All right. Good morning and welcome to the Annual Citizens Life Science Conference. It's my pleasure to introduce the next presenting company, BioAtla. Joining us on the stage is the team from BioAtla, Jay Short, CEO, joined by Eric Sievers, CMO, Sheri Lydick, Chief Commercial Officer, and Rick Waldron, CFO. Appreciate you guys being here.
Thank you, really.
I never know who exactly is in the audience or who's listening on the webcast who knows the BioAtla story. I always like to start off these discussions before we jump into details with maybe a two to four-minute overview of what BioAtla is about.
Sure. I'm happy to give you a little bit of an overview. We're a clinical stage oncology company headquartered in San Diego, California. We have four clinical assets. Clinical stage assets, three are in phase II. We also have a fundamentally interesting and important conditionally active biologic platform that allows us to increase the therapeutic index of our therapies, meaning that we're able to increase potency while at the same time increasing safety. That widening of that therapeutic window is fundamental and allows us to drug targets that otherwise would not be druggable without this technology. In addition, the company is in multiple active deal discussions, which we believe will allow us to advance at least a couple of our molecules into phase III together with partners. We are quite busy at the moment.
Great. Let's jump into, I guess before we jump into the pipeline, let's take it just a step back as we think about kind of the conditionally active biologic space, right? You guys are one set of players. There are other competitors that you have that are all trying to, in one way or another, get these antibodies or ADCs to get activated at the tumor microenvironment. Based on the data that you've generated to date and even the competitor data, as well as deals that are being done in the space, can you maybe confidently say that the platform has been validated and now it's just a point of developing the right study to move forward and prove it? Or is it kind of still up in the air and the platform still needs to be validated?
First off, the platform mechanistically is different than any other group out there. It has some significant advantages because it does not require an activation step. This means the kinetics are very good. When it goes to the tumor, it is able to bind immediately. When it leaves, it will not attack a normal tissue target. That is why we refer to it as reversible. It is a fundamental difference and it widens the therapeutic window further. It allows us to have higher potency. In terms of validation, we think one of the greatest examples we have seen is AXL as our target. We know that, and I think all of us know that there have been two other companies that went after this very important target. It is important because it is directly linked to KRAS mutations in lung cancer mechanistically.
GAS6, which is an activator of AXL, is one of the byproducts of KRAS mutations. That whole cycle is what causes tumor resistance. It is a really important target, not only for lung cancer, but in a lot of other indications. Yet two companies failed to be able to build a drug that could show the risk-benefit, meaning that they had too much tox for the ability to treat the tumor. Here we have seen very strong data. What I would particularly point out is the overall survival. This is one of the areas and one of the main reasons that drugs fail in second-line non-small cell lung cancer: the lack of overall survival. They will see some initial reduction in tumor size, but then it is not sustainable and patients really do not survive.
We're seeing very strong data going out over two years now, 59% survival. We haven't hit a median yet on overall survival. I think two other companies have tried to take it into the clinic. They've taken it into the clinic, but they failed on that. I think that's pretty black and white. I think the other quick example might be EpCAM. Amgen worked very hard and diligently to try to get that important target, which probably represented on upwards toward 90% of all tumor types and couldn't make progress to get it to a dose that's really going to matter. We already have, even at a low dose, seen three patients with double-digit tumor reduction. We think we're on the path for seeing responses in the near term. The safety is looking very encouraging at the moment.
Let Eric talk about that in a few minutes. Those are just a couple of quick examples. I think it's validated. We're on a very good path.
Excellent. Let's jump into the EpCAM program. We have some data coming out. First time we're seeing this data, if I remember correctly, at ESMO GI. You can correct me if I'm wrong. Can you kind of set the stage for us? What is it that you're looking for? What can help you kind of gauge that? What are the metrics for that go, no-go decision going forward?
Sure. I want to emphasize this is an interim look at an ongoing dose escalation study, first in human, phase I, very standard study design where we've dose escalated through cohorts of patients. We're now treating at a treatment dose of 300 micrograms at the treatment dose every week. We plan to continue dose escalating per the rules of the trial as far as we can go, as long as it's acceptably tolerated. We mentioned earlier that EpCAM is an attractive target. It's expressed so widely on adenocarcinomas that that would include non-small cell lung cancer, triple-negative breast cancer, colorectal cancer, pancreatic cancer. The list goes on. Any glandular tissue making EpCAM is really within our target. What we're seeing to date, we'll get into in the Congress, but we're setting expectations that roughly 25-30 patients will be discussed at this Congress.
We'll talk about the safety that we're seeing and then the level of activity. We've recently noted that we have a patient that is over a year without progression and then one that is now over eight months without progression, both with colorectal cancer.
Just to help remind us, this is not a CAB, right? This is a bispecific or.
It's a CAB. And it's in fact a double CAB. So we say it's a dual CAB. And what that means is that it's conditionally binding on the T cell arm, the CD3, as well as the EpCAM. And so what that does is it multiplies the conditionality. Jay, do you want to speak a little more to that?
Yeah, I can mention it. I mean, in our preclinical studies, because the tumor targeting arm, which is the EpCAM, that receptor is on the tumor cell. Then we have the CD3 receptor on the T cell. On many antibodies, you'll see it's a homodimer. One arm can bind and then it can still attack the tumor. Both arms bind, attacks the tumor. In this case, you have to have the EpCAM binding on the tumor cell and you have to have the binding to the CD3 on the T cell. Only if you get both of those binding do you get it and do you get it correctly. If you added in selectivity, just a simple way to think about it, if I got 10-fold selectivity on one arm and I got 10-fold selectivity on the other arm, I'll get 100-fold selectivity.
That multiplies how good the selectivity is. We see in our animal testing that we're approximately 200-fold selectivity based on this. It is fundamentally differentiated even from our other CABs in terms of how potent this is. We think that's a pretty powerful opportunity. Given its broad spectrum of expression, both on tumor cells and on normal cells, you really need a technology like this if you expect to turn that into a drug. That is what Amgen did not have back in the day.
Got it. If everything goes well according to plan, kind of what are the next steps, right? You mentioned this is an interim look. Do we then kind of wait for a recommended phase II dose? What is the path forward? Is it monotherapy? Do you evaluate combo? How does this kind of continue down the clinical development paradigm?
Yeah. So we're obviously looking for responses. We'll be gratified to see them when they occur. I have no sense of exactly when that's going to occur, whether it's at 300, at 900, or higher in terms of microgram dosing. We contemplate the use of combinations where a PD-1 inhibitor might be added to really enhance the T cell function and prevent T cell exhaustion. Those are considerations that we're making, as well as what indication. I thought that the very recent report from Amgen that tarlatamab had a survival benefit is very good for other T cell engagers in the clinic because it shows that in the lung environment, the T cell engager can create that immune synapse in small cell lung cancer. I'm particularly intrigued with non-small cell lung cancer.
Of course, colorectal cancer with 100% EpCAM expression, that makes it very straightforward without the need for a companion diagnostic.
I will add that in the animal modeling data as a monotherapy, which is the way we're really thinking it will work in that setting, it's about 200 micrograms was what the modeling suggests. There can be error around that, but we kind of feel like 300 micrograms is really the first level that we have a shot of starting to see the PRs. Based on the guidance of that, we think this can work quite well as a monotherapy. I mean, obviously we can do future combinations as long as we maintain the safety that we're currently seeing. I think we're a pretty exciting opportunity given other T cell engager companies that are seeing excitement across this field. To do it with EpCAM is a whole nother level. That's because it's such a broad pan cancer opportunity.
Just remind me, we should be expecting to see 300.
Yeah, I think 300, we should have some scans on that.
By the data update.
I'm hoping, yeah.
Hopefully we'll see something encouraging since already at subtherapeutic levels, we're starting to see hints of activity.
Yeah, if we see some good stable disease, maybe we see it in a PR. We'll have maybe three plus patients on that particular dose level. So we'll see.
I want to bring Sheri into this discussion because EpCAM as a target, I think a lot of investors have largely called it, dismissed it, right? Because you brought up several other companies that have tried and failed. What is the potential market opportunity here? How should we be thinking about that?
Yeah, I mean, so EpCAM, as Eric noted, is widely expressed across a number of different adenocarcinomas, breast, lung, colorectal. I think, as you know, it's also widely expressed on normal tissue. A dual CAB is really something that we think will be differentiated and we'll be able to take this to market. It could potentially be, given its expression, given what we can do with a dual CAB, could be a pan cancer drug across the adenocarcinomas that EpCAM is widely expressed. Clearly a multi-billion dollar opportunity if we're able to really bring this forward.
As an example, it's expressed 100% of colon cancer tumors. 100%. I mean, that's kind of very unusual for a cancer target. And multiple ones in the 90% plus percent.
Terrific. Look forward to seeing some of that data at ESMO GI. I want to switch gears to the AXL product, right, that you have in development. The KRAS mutant non-small cell lung cancer data look really impressive. I think in your most recent deck, you guys announced results yesterday. Your deck is updated. I'd urge investors to kind of take a look at that. You've shown kind of historical overall survival curves. You've shown what your current survival curve looks like. Could you maybe talk us through that and kind of help set expectations with the caveats that obviously cross-trial comparisons need to ultimately be proven out in double-blind or randomized studies?
Yeah, sure. So yeah, we've seen unprecedented one- and two-year landmark survival in KRAS-mutated non-small cell lung cancer of 67% and 59%, respectively. To put this into context, if you look at previous studies in patients who have KRAS non-small cell lung cancer treated with docetaxel, you're seeing one- and two-year landmark survival of less than 40% and less than 20%. A substantial survival benefit that we're seeing over the long term. I think it's also important to note that we're seeing a similar type of survival benefit in sarcoma, subtypes of sarcoma, which we just included in our corporate deck. This is important because seeing this type of survival in two different indications, I think, strengthens our conviction that MECV is actually improving the natural history of the disease and is allowing patients to live considerably longer despite what they might receive after.
I mean, we're excited about it. We believe that it's differentiated from what standard of care agents that are currently available on the market can do, as well as potentially investigative agents as well.
Now, can you just take us through that it's an ongoing study you're following? There are patients still on therapy and living longer, I believe. Just correct me if I'm wrong. When might the next update be that we can take a look at this? Also, I guess even more importantly, what are the next steps for this program, right? We can continue to follow and maybe do three-year landmark and things along those lines, but what can you do to either A, move it forward yourself, or trigger a potential partnership opportunity?
We have had guidance from the FDA that the trial would be against docetaxel, kind of standard of care in second line plus therapy. What we would hope to do is add a few patients randomizing against docetaxel as kind of a preparation for that phase III trial. In parallel, though, we are in discussions with several partners around this asset. We think that it is likely that one may be advanced together with somebody, but we will see. I think that from there, we have quite a bit of data in AXL, but we believe very strongly it is going to be a Q2W 1.8 mg per kilogram. That is going to be our dose. We are seeing high safety. We are seeing, I think, 25% confirmed response rate. The thing that ultimately gives you approval in this space is the overall survival.
That's wildly differentiated. As Sheri said, we've just mirrored the same type of activity in soft tissue sarcoma across multiple types with the AXL as well there. To see that happening in two different indications really gives us increased confidence that we're dealing with something very important and powerful. I think that's kind of our base plan. EpCAM, we're putting some basic small priority, maybe large priority on that one above all because we really want to drive that. It's very unique. There's low competition in multiple areas with that drug. I'd say full pressure on driving that, getting to finishing the dose escalation, driving expansion, then right behind and with that is the AXL activity. With ROR2 and with CTLA4, we're focused on partnering and have active discussions there.
Yep. I'm going to end with ROR2 and CTLA4. But just going back to the with Mec-V, the combination with docetaxel, sorry, not combination, when do you think you might start that?
I think our target is to have that data in the first half of 2026. Our runway will allow us to get to that end point and a little beyond. Hopefully we're believing that we'll be dropping a DLN before that happens. We will go much further.
Got it. When we look at the landscape, right, we have KRAS inhibitors. The landscape is changing, right? We think ultimately better for patients. As you guys look at it, where do you see this kind of potentially fitting in? Is it ultimately in combination? Is it straight up against docetaxel in the worst of the worst patients? How do you think about it?
I would just start off and let Eric finish this, but I just want to point out that we're not seeing a lot of overall survival good results that ultimately require the full approval. Okay? I think from a comparator standpoint, this is very strong. You may not have so much competition when it comes to that ultimate overall survival standpoint as a monotherapy. Clearly, there's opportunities in combination with safety. Eric, you can put a finer point on all that.
I see our approach as orthogonal and absolutely could be combined. We have not been combining with adagrasib or sotorasib or the Revolution Medicine drugs, but certainly could be done. We got a bit of a head start. Now we have data showing a remarkable three-year overall survival, no median overall survival yet with continued follow-up, eight patients continuing in long-term follow-up regardless of a variety of different treatments they have received. I think these results, these survival data speak for themselves. Obviously, we would need to prospectively confirm that in a randomized pivotal study against the standard of care docetaxel. Unlike the other agents, the survival endpoint has been particularly challenging as we saw from the ODAC with Amgen and sotorasib in the Code Break study not being interpretable for overall survival or clinical benefit.
Correct me if I'm wrong, Eric, but my understanding is there's a very, very high selectivity to mutant KRAS versus those that are wild-type KRAS patients. Has that already been determined in your study?
I think quite clearly we put out a poster in December at what was called the Hot Topics in Non-Small Cell Lung Cancer meeting. It's available on our website. We put all of our presentations there. We saw very clear survival benefit amongst the patients that got the AXL-ADC who had the mutated KRAS compared to the wild type. The wild type people who got the ADC is tracking right along where docetaxel would be. Ours has a plateau and a survival benefit. That is the moment we realized we found our target population biologically defined using mutated KRAS, the genotype.
I would just add that we continue to see a high correlation of AXL and KRAS expression. Mechanistically, there is evidence there that makes sense as to why we would see what we are seeing.
Got it.
We have an internal control. I mean, we've compared our overall survival with the non-mKRAS versus mKRAS, and it's definitely differentiated. You can see responses in the non-mKRAS group, but when it comes to overall survival, it's like black and white. And mechanistically, it's very logical. We're hitting the mechanism that's the driver.
In the last, call it two and a half minutes that we have left, I want to talk about partnerships because it's not only a way to help you extend your cash position. I'll end with Rick at the end regarding cash position, but extend your cash position, but then also get additional external validation and the like. How are you thinking about partnerships, especially with the ROR2 asset and the CTLA4? I think you have some updated data coming out at ASCO regarding your ROR2 asset. I'd love to kind of help set expectations and probably end with what do you think the chances are that a deal gets done this year?
I think the chances of a deal getting done are very high. We're very confident that we're going to do it. Because of the stage of the discussions, I also think that leaning on ROR2 just for a moment, I think this differentiated activity in HBV positive patients really differentiates from the pack. It's something that's poorly served with EGFR agents. This is a large but niche area, kind of in the $500 million-$750 million area. If we focus in second line HBV positive, you can have a more modest trial, an opportunity for accelerated approval. That's attractive to people. We think we're going to make some good progress there. Some of that data was first revealed in March, so that's kind of new, but it's making an impact.
Of course, I think the AXL safety does lend itself for people that like to think about combination therapies, already have a drug that can fit in. We know that there are some discussions in that area. I feel pretty strongly that we are going to move a partnership here with non-dilutive capital, and we will keep driving here. I do not know if that answers your question already, but we are pretty excited about it.
I like the confidence of a deal happening still.
It's based on the stage of those discussions.
Yeah. Perfect.
You never have a guarantee, but I feel if anything, it's likely that it's pretty likely.
Thirty seconds left. I asked Rick just regarding the cash position you guys reported yesterday. How long does that kind of take you? I will not speculate on how long, if you got a deal done, how long that takes you, but how about with the existing cash?
We know it goes into the first half of 2026, but maybe Rick, you can provide a little color on what's happening in the upcoming quarters at a general level.
Yeah. Yeah, we finished the first quarter at $32 million in cash. And as Jay just mentioned, that in itself is sufficient to carry us into 2025.
26.
2026 by itself. But it's always been the strategy of the company to develop its programs in partnership with corporations, major corporations. And we're in active discussions right now. And of course, that'll be non-dilutive financing to be able to carry these programs forward.
Excellent. Thank you guys very much. I really appreciate the update.
Appreciate it.