BCAB - NASDAQ

Greetings and welcome to the BioAtla Fourth Quarter and Full Year 2023 Earnings Call. At this time, all participants are in a listen-only mode. A brief question-and-answer session will follow the formal presentation. [Operator Instructions] As a reminder, this conference is being recorded. It's now my pleasure to introduce your host, Bruce Mackle, with LifeSci Advisors. Thank you, Mr. Mackle. You may begin.

Thank you, operator, and good afternoon, everyone. With me today on the phone from BioAtla are Dr. Jay Short, Chairman, CEO and Co-Founder; and Richard Waldron, Chief Financial Officer. Following today's call, Dr. Eric Sievers, Chief Medical Officer; and Sheri Lydick, Chief Commercial Officer, will join Jay and Rick for a short Q&A. Earlier this afternoon, BioAtla released financial results and a business update for the fourth quarter and full year ended December 31, 2023. A copy of the press release and corporate presentation are available on the company's website. Before we begin, I'd like to remind everyone that statements made during this conference call will include forward-looking statements, including, but not limited to, statements regarding BioAtla's business plans and prospects and whether it's clinical trials will support registration, plans to form collaborations and other strategic partnerships for selected assets; results, conduct, progress and timing of its research and development programs in clinical trials; expectations with respect to enrollment and dosing in its clinical trials, plans and expectations regarding future data updates, clinical trials, regulatory meetings and regulatory submissions, the potential regulatory approval path for its product candidates; expectations about the sufficiency of its cash and cash equivalents to fund operations and expected R&D expenses. These statements are subject to various risks, assumptions and uncertainties that can cause actual results to differ materially and are described in the filings made with the SEC, including the most recent annual report on Form 10-K and subsequent quarterly reports on Form 10-Q. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today, March 26, 2024, and BioAtla disclaims any obligation to update such statements to reflect future information, events or circumstances, except as required by law. With that, I'd like to turn the call over to Jay Short. Jay?

Thank you, Bruce, and thanks to everyone for joining us for our fourth quarter full year 2023 BioAtla earnings call. BioAtla is the inventor and leader in the development of novel therapies using a proprietary conditionally active biologics or CABs platform with improved selectivity for attacking tumor cells while avoiding healthy cells, thereby addressing critical unmet needs in oncology to improve patients' lives. We made considerable progress in 2023 across all of our ongoing clinical programs, including the Phase II trials for our first-in-class CAB-ADC product candidates, BA3011 and BA3021, targeting multiple solid tumor types. Our CAB-CTLA-4 IO antibody and our first dual CAB biospecific EpCAM CD3 T-Cell engager. We continue the positive trajectory into 2024, focused on further advancing our prioritized CAB programs generating data sets that potentially enable us to move into one or more registrational trials in the second half of the year. We believe that these near-term inflection points also support the formation of one or more strategic collaborations with major pharmaceutical partners this year, which can accelerate the development of selected assets and maximize their market opportunities. Additional details related to what I'm going to provide are available in today's press release and our updated company presentation, both of which are available on our website. I will now review our latest updates, beginning with our CAB-CTLA-4 antibody, BA3071, which is applicable in areas of high unmet need across multiple solid tumor indications, both for refractory and for first-line patients and represents a sizable commercial opportunity. We are pleased to report that our Phase II data at 350 milligrams flat dose continues to mirror our Phase I dose escalation data in terms of low incidence and severity of immune-related adverse events. In addition, I'm happy to report that we have cleared a higher dose of 700 milligrams, with tocilizumab for the first two cycles and are now evaluating the unprecedented one gram dose level. This is important since previous studies demonstrated improved overall survival in metastatic cancers, including melanoma, with higher levels of CTLA-4 inhibition. As a result, we are now enrolling patients at 700 milligrams in first-line melanoma patients and in a significant targeted first-line non-small cell lung cancer population in combination with PD-1 for readouts later this year. These data are also anticipated to position the company for one or more potentially registrational trials in first-line indications in the second half of this year. In addition, as part of our evaluation of safety and tolerability of BA3071, we are completing the Phase II expansion in treatment refractory melanoma and carcinoma with an initial data readout of approximately 20 patients in the second quarter. As already noted, the safety and efficacy data from the Phase I study demonstrating both a confirmed partial response and a confirmed complete response for two out of six patients is encouraging using the 350 milligram dose. And now we are enrolling the remaining patients at the 700 milligram dose. With our evolving clinical data, we believe BA3071 has the potential to be best-in-class CTLA-4 that holds the promise to be used as often as a PD-1 inhibitor and potentially expand the indications where combined immune checkpoint inhibition can be effective. In addition, the emerging safety profile suggests that BA3071 with PD-1 immune modulation may be suitable for further combining with CAB-ADC therapies that target AXL and/or ROR2 to achieve synergistic durable tumor control. Now turning to our CAB-ROR2-ADC asset, BA3021. For our ongoing Phase II trials in treatment refractory ROR2 agnostic patient populations, we previously reported encouraging responses in the Phase II melanoma and squamous cell carcinoma, the head and neck studies. As part of today's update, we now have both 28 melanoma patients and 12 head and neck patients dosed using the 1.8 milligram per kilogram Q2W regimen. And 20 head and neck patients dosed using the more intense 2Q3W regimen for a total of 32 head and neck patients. We anticipate having two plus scans in the melanoma cohort next month and two plus scans in the head and neck cohort in May with anticipated top line data readouts for both during our Q1 earnings call in May. Given the encouraging emerging data sets, we believe BA3021 is well positioned for a global strategic collaboration to maximize the potential of this CAB-ADC across multiple solid tumor indications. Onto our CAB-AXL-ADC, BA3011. Our Phase II potentially registrational study for undifferentiated pleomorphic sarcoma, or UPS, is on track to complete enrollment of approximately 20 AXL-agnostic patients at the 1.8 milligram per kilogram 2Q3W regimen next month with encouraging compliance and manageable safety. We anticipate having multiple scans across the patient group, potentially enabling a meeting with the FDA to discuss the remaining portion of the potentially registrational study in the second half of this year. We also reported clinically meaningful antitumor activity among patients with treatment refractory bone and soft tissue sarcomas, which remain a profound and tractable unmet need for new treatment options. We presented these data from Phase II Part 1 cohort enrollment as an oral presentation at the ESMO Sarcoma and Rare Cancers meeting earlier this month, and showed disease control at 12 weeks for 43% of the 87 patients treated with BA3011 monotherapy using the less intense regimen of 1.8 milligram per kilogram Q2W. We believe this represents a promising disease control made for patients with treatment refractory sarcomas. In the osteosarcoma cohort, we observed two partial responses out of 11 efficacy evaluable patients. The treatment was well tolerated associated with a manageable safety profile with no new safety signals to report. Now regarding our Phase II study in non-small cell lung cancer, last quarter, we reported multiple durable clinical responses with a differentiated safety profile among a challenging AXL-positive treatment refractory lung cancer population. Specifically, among 15 patients with EGFR wild-type tumors who had received prior PD-1 treatment, we observed five partial responses with a median duration of response of approximately five months using 1.8 milligrams per kilogram Q2W every other week dosing. Toxicity was manageable and few high-grade related treatment-emergent AEs were reported. We believe multiple responses in a treatment-refractory AXL-positive poor prognostic groups such as this one is clinically meaningful and relevant. Particularly since these patients have experienced failure of a median of three prior lines of therapy. As part of today's update, we have enrolled 33 target-agnostic patients using the more intense 1.8 milligram per kilogram 2Q3W regimen across both squamous and non-squamous patients. We are on track to evaluate clinical benefit in the target agnostic non-small cell lung cancer, non-squamous population in the second quarter of this year. Next, on to our potentially first-in-class dual CAB biospecific T-Cell engager antibody CAB-EpCAM x CAB-CD3 or BA3182. EpCAM is a ubiquitous target expressed from the surface of cancer cells, which requires the use of our CAB technology to achieve optimal selectivity and safety. Our Phase I/II dose escalation study continues to progress and is on track. We anticipate completion of the Phase I study with a full data readout anticipated in the second half of this year with potential initiation of a Phase II study also in the second half of this year. If shown to be safe and effective among cancer patients enrolled, our CAB-enabled T-Cell engager has the potential to treat patients with a wide range of metastatic tumors, including cancers of colon, lung, breast, pancreas and prostate among others. As we have previously discussed, ADCs are a promising treatment modality with broad applicability across multiple tumor types to further reduce the potential risk associated with neutropenia from off-target toxicity, we developed a novel next-gen carbohydrate linker system with superior serum stability, solubility and tumor-specific payload release, yielding our first glycoconjugate CAB-Nectin4-ADC BA3361. At the upcoming AACR meeting in April, efficacy data will be presented, demonstrating complete tumor regression in xenograft models. Including superior efficacy compared to an enfortumab vedotin analogue in a patient-derived pancreatic cancer model. We will also present both PK and toxicology data of nonhuman primates as well as the influence of our linker technology in specific cancer models. These data indicate that our NextGen CAB-Nectin4-ADC potentially is a more effective treatment with reduced toxicity. We plan to submit the IND in April. And finally, I am pleased to report our progress with the medical and scientific communities and important ongoing communications with numerous publications and presentations, including at conferences such as ESMO Sarcoma and Rare Cancers, SITC Spring and the AACR annual meeting in April, which can be found on our website. With that, I would now like to turn the call over to Rick to review the fourth quarter and full year 2023 financials. Rick?

Thank you, Jay. Research and development expenses were $22.7 million for the quarter ended December 31st, 2023 compared to $21.9 million for the same quarter in 2022. The increase of $0.8 million was due to clinical development expenses, primarily related to the launch of our BA3011 UPS potentially registrational trial in 2023 and overall accelerated enrollment across our clinical trials in 2023, offset by a decrease in expense for our preclinical programs in selected clinical indications due to our program prioritization in 2023. We expect our R&D expenses to decrease overall in the first half of 2024 due to recently completed enrollment in clinical trials for data sets expected to enable potentially registrational trials for our ADC programs, BA3021 and BA3011. General and administrative expenses were $5.9 million for the quarter ended December 31, 2023, compared to $6.7 million for the same quarter in 2022. The $0.8 million decrease was primarily due to lower stock-based compensation and D&O insurance premiums. Net loss for the quarter ended December 31st, 2023, was $26.9 million compared to a net loss of $27.6 million for the same quarter in 2022. Net cash used in operating activities for the full year ended December 31, 2023 was $104 million compared to net cash used in operating activities of $90.4 million for the same period in 2022. Our cash used for the quarter ended December 31st, 2023, was $29.8 million. Cash and cash equivalents as of December 31, 2023 were $111.5 million compared to $215.5 million as of December 31, 2022. We expect our cash utilization to decrease in the first half of 2024, allowing our current cash and cash equivalents to fund operations into the second half of 2025. And now back to Jay.

Thank you, Rick. BioAtla made considerable progress in 2023 across our ongoing clinical trials targeting various tumor types and we look forward to the multiple important milestones in the second quarter of this year, including initial data readout from our Phase II CTLA-4 IO antibody. Phase II in both melanoma and head and neck cancer and evaluation of clinical benefit in AXL-agnostic patients in our Phase II non-small cell lung cancer study. We are encouraged by the compelling clinical efficacy and safety that continues to emerge, highlighting our differentiated CAB technology across multiple therapeutic targets. With that, we will turn it back to the operator to take your questions.

Thank you. We will now be conducting a question-and-answer session. [Operator Instructions] Thank you. Our first question comes from the line of Kelly Shi with Jefferies. Please proceed with your question.

Hi. This is Dev on for Kelly Shi. I have a couple of questions. 1 on 3011 in UPS. Maybe if you can talk about your expectation and what you anticipate from the meeting from the FDA meeting that you plan in second half? Also, will you be discussing additional indication or will it be only for UPS?

Sheri, do you want to take that one, begin.

Sure. Thank you for the question, Dev. In terms of the second -- I'll take the second part of your question. So the meeting would be focused on UPS. This is our potentially registrational trial. So we would look to discuss the data set that we had generated with the first 20 patients. In terms of efficacy and tolerability. And I think I would pass the first part of your question over to Eric for additional comments.

Sure. I'm happy to take that. Thank you, Sheri. So our goals with the FDA meeting are really to plot out together an agreeable registration path. And I think we've guided previously that, that would be based on an overall response rate with a certain durability. We'll also be talking with the agency about Project Optimus. And whether the multiple different dosing regimens that we've explored in UPS are sufficient to achieve the Project Optimus guidelines. And we then hope to be able to provide guidance on our path forward after that meeting.

Great. Thank you for taking our question. Thank you.

Thank you.

Our next question comes from the line of Kaveri Pohlman with BTIG. Please proceed with your question.

Yeah, good evening. Congrats on the progress and thanks for taking my question. For CTLA-4, any additional color you can provide on the first-line melanoma and non-small cell lung cancer trials? Are these going to be single-arm trials and how many patients you plan to enroll?

Eric, do you want to start with that one?

Sure. Thank you, Kaveri. So we would expect to enroll about 15 to 20 patients in each of our first-line melanoma cohort in the first-line targeted non-small cell lung cancer by the end of the second half of 2024. We hope that this data set, both in melanoma and non-small cell lung cancer will help guide next steps for us. And I also want to emphasize, as Jay did, that we've passed the 700-milligram dose which is equivalent to a 10 per kilo dosing and are now evaluating one gram. So we're really of the belief that higher dose levels will be very important in extending survival as other studies have shown.

And I think that, I would just add, I think our goal here is from these studies is to inform us and allow the positioning for registrational trials which, in that case, would be randomized studies.

Got it. That's helpful. And for EpCAM CD3 biospecific trial, I understand it's for multiple solid tumors, but are you enriching or have you seen enrichment for patients with certain tumor types and can you set some expectations for what we will be seeing in second half? And what would good data look like?

I think, obviously, adenocarcinoma, but I think we're seeing some colorectal patients and we would expect to see a continuation along those lines as we go through the different dose layers to the ultimate dose selection level. And our goal is to report out on those with multiple scales, very much similar to what we did with CTLA-4 in December. With that readout as we position for Phase II studies. Eric, do you want to add anything to that?

I think I covered it. More than 70% of tumors are adenocarcinomas. So where we think we have plenty of coverage with this approach. And Kaveri, to your question, we're not needing to specifically pick patients based on target expression. EpCAM is so robustly expressed by tumors that we think that just using the adenocarcinoma approach will be getting patients likely to benefit.

Got it. Thanks for taking my question.

Thank you. [Operator Instructions] Our next question comes from the line of Arthur He with H.C. Wainwright. Please proceed with your question.

Hey, good afternoon, Jay and Team. Thanks for taking my question. So I just want to get your -- for the 3071 and the 3021 update. Is that going to be all together at the first quarter earnings call?

No, to be, our expectation is 3021, we will be giving top line update then, the key update for 3071, well, there could be an update on the dose escalation. We won't know for sure until we get a few weeks further down the road here since we're enrolling at the one gram level right now. But the first -- that is a possibility there, but we'll see as we get closer to time. I think for the readout of the monotherapy Phase II study with approximately 20 patients where we've -- majority have been recruited at 350 milligrams flat dose. And just a few remaining patients at the 700 milligram dose. That will be sometime in June and latter part of June, I'm estimating because we want to get as much scan data. And if you remember back on 3071, you definitely want to see two scans because you're initiating the immune system. So that we're going to give just a little more time. But all pretty, not very far away, quite frankly, coming quickly.

Got you. Got you. Thanks for that. And my second question is, so regarding the next candidate, I'm just curious to try to pick your brain is why another ADC not T-Cell engager. That's one. And the second question is on why Nectin-4 as a target. Thanks for that.

Well, I think, two things. We have both. We have an ADC that just happened to be ready first, and then we also have a biospecific, which I believe we've reported on in previous conferences. But I think that there are a couple of reasons why Nectin-4. Number one, there is an associated toxicity with the current marketed Nectin-4 that limits its applicability. Secondly, as we're going to report on in April at AACR, we're seeing efficacy in tumors that were not addressable with the current marketed drug. And so we see an opportunity to move, expand indications and also improve on existing indications. And that's driven, of course, by our novel NextGen carbohydrate linker, which reduces off-target levels of -- off-target toxicity that is a result of the payload coming off prior to entering the cancer cell. And so in general, we see both of these assets have an important opportunity for a validated target. And in general philosophically, I mean, you could ask the same question of CTLA-4. Here's a drug with incredible opportunity, but the toxicity has been very difficult to manage and has been used in a very limited extent relative to what its potential is. And I think we can make that argument across several different targets when we apply our CAB technology, which improves that selectivity between for the cancer cell and protects the normal cell.

I think thanks for the additional color. So if I may, can I squeeze one more. Just curious, I just quickly noticed the AACR presentation you're going to be doing at -- in April. Could you tell us more on the tetravalent T-Cell engage. I believe the B7-H3 target, what's the special of these design? I'm just curious.

Well, I think it's what we refer to as kind of a butterfly design. In other words, we have two arms of the antibody that both combined to the tumor cells. So that's the tumor cell engager. And then we also have two arms that come off the light chains that combined to CD3 receptor. Now we've since at least in terms of the EpCAM drug now that we're binding to a single CD3 arm at a time, whereas we can still bind to two different antigens on the tumor cell. So but this increases your ability to increases the potency of the drug to have this tetravalent structure even in the case where one arm combined to the ton like in the CD3 arm. Certainly, you're going to get not only affinity, but also avidity in the tumor targeting portion. So it's a very nice design from that perspective. But secondly, because -- there's only one form of this antibody that can be generated during manufacturing. It simplifies manufacturing and reduces cost of goods, which is also an advantage.

Got you. Thanks, Jay. I'll talk to you soon.

Thank you. Our next question comes from the line of Ren Benjamin with Citizens JMP. Please proceed with your question.

Hey, good afternoon guys. Thanks for taking the questions. As I think about 3071, I guess, one question is, now you're looking at the one gram dose level. At what point do you kind of stop dosing higher or can you just continue to go higher until you reach a DLT. And then I guess the second question is, when I'm thinking about the melanoma non-small cell combination with pembro cohorts, for which we'll have a data readout in the second half of this year. Can you talk, I don't know, roughly kind of metrics that you might need to meet, like, for example, in melanoma should I be thinking about you guys beating or trying to beat NIVO plus Yervoy from both an efficacy and safety perspective or are you more concerned about the safety aspect and the same kind of question for non-small cell lung cancer.

Eric, do you want to start on this one?

Sure. I think I'll take a start and then hand to Sherry. You had a really interesting question about really how high to go with CTLA-4 inhibition. It's really striking to look back at earlier randomized trials of ipilimumab 10 per kilo versus 3 per kilo, and the survival benefits are really quite striking at multiple years of follow-up. However, Ipi 10 per kilo was associated with considerable toxicity. So most sponsors that are pursuing CTLA-4 antibody really want to push the dose to achieve high exposures. And then we also want a good, high concentration trough in our pharmacokinetics, so that CTLA-4 blockade lingers of the full three weeks between doses. So our current plan is to treat the patients at one gram every three weeks. And we don't plan to go higher. We felt that represents 14.2 milligrams per kilogram, if you compared it to the Ipi dosing. And I think we can use that and just have a broad goal of giving as much CTLA-4 blockade as early in a cancer patient's treatment as possible and make this something that based on tolerability and its efficacy would be reached for as often as a PD-1 inhibitor. Sheri, do you want to address the questions of regarding what we would see in the context of melanoma and non-small cell lung cancer.

Sure, sure. Thank you, Eric, and thank you, Ren, for your question. I think basically, what we would like is to be meaningfully better than the current marketed standard of care. So what that means is meaningfully better not only in terms of efficacy, but also tolerability. So providing a regimen that will allow a patient who really experience the full benefit of the therapy. So in the context of melanoma whether that means being meaningfully better than Opdualag in terms of efficacy or meaningfully better than Opdivo, Yervoy. We aim to be meaningfully better than what those regimens currently provide.

Got it. And then what about for non-small cell?

On the non-small cell side, I'll just add and jump in here for a second. As you noticed, we mentioned that we're doing any targeted population, which is a significant large population, but it's a subset of all non-small cell lung cancer patients. And we're going to talk a bit more about that in a future conference. But at the moment, we're just simply keeping that at a high level at this point.

Got it. Okay. And just maybe just going back to Eric's answer just in regards to the 14.2 mgs per kg, significantly higher than what's been evaluated prior, do we have a sense as to kind of the PK/PD at this point? And how much sort of receptor occupancy or blocking we're already getting? Any sort of color there would be helpful.

Eric, I'll just jump in for a moment. I think that a lot of the studies that were done prior with ipilimumab have shown that you do continue to get an advantage up to 10 mgs per kg. We don't have the data of 14.2 mgs per kg, but we'll definitely be comparing the 10 to the 14.2 and our belief is we may not quite have saturated it yet at the 10, but the data is pretty clear when you compare one going one, three and up to 10 mgs per kg that you continue to get benefit. So I think, though, your point -- it's a reasonable question though. At what point does that efforts start become saturated. And I think certainly, there's plenty of the incentive to check out this one gram level. And we will hope to report out on that in the future.

And Ren maybe I'll jump in here with your question about the PK. So as these are conditionally binding antibodies, we would need to do tumor biopsies to explore a receptor occupancy because the antibody was designed to explicitly not bind in the periphery. So it turns out to be a more challenging question to answer and one that we haven't done those biopsies in humans to characterize receptor occupancy. And then your question about PK is that it is really behaving in a pretty standard manner. There are really no PK surprises to date.

Excellent. Thanks guys for taking the questions.

Thank you.

Thank you. There are no further questions at this time. I would like to turn the floor back over to Jay Short for any closing comments.

Thanks, everyone, for your attention, and we're looking forward to a very exciting second quarter. We'll be talking to you soon. Thank you.