BioAtla. The remaining team members are Eric Sievers, CMO, Sheri Lydick, CCO, and Rich Waldron, CFO. So thank you all for being here. It's very, very rarely that I get the entire management team up here, but I'm glad you guys were able to make it. I never know exactly who's in the audience and who's listening in on the webcast, who may or may not know BioAtla. So I'd like to start these Q & A's off with, maybe a two to, you know, five-minute discussion on BioAtla as a whole. So maybe you can just tell us about the company.
Well, thanks, Reni, and thanks for the invitation here. A pleasure to see everyone in our audience today as well. BioAtla is the inventor and leader in the area of Conditionally Active Biologics that are focused on directing therapeutics against low pH or acidic cancer cells. So it's a fundamental characteristic that all cancer cells have, and the advantage of this technology, it allows us to target cancer cells without attacking normal cells. And this is very important because it allows you to increase efficacy as well as improve safety, increasing effectively the therapeutic index. And so, also, I think it's worth noting some probably three key highlights within the company. The first, of course, is our assets, using this technology, which we refer to as CABs. And so we have three phase II clinical assets.
Two of those, of course, in the ADC area, that basically we're gonna be reporting out on some tomorrow at our Q1 earnings. Number two, we have a CTLA-4 and immuno-oncology therapy as well. So those are some of the key assets. I would also say that second highlight is the fact that they work across multiple indications. We're seeing anti-tumor activity in solid tumors. We're also seeing manageable tolerability across those agents as well, so that's very exciting. And I think the third key point is that as we increasingly start to talk about where we're gonna go in the marketplace, these assets are differentiated relative to other marketed, and in most cases, assets that are in development.
And then, in terms of what also is happening tomorrow, we're gonna report out on our ROR2 ADC, as well as an update on our CTLA-4 phase I data. And then finally, I would just say that, if we look forward to the second half, you know, one of the key things I would say, it's going to be... We'll be providing some data on our CTLA-4 in frontline patients in melanoma. In addition, we are targeting to have at least one potential registrational trial initiated, kicked off by the end of the year. And the second and the third point there would be that we're also targeting a strategic partnership in the second half of this year.
Finally, we do have a dose escalation going on a exciting T cell engager molecule EpCAM CD3, and so we're looking forward to reporting on that as well. So kind of a full agenda, but on the other hand, it's nice to see that a lot of our phase II activities are getting ready to potentially transition to phase III registrational trials, so we're excited about that.
Yeah, you guys are positioned really well in, you know, obviously the ADC space. A ton of activity in that space, especially from an M&A perspective, and a ton of investor focus. So maybe, you know, with ASCO, but just starting off, especially for our oncology companies, I always like to ask, right? There's a huge oncology conference coming up, ASCO. You guys have some, I believe, some data coming out at ASCO for BA3071. I believe it's also monotherapy and combination data, correct me if I'm wrong, but could you maybe help set the stage and highlight to investors, you know, what you feel will be the most important things that we should be-
Well, this is a great one for Eric, please.
Yeah.
Sure. Thank you, Reni. So, at ASCO, we will be, as just as you said, presenting data from both monotherapy and combination. Last year, we presented a pretty fulsome update about where we are with the CTLA-4 conditionally binding antibody. And at ASCO, we're going to be delivering more data about that. We'll be characterizing duration of treatment. We'll be talking quite a bit about toxicity of treatment because I think as everyone knows, CTLA-4, because it's been well-characterized for over 25 years, it's really about driving the dose as high as you can with acceptable tolerability.
So if we focus in on that, as we think about, you know, what kind of results could get investors excited? What are your kind of internal benchmarks? Can you talk a little bit about, you know, what it takes to move to the next stage, and what the next stage could look like?
Sure. I think I'm gonna focus mostly on dose. So, we know from large randomized studies that dose matters. Before PD-1s were around, there was a large trial of Ipilimumab given at 10 milligrams per kilogram versus 3 milligrams per kilogram, and long-term survival data clearly support the 10 over the 3, despite the fact that the 10 mgs per kg dose was considerably more toxic. So, survival still shows very significant differences in survival at multiple years of follow-up. So that really helps guide us that, that dose matters, and very importantly, because it's conditionally binding technology, we're delivering that dose into the cancer microenvironment because of the low pH.
So we're trying to drive new T cells, we're trying to keep them alive and non-exhausted with the PD-1 combination, and then we're enthusiastic to think about other combinations that are novel, that could further drive efficacy as well as result in a very tolerable regimen.
Okay. There's a monotherapy dose escalation study that's ongoing right now. I believe you're at 1 gram?
That's right.
Right?
Yeah.
In terms of the dose.
Although I think, from the dose escalation standpoint, it's a combination. We also have a phase II monotherapy that's going to be read out toward the end of this quarter.
Mm-hmm.
Just to clarify that.
Okay. So if safety's cleared, right, I guess, you know, what's the possibility that we keep escalating, right? Is there even a point to, right, given your comments about the 10 mg and the 3 mg differential, right?
Yeah.
And then, you know, kind of how should we be thinking about the next steps, you know, for...
Okay.
I'll just say because we're gonna have a call tomorrow, we're gonna give an update around that area, but I think we all have previously communicated that we had cleared the 700-milligram flat dose, and we had moved that dose into treating patients both in the monotherapy and also, more recently, into some of the first-line patients. However, even though not originally planned at the beginning of the study, we've actually moved to the 1-gram flat dose, and we'll give some update on that, hopefully tomorrow.
Right. So, so I guess just kind of going back to, like, once this update comes out, which I can't... You know, of course, I'd love to hear the announcement ahead of time, but, after this, as we think about sort of the next steps, how should we be thinking about it, right? Is it, is it suddenly a partnerable asset? Is it, "You know what? We're moving into phase IIs with the optimal dose in the optimal indications"?
I guess I'll start, Eric, and you-
Sure
... clean it up.
Mm-hmm.
So look, I think, given what Eric had just described on how important dose is, and I think we've done a lot of modeling on our CTLA-4 relative to ipi, and I think across the board, 'cause our drug tends to mirror ipi from an efficacy standpoint, but I think from a safety standpoint, we're; that's where we're likely to be highly differentiated. The data suggests at around the 700 milligram flat dose that you're getting into the area of EC50, but you're not maintaining it all the time. But it's still a good dose. I don't wanna cause any disparagement on it, but there is a significant potential advantage if you could make it to the 1 gram because it maintains above the EC50 the entire time.
You know, just to remind, this is a point of half maximal activity, EC50, so you would like to maintain that as a very minimum, and you'd like to be above it if you could do it. So I think from that standpoint, that's a driver. I think from a partnering standpoint, maybe I'll let Sheri touch on this one.
Yeah, yeah. So we definitely believe that CTLA-4, to really maximize the value of this asset, that a larger pharmaceutical partner who either has a PD-1 on market or one in development would be an ideal partner for this asset. We still, as you know, and as Eric will go through, we are currently enrolling in the phase II in combination with pembro in frontline melanoma. So I think, you know, we wanna see what that data has in the second half, in order to really be in a position to drive a strong partnership for this asset.
Got it. Okay. So that's an eventful second half. You know, switching gears, I guess very quickly, you know, you guys just followed another company that's in the Nectin space, and you guys have an IND that's approved, BA3361, an anti-Nectin. This is becoming an extremely competitive space, but you have an extremely compelling platform, you know, which should be able to benefit, obviously, patients from a safety perspective. I guess I'd love to kind of talk through that phase I trial, how you're thinking about that asset, you know, what you're looking for, given how competitive the landscape is-
Yeah
... you know, for that to move forward.
Well, I think there's a challenge with Nectin-4s that are, you know, with the Nectin-4 that's marketed, and it's that you have these side effects, rash being one of those, which you would really like to avoid. And all of our modeling data, preclinical data, really points to the fact that we, at least in those animal models, have been able to avoid that and still maintain a high enough dose for efficacy. The key other differentiating thing on this molecule is the fact that it's not only a CAB molecule, which is on the tumor-targeting arm, so it's, will not attack normal cells, or much reduced, at least. In addition, we... This is our first ADC, where with our new-...
Carbohydrate linker, so it's less prone to cleavage by elastase that's normally secreted by neutrophils, which gives you free MMAE that in many cases is not released where you don't want it to be released. Some people refer to it as instability, but it's really a cleavage. But the issue is that with the advantages with the carbohydrate linking, you reduce one of these off-target tox factors, and you have CABs, which also address the on-target tox factor. So it's a really wonderful, exciting combination to bring these two technologies together in one antibody. And so, I think that we have a chance from that standpoint.
Secondly, in the preclinical models, and we compared directly to analogs of the marketed drug, we're seeing activities and indications we do not see at all in the marketed drug, such as pancreatic cancer, and we think we have some sense of the mechanism for why that's the case, and we're presenting that at various conferences. I believe we touched on it at AACR. So, it's pretty exciting. The good news, in terms of going forward with the dose escalation, it really can essentially be an all-comers to address the side effects. We just want to go through it as quickly as we can.
Now, it's interesting, we have multiple opportunities how to take this forward, and, we'll talk more about the best way, because, you know, we, as Sheri already noted, we have partnership opportunities, and we have our own opportunities, so we'll see what makes sense. We'll talk more about that in the second half.
Okay. You know, you mentioned that there are multiple cancers, right, that you could go into. You know, there are a lot of Nectin-4 expressing, you know, tumors that... I think even with bladder, it's so highly expressed, you don't need a particular diagnostic, right, or anything.
Oh, yeah
... along those lines.
Yeah.
Is that how we should be thinking about, you know, the path forward as well, where we're not looking at-
Well, I think you would. Yes, you definitely would, because if you could solve the side effects, why wouldn't you go there?
Right.
You know, you're probably going to be able to keep people on study longer. You're going to have a lot of advantages, I think. But that doesn't mean you wouldn't, in a phase II , also bring up or, you know, or at least in a phase I-B, also bring up a couple other indications where you might make some key differences that were, you know, in tumors that have a very low bar, that might give you a quick opportunity to get to the market while you're driving these other things.
Got it. So, so when I think about things strategically, right-
Mm-hmm
... you know, I, I try to make the breakdown of, do we want to keep this to ourselves or partner it? Do we want to go into indications that are already established, and there's competition there, and we go kind of head-to-head with the competition, or we go into new indications where no one else is playing, but it's a validated target? How does... How do you guys kind of think about that?
I think, Sheri, this would look pretty good.
Yeah, I mean, I think that there are opportunities in both, right? To show proof of concept and an indication that we know is validated makes sense, but it's also depending on what we're seeing and how differentiated our asset can be, exploring different indications that may be entirely open from this, you know, perspective of the target makes sense as well. So I don't think we look at it as mutually exclusive, really. I think that there are opportunities for both paths.
I would also say, like CTLA-4, there is an advantage of having a history out there-
Mm-hmm
... and knowledge, and it really guides you. You know-
Mm
... if you're going to differentiate or not, and I think that's really has helped us with CTLA-4 a lot, what people have already done, and I think in Nectin-4, we'll see some of that same effect as well. It's not that these novel targets, like AXL or ROR2, you know, basically kind of first in class for sure with ROR2, and certainly on our type of molecule with AXL, but I think there's a path, a nice path forward here, especially if you solve the side effects.
Right. So, so let's pivot to, you know, ROR and AXL, right? We have 3021, we have 3071. You know, would love to kind of just remind us kind of where we are. I think we're having updates on both tomorrow. You know-
ROR2 tomorrow,
Oh, ROR2-
Less on the AXL, 'cause that's coming later in the quarter.
Got it. Okay. You know, can you just talk a little bit about, you know, the path, I guess, what to expect and the path forward for both those assets?
Well, that's gonna be hard for us to talk a little bit about until tomorrow.
Sure.
But I would just say that we're gonna give an update, and I think the other key thing is that our ADCs in phase II have been fully enrolled, and they're, you know, basically, that's what's allowing us to bring our costs down to clinical trials. That's always a factor you wanna... Even though our runway is still to the second half of 2025, but we're managing it, and we're on plan, but what's nice is that we're really getting to some very good endpoints in, you know, in terms of expense and clinical trial costs for these, and we'll give a chance to summarize those and hopefully create reports and move to the next point.
Can you remind us just the past, because they have been enrolled. We have seen a snapshot of this data.
Yep.
Can you just remind us what exactly we've seen so far in both programs?
In ROR2, what we saw, we had one patient in phase I, which we had a PR. Unfortunately, it looks like they got COVID and passed away during that time. That was. And unfortunately, the second patient also had a PR, so we had two out of two responses, and out of head and neck, and that's what we reported in November in the melanoma area with that. I believe we had four out of—was it eight? Yeah, four out of eight responses in that initial data as well. And but we also had complete response there that's gone, what, Eric, over three years? Once you-
Yeah, four and a half years.
4.5 years.
Yeah. So it's really that complete responder in melanoma that suggested there's an opportunity there, and we expanded that, and we'll be reporting that.
Yeah, and the only other thing I would just say is that we, in the data we'll report for the ROR2, we tested the every other week dosing we refer to as Q2W, as well as the day 1 and 8 of a 3-week cycle, so every day 1 and 8 every three weeks. So we reported those two, the less intense regimen and the more intense regimen, whereas the melanoma, we just tested the less intense regimen of Q2W. So we'll report out on those.
So, so unlike a lot of other earnings calls, right, or lack of earnings calls in biotech, you know, this is gonna be a pretty meaningful update-
Oh, yeah
... tomorrow. So investors should clearly be, you know, focused in on that. So, you know, Rich is here, and I, you know, I have to ask the obligatory kind of cash question and how long that cash lasts. So maybe you can, you know, give us a sense of what's happening.
Sure. We completed 2023 with $111 million in cash, and as Jay had mentioned, we have two programs in ADCs, which will be fully enrolled, and we'll be completing those trials over the next several months. So the cash burn will be coming down from in the first quarter or second quarter, and that cash position is sufficient to carry us into the second half of 2025. And of course, we have a very broad portfolio of programs here, so corporate collaborations is very important to us, not just from a cash point of view and finance point of view, but being able to aggressively develop the programs rapidly in several geographic areas.
Can you give us just a sense, right? So we see the M and A activity. We see, you know, the deals that are being done in the ADC space, right? Can you give us a sense of how the discussions or your BD efforts, you know, are going? Just some color.
Sure.
Yeah. Yeah, so we've had, we've had interest in, at various levels in several of our CAB assets, including, including the ADCs. Those discussions are progressing well. You know, I can tell you that, that we are focused on doing the right deal with the right partner, while still trying to maintain significant sharing in the U.S. And so, you know, all I can say is that those discussions are progressing, and that's a very important milestone for us in the second half of twenty of this year is to establish the right strategic collaboration with one- at least one of these assets.
That's what we had guided earlier in the year, that this would be a second half goal, and the reason for that is because we have more data readouts coming, and those tend to drive things, and so those groups are under CDA, and so they get a chance to see things a little earlier than sometimes the public does, but we feel pretty good about the second half goal.
So you heard it here first. You know, we're still on schedule for, you know, a deal in the second half. So, that's good. Yeah, 'cause you never know, right? Like, we've seen these things get delayed and-
Yeah
... pushed out, people drop out, so it's good to hear that things are moving forward. Just in the last couple of minutes left, you know, we talked about the different assets, and kind of sprinkled throughout our presentation, kind of, you know, how data's gonna be coming out, but maybe you can just summarize it for us-
Yeah
... as to, you know, what's coming up next, what's gonna drive investor interest in 2024.
Yeah, I think really probably four things to note, and some I've already mentioned, but just worth re-saying. We're gonna report out on first-line patients, primarily in melanoma, but we may have a little bit of first-line data in a subset of lung patients as well. We also, as we pointed out, are positioning for a registrational trial and a significant indication, so that's another key factor toward the end of the second half. Strategic partnership, just to reiterate that. I'll just add that, you know, we also have an opportunity on preclinical side, so, you know, there's a lot of people in pretty heavy need of new assets, which could work to our advantage if they can increase the market opportunity.
And finally, we have a T-cell engager, CAB, EpCAM, CD3, dual CAB, and we'll be finishing off the dose escalation for that asset. It's kind of an exciting area, just like ADCs. You know, there isn't one area that we're in that's not pretty exciting: ADCs, IO with next generation CTLA-4, fundamental for combination therapy, which all of these benefit from, and then finally, I think the T-cell engager. So, you know, and we think it's attracting the right groups to for good discussions.
We have data from all the studies. The T-cell engager is likely at 2025, or is that something-
No, no, that's the dose escalation for this year, and they have the chance of starting kicking off a phase II, but we can't know that yet really until we get to the third quarter and see where things are landing.
Excellent. Any other final comments? Any questions from the audience? Seeing none, I want to thank you guys very much for the time.
Thank you. Appreciate it.
Thank you very much.
Thank you, Reni.