BioAtla, Inc. (BCAB) Earnings Call Transcript & Summary

Sarcoma.

Yes. Sarcoma. Where are you in the pivotal Phase II for UPS?

Yes. And so here's the update. We have initiated Phase II of Part II, which is potentially registrational study, if positive. We have received written feedback from the agency on this study. We will be enrolling approximately 80 AXL-positive UPS patients. The FDA is supportive of investigating as well a more frequent dosing regimen. I think this is very important given the safety profile that emerged and the benefit risk was very positive and they were very supportive of us moving to a more frequent dosing regimen, which hopefully, will yield even better results in the UPS population. The first 40 patients with TMPS greater than 50 will be randomized to 2 different dosing arms, the standard dosing arm and the more frequent dosing arm. After we get through 40 patients, we will do an analysis of those and we will move forward with the one arm, which has the best benefit risk with an additional 40 patients. So, the primary efficacy analysis will be based on 60 patients treated at the selected regimen. Prior systemics are limited to 3 and below, I think, which is very important. We have, to this point, studied a much more refractory population than that. And we have seen -- if we take a look at UPS in Phase I and Phase II, we see a 50% overall response rate in this population, which is highly unusual, very, very difficult patients to treat. You would expect without treatment or with an ineffective standard of care for these patients to advance or progress very rapidly within 8, 10, 12 weeks and yet we're seeing a long-standing, long durability responses in the UPS population. So, we're very, very hopeful. It's obviously an area of very high unmet medical need. There's 4,000 to 5,000 patients a year in the U.S. alone that are UPS AXL or AXL-positive UPS. So, we're very excited about it. Just on the more frequent dosing regimen that the FDA has greenlighted for us, we've started to dose some patients in that. I think we have 4 patients or 3 patients that we have started. And the first patient scans that came in were 29.6% reduction in an LMS patient. So, hopefully, we can get even more efficacy out of this more frequent dosing. So again, just to summarize there, sorry if I was a little long winded. To summarize, we have received written feedback from the FDA. We're greenlighted to go. The study is initiated and we should be dosing in this study within the next few weeks.

So, maybe just going back to your AXL-positive lung indication. How big is that study? And how does the time line of starting that pivotal fits into a time line of your ongoing sarcoma study?

Yes. It's an interesting question and one we've talked a lot about. At this point, because we haven't finalized those interactions with the FDA, I can't give you an exact number in terms of what the powering should be. My guess is somewhere between 100 and 130 patients, somewhere in that range. And if we initiated that in the third quarter, given the prevalence of non-small cell lung relative to UPS, even though we start UPS in quarter 1 and non-small cell lung in quarter 3, the 2 could catch up, and we could have data for both programs around a similar time frame. I think we are thinking -- and again, we don't have the agreement from the FDA or the feedback, so I don't want to get too harsh on time lines, but we're thinking in terms of UPS that by the end of '24, given the powering that we see in the sizing that we could be in a place where we would have completed enrollment and filed by the end of '24, if everything goes according to plan. I'd like to be able to get the study going and really enroll patients and in order to finalize that. It maybe plus or minus a couple of quarters and we will update that when we get to the Q1 call, but our estimate right now is that we could be enrolled and filed by the end of '24.

Okay. Maybe switching gear to ROR2. What's the next update from ROR2? I think it's guided to 1Q. What do we expect there? How many patients work with data? And what are we really looking for?

So we -- for ROR2, we have a non-small cell lung program. It initiated about 6 months behind the AXL program, and we had our first data in the AXL program in August. So, 6 months would be February, March. I think we might have the first data. So, that will be a Q1 data event, whether we find an appropriate venue within Q1 or whether we save that for the Q1 call, it just depends on how things are. But that's a Q1 data then I would estimate somewhere 14, 16, 18 patients in that through multiple scans by the time we talk about that data in Q1. We saw -- just as a reminder, we're very excited about what we're seeing in AXL non-small cell lung. In ROR2 in Phase I, we had, I believe, 3 patients that were ROR2 positive and we had 2 very good durable responses in that population. So hopefully, we can start to see some of the same in ROR2. For melanoma, it's a little bit more complicated. We have dosed 3 patients between Phase I and Phase II. We have 2 complete responses out of those 3 patients. However, melanoma, the ROR2 positivity rate in melanoma is about 10%. And with the biopsy requirement, the sites standard onerous to have 9 negatives for every positive that they were doing in terms of biopsy. So, we are now implementing what I would call a liquid biopsy assay so that there can just be a blood draw, much less onerous than doing an actual physical biopsy. We're just executing and implementing that into the study as we speak. And we'll give an update on the Q1 call, whether that has -- we've been effective in changing the trajectory of that enrollment or not. But obviously, very, very promising to see 2 complete responses out of 3 patients. And again, multi-refractory IO failure melanoma. Head and neck cancer is the third indication for ROR2 and we're activating multiple sites. We're screening patients and we should be dosing in that program in the coming days. So, those are the 3 active programs. Also, if it's okay, to give an update on ovarian or is that a question. So, we also have for both AXL and for ROR2 program in platinum failure ovarian cancer. This is being done as an IIT. We have 7 patients enrolled or they have 7 patients enrolled in 1 arm in the AXL arm and 6 in the ROR2 arm, and we would expect some initial data from that sort of mid-year this year. Again, it's an IIT being conducted not by the company. So, I can't give exact time lines but we should have some data, hopefully, mid-year this year on both those programs, a very high degree of AXL-positivity, particularly in this ovarian population. So, we've got good hope there.

So, on the ROR2 NSCLC, how different is this compared to AXL-positive NSCLC? Is there an overlap that you have seen so far?

So, the number of patients where we see 35% of non-small cell lung refractory non-small cell lung patients, AXL-positive, it's more like 25% for ROR2. And interestingly, we see very, very few patients that are positive for both ROR2 and for AXL. So, they seem to be sort of separate patient populations that we're looking at here.

So, let's say the data for ROR2 is what you wanted to proceed to the next step. How will that work? As you think about resource allocation since you're both going towards the same NSCLC population?

So, they are 2 distinct subpopulations because there's not the crossover, right? So, I think there is a clinical and commercial opportunity for both sort of the -- what's embedded in your question and the bigger question for me, I think, is do you want to be doing 2 pivotal lung populations in the same centers, maybe you get them to biopsy tissue and check for both ROR2 and AXL and you can do that, but we're going to wait for those results, see what they look like and then decide either to do them concurrently and staggered or whether to do them sequentially one after the other. But both the ROR2 population and the AXL population, non-small cell lung are very significant and represent a very, very significant commercial opportunity.

Okay. And then maybe just beyond what we talked about today, AXL, ROR2, I think you also have CTLA-4, EpCAM that are underway. What are some of the key [ text ] that we should focus on in the next 12 months or so?

So, here's the CTLA-4, and I'll give a little bit of an update on where we are here. Maybe, Jay, you can talk to some of the preclinical data for this, which was really, really striking gives us some real hope that the things are moving forward. But for right now, we are at the third dosing cohort. I learned 2 or 3 patients had passed. I learned passed through, not passed in the bad way, but had gone through the levels with no DLTs, and were fine. And we got word about an hour ago that in the third cohort, the third patient has cleared and we're moving on and we'll start dosing in the fourth cohort, which is 210 milligrams. Important to note that this -- where we are with BA3071 CTLA-4 asset at 70 milligrams is the approved Epi dose in combination. And so far, we have seen no detail DLTs and we're looking forward to moving into the fourth cohort. So Jay, do you want to speak to the preclinical stuff?

Yes. I would just mention that -- remind everyone that you're getting on the order of 36% over 1/3 of the patients discontinue the combination therapy with this CTLA-4 PD-1. So, solving this -- and tox is a major issue, especially when you use the combination, you're seeing almost twice the survival. So, when we look at the preclinical data, we held similar efficacy through those studies, but it saw a dramatic improvement in safety. And it's that combination that we're trying to get to. And I think basically, our goal here is twofold. One is to get to as much as possible. But one way to win is a higher dose in the combination. The other way to win is keep patients on longer. You can't keep patients on this combination on the approved drugs today. So, we have 2 ways together. And I think given the strength of that preclinical data, we're quite hopeful that this was going to go in a very good direction and we like what we see so far.

And for me, this is going to be a very interesting proof of concept or proof of principle of the CAB technology playing out in the clinic. With the ADCs, you're somewhat limited by the toxic payload that you're delivering to patients. And so you sort of capped and how far it can go. This is a naked antibody and if the CAB technology plays out the way we think we can, we're hopefully going to be able to very significantly drive the dose here and keep patients on longer.

And it's kind of interesting as well because this is an unusual CAB, we were able to keep the activity off of pH 7.4, the blood level activity or alkaline for normal cells, but yet have it activated starting around pH 7.0. That was such a tight window and really shows the refinement of the technology in terms of being able to build in such selectivity.

Any thoughts on what are the potential indications given the target has already proven?

I'll let Scott...

Yes. I think you want to go down the route of, sorry, where is Epi, where is it effective? Where is it tolerated? Where do you see good responses? And we don't want to go down those routes. So, this is a Phase I, not all-comers, but sort of selective comers and that we're allowing patients in into indications in which Epi is proven to be effective. Ultimately, I think we don't need to do every indication here. I think a couple of studies and indications where the pattern of efficacy and safety is well established with Epi, we can do those studies and see if there's significant differentiation.

Okay. And on EpCAM?

No slide for that one. But I think it's exciting bispecific molecule. It's on probably on the order of vast majority of solid tumors express this receptor. It's been very difficult to handle in the past. It's almost essentially considered undruggable given its toxicity. We saw in preclinical studies, a 160-fold improvement in the therapeutic index and that's because we -- it's a T-cell recruiting bispecific, meaning 1 arm is directed at EpCAM and the other arm is directed at CD3. And when you design them in that fashion using CABs, you get the product of the 2 selectivities, the EpCAM selectivity times, the CD3 selectivity. And we never hit a maximum tolerated dose in those studies and we're well on our way to filing the IND here shortly. And I think our timeline is in good shape. So, we're very excited about it.

So, just given the number of assets that you have in your portfolio, how do you think about partnerships, specifically for BA3011, do you see the need to bring in a partner? And if so, when would be an opportunistic time to bring them in to accelerate what you have?

So, the word I think that's important there is a need. I don't think there's a need. Between Philippe and myself and Eric and Sheri, we have globally developed assets to commercialization before we know how to do this. We can do it ourselves. We have been very fortunate to be able to do 4 raises in the last couple of years, including one that closed last November, we're well capitalized. We've got a runway through 2025. Now having said that, the thing that I have in my mind is not me, but can we find a partner that will help us maximize the value of the asset, allow us to do global clinical development faster, global clinical development quicker, more indications, be prepared through medical affairs and commercial structure to be able to maximally commercialize the molecule globally. And I think that's where we're looking for a partner, partner globally that can increase the value of it rather than needing somebody to get it over the line. I think we've got sort of higher hopes than that for it. So, there's a lot of -- there's been a lot of inbound interest in the asset. The data is pretty striking in UPS and in lung. And we would hope to find a good global clinical commercial collaboration to help us move this forward.

Looking ahead the next 12 months or so, what are the key catalysts? And maybe just on the data catalyst, how many patients worth of data, what's the expectation that you think that you will want to see?

So, let me run through this a little bit here in a little bit more detail so that we all have the right expectations. We should begin dosing in UPS Phase II Part II, the registration part any day now in the coming weeks. So, that's an early Q1 event. For non-small cell lung, we should have the data from all of Phase II Part 1 midway through the first half and we plan to have a presentation of data at ASCO in May and so that's coming. We should also submit a request for written feedback in the middle of -- middle of the first half, probably before the end of the quarter, received that written feedback sometime midyear and initiate Phase II of the registrational part, Phase II Part 2 in the second half of this year, hopefully in the third quarter. So, lots going on there. As I mentioned earlier, we expect to receive that ovarian data sometime in the midyear period and we're excited to learn that. Non-small cell lung interim data for ROR2, we'll be -- hopefully, we'll discuss that significantly in the Q1 call. Melanoma, we'll give an update on whether the liquid biopsy assay has been effective in helping us change the direction of recruitment there. We should have some Phase II interim data in the second half in head and neck cancer. And the same time frame for ovarian sort of mid-year to have that for ROR2. For BA3071, which is CTLA-4 in the second half of the year, we should have first Phase I data, including some efficacy data there and also Phase II initiation in selected indications. And then, again, through -- for the CAB, EpCAM CAB-CD3 bispecific, sort of Q1 IND filing and hopefully, patient dose in Q1, late beginning in Q2, so.

How important is the -- in the last couple of minutes, I just want to see how important is the ovarian cancer, the IIT interim data that you have? Is there a bar that you would like to see before potentially considering folding back into your portfolio?

So, I think it's very important. There is a significant AXL expression in this population and significant ROR2 expression. It's an area of high medical need -- high unmet medical need. I don't know, Philippe, do you want to comment on the regulatory or commercial bars that we're looking for in terms of ovarian?

Yes. I mean the data we're going to get is from 10 patients for AXL and about 10 patients for ROR2. So, it will be preliminary data, but it will give us a good sense of the overall response rate. We should expect in these platinum failure population. And so from a bar -- from a response standpoint, I mean, the response in this platinum failure patient can be quite low. So, we think that anywhere between 30% to 30% response in that 10 patients worth of data would take us to the next stage of development.

Great. I think we're at the top of the hour. Thank you so much for joining us today at our fireside chat with BioAtla. And thanks, everyone, and thanks for the management team for joining us as well.

Thank you all very much.

Thank you.