Bioatla - Q2 2023
August 1, 2023
Transcript
Operator (participant)
Greetings, and welcome to the BioAtla 2023 earnings call. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Mr. Bruce Mackle, with LifeSci Advisors. Thank you, Bruce. You may begin.
Bruce Mackle (Managing Director of Investor relations)
Thank you, Operator. Good afternoon, everyone. With me today on the phone from BioAtla are Dr. Jay Short, Chairman, CEO, and Co-founder, and Richard Waldron, Chief Financial Officer. Following today's call, Dr. Eric Sievers, Chief Medical Officer, and Sheri Lydick, Chief Commercial Officer, will join Jay and Rick for a short Q&A. Earlier this afternoon, BioAtla released financial results and a business update for the Q2 ended June 30, 2023. A copy of the press release and corporate presentation are available on the company's website.
Before we begin, I'd like to remind everyone that statements made during this conference call will include forward-looking statements, including, but not limited to, statements regarding BioAtla's business plans and prospects, potential selective licensing, collaborations, and other strategic partnerships, whether its clinical trials will be potentially registrational, achievements of milestones, results, conduct, progress, and timing of its research and development programs and clinical trials, expectations with respect to enrollment and dosing in its clinical trials, plans and expectations regarding future data updates, clinical trials, regulatory meetings, and regulatory submissions, the potential regulatory approval path for its product candidates, expectations about the sufficiency of its cash and cash equivalents, 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 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, August 1, 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. Jay?
Jay Short (CEO)
Thank you, Bruce, and thanks to everyone for joining us for our second quarter 2023 BioAtla earnings call. BioAtla is the inventor and leader in the development of novel therapies using a proprietary Conditionally Active Biologics CABs platform with improved selectivity for attacking tumor cells while avoiding healthy cells, thereby addressing urgent unmet needs in oncology to improve patients' lives. We made significant progress last year across our multiple ongoing phase II trials for our two latest stage, first-in-class CAB ADC product candidates, BA3011 and BA3021, targeting solid tumor types with high unmet medical needs. As we are now a little over halfway through 2023, we continue our positive trajectory and remain on track to achieve our recently guided milestones outlined on the first quarter call in May.
We remain focused on further advancing the development of our innovative clinical programs, leveraging the broad applicability of our CAB technology across several clinical-stage antibody types, including CAB-AXL and CAB-ROR2 ADCs, CAB-CTLA-4 immuno-oncology naked antibody, and our first dual CAB bispecific EpCAM CD3 T cell engager. Additional details related to what I'm going to provide are available on our website as part of our updated company presentation that may be helpful to you. We remain excited about our lead asset, BA3011, for multiple indications. Previously, we shared the encouraging partial interim data on our BA3011 phase II Part one sarcoma study and our BA3011 phase II Part one non-small cell lung cancer study.
We also shared additional insights on how we have applied the learnings from our differentiated safety data and exposure-response analyses, as well as our UPS-related FDA interactions to study more frequent dose intensity regimens more broadly across our AXL ADC and our ROR2 ADC programs. The goal of studying more frequent dose-intensity regimens across programs is to provide data to allow us to set study parameters that maximize the company's likelihood of success for our phase II potentially registrational studies. A summary of our current dose regimens can be found in the updated corporate presentation on our website. Let's now move to our clinical, operational, and financial updates for the Q2 2023. First, we are advancing BA3011 in our ongoing sarcoma phase II studies, including a potentially registrational study in UPS.
Without specific treatments approved for UPS, there is a significant commercial opportunity as a standalone indication. We have shown strong execution and promising results with continued anti-tumor activity, lack of disease progression, and a differentiated safety profile of BA3011 in UPS to date. Based on these results, together with the continued differentiated safety profile and encouraging feedback from the FDA around the study design, last year, we initiated part two of the potentially registrational portion of the trial. The first 40 patients are being randomized 1 to 1 between the more frequent dose-intensive regimens. Following the first 40 patients, we plan to enroll an additional 40 patients at the selected dose to complete the study. The primary efficacy endpoint, ORR, will be based on approximately 60 patients treated at the selected dosing regimen. As an update, we achieved first patient in and are actively enrolling patients.
In addition to UPS, we have completed enrollment of the phase II, part one leiomyosarcoma cohort using the three Q, four W dosing regimen and are on track with an anticipated data readout on 10 to 15 patients in the second half of this year. The remaining bone sarcoma cohorts in phase II, part one, are on track to finish enrolling in the second half of 2023. With regards to safety profile across all sarcoma subtypes, there are no new safety signals to report. BA3011 continues to be generally well-tolerated, with a phase II safety profile across all doses, consistent with the profile we observed in phase I.
Regarding our BA3011 phase II study in AXL-positive, multi-refractory non-small cell lung cancer, we continue to be encouraged about the data from the Q2W dosing regimen, while we anticipate data from the more frequent dose-intensive regimens. Currently, the scant treatment options in patients who progress on immune checkpoint inhibitors have suboptimal overall response rates of approximately 10%-20% and four month PFS rates. part one of a phase II study in non-small cell lung cancer is ongoing in AXL-positive patients who have previously experienced failure of either PD-1, PD-L1, EGFR, or ALK inhibitors, and continues to enroll patients. Anticipated data for all dosing regimens, assisting with the study design for the potentially registrational portion of the trial, remains on track for the second half of this year.
We have submitted a meeting request to the FDA for potentially registrational BA3011, phase II, part two, non-small cell lung cancer study design and anticipate feedback in the H2 of this year, and as a result, remain on track to initiate the phase II, part two study in non-small cell lung cancer also in the second half of this year, maintaining our overall timeline for development of the non-small cell lung cancer indication. We continue to believe BA3011 has the potential to become a significant commercial asset for BioAtla, and of even greater importance, a first-in-class treatment for a significant number of patients who fail at least one prior line of therapy, thus addressing a significant unmet medical need.
Regarding the ongoing multi-center investigator-initiated IIT phase II clinical trial in patients with platinum-resistant ovarian cancer, the trial is fully enrolled and remains on track for the interim data readout, consisting of 10 patients in the H2 of this year. Turning to our second CAB ADC asset, BA3021, a CAB ROR2 ADC. Currently, BA3021 is the subject of phase two trials in the treatment of four different indications. We conducted a similar exposure-response analysis of ROR2-positive tumors to inform the more frequent dose intensity regimen of three Q, four W in our phase two, ROR2-positive, non-small cell lung cancer study. Based on this analysis, which is a similar strategy to our UPS phase two, part two, BA3011 study I mentioned earlier, we are screening and enrolling patients.
Based on the activity to date, we believe that we remain on track to obtain data this year to permit clinical trial prioritization across our portfolio. Regarding the melanoma phase II trial in patients who have previously experienced failure of PD-1 therapy, we are continuing to screen patients with a validated IHC liquid biopsy assay. As we stated last quarter, we have successfully identified ROR2-positive tumors using the liquid biopsy assay, which is allowing us to enroll ROR2-positive patients. We are on track to dose patients in the H2 of this year. In addition, our phase II head and neck study is ongoing in patients who have previously experienced failure of PD-1 therapy alone or in combination with platinum therapy. Earlier this year, we announced achievement of first patient in for this study.
Since that time, multiple patients have been dosed, and we continue to enroll patients. Regarding the ongoing multi-center investigator-initiated phase II clinical trial in patients with platinum-resistant ovarian cancer, the trial is fully enrolled and remains on track for the interim data readout, consisting of 10 patients in the second half of this year. Now turning to our phase I/II trial for our CAB-CTLA-4 antibody, BA3071. As a reminder, the phase I/II trial is being conducted in tumors known to be responsive to CTLA-4 treatment, and we are continuing to evaluate safety and tolerability of BA3071 in monotherapy and in combination with nivolumab. The trial is progressing as planned.
Last quarter, we shared that we started treating patients in the fifth cohort at 350 milligrams or five mgs per kg as monotherapy and in combination with three mgs per kg nivolumab. As part of today's update, I'm happy to report that the DLT observation period was cleared for the fifth cohort, and no DLTs were reported. We are currently enrolling patients in the sixth cohort at 700 milligrams or 10 mgs per kg as the monotherapy, or in combination with three mgs per kg of nivolumab, and remain on track for phase one data readout, anticipated in the H2 of this year. We also remain on track to initiate BA3071 phase two study, also in the H2 of this year.
We believe there are significant unmet medical needs with sizable commercial opportunities across multiple tumor types, where CTLA-4 can deliver efficacy with a manageable safety and tolerability profile that allows patients to stay on therapy for longer, and thus achieve the full benefit of this important new therapy. On to our potentially first-in-class dual CAB bispecific T-cell engager antibody, CAB-EpCAM and CAB-CD3, or BA3182. As mentioned during last quarter's call, we received FDA clearance of our IND for the treatment of advanced adenocarcinoma. We are now actively enrolling patients in this phase I study, with the full data readout remaining on track for next year.
Similar to our other three clinical-stage CAB assets, this antibody has shown significant promise in 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. We believe that our dual CAB design has the potential to address the tremendous unmet need across several of the most common subtypes of adenocarcinoma, including colon, lung, breast, pancreas, and prostate. Finally, we continue to pursue opportunities to share our progress with the medical and scientific communities, with an additional two trial and progress abstracts, one for BA3011 and another for BA3021, which were accepted for poster presentations at the upcoming World Conference on Lung Cancer this September. This brings the total confirmed medical meeting presentation tally to 11 since the beginning of the year.
Additional abstracts have been submitted for several upcoming meetings as well. With that, I would now like to turn the call over to Rick to review the Q2 2023 financials. Rick?
Richard Waldron (CFO)
Thank you, Jay. As of June 30, 2023, we had $168.7 million in cash and cash equivalents, compared to $215.5 million as of December 31, 2022. 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 US, 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 Q2 ended June 30, 2023, we reported a net loss of $35.8 million, compared to a net loss of $28.9 million in the same period of 2022. Research and development expenses were $31 million for the Q2 ended June 30, 2023, compared to $20.7 million for the same period in 2022. The increase of $10.3 million was primarily driven by our preclinical and 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 $6.2 million for the quarter ended June 30, 2023, compared to $8.3 million for the same quarter in 2022.
The $2.1 million change was attributable to a decrease in various administrative expenses for the 2023 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 asset BA3011, and satisfy requirements as a public company. Net cash used in operating activities for the six months ended June 30, 2023, was $46.7 million, compared to net cash used in operating activities of $42.1 million for the same period in 2022. The increase in net cash used in operating activities for the first six months of 2023 is primarily due to an increase in research and development expenses related to our program development efforts as compared to the first six months of 2022. Now, back to Jay.
Jay Short (CEO)
Thank you, Rick. We are pleased with the progress we have made to date and cumulative results that continue to support both the preliminary efficacy and safety from our differentiated proprietary CAB platform. We are encouraged with the compelling clinical profile that is emerging in treatment-refractory UPS and non-small cell lung cancer, and are eager to start evaluating data from our phase II studies with the addition of the more frequent dose intensity regimens. We also are excited by the continued clinical execution of our other promising CAB assets, in particular, our BA3071, CAB-CTLA-4, clearing the fifth cohort with no DLTs observed, and are well positioned to reach several value-creating milestones and key inflection points by year-end. Iowilla 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.
Operator (participant)
Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. One moment please while we pull for questions. Thank you. Our first question is from Kelly Shi with Jefferies. Please proceed with your question.
Speaker 12
Hi, this is Dave, on from Jefferies. Thank you for taking our questions. I have a question on the request that you submitted to FDA. Can you talk a little bit more, what kind of data have you provided to the FDA? Does it include enough data to make a decision on RP2D?
Jay Short (CEO)
Yeah, I think, what we've really approached the FDA with is questions related to a study design and basically both with respect to whether it's a randomized trial, single arm trial. We've provided a basic update of things that we have to date. Maybe Eric, you might want to add a little bit more on that.
Eric Sievers (Chief Medical Officer)
Sure. Your question was about whether we've provided data regarding a recommended phase II dose, I believe. Presently, we've submitted questions to the agency, just as Jay had mentioned, about the overall study design, randomization, some of those features. We anticipate preparing more information regarding our dosing regimens in the briefing book.
Kelly Shi (Senior Equity Research Analyst)
Right. One more thing. How many patient data do you expect to include in the follow-up? Do you have any internal bar to move forward for both ORR or PFS?
Jay Short (CEO)
Eric, you want to start with that one?
Eric Sievers (Chief Medical Officer)
Sure. We are evaluating patients, as shown in our corporate deck, at multiple dose levels, including more dose-intensive regimens. I anticipate we'll have a fulsome analysis of those data by the end of the year that we can provide to the agency as a part of the Project Optimus.
Jay Short (CEO)
I would add that, you know, we're assessing basically three different doses. It'd be every other week, and then, the two Q3W, as well as the three Q4W. We'll have a little bit more data on the Q2W, but what we believe we'll have sufficient data for all of the, all of the doses for our go-forward decision and how we're gonna approach it.
Speaker 12
Great. Thank you for taking our question.
Operator (participant)
Thank you. Our next question is from Brian Cheng with JPMorgan. Please proceed with your question.
Brian Cheng (VP and Equity Research Analyst)
Hey, guys. Thanks for taking my question to this morning, this afternoon. Just a couple from us. Maybe first on BA3021. Given the number of potential opportunities here for the molecule, how do you think of the factors to consider when making a prioritization decision? What is your latest thought on collaboration or partnership that could potentially built in this consideration?
Jay Short (CEO)
Yeah. You know, when we're making these kind of decisions, Brian, I think we're gonna be looking across the entire portfolio. We have to weigh, the AXL indications where, you know, the fact that we're in a lung AXL and also in a, you know, a more two lung, you know, the, you know, how many lung indications, you know, should we take forward at the same time? We'll be evaluating that, and that's gonna be related to data, and also, where things are. Safety-wise, I think we're across the board feeling very comfortable, across all the indications. I think, I know personally, I'm very interested to see how the head and neck, reads out. We're still accumulating data....
likewise in lung and, of course, on both of the AXL and ROR2, we're seeing, or we expect to see, on track to see ovarian cancer data as well. By the way, just as a footnote, at the time of our write-up on the script, we hadn't dosed the melanoma patient yet, but at least we crossed that line today. So I think that's truly going, and that's gonna give us a nice picture there as well, which we expected, but it's nice to see it's maybe a little ahead. Overall, I think we have more indications and more drug opportunities than most companies have. You've got an opportunity to really pick the best ones to advance, that also gives us some freedom for partnering as well.
I don't know, that's maybe a high-level response, and maybe I don't know if, sheri, you wanna add anything else to it. You don't, don't feel obligated.
Sheri Lydick (CMO)
Yeah. No, I think you covered it, Jay. Thank you.
Brian Cheng (VP and Equity Research Analyst)
Yeah, maybe just one more on BA3071. Any color on clinical activity so far with the fifth cohort dosing? Just how should we think about the potential indications, you know, for the phase II dose expansion cohorts?
Jay Short (CEO)
Yeah. I mean, safety-wise, and, and, you know, we're very happy with that. We're also very encouraged, without getting into any specifics, but with the data and readouts that we're seeing already. So I would say, as we said in the script, we're excited about that asset, and we continue to be. I think, you'll recall that we're testing this across eight different indications, all known to have, some responsiveness to CTLA-4. So we're, we've done a fair bit of analysis on which ones we are likely to take forward, but, you know, I think we're going to, see how the next cohort, reads out and, tighten that, tighten that view. I think at this point, I certainly wouldn't be ruling out any indications.
However, there would be some that are, you know, I think that have a great opportunity, and I would prefer not to list them now because this is an evolving asset, and I really like the data we're seeing with the combination with PD-1 at, PD-1 at threemg/kg and clearing the five mg/kg, and we're already have, you know, dosed the patients at this next level. It's ongoing.
Brian Cheng (VP and Equity Research Analyst)
Great. Thanks for taking my question.
Jay Short (CEO)
You know, I should have added, Brian, that one nice thing about CTLA-4 is that it also opens up the door for future combination therapies. Just like in a, an analogous way that PD-1 has done with so many different other therapies. One can't help but sit back and think about those possibilities in addition to, you know, just combining with PD-1.
Operator (participant)
Thank you. Our next question is from Kaveri Pohlman with BTIG. Please proceed with your question.
Kaveri Pohlman (Director and Senior Biotechnology Analyst)
Yeah, good evening, and thanks, Jay. phase II trial, it's a relatively small sample size. Any color on when do you think you'll be able to complete the frequent dosing study? Will you be reporting efficacy data from these cohorts after selection of the right schedule, or that won't be allowed, since some patients will be part of the pivotal trial?
Jay Short (CEO)
Well, if we're, if we're talking about lung, we do anticipate, well, we'll have the data, enough data, for the more frequent dosing to make our plan for going forward into a registrational study this half of this year. We are and have identified a medical meeting where we intend to provide an update on our data, both for the every other week dosing as well as the more frequent dosing. We're gonna report on that meeting after we formally get accepted at the, at, at that meeting, but we, we believe that's on track for communication this year. That's with AXL in lung.
The UPS, of course, is registration or potentially registrational now, and we'll, you know, we'll not be reporting on that until later next year once we get further down the line on that. Then the ovarian studies, we intend to report out on those, both for the AXL and ROR2, and we're certainly hopeful that we'll have sufficient data on the ROR2 asset to allow us to affect the prioritization across our portfolio, both from the standpoint of what we wanna take forward, what we might wanna partner, etc. I'm not sure that we're gonna report out on efficacy data on ROR2 this year, we'll certainly have some sense of the prioritization.
Of course, CTLA-4, I think also we're gonna be We, we'll be giving updates, routine updates on as we progress through phase I. I think as, we'll also guide a little bit on where we're gonna head with the phase II study as well. The actual readout on that is probably Most of our plan, as we've reported earlier in the year, is to align with medical meetings for our readouts, but we'll try to bring in as many of those as we can into this year.
Kaveri Pohlman (Director and Senior Biotechnology Analyst)
Got it. That's very helpful. I, I believe for ovarian cancer results, you mentioned that you have completed the enrollment, but can you tell us how long these patients have been on treatment, and will you be able to provide any results on durability?
Jay Short (CEO)
Well, you know, these have started some time ago, and I maybe allow Eric to give some better feedback on the timeline. I'll just remind everyone, these are IIT studies, so the actual, we're waiting on the data ourselves. We're hope, we know it is not too far off in the future. We've been told by IIT studies, we know they're fully enrolled, so we should have a nice snapshot. Eric, maybe you want to get a sense when things started. Keeping in mind that all the patients have come on board at different times, so it's hard to give a specific number. Eric, you want to add some more color to it?
Eric Sievers (Chief Medical Officer)
Jay, I think you've characterized that really well. You know, we started working with the Canadian Cancer Trials Group back in, in 2020 about this. Then we had a mature protocol and started enrolling patients at different times in the two different protocols. I mean, the two different regimens, one for the ROR2 asset and the other for AXL. We are looking forward to seeing these data as well.
Jay Short (CEO)
I think we'll get a, get some insight on the durability. Obviously, the latter patients in that study will have a little less than the earlier ones, but that's the way it works.
Kaveri Pohlman (Director and Senior Biotechnology Analyst)
Got it. Maybe a last one. Besides exploring the dosing schedule, do you also plan to continue to explore AXL expression score for each tumor type to confirm the patient population that responds best to the treatment? Any changes you expect or need to make in terms of your companion diagnostic test?
Jay Short (CEO)
I think the companion diagnostics path forward, you know, was in good shape. I would just say, though, you know, I think we reported out earlier in the year that we had one PR at the 1% TMPL score level in lung. We are, we are exploring a bit further without getting into too many details at this point. Yes, that's certainly on our mind, and we're evaluating things.
Kaveri Pohlman (Director and Senior Biotechnology Analyst)
Excellent. Thanks for taking my question.
Operator (participant)
Thank you. Our next question is from Arthur He with H.C. Wainwright. Please proceed with your question.
Arthur He (Equity Research VP and Senior Equity Analyst)
Hi, good afternoon, Jay, Eric, and sheri. Thanks for taking my question. For the BA3071 data update, could you tell us what the current five mg/kg in combo, what's the average cycles of this BA3071 being dosed?
Jay Short (CEO)
It know, it can't be very long because I think we reported out that, we were just dosing them in our kind of, May timeframe, something like that. That May, June area, I think also at some of the conferences we may have mentioned in June. You know, you can only expect it to be, a couple, a few months, but, you know, I think in general, we're encouraged, with what we're seeing.
Arthur He (Equity Research VP and Senior Equity Analyst)
Okay. thanks for that. I'm just curious.
Jay Short (CEO)
By the way, Arthur, I should add, though, but we have earlier, we have earlier dose, dose levels that just happened to be earlier. Several of those have gone on for, quite some time.
Arthur He (Equity Research VP and Senior Equity Analyst)
Yeah.
Jay Short (CEO)
Well over the three to four cycles that are normally attainable.
Arthur He (Equity Research VP and Senior Equity Analyst)
I see. I see. Yeah. For the 10 mg/kg, 10 mg/kg, is still in the monotherapy dosing stage, or it's already reached the combo dosing?
Jay Short (CEO)
I think it's, you know, we don't have a precise... I know one has made it, but I don't have much more information, and I don't know the status. That's about all I'm gonna give right now. Let's just see how-
Arthur He (Equity Research VP and Senior Equity Analyst)
Sure.
Jay Short (CEO)
It plays out here.
Arthur He (Equity Research VP and Senior Equity Analyst)
Sure, no worries. My second question is on the EpCAM program. Congrats on the progress. For the data update we expect for the next year, could you first give some update on the enrollment status for the study? Regarding the update, what kind of data set we could expect? Thanks.
Jay Short (CEO)
Well, the enrollment's active, active across many centers, which we had to roll out across. So we're, we're happy that that's rolling, and I think it fits our timeline, and we should be able to... I don't know when we're gonna get the first update on that. It'll certainly be, we're just basically would be a little bit similar to how we're handling CTLA-4, but I don't think we would give too much insight on the early doses, because they're probably less relevant. As we start to march up toward, I would say, EC50, where we start seeing efficacy expectations, then I think we'll communicate more on it. You know, I clearly we're on track for next year as everything looks right now. That's an exciting asset, no question.
Arthur He (Equity Research VP and Senior Equity Analyst)
Awesome. Thank you. Thank you for taking my question. Congrats on the progress.
Jay Short (CEO)
Thank you.
Operator (participant)
Thank you. Our next question is from Tony Butler with EF Hutton. Please proceed with your question.
Tony Butler (Senior Managing Director)
Thanks very much, Jay. two questions on BA3071, please. one is, at 700 mgs Q3W, will you have enough durability in the three to six patients that actually tells you that you need to move forward with whatever two-ish or three-ish cohorts you wish to move forward with? That's question one. Number two is, though you said you've done a lot of work on each of those seven cohorts, the notion that any one may be better than another, I guess, are you limited to two, is really what I'm saying, which is what you stated in your corporate presentation. Thank you.
Jay Short (CEO)
What do you mean limited to two? Two combination-
Tony Butler (Senior Managing Director)
Well, it says select up to two for potential-
Jay Short (CEO)
Oh, oh.
Tony Butler (Senior Managing Director)
phase II dose expansion.
Jay Short (CEO)
Yeah, yeah, yeah.
Tony Butler (Senior Managing Director)
No, no, no. It could be, for example, an RCC or whatever.
Jay Short (CEO)
Okay.
Tony Butler (Senior Managing Director)
Yeah.
Jay Short (CEO)
Yeah. I, I think, we have a lively discussion around that exact point, Tony. I'm kind of glad you asked it. I think the reason we set up, you know, that 2 was because we're confident we're doing two. I don't mean that... I don't mean that to say we're not gonna, couldn't do more than two, but for now, I think two looks pretty solid, and there's a there could be a decent argument to consider more. I think, with respect to what dose we end up with and durability, I think, you know, that remains to be seen.
You know, one's gotta love the fact that you're at five mgs per kg, with a +3 on the PD-1 side, and you haven't got a DLT, and now we're able to at least dose the people, and we'll just see where, where patients and where it goes at the 10 mg per kg with three mgs per kg on PD-1. You know, this is, it's close to uncharted territory. You know, you adjust for PK and adjust for a few other things. We, we really like where this asset's going, and I think it's gonna-- I, I'm hopeful it'll highlight what I think is the powerful advantage of CAB technology.
Tony Butler (Senior Managing Director)
Within that statement, and thank you for it, we too, but the real notion is, is there any reason to assume, even though you may, for the sake of discussion, we don't know, any notion to say that 2x BA3071 dose, about 350 to 700, let's say, really gives you added efficacy despite the fact that the side effect profile.
Jay Short (CEO)
Well, I think we know it from other.
Tony Butler (Senior Managing Director)
Let's say, manageable.
Jay Short (CEO)
Yeah, I, I think you know from past studies with other CTLA-4 is if you can, two things: if you could potentially increase the dose or, and/or if you could keep patients on more cycles, you do translate to better outcomes if you can manage the safety. And I think there's a, there's a fair bit of literature around that. That's not quite as much the case with PD-1, and, but with CTLA-4, there is a, there is support for that, and that actually was the original objective. Could we, number one, get to a higher dose in combination with PD-1? That's one question. The second question was, could we get beyond 3 to 4 cycles in the combination therapy with CTLA-4 PD-1? And the third question is: Could we do both?
That's what we're on the precipice of answering, and I think we've already answered a portion of it with the five mgs plus three mgs that we cleared. Of course, we'd like to see a readout for a few more months. All of these things going forward here are additive, but we're in the right timeframe to look at it, and I think we're gonna have a great you know, encouraging answer, I'm hopeful, later this year.
Tony Butler (Senior Managing Director)
Been very helpful. Thanks so much.
Operator (participant)
Thank you. Our next question is from Reni Benjamin with JMP Securities. Please proceed with your question.
Reni Benjamin (Managing Director and Senior Equity Research Analyst)
Hey, guys. Thanks for taking the questions. You mentioned that you identified the ROR2 positive tumors using the liquid biopsy. Can you talk a little bit about how many patients were identified, and what does this kind of tell you about the proportion of ROR2 patients in the real world versus kind of epidemiological studies and the numbers we get from that?
Jay Short (CEO)
It's kind of interesting. In melanoma, you know, you'll recall that we saw approximately 7% positivity rate for ROR2 in melanoma using an IHC assay, you know, a histochemical assay. As we transition to the liquid biopsy, we haven't given a definitive number, but I can tell you it's certainly a double-digit positivity rate. It's clear that the liquid biopsy, 'cause we've done a lot of validation around this assay, has, you know, seems to be more sensitive, being able to pick up patients that are ROR2 positive, but at a lower, probably a more sensitive level, so we're seeing more patients. That's an advantage that goes beyond the fact that it's much easier to perform that assay.
I think the lesson here is, is that every assay has a certain sensitivity and, and of course, the only patients that we had studied, or we had one patient in, evaluable patient in phase I, we had one valuable patient that had come across in the phase II study. Partly only one in one that were valuable because of the low positivity rate. If you can start to move the positivity rate up, then you're gonna get a lot more patients willing to come on board to do the study. It's a lot easier to take a blood draw than it is to go and get a tumor biopsy from the patient. The question remaining is, what is that threshold that allows you to see that activity?
You know, with ADCs, there's a lot of history saying that there could be a wide range of reaction. Like in our head and neck, we saw something in the teens, you know, it was TPS score in the teens, and we saw a PR right out first dose. Long story short, this liquid biopsy is allowing us to see a larger number of patients from a positivity standpoint. The next question we're hoping to answer is, do we maintain a strong response rate in this group? We should be able to answer that in the near future.
Reni Benjamin (Managing Director and Senior Equity Research Analyst)
Got it. I, I think I've asked you this before, but now that you're dosing, you know, the melanoma patients, do you kind of wait to see how this reads out before, you know, testing, the other indications with this liquid biopsy? You know, do you kind of I, I think in the past you may have said that, with these other indications, you have quite a robust ROR2, you know, expression, and so we don't really need to use the assay.
Jay Short (CEO)
We, yeah, I think, rolling it out. We definitely are working at the research level to make sure we have it covered in these other areas, including AXL, if we need it. However, to roll it out with the expense that you might have to, want to put behind a companion or need to put behind a companion diagnostic, no, we wouldn't do that until we got more confirmation beyond what we have at the moment. Because we're. Keep in mind, we're also wanting to manage our capital, and we're forecasting to get into 2025. That means you gotta be, you gotta be prudent on how you do things.
Reni Benjamin (Managing Director and Senior Equity Research Analyst)
Got it. One final one for me. The phase II, you know, investigator-sponsored ovarian study in platinum-resistant ovarian cancer, you're getting the 10 patients. What kind of data do you need to see, you know, or, or foe you would you like to hit so that, I don't know, it would be kind of brought back in-house and developed under a corporate IND versus-
Jay Short (CEO)
Yeah
Reni Benjamin (Managing Director and Senior Equity Research Analyst)
... you know, leaving it as an IS, as an IST? Is this something, is this an indication that you would really just like to be seen, you know, developed by somebody, somebody else, even if it's an academic partner?
Jay Short (CEO)
Well, we've had, we've had corporate, we've had, companies ask us about the ovarian cancer, so, there's interest out there. What the exact cutoff is, is interesting because it, you know, depends on how that whole field is emerging a little bit. I think the bar is fairly low at the moment in terms of what you need to see, to advance this. I, I think, how we'll take that forward is gonna be linked to the data. What that exact cutoff will be, is still being debated, but, you know, beyond that, it's hard to answer at this particular second. We have our own thoughts. I mean, I would say, I'll just throw out, I think 20% is still quite viable if you're seeing responses in that.
Keeping in mind, though, a lot of these drugs get approved on PFS and not ORR. I just, you know, we have to keep all... As well as overall survival, we have to keep all of these various aspects in mind. We'll keep an eye on it, and we look at it as an upside. It's a study that we wouldn't have been able to fund ourselves at that time. You know, it's, it's in combination with PD-L1, it's gonna be an interesting readout one way or the other.
Reni Benjamin (Managing Director and Senior Equity Research Analyst)
Got it. Terrific. Thanks for taking the questions.
Operator (participant)
Thank you. We have reached the end of our question-and-answer session, and with that, I would like to turn the floor back over to CEO, Dr. Jay Short, for closing comments.
Jay Short (CEO)
Well, I just appreciate everyone's attendance and we've got a very active fall here coming up, and we really look forward to speaking with everyone at meetings and other venues as we go forward. Thank you for your attention today.
Operator (participant)
Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.