Bioatla - Q4 2022

Transcript

Operator (participant)

Greetings, welcome to the BioAtla fourth quarter and full year 2022 earnings call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please note this conference is being recorded. I'll now turn the conference over to your host, Bruce Mackle. You may begin.

Bruce Mackle (Managing Director and Investor Relations)

Thank you, operator, and good afternoon, everyone. With me today on the phone from BioAtla are Dr. Jay Short, Chairman, CEO, and Co-founder, Richard Waldron, Chief Financial Officer, and following today's call, Philippe Martin, Chief of Clinical Development and Operations, Eric Sievers, Chief Medical Officer, and Sheri Lydick, Senior Vice President, Commercial Strategy, 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, 2022. A copy of the press release is 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 business plans and prospects, potential selective licensing, collaborations, and other strategic partnerships, whether our clinical trials will be potentially registrational, results conduct, progress, and timing of our research and development programs and clinical trials, expectations with respect to enrollment and dosing in our clinical trials, plans regarding future data updates, clinical trials, regulatory meetings, and regulatory submissions, the potential regulatory approval path of our product candidates, expectations about the sufficiency of our cash and cash equivalents, and expected R&D and G&A 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 23rd, 2023. 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?

Jay Short (Chairman, CEO, and Co-Founder)

Thank you, Bruce. Thanks to everyone for joining us for our fourth quarter and full year 2022 BioAtla earnings call. BioAtla has made significant progress in 2022 across our five ongoing phase II trials for our two latest stage first-in-class CAB ADC product candidates, BA3011 and BA3021, targeting multiple solid tumor types. We continue the positive trajectory in 2023, intently focused on further advancing the development of our innovative clinical and pre-clinical programs across our platform, leveraging the broad applicability of our CAB technology across several clinical stage antibody types, including AXL and ROR2 ADCs, targeted CTLA-4 IO naked antibody, and our first dual CAB bispecific EpCAM and CD3 T-cell engager.

Before providing the update, I'd like to remind everyone that additional details related to what I'm going to present are available on our website as part of our updated company presentation that may be helpful to you. We are excited by the promising clinical responses to date that are generally meeting, and in several cases, exceeding our interim study target responses. We recognize the resulting impact from providing incremental data updates on small sample sizes. In view of the near-term completion of these studies, going forward, we plan to release more mature datasets across our programs. As a reminder, we are using these studies to provide sufficient data to allow us to set study parameters that maximize the company's likelihood of success for our phase II potentially registrational studies.

While this communication approach will modestly affect our data updates for Q2, we do not anticipate that this will delay the overall program development timelines while we advance what I believe will be a transformational platform in the treatment of solid tumors. Let's now move to our clinical, operational, and financial updates for 2022, as well as our progress from the beginning of the year. In order to maximize the differentiated benefit risk profile of our CAB ADCs, we've looked at different doses and dosing regimens throughout phase I and phase II, Part 1. Based on the sizable dataset we've accumulated, we were able to complete a thorough exposure response analysis, leading to the selection of a more frequent dose-intensive regimen for our UPS phase II, Part 2 study.

While the profile of the 1.8 mg/kg Q2W or once every two weeks dosing regimen is positive, the more frequent dose-intensive regimens at the 1.8 mg/kg to Q3W or twice in a three-week cycle, and the 1.2 mg/kg 3Q4W or three times in a four-week cycleWhich uses the 1.8 milligram per kilogram starting dose are expected to provide approximately 38% and 44% more exposure respectively than the previous Q2W dosing regimen. Based on our exposure response analysis, we anticipate that these more frequent dose-intensive regimens will further improve antitumor activity while having similar or even improved safety profiles compared with the Q2W dosing regimen.

This dose strategy was supported by the FDA as part of our UPS phase II, Part 2 study design discussions and is in alignment with FDA's Project Optimus. In view of these things, we continue to be excited about this, the first of our two lead assets, BA3011, for multiple indications. Previously, we shared the partial interim data on our BA3011 phase II, Part 1 sarcoma study and our BA3011 phase II, Part 1 non-small cell lung cancer study. Today, we are providing additional insights, including how we are applying the learnings from our encouraging safety data and exposure response analyses, as well as our UPS-related FDA interactions to study more frequent dose-intensive regimens more broadly across our AXL ADC and ROR2 ADC programs. First, I will discuss our BA3011 phase II sarcoma study and our overall sarcoma strategy.

UPS is one of the largest sarcoma subtypes representing nearly 15% of all soft tissue sarcomas. It is also one of the most aggressive subtypes with one of the highest recurrence rates. There are currently no FDA treatments specifically approved to treat UPS, and patients tend to progress very rapidly. Thus, UPS represents a significant commercial opportunity as a standalone indication, and we are focused on moving quickly to registration in UPS. Last year was marked by continued strong execution, promising results with continued antitumor activity, lack of disease progression, and a differentiated safety profile of BA3011 in UPS. As an update to the phase II, Part 1 UPS study, we currently see an overall objective response rate or ORR of 50%, median progression-free survival or PFS of 11 months, and a duration of response exceeding 8 months.

Based on these results together with the continued differentiated safety profile and encouraging feedback from the FDA around the study design, we initiated Part 2 of the potentially registrational portion of the trial. This month, the first six leiomyosarcoma patients cleared the DLT observation period using the 3Q4W dosing in Part 1 of the phase II study, which was a study requirement to begin enrolling patients in phase II, Part 2 of the UPS trial. We now anticipate first patient in for this study soon in the first half of this year. These first 40 patients with a TmPS greater than or equal to 50% are now enrolling and will be randomized 1-to-1 between 3Q4W or 2Q3W dosing regimens. Following this, we plan to enroll an additional 40 patients at the selected dose to complete the study.

Overall, the primary efficacy endpoint ORR will be based on approximately 60 patients treated at the selected dosing regimen. In addition to UPS, we continue to see positive antitumor activity across several soft tissue and bone sarcoma subtypes, where we previously reported an observed PFS rate at 12 weeks of 60% in liposarcoma, 50% in synovial sarcoma, and 67% in osteosarcoma. We are very encouraged that all three subtypes continue to meet our predefined go criteria to advance into part 2 of the phase II study. We also continue to enroll the remaining sarcoma subtypes.

With respect to leiomyosarcoma, as I mentioned earlier, we recently cleared the DLT observation period in the first six patients using the more frequent dose-intensive 3Q4W regimen and are continuing this study in leiomyosarcoma for 10 to 15 patients to evaluate this dosing regimen for potentially opening up a broad soft tissue sarcoma phase II study in the future. With regards to the safety profile across sarcoma subtypes, BA3011 continues to be generally well-tolerated with a phase II safety profile consistent with the profile we observed in phase I. Given the encouraging antitumor activity we're observing, coupled with a significant unmet need, UPS represents a solid early indication for BioAtla as we plan for the transition into a commercial stage company. We also see real value in potentially expanding our sarcoma footprint over time to include other sarcoma subtypes.

Ultimately, BA3011 has the potential to treat over 25,000 sarcoma patients per year and generate up to $2 billion in revenue worldwide in this area, a very high unmet need. Regarding our BA3011 phase II study in AXL-positive multi-refractory non-small cell lung cancer, we continue to be enthusiastic about the responses we're observing. There are limited treatment options for patients who progress on our immune checkpoint inhibitors and available treatments in the second line and beyond setting. These patients have suboptimal overall ORRs of approximately 10%-20%. As a reminder, Part 1 of a phase II study in non-small cell lung cancer is ongoing in AXL-positive patients who have previously experienced failure of either PD-1, PD-L1, EGFR or ALK inhibitors. The previously reported preliminary efficacy with an ORR of approximately 40%-44% was observed so far in this study.

This response rate is highly competitive in this PD-1 failure population and supportive of moving forward to the phase II potentially registrational part of the study. Based on the preliminary interim observations, we believe BA3011 will be highly commercially relevant with an ORR well above current ORRs observed in a multi-refractory patient population. Leveraging our insights and FDA discussions on UPS, we expanded our phase II Part 1 non-small cell lung cancer study to include the more frequent dose-intensive regimens 2 Q3W and 3 Q4W. We are currently enrolling these patients as we prepare our submission for a meeting request to confirm the design of the potentially registrational phase II Part 2 study with the agency in the first half of this year, with feedback anticipated in the second half, complete with the final dose selection.

We anticipate reporting all of these data after the phase II Part 1 is effectively complete, which is anticipated in the second half of 2023. Most importantly, we also expect that we will initiate the potentially registrational study in non-small cell lung cancer in the second half of this year, preserving our overall timeline for development of the non-small cell lung cancer indication. With respect to market size, a significant proportion of non-small cell lung cancer patients express AXL. We estimate that there are over 100,000 AXL-positive addressable patients per year worldwide. The second line plus indication has the potential to add approximately $2.5 billion-$3 billion in worldwide revenue at peak. Taken together, sarcoma and non-small cell lung cancer, we believe BA3011 has the potential to become a significant commercial asset for BioAtla across multiple solid tumor types.

Of even greater importance is that BA3011 has the potential to be a best-in-class treatment for a significant number of patients who fail multiple lines of therapy, thus filling a significant unmet medical need. To round out our CAB ADC BA3011 program, we are supporting an ongoing multi-center investigator-initiated phase II clinical trial BA3011 in patients with platinum-resistant ovarian cancer. We are anticipating interim data consisting of 10 patients in the second half of this year. Turning to our second lead CAB ADC product candidate, BA3021, a CAB ROR2 ADC. As a reminder, there are no other therapies targeting ROR2 in the clinic, so we have the potential to have a first-in-class treatment for solid tumors. To date, we have three phase II trials ongoing with BA3021.

As previously reported, our phase I clinical data, we saw impressive responses in ROR2 positive patients refractory to PD-1 therapy, including 2 PRs in non-small cell lung cancer, 1 PR in head and neck cancer, and 1 complete response in a melanoma patient who remains in complete remission off treatment for over 2 years. Based on a similar exposure response analysis done in AXL positive tumors, we are pursuing the same strategy in our phase II ROR2 positive non-small cell lung cancer study and currently enrolling patients in the more frequent, more intensive dosing regimen of 3Q4W in the first half of this year and plan to share data when we have sufficient evidence to determine how to proceed with our potentially registrational study.

Regarding the melanoma phase II trial in patients who have previously experienced failure of the PD-1 therapy following an additional CR in an evaluable patient identified using our validated IHC assay, we are screening patients with a validated liquid biopsy and anticipate providing an enrollment update on or around the first quarter 2023 earnings call in May. Our phase II head and neck study is ongoing in patients who have previously experienced failure of PD-1 therapy alone or in combination with platinum therapy. We have achieved first patient in for this study. The observed ROR2 positivity rate is high and in line with our expectations. We anticipate providing an enrollment update on or around the first quarter 2023 earnings call in May.

To round out our CAB ADC BA3021 program, we are supporting a multi-center investigator-initiated Phase II clinical trial of BA3021 in patients with platinum-resistant ovarian cancer. We are anticipating interim data consisting of 10 patients in the second half of this year. I'd like to talk briefly about our phase I/II trial for CAB CTLA-4 antibody BA3071. The phase I/II trial is being conducted in tumors known to be responsive to CTLA-4 treatment and will evaluate safety and tolerability of BA3071 in monotherapy and in combination with nivolumab. The trial is progressing as planned. As part of today's update, I'm pleased to share that the DLT observation period was cleared for the fourth cohort. At a dose of 210 mg or 3 mg per kilogram in combination with 3 mg per kilogram of nivolumab. No DLTs were reported.

We are now progressing to the fifth cohort at 350 mg or 5 mg/kg as a monotherapy or in combination with 3 mg/kg in nivolumab, anticipate the planned phase I data readout in the second half of this year. Moving on to our earlier stage pipeline, namely our potentially first-in-class dual CAB bispecific T-cell engager antibody, CAB EpCAM and CAB-CD3 or BA3182. We recently received FDA clearance of our IND for the treatment of advanced adenocarcinoma and are on track for the first patient in for the phase I study in the first half of this year, with the complete phase I data readout anticipated next year.

Similar to our other three clinical CAB product candidates, this antibody holds much promise in view of the in vivo preclinical studies demonstrating an over 100-fold improvement in the therapeutic index relative to the non-CAB variants due to the combined selectivity of the dual CAB design. Several of the most common subtypes of adenocarcinoma that have tremendous unmet need that we can potentially address include colon, lung, breast, pancreas, and prostate. BioAtla also continues to progress several candidates through IND-enabling studies, including CAB bispecifics and next generation ADC antibodies, and we still anticipate IND submissions for additional candidates potentially this year and next.

With respect to important ongoing communications, the company has seven accepted recent and upcoming poster presentations, including an ESMO Sarcoma and Rare Cancers Congress, the European Lung Cancer Congress, and AACR, the latter of which will include preclinical data related to next generation ADCs and multiple bispecifics. With that, I would now like to turn the call over to Rick to review the fourth quarter and full year 2022 financials. Rick?

Richard Waldron (CFO)

Thank you, Jay. As of December 31, 2022, we had $215.5 million in cash and cash equivalents compared to $245 million as of December 31, 2021. We expect current cash and cash equivalents will be sufficient to fund planned operations, including all ongoing CAB product development programs into 2025. As a reminder, we control all CAB product market rights in the U.S., Europe and Japan. Our business strategy includes advancing commercial preparations in key global markets while exploring opportunities to extend our cash runway by generating upfront cash through the selective licensing of product rights in certain territories or collaborations with other biopharmaceutical companies that could also provide to us development milestones and royalties upon regulatory approval and commercialization and create additional value for stockholders.

For the full year ended December 31, 2022, we reported a net loss of $106.5 million compared to a net loss of $95.4 million in the same period of 2021. Research and development expenses were $79.3 million for the full year ended December 31st, 2022, compared to $58.3 million for the same period in 2021. The year-over-year increase of $21.1 million was primarily driven by our clinical product development efforts. We expect our R&D expenses to remain variable from quarter to quarter and generally increase as we continue to invest in R&D activities to advance our product candidates in our clinical programs.

General and administrative expenses were $28.8 million for the year ended December 31, 2022, compared to $38.4 million for the same period in 2021. The $9.6 million change was attributable to a decrease in stock-based compensation for the 2022 period. We expect our G&A expenses to moderately increase to support development of our product candidates, advance our intellectual property portfolio, support focused pre-commercialization activities for our product candidate BA3011, and satisfy requirements as a public company. Net cash used in operating activities for the 12 months ended December 31, 2022 was $90.4 million compared to net cash used in operating activities of $62.2 million for the same period in 2021.

The increase in net cash used in operating activities for the 12 months of 2022 is primarily due to an increase in research and development expenses related to our program development efforts as compared to the 12 months of 2021. Now back to Jay.

Jay Short (Chairman, CEO, and Co-Founder)

Thank you, Rick. We are pleased with the progress we have made in 2022 and our cumulative results that continue to support both the preliminary efficacy and safety from our differentiated proprietary CAB platform. We're excited with the compelling clinical profile that is beginning to emerge in treatment refractory UPS and non-small cell lung cancer, and are eager to continue advancing the phase II studies with the addition of more frequent dose-intensive regimens and providing clinical updates when more robust data sets become available. We also remain encouraged by the continued execution of our other promising CAB assets in multiple cancer indications and are well poised to reach several value-creating milestones and key inflection points in the next several months. BioAtla remains confident about the future, with the goal of pursuing indications of high unmet medical need that we feel will have significant impact for patients and our shareholders worldwide.

With that, we will turn it back to the operator to take your questions.

Operator (participant)

Thank you. At this time, we'll be conducting a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment please while we poll for questions. Our first question comes from the line of Brian Cheng with J.P. Morgan. Please proceed with your question.

Brian Cheng (VP and Senior Biotech Analyst)

Hey, Jay, and team. Thanks for taking my questions today. A couple of questions, maybe just first on your AXL program, in, especially in the non-small cell lung cancer piece. Maybe just one on your latest thinking about the pivotal trial design. Can you provide some color on your latest thinking about the pivotal trial design? What are the patients mix that you intend to enroll? Secondly is that, you know, you're waiting for, you know, your feedback from the FDA. Any gating factor that, you know, that could potentially come up between now and your start time for the pivotal trial? One more point is that, are we expecting any AXL updates for your ongoing non-small cell lung cancer study?

I have a couple follow-up. Thank you.

Jay Short (Chairman, CEO, and Co-Founder)

Thanks, Brian. We are preparing a request for feedback to the FDA as we speak, and we intend to have that in later in this first half. Obviously, a gating factor is feedback from that FDA discussion and that'll be the gating factor for phase II, Part 2. What was nice about this timeframe is that we were able to take the learnings from third quarter in our discussions in part from the UPS discussions, also with our increasing number of patients so that we could do a more thorough exposure response analysis. We put those together, realized that we could bring in this more frequent, dose-intense treatment in the same timeframe that we're working with and discussing with the FDA.

When you step back and answer the question about what's the next readout, we think the best time to do that is after we get the FDA feedback, because we will have not only the Q2W dosing data completed, which we feel very positive about, but we'll also now have an opportunity to compare that to the 2Q3W and the 3Q4W more frequent dosing. This gives us a chance to really make sure that we're going into the registrational portion of the trial. Of course, if it's registrational, if the FDA will allow us to do that. That's some of the feedback we need to get yet. That's how we're looking at it.

You know, our job is to make sure we've maximized our potential for success. We think we have a good baseline with the Q2W, and we have a chance for upside with these other doses, and we'll be comparing them. I don't know if that answers your question, Brian, but hopefully it gives you a little flavor of it.

Brian Cheng (VP and Senior Biotech Analyst)

That was very helpful. Maybe just on one on the ROR2 side, you know, we're curious what you saw in the initial, you know, 2 patients that you dosed in the non-small cell lung cancer piece. I don't know if you can shed any light on just, you know, just the efficacy that you saw and, you know, given that you already are doing some work with the AXL, non-small cell lung cancer, can you shed some light on how, you know, the ROR2 program in lung cancer, efficacy profile compared to what you saw with the AXL program?

Jay Short (Chairman, CEO, and Co-Founder)

Well, we can only do that for phase I. We don't have enough patients yet. Originally, we were targeting to report out on our Q1 earnings call, which just to be clear, this is the Q4 earnings call. The Q1 earnings call is in May. Given the fact that we have the opportunity to bring in the more frequent dose intensives information in comparison, what we've done is that's the one milestone or timeline that we've pushed out in terms of reporting. It actually doesn't change our overall phase II timeline in terms of the pivotal side at all. It allows us to now make a comparison between these more frequent dosing and the Q2W.

Today, we don't have enough data to make a comment, but I think we'll have a much better picture as we wait to the second half. Our goal, of course, is to have the information required to go back into the FDA for more two and get a picture of that. We also should have. We're going to update in May, but we're hoping to have a much better picture of what our recruitment rate is in the head and neck. Then of course, we'll hopefully get a snapshot of what's happening on the circulating tumor cell assay in melanoma.

Brian Cheng (VP and Senior Biotech Analyst)

Great. Thank you. Thanks for taking my question.

Jay Short (Chairman, CEO, and Co-Founder)

Brian, just to end one thing. We have submitted to one of the upcoming conferences. We haven't got feedback yet from the meeting, but we intend to present the exposure response analysis data as soon as possible so people can get a flavor and get, you know, under the hood on these other more, more frequent dose-intense regimens.

Brian Cheng (VP and Senior Biotech Analyst)

For the ROR2.

Jay Short (Chairman, CEO, and Co-Founder)

For ROR2 and AXL.

Brian Cheng (VP and Senior Biotech Analyst)

Oh, okay. Got it. Thank you. Thank you.

Operator (participant)

Our next question comes from the line of Kelly Shi with Jefferies. Please proceed with your question.

Kelly Shi (SVP and Senior Equity Research Analyst)

Thank you for taking my questions. My first question is about AXL program in UPS. You mentioned at a more frequent dosing, 3Q4W, the DLT window has been cleared for first six patients in LMS subtype. I'm curious, would you share the efficacy outcome for the six patients in near term? Also, for the phase II, Part 2, you're gonna evaluate two different dosings, 3Q4W and then 2Q3W. In the first 40 patients, I'm curious, does FDA require another meeting after these 40 patients and talking about efficacy and safety for the decision on the dosing regimen for the next 40 patients in Part 2? Thank you.

Jay Short (Chairman, CEO, and Co-Founder)

Thank you, Kelly. I'm gonna let Philippe help me on this one a little bit, but I'm gonna start by saying you did get a snapshot in January of the first scan of one of the patients at the 3Q4W when we reported out in an glioblastoma that we saw a 29.6% tumor reduction on first scan. That was the first patient. we are moving toward, you know, 10 to 15 patients, and we believe that we're just going to wait until we get those because we think they'll come in in a timely fashion for second half of this year. obviously, we're very, very hopeful that we're gonna see some interesting data coming out of that.

Philippe, maybe you can add to this answer.

Philippe Martin (Chief Clinical Development and Operations Officer)

Yeah. With regard to the timelines for the 3Q4W LMS cohort, we'll wait until we have approximately 15 patient worth of data, which is expected in the second half of this year, as Jay mentioned. Your question about FDA requirement. FDA does not require us to meet with them after the first 40 patients, but that's certainly our intention, is to meet with them and to make sure that we align on the dose we are selecting for the next 40 patients to be enrolled, because that will be the dose we ask to be registered. We'll be planning on having a meeting with the agency once we have the first 40 patients enrolled in UPS.

Kelly Shi (SVP and Senior Equity Research Analyst)

Okay. Thank you very much. I also have a follow-up, if I may. For the UPS phase II, do you plan to provide any data update in this year? Also at the moment, would you be able to share the information regarding how many sites have been activated?

Jay Short (Chairman, CEO, and Co-Founder)

Philippe, it's you.

Philippe Martin (Chief Clinical Development and Operations Officer)

Yeah. The data we just provided in this update is the data on all the UPS patients we've treated to date. The median PFS has evolved from the last time we reported the data. We are now at approximately 11 months, which I think the last time we reported data, we were at about 6.8 months, something like that. The PFS is evolving positively. Some patients are still on treatment, that might continue to evolve. I think you got a very, basically, the data we are reporting today is very close to the final data in UPS. What was your other question? I'm sorry. Other part of the question.

Kelly Shi (SVP and Senior Equity Research Analyst)

Yeah. I meant for the phase II.

Philippe Martin (Chief Clinical Development and Operations Officer)

Ah.

Kelly Shi (SVP and Senior Equity Research Analyst)

-potential repetitive trial. Do you plan to have another data update this year? At the moment, how many sites have been activated?

Philippe Martin (Chief Clinical Development and Operations Officer)

I think we can. I don't believe we anticipate to have data update. This is a registration study. Patients are being randomized, so we're not being, we're not planning on giving a data update, but we'll certainly provide enrollment updates. What was good with this study is that we were able to leverage all the UPS, all the soft tissue sarcoma and bone sarcoma sites we had for initially for phase II Part 1. These sites are being transitioned to the second part of the studies, which is about 40 sites altogether in the U.S., Hong Kong and Taiwan.

Kelly Shi (SVP and Senior Equity Research Analyst)

Okay. Great. Thank you.

Operator (participant)

Our next question comes from the line of Tony Butler with EF Hutton. Please proceed with your question.

Tony Butler (Senior Managing Director and Healthcare Equity Research Analyst)

Yes, thanks very much. So a question around the CTLA-4 program, in ClinicalTrials.gov and one would anticipate. Clearly there's been dosing for a variety of tumors. The first question is, has enrollment been included, and have the patients have all of the tumors which are listed on ClinicalTrials.gov been dosed in your early dosing schedule? Importantly, and if not, that's fine, but is there has it been skewed to one particular tumor or another? That's question 1. Number 2 is, in the same program, what actually could you enunciate which parameters that you're simply looking for? Is it just simply DLT? Then when do you think that you will get to an appropriate dose that you can then start looking at efficacy? Will that be within this first half?

You think it takes the entire year? Thanks very much.

Eric Sievers (Chief Medical Officer)

I'm gonna split this with Philippe, I think that when you're at 1 mg/kg, you're in an approved dose range, especially in combination with 3 mg/kg PD-1. We passed that cohort. We just passed the 3 mgs per kilogram in combination with 3 mgs per kilogram of PD-1. There's another cohort that's in that efficacy range. We're enrolling now for the 5 mg/kg in combination with 3 mgs per kg PD-1. Everything on out, including the last two cohorts, have the potential for looking at efficacy. Of course, we will look at that, but you know, I think...

This study in general, I think is on track to be done in times such that we can actually kick off or initiate our phase II trial in the BA3071 with the CTLA-4. It's on a very good pace and we're thrilled to see the data is coming in the way we had hoped it would so far. There were some other questions about the tumor types and maybe even a comment or two regarding efficacy readouts and so forth that maybe it would be better for Philippe to answer.

Philippe Martin (Chief Clinical Development and Operations Officer)

Yeah. Thanks, Jay. I think the only tumor type we have not enrolled is HCC at this point. All the other tumor types have been enrolled. We're seeing quite a bit of activity and quite a bit of patients coming to our study in all the tumor types that we have listed. We'll as Jay mentioned, we've really surpassed efficacy threshold levels that we were expected. ipilimumab is approved at 1 milligram per kilogram in combination with nivolumab at 3 milligram per kilogram. In certain indication, 3 milligram ipilimumab plus 1 milligram nivo in other indications. We have reached levels with these cohorts where we certainly expect to see efficacy.

We'll also be looking at other markers of efficacy, such as ctDNA, tumor burden, so on and so forth, to also help us make a decision on which dose to take forward into the phase II part of the study.

Tony Butler (Senior Managing Director and Healthcare Equity Research Analyst)

Jay, Philippe, thanks very much. Very helpful.

Philippe Martin (Chief Clinical Development and Operations Officer)

Yep. Welcome.

Operator (participant)

Our next question comes from the line of Arthur He with H.C. Wainwright. Please proceed with your question.

Arthur He (Senior Equity Research Analyst)

Hey, good afternoon, Jay and team. Thanks for taking my question. Just follow up on the CTLA-4 program. So far in your study, could you give us a little bit color on the average repeating dosing of the study 71 and how about the maximal repeating dosing have been so far reached?

Philippe Martin (Chief Clinical Development and Operations Officer)

So if you're-

Eric Sievers (Chief Medical Officer)

So-

Philippe Martin (Chief Clinical Development and Operations Officer)

Happy for you to take.

Eric Sievers (Chief Medical Officer)

Yeah, we're starting to get in the weeds, we've had patients that have been on treatment for quite some time. By quite some time, I mean 11 cycles. You know, again, we gotta look at each cohort individually and see what is going on with these patients. So far the drug is even at doses that are above the doses approved with ipi plus nivo, there's really nothing to report. We've only had one SAE so far that was unrelated to treatment and was in one of the early cohorts. So far the drug is very well-tolerated. Patients are able to stay on treatment.

Again, we need more time to be able to tell you exactly how long patients are able to stay on treatment at a specific cohort. What we can say is that so far, no DLTs, really not much to report from safety and tolerability standpoint.

Arthur He (Senior Equity Research Analyst)

Great. Thanks for the color. Regarding the AXL program, for the sarcoma part of the study, I'm just curious, what's the rationale to testing the more frequent and intensive dose regimens in the LMS cohort? Why not go for the other subtype of the sarcoma? Just curious.

Jay Short (Chairman, CEO, and Co-Founder)

Well, first off, it's worth mentioning that these more frequent dosing, more intense dosing, actually from those that like to follow Cmax and Cmin, that actually on the 3Q4W, we're lowering the Cmax, which is often associated with any toxicity, but we're also increasing the Cmin. From a modeling standpoint, this is very exciting. The other side of it is, you know, I think when you look back at our phase I data, we saw some PRs in the leiomyosarcoma and those, you know, came in the phase I study where we used Q2W and 2Q3W. What was interesting is we didn't see a PR in the phase II using the kind of Q2W.

This we felt by going into LMS, we certainly could answer the safety question quickly and the FDA was agnostic in which indication we went to, so it gave us a chance to look at LMS to see if we could also tease out PRs, which really could open up a broad, in the future, a potential broad soft tissue sarcoma expansion study. It also answers the safety question. We kinda kill 2 birds with 1 stone. Of course, those 6 wouldn't have counted, like, for the UPS portion of our first part of our phase II, Part 2 potential registrational study.

It just really was a way to optimize a whole bunch of questions very quickly without in any way delaying the UPS, potentially registrational study.

Arthur He (Senior Equity Research Analyst)

Thanks for the color. I appreciate it.

Jay Short (Chairman, CEO, and Co-Founder)

Yeah.

Operator (participant)

Our next question comes from the line of Reni Benjamin with JMP Securities. Please proceed with your question.

Reni Benjamin (Managing Director and Senior Biotechnology Analyst)

Hey, guys. Thanks for taking the questions. I guess just sticking with the more frequent dosing regimens, can you talk a little bit about what you'd like to see before declaring, you know, a go-forward dose? Are you looking for just improvements in the ORR or just deep, or deeper responses? Or is it primarily from a safety perspective that'll lead you to declare a go-forward dose? I guess related to that, if you don't see anything meaningful or something that doesn't meet your hurdle, how do you choose the appropriate, you know, dose kinda going forward into the registrational study?

Jay Short (Chairman, CEO, and Co-Founder)

I'm gonna start on this one and let Philippe add to it. First, it's important to recognize the reason we even have the freedom to use this more frequent, intense dose regimen and add it in is because of the CAB technology. We're expecting all 3 of these different dose regimens, Q2W, Q 2 3 W, and 3Q4W to all be safe. That's not the question we're exploring. It's in fact, the CABs allow us that freedom to do it, and the FDA was extremely supportive of that in the UPS study. Our reason for exploring it is we have a chance to potentially even drive greater efficacy, and we're happy with the efficacy we're seeing in Q2W, so don't misinterpret that.

If you have a chance to increase the efficacy, and you can do it in a way that does not extend your overall development timelines, it was a great opportunity to do that. In the UPS setting, we did it inside the Part 2 of the phase II study. Fortunately, in the AXL and ROR2 setting for lung, we're able to do it in the Part 1. We're getting that done while we're in the same time in the process, at least for AXL, having discussions with the FDA. Likewise, ROR2 has always been, you know, six months or so behind AXL, and so we'll, but it, so it has no delay effect on it. It gives us a chance to really potentially see even more efficacy and stronger responses.

Philippe, do you wanna add to that?

Philippe Martin (Chief Clinical Development and Operations Officer)

I mean, just to add to the first part of your question, which is, If the 3Q4W doesn't work, or doesn't meet our criteria or looks about the same as what we've seen with the other dosing regimen, that's fine. We are happy with the other dosing regimen, and we'll move forward with the 2Q3W and the Q2W at that point in time, and select a dose. It's not that we have to have the 3Q4W work for us to move forward. We're just trying to maximize the efficacy we can get, and leverage the CAB platform. That's it.

Reni Benjamin (Managing Director and Senior Biotechnology Analyst)

Got it. Just two other questions. I guess the first, can you comment or just let us know, are the patients who responded in non-small cell lung cancer, in the non-small cell lung cancer study, are they still responding now?

Philippe Martin (Chief Clinical Development and Operations Officer)

Jay, do you wanna take that or?

Jay Short (Chairman, CEO, and Co-Founder)

I think you should take that one.

Philippe Martin (Chief Clinical Development and Operations Officer)

Yeah, I mean, we have decided not to update the data. I can tell you that some of the patients are still responding, yes.

Reni Benjamin (Managing Director and Senior Biotechnology Analyst)

Excellent. You know, just switching gears to the EpCAM, you know, bispecific. You know, as I look at kind of the clinical trial design, it seems kind of complicated to me with, you know, like a standard titration and then a standard titration with priming. I'd love to just get some feedback or some commentary on, you know, where you think the therapeutic dose might be and what's the, I guess, the point or how these titrations help you get to, you know, what's the ideal dosing, I guess, for this asset?

Jay Short (Chairman, CEO, and Co-Founder)

I'll start, and Philippe can add into this. In group A, we're thinking that the 125 microgram per kilogram, you know, you might see efficacy below that, but that's around the EC50 level. We think that's a dose level that you could really start to see some things. Obviously we think it could go above that given our safety profile and our preclinical studies. Philippe, you can add some additional to that, and maybe you could also add in some of the logic around what the FDA is wanting to see with respect to the group B titration.

Philippe Martin (Chief Clinical Development and Operations Officer)

Yeah. There hasn't been that many, but so far it is a typical design for a bispecific CD3 T-cell engager. The FDA is particularly concerned about cytokine release syndrome that have been observed with some other CD3 bispecifics. This is all set up to try to mitigate all this and make sure that we're not putting patients at risk. We have not seen any during our tox study, neither have we seen neurotoxicity or even infusion reactions. We still have to follow that type of design in case we were to see grade 2 and above cytokine release syndrome. That's really all done to manage that. The accelerated titration phase is fast.

It is one patient per cohort. It's a 14 days, DLT observation period. We can go through it relatively quickly and then move into a more standard titration at dose levels that we believe will be efficacious. These drugs are extremely potent and so that is why we're starting at that low of a dose to begin with. All of this is not atypical, is what I'm trying to tell you.

Reni Benjamin (Managing Director and Senior Biotechnology Analyst)

Terrific. Thanks very much for taking the questions.

Operator (participant)

We have reached the end of the question and answer session. I'll now turn the call back over to Jay Short for closing remarks.

Jay Short (Chairman, CEO, and Co-Founder)

Well, I wanna thank everyone for their time today, and also thank the BioAtla team. We look forward to speaking with you again, at least in May with our next quarterly earnings call. Thank you.

Operator (participant)

This concludes today's conference. You may disconnect your line at this time. Thank you for your participation.