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spk04: Good day and welcome to the BioALTA third quarter 2022 earnings conference call. Pardon me, BioATLA. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on a touch tone phone. To withdraw your question, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to Bruce Meckel from Life Science Advisors. Please, go ahead.
spk13: Thank you, Operator, and good afternoon, everyone. With me today on the phone from BioAtla are Dr. Jay Short, Chairman, CEO, and Co-Founder, Scott Smith, President, Philippe Martin, Chief of Clinical Development and Operations, Sherry Lydek, Senior Vice President, Commercial Strategy, and Richard Waldron, Chief Financial Officer. Earlier this afternoon, BioAtla released financial results and a business update for the quarter-ended September 30, 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 BioAtlas 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 for 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 quarterly report on Form 10-Q. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today November 3rd, 2022, 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?
spk03: Thank you, Bruce. Thanks to everyone for joining us for our third quarter 2022 BioAtla earnings call. We continue the positive trajectory for advancing the development of our innovative clinical and preclinical programs enabled by the broad applicability of BioAtlas CAB technology. The third quarter was marked by continued strong execution with promising results across our five ongoing Phase II trials for our two latest stage CAB ADC product candidates, BA3011 and BA3021 across multiple solid tumor types for these first-in-class therapeutic candidates. Additionally, we are excited with the continued anti-tumor activity and lack of disease progression along with multiple partial responses as we continue to enroll additional patients in our BA3011 Phase II non-small cell lung cancer study as well as recent feedback from the FDA for from our proposed path forward for our BA3011 Phase II sarcoma study. But before I go any further, I'd like to remind everyone that additional details related to what we are going to present are available on our website as part of our updated company presentation that may be helpful to you. We previously shared interim data on our BA3011 Phase II sarcoma study and our BA3011 Phase II Non-Small Cell Lung Cancer Study, and we now look forward to providing additional insights on both. Further, on today's call, we will discuss additional updates for our other clinical programs. Our Phase II BA3021 studies continue to progress, and we anticipate enrollment completion of up to 20 patients in our Non-Small Cell Lung Cancer Study by year-end for reporting in January. Our validated liquid biopsy assay and the melanoma study is being implemented using our assay before year-end. In addition, our head and neck study is ongoing, and we anticipate dosing multiple patients by year-end. Our phase 1-2 basket trial for our CAB CTLA-4 antibody, BA3071, is progressing nicely with the first two cohorts completed and the third cohort expected by year-end. We also received encouraging pre-IMD feedback from the FDA for our dual-CAB bispecific T-cell engager antibody, EPCAM CD3 or BA3182, and remain on track for an IMD submission of the fourth quarter of this year. Additionally, we remain on track with IMD submissions for up to two next-generation CAB candidates next year. We are pleased with our cumulative results that continue to support both the preliminary efficacy and safety from our differentiated proprietary CAB platform thus far in 2022, and we are well poised to continue with strong execution. We have several additional upcoming catalysts as well as important results to be covered in today's discussion, including exciting updates from our Phase II sarcoma study as well as updates from our Phase II non-small cell lung cancer study with our lead asset, BA3011. With that, I would now like to turn the call over to Philippe for additional details. Philippe?
spk09: Thank you, Jay, and good afternoon, everyone. I would like to start by providing an update on our Phase II study in non-small cell lung cancer with our CAB-axle ADC BA3011. As a reminder, Part I of a Phase II study in non-small cell lung cancer is ongoing in actual positive patients who have previously experienced failure of PD-1, EGFR, or ART inhibitor therapies. As of October, we have enrolled 24 patients. Of these patients, 14 are efficacy evaluable. These patients had failed on average three prior lines of systemic therapies, 13 patients had failed the PD-1 inhibitor, and one had failed EGFR inhibitors. These 14 patients are composed of 12 non-squamous and two squamous cell carcinoma patients. Regarding non-squamous patients, 8 of 12 were administered BA3011 monotherapy and 4 of 12 received BA3011 in combination with a PD-1 inhibitor, nivolumab. In non-squamous patients, we have observed to date four partial responses or PRs in the monotherapy group. representing an objective response rate, or ORR, of 50%. In PD-1 failure patients, the ORR in non-squamous patients is 57%. In the combination group, we have observed one complete response, or CR, for an ORR of 25%. These observations remain consistent with the preliminary data reported last quarter and confirms the efficacy signal observed in phase one. Of the two evaluable squamous cell carcinoma patients, no new patient were enrolled this quarter and we have not yet observed a response in this subtype. All patients enrolled were Axyl positive with a TMPS of 1% or more. The rate of Axyl positivity in the non-small cell lung cancer population continues to be high. We estimate it to be approximately 35% for the non-squamous population and approximately 30% for the squamous population. based on over 200 non-small cell lung cancer tumor samples tested so far for axial expression. As of the latest safety data cut, the safety and tolerability profile from the Phase II non-small cell lung cancer study continues to be differentiated from other MMAE ADCs in monotherapy and in combination with nivolumab. No new signals have been identified from Phase I, no treatment-related deaths, and few grade III-IV AEs were reported. To put this data into perspective, and notwithstanding the relatively small sample size of our dataset, the preliminary efficacy observed in this study, and in particular that observed for the BA3011 monotherapy non-squamous group, is highly competitive in this PD-1 refractory population and supportive of moving forward to the potentially registrational part of this study. As of data cutoff, we have enrolled 24 patients, which will allow us to perform an interim analysis by year-end. In the meantime, we continue to enroll patients in Pac-1 to help us better define which population and which treatment cohort or cohorts we will be advancing to the potentially registrational part of the study. Moving on to sarcoma, previously we presented interim data. both our phase one and ongoing part one of the phase two trial of BA3011. In part one, we found that UPS and osteosarcoma subtypes responded to BA3011, which provided the rationale for moving forward into part two of the study based on predefined internal go-no-go criteria of either at least one partial response or complete response per subtype or progression-free or PFS rate of at least 40% at three months. During our call last quarter, we shared data from additional cohorts where we observed a PFS rate of 60% in liposarcoma, a PFS rate of 50% in synovial sarcoma, and a PFS rate of 67% in osteosarcoma. All three subtypes exceeded our predefined goal criteria to Part 2 of Phase 2. To date, we continue to see similar or slightly improved PFS rate in all three sarcoma subtypes and are very encouraged that all three subtypes continue to meet our predefined goal criteria to advance into part two of the phase two study. With regard to the safety profile across sarcoma subtypes, BA3011 continues to be generally well tolerated with a phase two safety profile consistent with the profile observed in phase one. As communicated previously, we had asked FDA for written feedback on our proposed registration plans in UPS. Written feedback was received in October, and we are pleased with the FDA response to this proposed study design. In particular, the agency was not opposed to the selection of objective response rate, ORR, as a primary endpoint in this population, with initially proceeding with a total sample size of 80 patients and had minor comments regarding our inclusion-exclusion criteria. FDA was also supportive of including a more intensive dosing arm as part of this study. Based on this written feedback from the Agency and the compelling profile observed for BA3011 in this population, we believe we have a path forward to advance BA3011 toward registration in UPS. We are currently finalizing the protocol following the Agency's feedback and plan to start the infatuation by the end of this year. Additionally, we plan on moving forward with additional sarcoma subtypes as part of a label expansion strategy following BA3011 approval in UPS. I'd like to thank you for your attention, and Sherry will now highlight the significant unmet medical need and commercial opportunity in UPS and non-small cell lung cancer. Sherry?
spk06: Thank you, Philippe, and good afternoon, everyone. With the data observed today in our Phase II sarcoma study, the FDA guidance received and the high unmet medical need in undifferentiated pleomorphic sarcoma, or UPS, We are excited to move quickly in pursuit of our leading indication for BA3011. 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. In addition, axial positivity rate in UPS is quite high at around 80%, and we estimate there are approximately 3,000 to 4,000 axial positive addressable UPS patients per year in the U.S. alone. Adding in Europe and rest of world, the number of addressable UPS patients who could potentially benefit from BA3011 exceeds 10,000 per year, which we estimate to be a worldwide commercial opportunity of approximately $750 million at peak. As such, UPS represents a solid initial indication for BioAtla as we seek to transition into a commercial stage biotech company. Additionally, based on data observed in other sarcoma subtypes, there is an opportunity to expand our label and footprint to include osteosarcoma, liposarcoma, synovial sarcoma, and perhaps other sarcoma subtypes. Ultimately, BA3011 has the potential to treat 25,000-plus sarcoma patients per year and generate up to $2 billion in revenue worldwide in this area of very high medical need. Furthermore, we continue to be enthusiastic by the responses we're observing with BA3011 in multi-refractory non-small cell lung cancer. There are limited treatment options for these patients who progress on immune checkpoint inhibitors, and available treatments in the second line and beyond setting have suboptimal overall objective response rates of approximately 10 to 20%. With respect to market size, a significant proportion of non-small cell lung patients express Axel, and we estimate that there are approximately 40 to 50,000 axel-positive addressable patients per year in the U.S. and over 100,000 per year worldwide. This second line plus indication has the potential to add approximately 2.5 to 3 billion in worldwide revenue at peak. The fact that we continue to see anti-tumor activity in non-small cell lung as we enroll more patients is very encouraging. And based on 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. 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. Now, I would like to turn the call over to Scott Smith, President of BioATLA, to provide an overview and updates to our ongoing clinical programs. Scott?
spk14: Thank you, Sherry, and good afternoon. Before I review our key operational updates for the quarter, I want to share my excitement around our lead asset, BA3011, with updates on Part 1 of the Phase 2 non-small cell lung cancer study and the proposed path forward in soft tissue sarcoma, specifically UPS. First, in non-small cell lung, we are thrilled with the continued responses we're observing as we enroll additional patients. As of data cutoff, we have enrolled 24 patients, 14 of which are efficacy-evaluable. We continue to see responses in both monotherapy and combination therapy with nivolumab in non-squamous, non-small-cell lung with four out of eight partial responses to monotherapy and one complete response out of four patients in the combination arm. These responses are quite remarkable, especially in this multi-refractory patient population. We anticipate a full interim data set of approximately 20 patients through multiple scans by the end of this year. We will wait for the full interim data analysis before making detailed future study determinations, but we are thrilled to see compelling antitumor activity thus far with 3011 in both monotherapy and in combination with NEVO. Moving on to UPS, as Philippe noted, we are very pleased to be moving into part two of the study. potentially registrational portion of the trial. We are currently finalizing the protocol and anticipate that study enrollment and dosing will commence by year end. In addition to UPS, we continue to see positive anti-tumor activity across several soft tissue and bone sarcoma subtypes. We have already exceeded our internal GO criteria for osteosarcoma, liposarcoma, and synovial sarcoma, and continue to enroll other sarcoma subtypes. In terms of our overall sarcoma strategy, we are initially focused on UPS with an opportunity to expand our label to include other sarcoma subtypes should we obtain approval in UPS. UPS represents a significant commercial opportunity as a standalone indication. However, given the encouraging anti-tumor activity we're observing in other subtypes, coupled with a significant unmet medical need, we see real value in potentially expanding our sarcoma footprint over time. Now, turning to our second lead CAB ADC product candidate, BA3021, a CAB War II ADC. As a reminder, there are no other therapies targeting War II in the clinic, so we have the potential to have a first-in-class treatment for solid tumors. In phase one, we saw impressive responses in War II positive patients refractory to PD-1 therapy, including two PRs in non-small cell lung, one PR in head and neck cancer, and a complete response in a melanoma patient who remains in complete remission off treatment for over two years. To date, we have three Phase II trials ongoing with 3021, and I'm happy to provide an update as to where we are with each, beginning with non-small cell lung. The non-small cell lung trial in refractory patients is enrolling as planned and currently dosing with an interim update of the preliminary cohort 20 patients following at least three months of therapy anticipated the beginning of next year. Turning to the melanoma trial, which is being conducted in patients refractory to PD-1 therapy, non-invasive liquid biopsy assay has been validated, and we anticipate initiating screening with this assay by the end of the year. We remain very excited about the potential of 3021 in melanoma patients, particularly with the potential acceleration of enrollment following full implementation of the liquid bioassay. The third phase two study we've initiated with 3021 is in refractory patients with head and neck cancer. This study continues to enroll and is actively screening patients. We anticipate multiple patients dosed at the year end. To round out our CAB ADC programs, we are supporting a multi-center investigated initiated phase two clinical trial of 3011 or 3021 in patients with platinum-resistant ovarian cancer. To date, a total of 10 patients have been dosed, five in each program. This trial is ongoing, and we will provide an update as one becomes available to us. Now I'd like to talk briefly about updates for our TAV CTLA-4 antibody, BA3071. This Phase I-II trial is being conducted in tumors known to be responsive to CTLA-4 treatment and will evaluate safety and tolerability of 3071 in monotherapy and in combination with nivolumab. This trial is progressing as planned with the first two cohorts completed without any DLTs or SAEs reported. The third cohort, which is at a dose equivalent to the approved dose of ipilimumab, is ongoing with the DLT observation period anticipated to conclude by year end. Turning to our preclinical pipeline, BioATLA has several candidates in IMD enabling phase that include CAB bispecifics and second generation ADC antibodies. Regarding our CAB-XAM-CAB CD3 bispecific BA3182, we received written pre-IMD feedback from the FDA that our preclinical package was adequate to move forward. And we will remain on track with IMD submission by the end of this year. We also remain on track for potential near-term IMD submissions for preclinical next-generation CAB candidates in 2023 and beyond. With that, I'd like to hand it over to Rick to review the third quarter 2022 financials. Thank you, Scott.
spk07: As of September 30, 2022, we had $178.1 million in cash and cash equivalents compared to $245 million as of December 31st, 2021. We expect current cash and cash equivalents will be sufficient to fund planned operations including all ongoing CAB product development programs into second half 2024. 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 third quarter ended September 30, 2022, we reported a net loss of $25.8 million compared to a net loss of $22.9 million in the same quarter of 2021. Research and development expenses were $19.8 million for the quarter ended September 30, 2022, compared to $16.6 million for the same quarter in 2021. The increase of $3.2 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 and our clinical programs. General and administrative expenses were $6.3 million for the quarter ended September 30, 2022, compared to $7.1 million for the same quarter in 2021. The $800,000 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 pre-commercialization activities for our product candidate BA3011, and satisfy requirements as a public company. Net cash used in operating activities for the nine months ended September 30, 2022 was $66.1 million compared to net cash used in operating activities of $41.3 million for the same period in 2021. The increase in net cash used in operating activities for the first nine months of 2022 is primarily due to an increase in research and development expense related to our program development efforts as compared to the first nine months of 2021. And now back to Scott.
spk14: Thank you, Rick. We are very pleased with the progress that we have made this quarter across the portfolio. We are excited with the compelling clinical profile that is beginning to emerge in treatment refractory non-small cell lung cancer. and are eager to advance into the potentially registrational part of the Phase II study in UPS. We also remain encouraged to continue execution around our other promising CAB assets in multiple cancer indications. We are well poised to reach several value-creating milestones and key inflection points with our innovative CAB assets and remain enthusiastic about the future. BioOutlook will continue to have strong focus on execution with the goal of pursuing indications of high unmet medical need that we feel will have significant impact for patients and their shareholders worldwide. With that, we will now turn back to the operator and take your questions.
spk12: Thank you.
spk04: We will now begin the question and answer session. Ask a question, you may press star, then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star, then 2. At this time, we will pause momentarily to assemble our roster. Our first question comes from Brian Chang from J.P. Morgan. Brian, please go ahead.
spk01: Hi, congrats on the progress and thanks for taking my question. Can you provide some color on the time to respond and the durability of response that you've seen across the 14 patients that you presented today for axial positive and SCLC? And then I have one follow-up on UPS.
spk14: Thank you, Brian. Thank you for the question. Yep, thank you, Brian. Thank you for the question. I will ask Philippe to give some color around the two parts of your first question around the time to respond and also initial thoughts on durability, although I will say it is awfully early for us in the study to be able to have any definitive view on duration or durability at this point. But Philippe?
spk09: Yeah, thanks, Scott. So we saw response as early as first cycle. Generally, response would be observed at first cycle or second cycle. First scan, I'm sorry, or second scan. That's what I meant, first scan, second scan. Scan is at six weeks. And with regard to durability of response, As Scott said, it's early for us to give you a number, but the patients that have been responding have been on treatment as long as nine cycles, so about nine months on treatment. So, so far, we are not seeing a problem with durability.
spk01: Great. And then on the UPS front, we noticed that there is a more intensive dosing arm that you have planned for Part 2, Phase 2 for the UPS side. I thought that the response that you had previously was already pretty competitive in the space. So I'm wondering if you can shed some light on why there is an additional more intensive dosing arm. What is the importance of this dosing arm, and is this more of an exploratory exercise to see if you can get a better response? Thank you.
spk14: Yeah, thank you very much for the question, Brian. We have seen, if we combine our Phase 1 and Phase 2 UPS patients, we're seeing a 50% response rate, which is very, very high in this particular population. UPS, like other sarcomas, is a very difficult disease, very difficult to get patients under control, and so this high-intensity dose arm is just exploratory to see if we can get even better efficacy. We will also have an arm at the current 1.8 milligrams per kilogram dose that will move forward. And after we have an initial bolus of patients, we will choose one of those two arms to move forward. So overall, I think it's a very positive signal that the safety and tolerability that we have seen so far allows us to try a more intensive arm. If we don't see good benefit-risk coming out of that, we'll go to the current arm. So I think overall, a very positive result.
spk01: Great, thanks Scott, thank you.
spk04: Our next question, it comes from Kelly Shee from Jefferies. Kelly, please, go ahead.
spk05: Congrats on the great progress and thank you for taking my questions. Firstly, so for the 24 patients enrolled into the non-small cell lung cancer cohort FOS3011, And how many of the 10 patients not efficacy-evaluable are actually non-squamous? And when should we expect the next data update? And also, do you intend to enroll more patients beyond these 24 patients and also have follow-up?
spk14: Thank you very much for the question, Kelly. Yes. We have actually now the 24 patients with the data cut off in late October. We have now enrolled 27 patients. We expect to make our decisions on how to structure part two of the study and make our decisions on how to approach the agency and the FDA on part two based on a bolus of 20 patients evaluable through multiple scans. But we do, under the protocol, have an opportunity to enroll up to 40 patients. And, you know, there are some questions still outstanding that we'd like to answer around squamous versus non-squamous, monotherapy versus combination therapy, et cetera. So we will continue to enroll some more patients. But the initial cohort that we are going to use to make decisions off from this is 20 patients or so. Of the additional patients who have not yet gone through multiple scans that are in the study. I believe they're all non-squamous. I don't know personally the L27, but 24 of the cutoff, I believe they're all non-squamous patients. Philippe, any correction?
spk09: No, that is correct. And to answer your first question, 12 out of the 14 efficacy-available patients were non-squamous patients. We still have two squamous patients. These are the same patients. we had talked about during the last update. We've not enrolled new squamous patients.
spk05: Great, thanks. And also, for the UPS, can you actually share more details regarding the FDA feedback and also more color on the registration of trial design?
spk14: Yes. Thanks, EPS, Kelly, and Philippe. Do you want to talk a little bit about a little bit more context on the written response from the FDA and the design moving forward?
spk09: Yeah, so we sent a proposal to FDA for the registration part of the study. FDA, we asked for ORR as a primary endpoint. We also asked for sample size of 80 patients and also asked for including a more intensive dosing arm which FDA had no objections to. The study design is the 1.8 milligram dose in one arm and then the more intensive dosing in another arm. We're randomizing patients 20 in each of these two arms and then we'll make a decision on which of these two dose we go forward with and then add an additional 40 patients after that so that At the registrational dose, we'll have 60 patients total.
spk05: Super helpful. Congrats again.
spk09: Thanks.
spk12: Thank you, Kelly.
spk04: Our next question is coming from Tony Butler from Roth Capital. Tony, please go ahead.
spk02: Thanks very much. I continue to be impressed with the non-small cell lung cancer data, especially in those with previous PD-1, part two where I believe last quarter you made comments that you'd like to enroll 100 patients. Are you suggesting today or are you saying today that that in fact could be registrationable? And it's true. Could the trial actually, would it be a trial without a control group? And do you think that it would include monotherapy and combo at least within those 100 patients, in other words 50-50? That's question one. And number two, am I correct or do I remember correctly, maybe that's a better way to put it, that a 20% response rate in SCLC is commercially relevant for 3011. Thank you.
spk14: Yeah, so thank you very much for the question, Tony. So, you know, the design of any part two here is obviously contingent and subject to discussion with the FDA. I believe there is a path and some precedence in this multi-refractory PD1 failure lung population to be able to do a single arm ORR study. I'm not able to determine at this point in time whether we move just the monotherapy arm or the mono and combo arms forward. We want to reserve the right to collect a little bit more data to be able to assess that more properly. We're thrilled with the response rates that we're seeing. It's, I think, a great sign that we're seeing significant efficacy in monotherapy. As we have gone from the Q2 to the Q3 disclosure, we maintain 50% response rate in the non-squamous monotherapy arm, 57% if you just look at PD-1 failure population there. So, you know, very, very strong data. Based on our internal discussions and thoughts before the study started, we believe, again, this multi-refractory PD-1 failure population, that a 20% ORR rate could be registrational, of course, pending agency review and benefit-risk and some of those things. We thought that 25 and above would be commercially viable. It's important to note that the group of axopositive non-small cell lung patients is quite large. trending in between 35 and 40% of the refractory population. And so, you know, being able to get to those response rates above 25% in this large population, I think will be highly commercially viable for us.
spk02: I appreciate that. I may ask one follow-up. Obviously, we don't have a waterfall plot, but you would have a view about this from subsequent scans, at least over time. have responses or do you have patients where responses deepen over time? Thanks.
spk14: I think generally the pattern in past patients has for their responses to deepen over time. I think we've talked about, for example, the complete response patient and the partial response on first scan and a complete response on second scan. Most of the patients that we have seen in phase one and phase two do continue or deepen the response over time. Philippe, do you want to put any more color on that?
spk09: No, I think you've answered the question, Scott. We generally see patients depending their response over time. I think that's what we've seen in phase one and certainly what we're starting to see here in phase two.
spk12: Scott, Philippe, thank you. Thank you, Tony. Thank you, Tony.
spk04: We have a question from Arthur Hay from HC Wainwright. Arthur, please go ahead.
spk10: Hey, good afternoon, everyone. Congrats on the strong data to confirm the activity for B311. Just regarding the non-small cell lung cancer trial, I just wonder, for the rest of the 10 patients How many patients receive the mono therapy compared to the combination therapy?
spk14: Thank you for the question, Arthur. I believe as we go from the 14th to the 24th, I believe that the distribution of mono and combo is relatively even between mono and combo between the two groups, yes. So we'll start to catch up and see some more combination patients come in. I think this may be just a little artifact of being early here. uh but we should see uh some more combinations combination patients come in which we're excited about because not only did we see a complete response there but we'd also like to have more data to fully evaluate you know the risks and benefits of the combination arm so thanks for that question gotcha that makes sense uh and uh for the uh for the for the ba 30 21 program um
spk10: Regarding the non-small cell lung cancer enrollment, could you give us an update regarding the status and currently how many active sites in the U.S.?
spk14: So I'll let Philippe in a minute answer the active sites in the U.S. I don't have the number exactly with me, but I will say that the ROR2 lung program is probably three to four months behind where we are with the Axel program. It started later, and Axel was ahead of it and continues to be that way. We are seeing reasonable enrollment. I would expect to have a good group of patients for us to take a look at by the time we get to year end this year, and we want to get through multiple scans. So, you know, I think right now the timing that we're looking at to talk about that data set is likely, you know, Q1, 2023, whether during the actual quarter of the Q1 call. But I think that's a Q1 2023 event when we have enough patients through multiple scans to be able to really understand that data. And like I say, going well, I think the execution of that study probably three to four months behind where we were with that. So, Salif, any thoughts on the exact number of sites?
spk09: Yeah, we have approximately 35 sites initiated Some of these sites are in Hong Kong and Taiwan, but the vast majority, about 30 of them, are in the U.S. We're also in the process of initiating sites in Europe as we receive approval to do that across a number of countries. So we're currently 35, but it will continue to grow.
spk10: Oh, thanks. If I could, I just raised one last question for the BA3011. Have you guys seen any correlation between the AFL expression with the clinical activity for the drug? Yes.
spk14: So I think if we're talking about the sarcoma program for 3011 or the Axel ADC, we definitely see a relationship. And You know, we saw the relationship relatively early in phase one. These sarcoma patients have heavy tumor burdens, and it seems like you need high levels of axial expression, i.e., over 50% to really move the needle. Now, in sarcoma, it's a very bimodal. Patients either express it at a very small degree or none at all, or at a very large degree. There's not a lot of middle ground there. But we see a relationship between axial expression and response for sarcoma for a long time. It looks a little bit different. It's probably too early for me to make any definitive statement on the relationship between expression and response. We are seeing responders at lower levels of axial expression in non-small cell lung and at high levels. So I would like to gather some more data. I'd like to get this next six, seven patients through multiple scans, take a look at that full 20-patient subset and make some determinations relative to axial expression and response, but it does look different than than we saw with Serco.
spk10: Got it. Thanks, Scott. And again, congrats on the progress. Talk to you soon.
spk12: Thank you very much.
spk04: I would like to remind you, if you would like to pose a question, just press star, then one. Our next question comes from Ren Benjamin from JMP Securities. Ren, please go ahead.
spk08: Thanks. Good afternoon, guys, for taking the questions. Congrats on the progress. I'd love to maybe just start off with, you know, the non-evaluable patients that you have so far. Can you just tell me how many are on drug? You know, as of now, it seems like several maybe just don't have scans yet. Can you give us the breakdown of that? And can you also just remind us if all the responses to date have been confirmed? And I guess finally, are there any learnings that you have been able to ascertain from the non-responders that might help you to further define an exclusion criteria?
spk14: Good. So to answer your last question first, I don't know that we have really defined learnings yet from the non-responders. I know from a couple non-responders, they were more heavily pretreated and failed more prior lines of therapy than others. So that seems to be a trend which continues. In terms of a confirmation, so of the five patients that responded, the four partial responses and one complete response, three of those are confirmed. Two have come in more recently, and they have not had second scan yet. So once those second scans come in and if they remain, we will confirm those. The trend has been for patients who do respond early continue to improve response. So our hope is that those two will be confirmed, but they just haven't been confirmed yet because they haven't had a second scan. And then the first question you asked, I'm sorry, I didn't get time to write that down.
spk08: That's okay. Sorry, I probably shouldn't have asked all three at once. No, no, go ahead. Just the non-evaluable patients, are they still on drug? I couldn't do the math just right. There are 24 enrolled. There are 14 efficacy. I think, you know, 10 are non-evaluable, but there might be a further breakdown.
spk14: Yes. You know, I believe the majority of those, and Philippe, again, can break down the exact numbers for us. The majority of those, the large majority, are patients that are dosed, just have not had scans or not have had two scans yet. instead of the on-drug, there's a couple that aren't, though, I believe. But Philippe, do you want to address those?
spk09: Yes. So 24 patients enrolled, 14 efficacy-evaluable. The 10 difference is that we had six patients that are currently ongoing, being treated, but haven't reached their first scan. We had two patients at time of data cutoff that were not dosed yet. And we had the two patients that we drew consent early which are the same patients we mentioned at the last quarterly call. So that's the breakdown for the 10 patients.
spk08: Terrific. Thanks, Philippe. And just one final one for us. As I evaluate the combo data, you know, the response rates, Can you help maybe define what would be a good go-to? At what point do you kind of cut bait or maybe evaluate a different checkpoint or a different combination?
spk14: Yeah, I think it's hard for me to answer that question with exact numbers. I think what you want to see in general is you want to see something emerging from that that is better than what you're seeing from the drug and monotherapy. You want to see a better benefit-risk emergence emerging or there's no sense going in combo unless there's a subset of patients who are more likely to benefit from combination than they are from monotherapy. I think what we're seeing in combination therapy is maybe more of an artifact of numbers, and that's why we're really excited to get some more combination patients in to see what's going on there, because we'd like to see you know, efficacy at or above what you're seeing in monotherapy and not significant additive toxicity. I think that's overall what we're looking for. So we have not given up on the combo arm by any means. Of the four patients there, we do have a complete response. We have two patients who went out of the study because of toxicity that I believe was reported as related to nivolumab. So, you know, small numbers. Let's get another four, five, six, up to 10 patients in that arm when we can take a look and and see what's there. But, you know, what is really sort of heartening to us is that, you know, you see four to eight patients in monotherapy responding. Those patients, all five patients that responded here are still in response and remaining steady, which is very, very encouraging as well. And, you know, the drug certainly seems to be active in monotherapy, and we've got a little more work to do and a few more patients in the combination side to make, you know, final determination there.
spk08: Perfect.
spk12: Thanks very much for taking the questions and congrats. Thank you.
spk11: And this concludes our question and answer session.
spk04: I would like now to turn the conference back over to Scott Smith, President of BioAtla, for any closing remarks.
spk14: Yeah, just thank you all very much for your time and attention. We're really proud of the progress that we've made not only from Q2 to Q3, but this whole year. The year started off as a tough year for clinical development from the Omicron COVID-19 perspective, but we fought through that. We remediated, and the pace of clinical development is going very well. The results are going very well. More than anything, I think, when we take a look at the safety and efficacy data, the benefit-risk that's emerging here, at least for 3011, we've got enough patients to make this assessment, you really seem to see the cap technology playing out in the clinic. You see side effect profile, which is very much in line with the idea of using technology to greatly eliminate or to sort of greatly reduce or eliminate on target off tumor toxicity and eliminate some of that baggage that you get with cancer antigens, which are are very promising, but also exist on healthy tissue as well. So we're seeing the CAD technology move forward in the clinic. The execution's been well. We're really excited about moving 3011 into what could be a potential registrational study in UPS, moving forward into part two of the lung study. And we're really excited about next year as well, with 4.2 data coming, CTLA-4 data coming from the phase one, two study there. And also we should be bringing a CAB, EPCAM, CAB CD3 bispecific into the clinic by the end of this year and start dosing that next year. So we should have four candidates in the clinic next year and approximately 10 cancer indications. And we're really excited, not just about 3011, which we're very excited about, but the whole portfolio going forward.
spk12: So thank you all very much for your time and attention.
spk11: The conference has now concluded. Thank you for attending today's presentation.
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