This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk03: Greetings, and 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.
spk01: Thank you, operator, and good afternoon, everyone. With me today on the phone from BioAtlas 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 Sherry 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 31st, 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's 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 10Q. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today, March 23rd, 2023, 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, okay?
spk09: Thank you, Bruce, and thanks to everyone for joining us for our fourth quarter and full year 2022 Biolabra earnings call. Biolabra 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 preclinical programs across our platform, leveraging the broad applicability of our CAB technology across several clinical stage antibody types, including Axyl and Ward II 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. However, 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 data sets 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 two 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 one and phase two part one. Based on the sizable data set 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 two part two study. While the profile of the 1.8 milligrams per kilogram Q2W or once every two weeks dosing regimen is positive, The more frequent dose-intensive regimens at the 1.8 milligrams per kilogram, 2q3w, or twice in a three-week cycle, and the 1.2 milligrams per kilogram, 3q4w, or three times in a four-week cycle, which 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 anti-tumor 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 2, 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 the first of our two lead assets, BA3011, for multiple indications. Previously, we shared the partial interim data on our BA3011 Phase II Part I Sarcoma Study and our BA3011 Phase II Part I Non-Small Cell Lung Cancer Study. Today, we're providing additional insights, including how we're 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 anti-tumor activity, lack of disease progression, and a differentiated safety profile of BA3011 in UPS. As an update to the Phase 2, 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 two 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 one of the phase two study, which was a study requirement to begin enrolling patients in phase two part two 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 one to one between three Q4W or two Q3W 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 anti-tumor 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 two of the phase two study. We also continue to enroll the remaining sarcoma subtypes. With respect to Lyomyosarcoma, 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 Lyomyosarcoma for 10 to 15 patients to evaluate this dosing regimen for potentially opening up a broad soft tissue sarcoma phase two study in the future. With regards to the safety profile across sarcoma subtypes, BA3011 continues to be generally well tolerated with a phase two safety profile consistent with the profile we observed in phase one. Given the encouraging anti-tumor activity we're observing, coupled with a significant unmet need, UPS represents a solid early indication for BioAtlas 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 DA3011 Phase II study in axopositive multi-refractory non-small cell lung cancer, we continue to be enthusiastic by the responses we're observing. There are limited treatment options for patients who progress on immune checkpoint inhibitors and available treatments in the second line of the onsetting. These patients have suboptimal overall ORRs of approximately 10% to 20%. As a reminder, part one of a phase two study in non-small cell lung cancer is ongoing in actual 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% to 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. Further, leveraging our insights and FDA discussions on UPS, we expanded our phase two part one non-small cell lung cancer study to include the more frequent dose-intensive regimens 2Q3W and 3Q4W. We are currently enrolling these patients as we prepare our submission for a meeting request to confirm the design of the potentially registrational phase two part two 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 two part one 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 Axel. And we estimate that there are over 100,000 axopositive addressable patients per year worldwide. This second line plus indication has the potential to add approximately $2.5 to $3 billion in worldwide revenue at peak. Taking together sarcoma and mild small cell lung cancer, we believe BA3011 has the potential to become a significant commercial asset for bioalloy across multiple solid tumor types. Of even greater importance is that BA3011 has a 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 multicenter 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. 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. To date, we have three Phase II trials ongoing with BA3021, As previously reported in our phase one clinical data, we saw impressive responses in war two positive patients refractory to PD-1 therapy, including two PRs in non-small cell lung cancer, one PR in head and neck cancer, and one complete response in a melanoma patient who remains in complete remission off treatment for over two years. Based on a similar study, Exposure response analysis done in actual positive tumors. We are pursuing the same strategy in our phase two or two 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 2 trial in patients who have previously experienced failure of the PD-1 therapy, following an additional CR in an invaluable 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. In addition, our phase two 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. So far, the observed VOR2 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 80 CBA BA3021 program. We're 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. Now 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 and monotherapy in a 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 milligrams 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 milligrams or 5 milligrams per kilogram as a monotherapy or in combination with 3 milligrams per kilogram in nivolumab and anticipate the planned phase 1 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, FCAM, 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 one study in the first half of this year, with a complete phase one 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-my specifics 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 of full-year 2022 financials.
spk11: Rick?
spk07: 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 31, 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-month end of 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. And now, back to Jay.
spk09: 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 are 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 of more frequent dose-intensive regimens and providing clinical updates when more robust datasets become available. We also remain encouraged by the continued execution of our other promising CAB assets and 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 needs 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.
spk03: 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 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. To participate using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.
spk11: One moment, please, while we poll for questions. Our first question comes from the line of Brian Chen with JPMorgan.
spk03: Please proceed with your question.
spk05: Hey, Jay and team. Thanks for taking my question today. A couple questions, maybe just first on your AXO program, especially in the non-small cell lung cancer piece. And so 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 in? And secondly is that you're waiting for your feedback from the FDA. Any gating factor that could potentially come up between now and your start time for the pivotal trial? And then one more point is that are we expecting any ASCO updates for your ongoing non-small cell lung cancer study? And I have a couple follow-up. Thank you.
spk09: Hey, thanks, Brian. So 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 will be the gating factor for Phase 2, 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 UPS discussions, also with our increasing number of patients so that we could do a more thorough exposure response analysis. So we put those together, realized that we could bring in this more frequent dose-intense treatment in the same time frame that we're working with and discussing with the FDA. So 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. And so this gives us a chance to really make sure that we're going into the registrational portion of the trial. And, of course, it's registrational if the FDA will allow us to do that. So that's some of the feedback we didn't get yet. But that's how we're looking at it. And, you know, our job is to make sure we've maximized our potential for success. So 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 on it.
spk05: Yeah, that was very helpful. And then maybe just one on the raw two side. We're curious what you saw in the initial couple patients that you dose in the non-small cell lung cancer piece. And 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 Axil non-small cell lung cancer, can you shed some light on how, you know, the RAL2 program in lung cancer efficacy profile compared to what you saw with the Axil program?
spk09: Well, we can only do that for phase one. 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. So the Q1 earnings call is in May. But given the fact that we have the opportunity to bring in the more frequent dose-intensive 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 two timeline in terms of the pivotal side at all, but it allows us to now make a comparison between these more frequent dosing and the Q2W. So 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 Ward 2 and get a picture of that. We also should have a – 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 back. And then, of course, we'll hopefully get a snapshot of what's happening on the circulating tumor cell assay in melanoma.
spk05: Great. Thank you. Thanks for taking my question.
spk09: By the way, 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 under the hood on these other more frequent dose-intense regimens.
spk11: For the raw, too. 4.2 and AXEL. Oh, okay. Got it. Thank you. Thanks.
spk03: Our next question comes from the line of Kelly Sheet with Jefferies. Please proceed with your question.
spk04: Thank you for taking my questions. My first question is about AXEL 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? And also for the phase two, part two, you're going to evaluate two different dosings, 3Q4W and 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 two. Thank you.
spk09: Thank you, Charlie. I'm going to let Phyllis help me on this one a little bit, but I'm going to 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 glioma sarcoma that we saw a 29.6% tumor reduction on first scan. So that was the first patient. But we are moving toward 10 to 15 patients, and we 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. But obviously, we're very hopeful that we're going to see some interesting data coming out of that. But, Philip, maybe you can add to this answer.
spk06: Yeah, we forgot to the... to the timeline for the 34W LMS score. We'll wait until we have approximately 15 patients' worth of data, which is expected in the second half of this year, as Jay mentioned. And then your question about FDA requirements, 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. So we'll be planning on having a meeting with the agency once we have the first 40 patients enrolled in UPS. Thank you.
spk04: Okay, thank you very much. I also have a follow-up, if I may. So for the UPS Phase 2, do you plan to provide any data update in this year? And also, at the moment, would you be able to share the information regarding how many sites have been activated?
spk11: Philip, it's you.
spk06: Yeah, so 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.
spk11: We are now 6.8 months, something like that.
spk06: So the PFS is evolving positively. Some patients are still on treatment, so that might continue to evolve. But 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?
spk04: Yeah, so I meant for the phase two, the potentially cumulative trial, do you plan to have another data update this year, and at the moment, how many sites have been activated?
spk06: I don't believe we anticipate to have data update. This is a registration study. Patients are being randomized, so 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 initiated for Phase II Pac-1. So these sites are being transitioned to the second part of the streams, which is about 40 sites altogether in the U.S., Hong Kong, and Taiwan.
spk11: Great. Thank you. Our next question comes from the line of Tony Butler with EF Hutton.
spk03: Please proceed with your question.
spk08: 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. So the first question is, has enrollment been, has it included and have the patients have all of the tumors which are listed on ClinCharles.gov, been dosed in your early dosing schedule? And importantly, and if not, that's fine, but has it been skewed to one particular tumor or another? That's question one, where two is, in the same program, what actually, could you enunciate which parameters that you're simply looking for? Is it just simply DLT? And 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.
spk09: I'm going to split this with Philly. So I think that when you're at one milligram per kilogram, you're in an approved dose rate, especially in combination with three milligrams per kilogram PD-1. So we passed that cohort. We just passed the three mgs per kilogram in combination with three mgs per kilogram of PD-1. So there's another cohort that's in that efficacy range. We're enrolling now for the five milligrams per kilogram in combination with three mgs per PD1 so everything on out including the last two cohorts have the potential for looking at efficacy And of course we will look at that But you know I think So this study in general I think is on track to be done in times In times such that we can actually kick off or initiate our phase two trial in the BA3071 of the CTL-A4. So we're 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. But there were some other questions about the tumor types and maybe even a comment or two regarding efficacy readouts and so forth that maybe would be better for Philippe to answer.
spk06: Yeah, thanks, Jay. So I think the only tumor type we have not enrolled is HCC at this point. All the other tumor types have been involved. 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. And so, as Jay mentioned, we've really surpassed If you can see threshold levels that we were expecting, ipilimumab is approved at 1 mg per kg in combination with nivolumab at 3 mg per kg. In some indications, 3 mg ipilimumab plus 1 mg nivolumab in other indications. So we have reached levels with these cohorts where we certainly expect to see efficacy. But 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 two part of the study.
spk11: Jay, Philippe, thanks very much. Very helpful. Our next question comes from the line of Arthur He with HCU Wainwright.
spk03: Please proceed with your question.
spk02: Hey, good afternoon, JMT. Thanks for taking my question. So, just follow up on the CTLA-4 program. So, so far in your study, could you give us a little bit of color on the average of repeating dosing of the
spk06: uh 371 and how about the maximal uh repeating dosing have been so far reached so yeah we're starting to get in the weeds but uh uh we've had patients have been uh on on treatment for quite some time. And by quite some time, I mean 11 cycles. But again, we got to look at each cohort individually and see what is going on with these patients. But so far, the drug is even at doses that are above the doses approved with EP plus NEVO, There's really nothing to report. We've only had one assay so far that was unrelated to treatment and was in one of the early cohorts. So, 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. But what we can say is that so far, no DLTs, really not much to report from safety or ability standpoints.
spk02: Great. Thanks for the color. And regarding the Axel 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.
spk09: I think, well, first off, it's worth mentioning that these more frequent dosing, more intense dosing, actually from those that like to follow C-max and C-min, it actually On the 3Q4W, we're lowering the C-max, which is often associated with any toxicity, but we're also increasing the C-min. So from a modeling standpoint, this is very exciting. So 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 Lyomyosarcoma, and those... you know, came in in the phase one study where we used Q2W and 2Q3W. So what was interesting was we didn't see a PR in the phase two using the kind of Q2W. And so 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. And it also answers the safety question. So we kind of killed two birds with one stone. And, of course, those six wouldn't have counted for the UPS portion of our first part of our phase two, part two, potentially registrational study. And so 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.
spk11: Thanks for the call. Appreciate it. And our next question comes from the line of Wren Benjamin with JMP Securities.
spk03: We'll see what your question is.
spk10: 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 would like to see before declaring a go-forward dose? Are you looking for just improvements in the ORR or just deeper responses? Or is it primarily from a safety perspective that will lead you to declare a go-forward dose? And 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 kind of going forward into the registrational study?
spk09: So I'm going to start on this one and let Philly add to it. But 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. So we're expecting all three regimens of these different dose regimens, Q2W, 2Q, 3W, and 3Q, 4W, to all be safe. That's not the question we're exploring. In fact, the CABs allow us that freedom to do it, and the FDA was extremely supportive of that 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. But if you have a chance to increase advocacy and you can do it in a way that does not extend your overall development timelines, it was a great opportunity to do that. And in the UPS setting, we did we did it inside the part two of the phase two study. Fortunately, in the Axle and War II setting for lung, we're able to do it in the part one. So we're getting that done while we're in the same time in the process, at least for Axle, having discussions with the FDA. And likewise, War II has always been, you know, six months or so behind Axle. And so it has no delay effect on it. And it gives us a chance to really potentially see even more efficacy and stronger responses. So, Philippe, do you want to add to that?
spk06: Yeah, I mean, just to add to the first part of your question, which is which one do you, if the 324W doesn't work or doesn't meet our criteria or looks about the same as what you've seen with the other dosing regimens, then that's fine. We are happy with the other dosing regimens. and we'll move forward with the 2Q3W and the Q2W at that point in time and select those. It's not that we have to have the 2Q4W work for us to move forward. We're just trying to maximize the efficacy we can get and leverage the CAP platform. That's it.
spk10: 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?
spk11: Jay, do you want to take that? I think you should take that one.
spk06: Yeah, I mean, we have decided not to update the data, but I can tell you that some of the patients are still responding, yes.
spk10: Excellent. And then, you know, just switching gears to the EPCAM, you know, by specific, the, 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 guess I'd love to just get some feedback or some commentary on where you think the therapeutic dose might be and what's the point or how these titrations help you get to what's the ideal dosing, I guess, for this asset.
spk09: Yeah, I'll start, and Philly can add in to this, but in Group A, we're thinking that the 125 microgram per kilogram, you might have to see below that, but that's around the EC50 level, so 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, but... And, Philip, you can add some additional to that. 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.
spk06: Yeah. So it is a typical – 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 storm that have been observed with some other CD3 bispecifics. And so 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 talk study. Neither have we seen neurotoxicity or even infusion reactions. But we still have to follow that type of design in case we were to see grade 2 and above cytokine release syndrome. So that's really all done to manage that. The X-ray titration phase is fast. It is one patient per cohort. It is a 14-day DLT observation period. So we can go through it relatively quickly and then move into a more standard titration at those 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. But all of this is not atypical is what I'm trying to tell you.
spk11: Terrific. Thanks very much for taking the questions. And we have reached the end of the question and answer session.
spk03: I'll now turn the call back over to Jay Short for closing remarks.
spk09: Well, I want to thank everyone for their time today and also thank the BioAtlas team. And we look forward to speaking with you again, at least in May, with our next quarterly earnings call. Thank you.
spk03: And this concludes today's conference, and you may disconnect your lines at this time. Thank you for your participation.
Disclaimer