Q4 2022 Bioatla Inc Earnings Call
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Speaker 2: Greetings and welcome to the BIO-ATLA 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. If you have any questions, please post them in the chat box below.
Speaker 2: Please note this conference is being recorded. I'll now turn the conference over to your host, Bruce Mackle. You may begin.
Speaker 3: Thank you, operator, and good afternoon, everyone.
Speaker 3: With me today on the phone from BioAtlas are Dr. Jay Short, Chairman, CEO , and Co-Founder, Richard Waldron, Chief Financial Officer, and Dr. Jay Short.
Speaker 3: And following today's call, Felipe Martin, Chief of Clinical Development and Operations, Eric Severs, Chief Medical Officer, and Sherry Lydick, Senior Vice President, Commercial Strategy, will join Jay and Rick for a short Q&A....
Speaker 3: Earlier this afternoon, BioATLA released financial results and a business update for the fourth quarter and full year ended December 31, 2022.
Speaker 3: A copy of the press release is available on the company's website.
Speaker 3: 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, and minimum capacity ind utility agreements, and stomping on Bright
Speaker 3: collaborations, and other strategic partnerships, whether our clinical trials will be potentially registrational.
Speaker 3: 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. On recording magic Joelle
Speaker 3: the potential regulatory approval path of our product candidates, expectations about the sufficiency of our cash and cash equivalents.
Speaker 3: and expected R&D and G&A expenses.
Speaker 3: 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 .
Speaker 3: You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today, March 23, 2023, and BioAtlas disclaims any obligation to update such statements to reflect future information, events, or circumstances except as required by law.
Speaker 3: With that, I'd like to turn the call over to Jay Short. Jay? Hi, I'm Jay Short.
Speaker 4: Thank you, Bruce, and thanks to everyone for joining us for our fourth quarter and full year 2022 Biola earnings call. Biola has made significant progress in 2022 across our five ongoing Phase 2 trials for our two latest... Biola although, Chapman's
Speaker 4: stage first in class tab ADC product candidates BA3011 and BA3021 targeting multiple solid tumor types.
Speaker 4: We continue the positive trajectory in 2023 and tentatively focus on further advancing the development of our innovative clinical and preclinical programs across our platform, leveraging the broad applicability of our CAAP technology across several clinical stage antibody types, including AXEL and Lord II ADCs.
Speaker 4: targeted CTLA-4 IO naked antibody, and our first dual cap bispecific EpCAM and CD3 T-cell engager.
Speaker 4: everyone, but 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 today that are generally meeting and in several cases exceeding our interim study target response.
Speaker 4: our programs.
Speaker 4: 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.
Speaker 4: for our Phase II potentially registration studies.
Speaker 4: 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......
Speaker 4: 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 KAB-80Cs, we've looked at different doses and dosing regimens throughout Phase 1 and Phase 2 Part 1.
Speaker 4: 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 2 Part 2 study.
Speaker 4: While the profile of the 1.8 milligrams per kilogram Q2WR once every two weeks dosing regimen is positive, this is mainly a
Speaker 4: 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.
Speaker 1: which
Speaker 4: uses the 1.8 milligram per kilogram starting dose, are expected to provide approximately
Speaker 4: 38% and 44% more exposure respectively.
Speaker 4: then the previous Q2W dosing regimen.
Speaker 4: 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.
Speaker 4: This dose strategy was supported by the FDA as part of our UPS Phase II study design discussions and is an alignment with FDA's project optimists.
Speaker 4: In view of these things, we continue to be excited about the first of our two lead assets, DA3011, for multiple indications.
Speaker 4: 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.
Speaker 4: Today, we are providing additional insights, including how we are applying the learnings from our Encouraging Safety data and then...
Speaker 4: and exposure response analyses, as well as our UPS-related FDA interactions to study more frequent dose-intensive regimens more broadly across our actual ADC and Word2 ADC programs.
Speaker 4: First, I will discuss our BA-3011 Phase II Circumstance Study and our overall Circumstance Strategy.
Speaker 4: 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. transcription at contractors refused to spilled oneeveryone's
Speaker 4: Thus, UPS represents a significant commercial opportunity as a standalone indication and we are focused on moving quickly to registration in UPS.
Speaker 4: 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 and GPS.
Speaker 4: as an update to the Phase II Part I UPS study. We currently see an overall objective response rate or ORR of 50%, median progression-free survival or PFS of 11 months. The Phase II Part I UPS study.
Speaker 4: and a duration of response exceeding eight 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.
Speaker 4: with a duration of response exceeding eight 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 investigational portion of the trial.
Speaker 4: This month, the first six
Speaker 4: Lyo-myosarcoma patients cleared the DLT observation period using the 3Q4W dosing in Part 1 of the Phase 2 study, which was a study requirement to begin enrolling patients in the
Speaker 4: In Phase 2, Part 2 of the UBS trial.
Speaker 4: 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 3Q4W or 2Q3W dosing risk.
Speaker 4: Following this, we plan to know an additional 40 patients have a selected dose to complete the study.
Speaker 4: Overall, the primary efficacy endpoint, ORR, will be based on approximately 60 patients treated at the selected dosing regimen.
Speaker 4: In addition to UPS, we continue to see positive anti-tumor activity across several soft tissue and bone telecomaseptides where we previously reported an observed PFS rate at 12 weeks of 60%.
Speaker 4: in lipos queer trashes.
Speaker 4: 50% is synovial sarcoma and 67% in osteosarcoma.
Speaker 4: 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.
Speaker 4: We also continue to involve the remaining sarcoma subtypes.
Speaker 4: With respect to lyeomyosarcoma, 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 lyeomyosarcoma for 10 to 15 patients to evaluate this dosing regimen for potentially opening up.
Speaker 4: 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.
Speaker 4: Given the encouraging anti-tumor activity we're observing, coupled with a significant unmet need, UPS represents a solid early indication for Biowatlas we plan for the transition into a commercial stage company.
Speaker 4: We also see real value of the disillexpanding our Sarkoma footprint over time to include other Sarkoma subtypes.
Speaker 4: Ultimately, BA 3011 has the potential to treat over 25,000 succumbent patients per year and generate up to $2 billion in revenue worldwide in the area of very high unmet need.
Speaker 4: Regarding our DA311 phase 2 study in axial positive, multi refractory non-small cell lung cancer.
Speaker 4: we continue to be enthusiastic by the responses we're observing. There are limited treatment options for patients who progress on new checkpoint inhibitors and available treatments in the second line of the onsetting.
Speaker 4: These patients have suboptimal overall ORRs of approximately 10 to 20 percent.
Speaker 4: As a reminder, part one of a Phase II study in non-small cell lung cancer is ongoing in actual positive patients who have previously experienced failure of either PD-1, PD-L-1, EGFR or ALC inhibitors.
Speaker 4: The previously reported preliminary efficacy with an ORR of approximately 40 to 44 percent was observed so far in this study.
Speaker 4: This response rate is highly competitive in this PD-1 failure population and supportive of moving forward to the phase 2, potentially registrational part of the study.
Speaker 4: 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.
Speaker 4: Further, 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 2q3w and 3q4w. We are currently enrolling these patients as we prepare our submission for a meeting results.
Speaker 4: reporting all of these data after the Phase 2 Part 1 is effectively complete, which is anticipated in the second half of 2023.
Speaker 4: Most importantly, we also expect that we will initiate the potentially registration study in a 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.
Speaker 4: With respect to market size, a significant proportion of non-small cell lung cancer patients express axle.
Speaker 4: And we estimate that there are over 100,000 exalt positives addressable patients per year worldwide.
Speaker 4: The second line plus indication has the potential to add approximately $2.5 to $3 billion in worldwide revenue at peak.
Speaker 4: Taken together, sarcoma and mild small cell lung cancer, we believe BA3011 has the potential to become a significant commercial asset for biolat across multiple solid tumor types.
Speaker 4: 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 medical need.
Speaker 4: So round out our CAVADC BA-311 program, we are supporting an ongoing multi-center investigator initiated phase two clinical trial, BA-311, in patients with platinum resistant ovarian cancer.
Speaker 4: We are anticipating interim data consisting of 10 patients in the second half of this year.
Speaker 4: Now turning to our second lead, CAB ADC product candidate BA3021, a CAB War II ADC.
Speaker 4: As a reminder, there are no other therapies targeting or two in clinic. So we have the potential to have a first in class treatment for solid tumors. The date we have three phase two trials ongoing with VA 30021. As previously reported, our phase one clinical data, we saw impressive responses in or two positive patients refractory to PD-1. They're being...
Speaker 4: done in actual positive tumors, we are pursuing the same strategy in our Phase II or II 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.
Speaker 4: Regarding the melanoma phase two trial in patients who had previously experienced failure of the PD-1 therapy, following an additional CR in an invaluable patient identified using our validated IHC assay,
Speaker 4: 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 2 head and neck study is ongoing in patients who have previously experienced failure of PD-1 therapy alone or in combination with platinum therapy.
Speaker 4: We have achieved first patient in for this study. So far the observed or two positivity rate is high and in line with our expectations.
Speaker 4: We anticipate providing an enrollment update on or around the first quarter 2023 earnings call in May.
Speaker 4: To round out our CAVADC BA 3021 program, we are supporting a multi-center investigator initiated Phase II clinical trial of BA 3021 in patients with platinum-resistant ovarian cancer.
Speaker 4: We are anticipating NRM data consisting of 10 patients in the second half of this year. Now I'd like to talk briefly about our phase one, two trial for CAHPS CTLA-4 antibody BA3071. The phase one, two trial is being conducted in tumors known to be responsive to CTLA-4 treatment and will evaluate safety and tolerability of BA.
Speaker 4: and monotherapy in combination with the molymap. The trial is progressing as planned. As part of today's update, I'm pleased to share that the BLT observation period was cleared for the fourth cohort.
Speaker 4: at a dose of 210 milligrams or three mg per kilogram in combination with three mg per kilogram of Mavolumab. No DLTs will report it.
Speaker 4: 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 the Volimab and anticipate the planned Phase 1 data readout in the second half of this year. Moving on to our...
Speaker 4: earlier stage pipeline, namely our potentially first in class dual-CAB bispecific T cell engager antibody CAB-FCAM and CAB-CD3 or BA3182.
Speaker 4: We recently received FDA clearance of RIMD for the treatment of the dance at Yena Karsanoma and our own track for the first patient and for the first phase one study in the first half of this year. With the complete phase one day to read out, it dissipated next year.
Speaker 4: similar to our other three clinical CAP product candidates.
Speaker 4: 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.
Speaker 4: Several of the most common subtypes of adenocarcinoma that have tremendous unmet needs that we can potentially address include colon, lung, breast, pancreas, and prostate.
Speaker 4: BioATWA also continues to progress several candidates through IND-enabling studies, including cab-line specifics and next-generation ADC antibodies, and we still anticipate IND submissions for additional candidates, potentially this year and next.
Speaker 4: 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 one cancer Congress, and AACR. The latter of which will include preclinical data related to next generation ADCs and multiple by specifics.
Speaker 4: With that, I would now like to turn the call over to Rick to review the fourth quarter of full year 2022 financials. Rick. mean thousand amounts of financials associated with some of us usingray.
Speaker 5: 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...
Speaker 5: 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 pharmaceutical companies that could also provide
Speaker 5: 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 report on a net loss of 106.
Speaker 5: $0.5 million compared to a net loss of $95.4 million in the same period of 2021.
Speaker 5: 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.
Speaker 5: The year-over-year increase of $21.1 million was primarily driven by our clinical product development efforts. The year-over-year increase of $21.1 million was primarily driven by our clinical product
Speaker 5: 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. We expect our R&D expenses to remain variable from quarter to quarter and generally increase
Speaker 5: 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.
Speaker 5: 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.
Speaker 5: advance our intellectual property portfolio, support focused pre-commercialization activities for our product candidate, BA 3011 and satisfy requirements as a public company.
Speaker 5: 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.
Speaker 5: The increase in the 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.
Speaker 5: And now back to Jay.
Speaker 4: 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 CAHPS platform. Tomorrow we will brief you about the employ we are bringing in to get you dialed in on
Speaker 4: We are excited with the compelling clinical profile that is beginning to emerge in treatment refractory UPS in non-small cell lung cancer and are eager to continue advancing the phase two 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.
Speaker 4: 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.
Speaker 4: with the goal of pursuing indications of high unmet medical needs that we feel will have significant impact for patients and our shareholders worldwide.
Speaker 2: With that, we will turn it back to the operator to take your questions. Thank you. At this time, we'll be conducting a question and answer session.
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One moment please while we poll for questions.
Our first question comes from the line of Brian Chen with JP Morgan. Please proceed with your question. Please proceed with your question.
Hey, Jay and team, thanks for taking my question today. A couple questions, maybe just first on your ACTO program, 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 proctivital trial design? What are the patients mixed that you intend to enroll? And secondly, 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 ASO updates?
for your ongoing non-small cell lung cancer study, and I have a couple follow-ups. Thank you. 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.
from third quarter in our discussions with, in part from the 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, realize 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. 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, so this gives us a chance to really...
make sure that we're going into the registration portion of the trial. Of course, it's registration if the FDA will allow us to do that. That's some of the feedback we didn't get yet. That's how we're looking at it. 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 an upside with these other doses.
small-cell lung cancer, PEAS.
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 axial 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 axial program? Well, we can only do that for phase one. We don't have enough patients yet. Originally we were...
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...
the 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 but it allows us to now make a comparison between the...
these more frequent dosing on 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. And our goal, of course, is to have the information required to go back into the FDA for WO2.
We will also have an update in May, but we are hoping to have a much better picture of what our recruitment rate is in the head and neck. And then, of course, we will hopefully get a snapshot of what is happening on circulating 21st century in Illinois.
Great, thank you. Thanks for taking my question. 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 mornings.
more frequent dose intense regimens. For the RAR-2. For RAR-2 and axial.
Oh, okay, got it. Thank you. Thank you. Our next question comes from the line of Kelly Sheet with Jeffrey. Please proceed with your question.
Thank you for taking my questions. My first question is about an actual program in UPS. You mentioned at a more frequent dosing, 3Q4W, the DLT window has been cleared for first the six patients in LMS stufftime and 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 dosing 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? And do we need to listen to the CDC'shn kit?
in part two. Thank you.
Thank you, Charlie. 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 a gliomyosarcoma that we saw 29.6.
percent tumor reduction on first scan. So that was the first patient. But we are moving toward 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. But obviously we're very...
I'm very hopeful that we're going to see some interesting data coming out of that. Phillip, maybe you can add to this.
to this answer. Yeah, we've got to the timeline for the 3P4W LMS score. We'll wait until we have approximately 15 patient worth of data which is expected and figure out this year.
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.
once we have the first 40 patients involved.
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 updating this year and also at the moment would you be able to share the information regarding how many.
sites have been activated? Really pursue Yeah, so the data we just provided in this update is the data of all the UPS patient with We treated to date the medium PFS as evolved from the last time we reported the data we are now
6.8 months, something like that. So the PFS is evolving positively, some patients are still on treatment, so that might continue to evolve. I think through that 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? Bye.
Yes, so I meant for the phase two, the potentially pivotal trial, do you plan to have another data update this year and at the moment how many sites have been activated? I think we can, I don't believe we anticipate to have data update. This is a registration study, patients are being randomized to go.
sites we had for initiated for phase 2 pack 1 so these sites are being transitioned to the second part of the studies which is about 40 sites all together in the US Hong Kong in Taiwan
sites we had for Initiated to phase two pack one. So these sites are being transitioned to The second part of the studies which is about 40 sites all together in the US, Hong Kong and Taiwan Okay, great. Thank you
Our next question comes from the line of Tony Butler with EF Hutton. Please proceed with your question.
Thanks very much. A question around the CTLA-4 program.
in clinical trials.gov and one would anticipate, clearly there's been dosing.
or 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 clinical trials.gov, been dosed in your early dosing schedule, and importantly, and if not, that's fine, but is there, has it been skewed to one particular tumor or another? That's question one. Question two is, in the same program,
What actually, could you, and I'll tell you which parameters that you're simply looking for. So just simply DLP.
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. I'm gonna split this with Philly. I think that when you have 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 MiGs per kilogram in combination with three MiGs 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 MiGs per TIG PD-1. So everything on out, including the last two cohorts.
Law or initiate our Phase II trial in the BA3071 with the C-TIL 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...
of a key and
quite a bit of patients coming to our study in all the tumor types that we have listed and so we'll as G.M. mentioned we really surpassed efficacy threshold levels that we were expecting. Ipilimumab is approved at 1 mg per kg.
In combination with the Evolumab, a 3 milligram per kilogram, with some in-indication, 3 milligram, e.g. e.g. e. Evolumab plus 1 milligram, e.g. e.g. e.g. e.g. with other indications. So we have reached level with the discohelts where we certainly expect to see efficacy. But we 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. Jay, Philippe, thanks very much, very helpful. Thank you.
Our next question comes from the line of Arthur He with HCU-Wainwright. Please proceed with your question. Please proceed with your question.
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 3E71, and how about the maximal repeating dosing habit?
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 a basis that are above the basis approved with EP personal. There's really nothing to report. We only have one issue 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 DLT is really not.
more frequent and intensive dose regimen in the LMS cohort. Why not go for the other subtitle, the sarcoma? Or subt methods each film Caribbean,
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-Men, 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-Men. So from a modeling standpoint, this...
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, potential broad soft tissue sarcoma.
And it also answers the safety questions. So you kind of tell 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, a registrational study. And so, it's just really a way to optimize a whole bunch of questions very quickly without in any way delaying the UPS potentially registration study.
potentially, a 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, a registrational study. Thanks for the call. I appreciate it.
Our next question comes from the line of Ren Benjamin with JMP Securities. Please proceed with your question. Hey guys, thanks for taking the questions. I guess just speaking with the more frequent dosing regimens, can you talk a little bit about what you'd like to see?
see before declaring a go-forward dose? Are you looking for just improvements in 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 dose going forward into the registration study? So I'm going to start on this one and I feel really bad 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.
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 efficacy, and you can do it in a way that way
that does not extend your overall development timeline. It was a great opportunity to do that. And in the UPS setting, we did it inside the part two of the phase two study.
Fortunately, in the Axial and War II setting for lung, we're able to do it in the Part I. So we're getting that done while we're in the same time in the process, at least for Axial, having discussions with the FDA. And likewise, War II has always been six months or so behind Axial, and so it has no delay effect on it. So it gives us a chance to really...
potentially see even more efficacy and stronger responses. So, Philippe, do you want to add to that? 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 see in the other design regime, and then that's fine. We are happy with the other questions.
the camp level that's it got it just two other questions I guess the first can you comment or
Jay, do you want to take that or? I think you should take that one.
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
Excellent. And then just switching gears to the APCAM in a bi-specific. As I look at the clinical trial design, it's...
It seems complicated to me with 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 how these...
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? Yeah, I'll start and we'll leave to now then to this. But in Group A, we're thinking that the 125 microgram per kilogram, you might see us to see below that, but that's around the UC 50 level. So we think that's a dose level that...
to the group B titration.
Yeah so it is a typical, there hasn't been that many, but so far it is a typical design for a bi-specific 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 are we seeing neurotoxicity
or even infusion reactions but we 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. You will be at the titration phase, it's fast. It is one patient per cohort. It is a 14-day VLT observation period, so we can go through it relatively quickly.
and then moving to a more standard titration at those levels that we believe will be efficacious. These are extremely important 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.
to a more standard titration at those levels that we believe will be efficacious, which are extremely important. And so that is why we're starting at that low of a dose to begin with. But that is not all of this is not a typical is what I'm trying to tell you. Terrific. Thanks very much for taking the questions.
And we have reached the end of the question and answer session. I will now turn the call back over to Jay Short for closing remarks. I want to thank everyone for their time today and also thank the BioAtlet team. We look forward to speaking with you again at least in May with our next quarterly earnings call. Thank you.
And this concludes today's conference and you may disconnect your lines at this time. Thank you for your participation.
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