Bioatla Inc (BCAB) 2022 Q1 法說會逐字稿

Good day and thank you for standing by. Welcome to the BioAtla first-quarter 2022 financial results and business conference call. (Operator Instructions) Please be advised that today's conference is being recorded. (Operator Instructions)

I would now like to hand the conference over to Bruce Mackle, LifeSci Advisors. Please go ahead.

Thank you, operator, and good afternoon, everyone. With me today on the phone are Dr. Jay Short, Chairman, CEO, and Co-Founder; Scott Smith, President; Philippe Martin, Chief of Clinical Development and Operations; Sheri Lydick, Senior Vice President, Commercial Strategy; and Richard Waldron, Chief Financial Officer. Earlier today, BioAtla released financial results and a business update for the quarter ended March 31, 2022. A copy of the press release is available on the company's website.

Before we begin, I would like to remind you that statements made during this conference call that are not historical facts or forward-looking statements within the meaning of the federal securities laws, including, but not limited to, statements regarding our business plans and prospects, financial and operating performance and expectations, operating costs and expenses, products pipeline, clinical trial, and regulatory timing and associated resource requirements, our programs and potential partnerships, and the advancement of our CAB technology and product candidates.

These forward-looking statements are based upon BioAtla's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, as described in BioAtla's annual report on Form 10-K, filed February 28, 2022, and subsequent filings with the Securities and Exchange Commission.

Accordingly, you should not place undue reliance on these statements. All forward-looking statements made during this conference call are based on management's assumptions and estimates as of today, May 4, 2022. BioAtla undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after today, except as required by law. With that, I would like to turn the call over to Jay Short, Chairman, CEO, and Co-Founder of BioAtla. Jay?

Thank you, Bruce. Thanks to everyone for joining us for our first quarter 2022 and first-ever BioAtla earnings call. BioAtla is a clinical-stage biotechnology company focused on transforming cancer therapy with the development of our novel class of highly specific and selective antibody-based therapeutics for the treatment of solid tumor cancer.

Our conditionally active biologics or CABs target known and widely validated tumor antigens that have previously been difficult or impossible to target, by exploiting characteristic pH differences between cancer cells and normal healthy cells.

Since our IPO in December of 2020, the broad applicability of our CAB technology has allowed us to continue advancing the development of our innovative clinical and preclinical programs. We have five potentially registration-enabling ongoing Phase 2 trials for our two latest stage CAB-ADC product candidates -- mecbotamab vedotin, or BA3011; and ozuriftamab vedotin, or BA3021 -- across multiple solid tumor types for these first-in-class therapeutic candidates.

BioAtla is also supporting a multi-center investigator-initiated trial for both our lead assets in platinum-resistant ovarian cancer. Additionally, a Phase 1 basket trial for our CAB-CTLA-4 antibody, BA3071, has been initiated and is currently ongoing. Finally, BioAtla has several candidates in our IND-enabling preclinical pipeline that include CAB bispecific and next-generation ADC antibodies, targeting unmet medical needs in multiple types of solid tumors.

We are pleased with our continued progress during the first quarter across our many clinical programs and believe we are well poised for another strong year of execution in 2022. Most importantly, we are excited to share the updates on our ongoing clinical programs with you today, in particular, interim clinical data from our Phase 2 sarcoma study with our lead asset, BA3011.

With that, I would now like to turn the call over to Philippe Martin, Chief of Clinical Development and Operations, to provide a topline interim clinical data update from our Phase 2 sarcoma study. Philippe?

Thank you, Jay, and good afternoon, everyone. Before providing a topline interim update on our Phase 2 sarcoma study, I would point out that we have put this slide of topline interim clinical data on the Investors section of our company website under events and presentations.

Our ongoing potentially registration-enabling open-label Phase 2 trial of BA3011 was designed to evaluate the efficacy and safety of BA3011 in adults and adolescent patients with refractory soft tissue and bone sarcoma. There are two parts to the Phase 2 portion of the trial.

In Part 1, we enrolled approximately seven patients across seven different sarcoma subtypes to receive BA3011 monotherapy and across all sarcoma subtype to receive BA3011 in combination with nivolumab, split equally between CD20-positive and CD20-negative tumor expression. Patients were selected based on AXL expression in each sarcoma subtype.

The subtypes in soft tissue sarcoma included leiomyosarcoma, synovial sarcoma, liposarcoma, other soft tissue sarcomas, including undifferentiated pleomorphic sarcoma or UPS; while bone sarcoma subtypes included osteosarcoma, Ewing sarcoma, and other bone sarcomas, such as chordoma and/or chondrosarcoma.

The purpose of Part 1 of the Phase 2 study was to identify sarcoma subtypes that do not respond to BA3011 treatment and eliminate these subtypes for moving forward into Part 2 of the study. Predefined go/no-go criteria for the interim analysis determines which subtype may advance to Part 2 of the study. This threshold for a go decision is either at least one partial response or complete response per subtype or progression-free survival or PFS rate of at least 40% at three months.

Our preliminary interim analysis of Part 1 of the Phase 2 study that we will share today is based on an efficacy data cut-off date of April 28, 2022. We achieved and even exceeded predefined criteria in multiple sarcoma cohorts including UPS and osteosarcoma.

Specifically in UPS, in the monotherapy cohort, we observed one PR of five patients which satisfied our predefined go criteria in Part 2 of Phase 2. We observed an additional PR in our UPS patient in the combination cohort, resulting in a total of two PR out of six UPS patients treated, with an objective response rate of 33%.

This is consistent with what was observed in Phase 1. And when combining Phase 1 and Phase 2 data at the recommended Phase 2 dose of 1.8 milligram per kilogram, PRs were observed in four of eight UPS patients with an ORR of 50% and a PFS at three months of 50%. Importantly, we are observing durable responses, and partial responders are able to remain on treatment for extended periods of time. Some of them are on study for over two years.

In the Phase 2 osteosarcoma cohort, we enrolled a total of six patients and observed the PFS rate of 67%, which exceeded our predefined go criteria to Part 2 of Phase 2. When combining Phase 1 and Phase 2 data, the recommended Phase 2 dose of 1.8 milligram per kilogram, we enrolled a total of seven patients with a PFS rate at three months of 57%.

For context, recent studies have shown that the placebo PFS rate for first- and second-line metastatic osteosarcoma patients at eight weeks is at or around 0%. When combining all Phase 1 and 2 bone sarcoma patients, we enrolled a total of 17 patients and observed a PFS rate at three months of 56%.

We're encouraged by these interim results in UPS and osteosarcoma. And in view of the significant unmet need, we believe we have an opportunity for potential accelerated regulatory approval for BA3011 in these sarcomas. We intend to advance these two sarcomas as two separate cohorts and are working toward a meeting with the FDA by July of this year and anticipate enrollment into Part 2 to begin shortly thereafter.

Consistent with the purpose of Phase 1, we also identified a cohort that will not advance into Part 2. That cohort is leiomyosarcoma. The PFS rate observed in leiomyosarcoma cohort was 27%, thus, below the threshold established by the predefined criteria. This rate is pending confirmation as some patients are still on treatment; they have not yet reached three months.

Based on the data so far, we are hopeful that other cohorts will be moving forward into Part 2 or Phase 2 soon as more patients get through the three-month mark. We are continuing to enroll in those patients -- across four additional cohorts: synovial sarcoma, liposarcoma, Ewing sarcoma, and other bone sarcomas. An update will be provided as soon as the go/no-go decision is reached for each of these cohorts.

With regards to the safety, BA3011 is generally well tolerated with a Phase 2 safety profile consistent with the profile observed in Phase 1. As of the safety data cut-off of March 31, 2022, there were no treatment-related deaths, and we observed few treatment-related serious adverse events and adverse events leading to discontinuation.

Treatment-related AEs were generally consistent with MMAE toxicity. Related AEs generally did not lead to treatment discontinuation. Only two patients out of the 68 discontinued treatment due to treatment-related AEs; both were grade 2 peripheral neuropathy.

With that, I would like to thank you for your attention and would now like to turn the floor over to Sheri Lydick, Senior Vice President, Commercial Strategy, who will highlight the significant unmet need and commercial opportunity in sarcoma. Sheri?

Thank you, Philippe, and good afternoon, everyone. As you all know, sarcoma is a relatively rare type of cancer with a high unmet medical need. There are limited therapeutic options, and the five-year survival rate for advanced refractory metastatic sarcoma is only approximately 20%. In part as a consequence to the high unmet medical need, the regulatory threshold for investigational therapies is quite low.

Essentially, all approved therapies fall at or well below 15% ORR, suggesting that a drug with an ORR at or above this threshold would be a welcome addition to limited treatment options for these refractory sarcoma patients. UPS is one of the largest sarcoma subtypes, representing nearly 15% of all soft tissue sarcomas. UPS is also one of the most aggressive subtypes with one of the highest recurrence rates.

Patients with refractory UPS often progress very rapidly. The standard treatment is surgical removal, and there are no FDA treatments specifically approved to treat UPS. Ewing sarcoma is a malignant tumor of the bone that's often diagnosed in children and young adults. Osteosarcoma is the most common malignant primary bone tumor, excluding multiple myeloma, accounting for 30% of all such malignancies. They are frequently aggressive tumors often occurring in childhood.

Nearly 20% of osteosarcoma patients have metastasis at diagnosis. And of the remainder, 50% will eventually progress to clinical metastasis. Surgical excision remains the mainstay of curative treatment with chemotherapy and radiotherapy often used in conjunction with suboptimal success.

In addition to the high unmet medical need, UPS and bone sarcoma represent a significant commercial opportunity. Combined, there are approximately 5,000 to 7,000 addressable UPS and osteosarcoma patients per year in the US with the potential to generate upwards of $1 billion in worldwide revenue. The FDA has granted orphan drug designation to BA3011 for treatment of soft tissue sarcoma.

The US sarcoma patient population and the medical professionals who treat them can be served by a highly trained, yet relatively small, group of marketing professionals and commercial infrastructure that can target high-volume sarcoma centers at launch. Based on the encouraging interim data just shared from our Phase 2 BA3011 sarcoma study, we are excited that our lead CAB-ADC asset, BA3011, moves us closer towards our transition to a commercial-stage company, while filling a significant unmet medical need for sarcoma patients.

Now, I would like to turn the call over to Scott Smith, President of BioAtla, to provide an overview and updates to our other ongoing clinical programs. Scott?

Thank you, Sheri, and good afternoon, everyone. I'm going to take a few minutes to run through some key operational updates and upcoming milestones. Before I do, I wanted to reiterate my excitement about the interim Phase 2 sarcoma data from Part 1 of the study. Given the significant unmet medical need and commercial opportunity in sarcoma, we are thrilled to move one step closer toward potential first-in-class accelerated regulatory approval path of BA3011 in multiple sarcoma subtypes.

Looking beyond sarcoma, we have a Phase 2 trial ongoing with 3011 in refractory non-small cell lung cancer. Over 40 sites are active in this trial, and we're actively enrolling and dosing patients. We anticipate the preliminary cohort of 20 patients to be fully enrolled by the end of this quarter, with an interim update anticipated on or around our second-quarter earnings call.

Now turning to our second lead CAB-ADC product candidate, BA3021, a CAB-ROR2-ADC. As a reminder, there are no other therapies targeting ROR2 in the clinic. So we have the potential to have a first-in-class treatment for solid tumors.

In Phase 1, we saw impressive responses in ROR2-positive patients refractory to PD-1 therapy, including two confirmed PRs in non-small cell lung, one PR in head and neck cancer, and a complete response in a melanoma patient who remains in complete remission off treatment for over two years. We have initiated three Phase 3 trials with 3021. And I'm happy to provide an update as to where we are with each, beginning with non-small cell lung.

The non-small cell lung trial in refractory patients is currently dosing, and we anticipate a preliminary cohort of up to 20 patients to be enrolled in the second half of 2022, with an interim update planned after these patients have received at least three months of therapy, likely in the second half of this year.

Turning to the melanoma trial, which is being conducted in patients refractory to PD-1 therapy, we have run into challenges with trial recruitment and have enrolled only one patient to date. The ROR2 positivity rate has been lower than anticipated at around 10%. So it's been a challenge obtaining invasive tissue biopsies in these patients, which we believe has significantly impacted our ability to recruit to trial.

We are working diligently on liquid biopsy with our partner, Veracyte. We are currently in the validation phase and anticipate this non-invasive assay will be available to us in the melanoma trial soon. We believe there will be a significant acceleration in enrollment with the availability of this liquid biopsy.

While we only had one melanoma patient enrolled in Phase 2, I'm very happy to report that this patient has also achieved a complete response. When you take into account the complete response we observed from Phase 1, we now have two out of two ROR2-positive PD-1 refractory patients with a complete response, which is quite remarkable. While we're unsure of timing at this point, we remain very excited about the potential of 3021 in melanoma patients. We are working towards providing an interim update in the second half of this year.

The third Phase 2 study that we've initiated with 3021 is in refractory patients with head and neck cancer. We anticipate the first patient to be dosed in the second quarter of this year. To round out our CAB-ADC programs, we are supporting a multi-center investigator-initiated Phase 2 clinical trial of 3011 or 3021 in patients with platinum-resistant ovarian cancer. This trial was initiated and currently screening patients in Canada and the United States.

I would now like to talk briefly about updates for our CAB-CTLA-4 antibody, BA3071. The Phase 1/2 trial is ongoing, and we'll examine safety and tolerability of 3071 in doses ranging from 7 milligrams every three weeks to 700 milligrams every three weeks as monotherapy and in combination with nivolumab.

We are very excited to have this asset back in BioAtla's portfolio and believe there's a tremendous unmet need and commercial opportunity for a safer and better tolerated CTLA-4. We anticipate the first patient dosed in the second quarter of this year.

Turning to our preclinical pipeline, BioAtla has several candidates in IND-enabling phase that include CAB bispecific and second-generation ADC antibodies. We remain on track for an IND submission for a CAB-EpCAM/CAB-CD3 bispecific antibody this year, as well as for additional IND filings for multiple preclinical CAB bispecific and next-generation CAB-ADC candidates in 2023.

On the BD front, we announced early in Q1 that we entered into a clinical collaboration with BMS to investigate our two lead CAB-ADCs in combination with BMS' nivolumab. With that, I would like to hand over to Rick to review the first-quarter 2022 financials.

Thank you, Scott. Thank you. BioAtla's financing strategy is an integral part of our product growth and overall corporate strategy. Our primary objective is to cost effectively fund our operations across current product candidates through the commercialization stage or other major development inflection points, while expanding our product candidate pipeline. This is intended to optimize our opportunities for future financing and enhance value for the stockholders.

As of March 31, 2022, we had $219.4 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 the second half of 2024. We control all CAB product market rights in the US, Europe, and Japan.

Selective licensing of product price in certain territories or collaborations with other biopharmaceutical companies could generate for us upfront cash, development milestones, and royalties upon regulatory approval and commercialization that could extend our cash runway and create additional value for stockholders.

For the first quarter of 2022, we reported a net loss of $24.3 million compared to a net loss of $18.7 million in the first quarter of 2021. All of the $5.6 million increase is attributable to the increase in research and development expenses, from $10.4 million in 2021 to $16.9 million in the first quarter of 2022, primarily driven by expansion of our product development efforts including clinical development for CAB-CTLA-4 BA3071 and preclinical development of additional CAB candidates.

We expect our R&D expenses to increase as we continue to invest in R&D activities to advance our product candidates and clinical programs and to expand our product candidate pipeline.

General and administrative expenses were $7.4 million for the first quarter of 2022 compared to $8.4 million for the first quarter of 2021. The $1 million decrease was attributable to a decrease in stock-based compensation for the 2022 period. We expect our G&A expenses to increase to support development of our product candidates, expand our intellectual products property portfolio, support pre-commercialization activities for our lead product candidate BA3011, and meet all requirements as a public company.

Net cash used in operating activities for the three months ended March 31, 2022, was $25.1 million compared to net cash used in operating activities of $15 million for the same period in 2021. The increase in net cash used in operating activities for the first quarter of 2022 is primarily derived from the $5.6 million increase in net loss, the $1 million decrease in stock-based compensation, and $3.5 million greater change in certain working capital accounts compared to the 2021 first-quarter results.

And now, back to Scott.

Thank you, Rick. Since our IPO in December of 2020, we have continued to advance the development of our innovative clinical and preclinical programs and have achieved a number of value-creating clinical milestones with our CAB assets. As BioAtla continues to build our medical affairs and commercial capability and given the strength of our balance sheet, we will continue to make efficient use of our capital resources to continue to focus on solid tumors with the greatest therapeutic and market potential.

In addition, we will strategically prioritize our resources in order to execute our efficient and strategic clinical trial designs, thereby achieving key value inflection points for our company and for our shareholders.

We're very excited about the potential range of opportunities for CAB antibodies to create long-term sustainable value, transforming cancer therapy, and have a meaningful impact on patients' lives across multiple solid tumor types.

Thank you for your attention. And with that, we will turn it back to the operator to take your questions.

(Operator Instructions) Anupam Rama, JP Morgan.

Hey, guys. Thanks so much for taking the question. My first question is, can you give us a sense of -- for the liposarcoma, the synovial, and Ewing sarcoma, if you'll have some of the data in hand when you go meet with regulators, I think you said in July. And then, the second question on the safety side, the two patients with peripheral neuropathy, anything in the baseline characteristics worth noting there for those two patients? Thanks so much.

Thank you for your question, Anupam, and good afternoon. Hope all's well. I'm going to ask Philippe Martin to directly answer the two questions that you put forward there. So Philippe?

Thank you for your question. Yeah. So by July, we anticipate we will have all the data from the remaining cohorts that are still -- that we're still recruiting, at the time we'll be meeting with the agency. Again, I would like to point out that we are working with the agency right now to schedule the meeting. July is a tentative date that should work based on general timelines, but it's based on the agency availability. So I just want to make that clear to you.

And then for the peripheral neuropathy baseline for those two patients, I believe one of the two patients had prior history of peripheral neuropathy before joining the trial. We've seen a few of those patients coming in with grade 1 peripheral neuropathy; we are allowing that. And the patient has progressed to grade 2. But I mean two, to this consideration, out of 68 patients is a rate that is definitely acceptable going forward.

Particularly in this multi-refractory patient population that we're studying, many of whom are coming in with history of peripheral neuropathy. So again, I think it shows a little bit of the CAB technology playing out in the clinic, because the rates are quite low relative to other ADCs studied in this multi-refractory patient population.

Would you disclose some of the data from the other cohorts like Ewing and synovial and liposarcoma when you have them or -- how should we be thinking about the disclosure around those cohorts?

Yeah, so we didn't want to disclose cohorts where we're continuing to enroll right now, and we haven't made a decision on. And we don't have enough information on them. It's important to note that in Phase 1, we saw responses in UPS, we saw responses in bone and Ewing, and we saw one in leiomyosarcoma. And in those areas, we have confirmed in phase -- for at least -- for bone and for UPS, we've confirmed what we saw on Phase 1.

We wanted to run that leiomyo cohort quite large, because we didn't see a response in Phase 1. And we didn't see a response, and we didn't see the right kind of PFS to move it forward in Phase 2. Once we have the right information, we will talk to you about these cohorts. We'll certainly update you in the next conference call. We should have a good amount of information to take it to the agency and make a decision going forward.

But I'll just say, I'm really pleased that we are moving forward right now in UPS and osteo, two of the larger sarcoma subtypes. And the data that we're seeing is really compelling and very -- sort of validates -- or [validative] of what we saw in Phase 1.

Got it. Thanks so much for taking the questions.

Tiago Fauth, Credit Suisse.

Thank you for taking the question. So just one quick -- check the box here. So a few different charts had different values for the tumor membrane percentage score for the sarcoma. So just to confirm, the Phase 2 data that you presented today, those are all in patients 70%-plus, correct?

That's correct. We allowed 50% or more but the patients you're seeing for UPS were all 70% or more.

Got it. And perhaps the follow-up is basically given the responses that you've seen so far, is there any specific underlying biologic rationale on why the drug will be active solely on those subtypes? From the Phase 1, it seemed that response was likely more correlated with just AXL expression. And if you look anyway -- you even had a leiomyosarcoma response that you do not see on the Phase 2. You basically had one response across 45% -- 45 patients on the monotherapy arm.

So how confident are you that there is a strong signal here and that that's not perhaps just false-positive selection perhaps going forward? I'm curious if there is a rationale on why you could see such different results.

Yeah. So I don't think the results are very different than -- I mean I think the results we saw in Phase 2 are in line with what we saw in Phase 1. We saw a signal in UPS, and we reproduced that signal in Phase 2. In leiomyosarcoma, the patients we are seeing, we saw in Phase 2 were very advanced patients that had failed three or more prior lines of therapy. We saw a number of patients progressing extremely rapidly, because these patients were probably too advanced to be able to see a response.

The PFS that we are quoting of 27%, that number will probably change as we are having a number of leiomyosarcoma patients that are still going -- are still on treatment and will reach -- and have not reached the 12-week -- the three-month time point yet. But that number is still too low for us to move forward to think that we'll be competitive in that leiomyosarcoma environment.

And then for osteosarcoma, I think it's been clearly established that the progression-free survival endpoint is the most relevant measure of anti-tumor activity in advanced osteosarcoma rather than objective response. Because tumor shrinkage in the calcified lesions of advanced osteosarcoma may not accurately reflect the true anti-tumor activity of the molecule. So the expert of osteosarcoma community has favored the use of progression-free survival as a more efficient and reliable endpoint in Phase 2.

When you see the type of response we're seeing in osteosarcoma in terms of PFS at three months of 67%, that is highly encouraging for us to move into a Phase 2 study, in light of the fact that these patients were advanced patients. They had, on average, three prior lines of therapy.

With patients that are metastatic and have one to two prior lines of treatment, studies have shown that these patients generally progress within eight weeks. We see a rate of progression of 100% when these patients are not treated.

And other chemotherapies have quite low PFS rate at 12 months around 14%. So it's a striking difference here, and that's why we believe we have a strong rationale to move forward in osteosarcoma.

I want to add one other thing to what Philippe was saying. And that is, for UPS where we saw a very strong signal in Phase 1, we saw two responses: one in mono, as you say; and one in combination. But we saw two responses in a very small number of patients.

We could have enrolled 10 patients fully in UPS and another five or 10 in combination UPS, but we saw signal both in mono and in combination very quickly. So we decided not to fill that up and move quickly to Phase 2. Given the fact between Phase 1 and 2 in UPS, we've got 50% response rate, it's likely we would have seen other responses had we continued to fill up that cohort. But we had enough security to move forward into the registrational or Part 2 of Phase 2 and the registrational part of this cohort.

So we were very pleased with what we saw there and very [validative] of what we saw on Phase 1.

Yeah, no, I appreciate the context and the extra information. Thanks for taking the question.

Thank you.

Kelly Shi, Jefferies.

Thank you for taking my questions. First, could you share what is the enrollment status and median follow-up time for the four cohorts which you are yet to report the clinical results?

So the question -- just let me repeat, Kelly. Thank you for the question. But let us make sure I have it right. You want to know the timing for filling up the cohorts which we did not report on because they weren't full at this point in time or we couldn't make a decision?

Yeah. And specifically, I think I'm just curious about the median follow-up for the enrolled patients in that four cohorts, if you could disclose.

I'm sorry, I didn't understand that part 2 of the question, Kelly.

So the median follow-up time for the four cohorts you have not presented clinical outcome.

Median follow-up time?

Yeah, median follow-up time for the enrolled patients in that four cohorts. Are you able to disclose?

No, we haven't disclosed that now.

Okay. And also --

We will update these other cohorts as we get to the Q2 call and let you know where we are with them. I will say just from where we are, even though we can't be definitive, certainly we see a couple of cohorts here that we're very encouraged by, that we're preparing to move forward as well. But we want to get some more enrollment there, because they're not sarcoma types that we saw on Phase 1.

So we want to get a few more patients in there to make a fulsome decision. But I do believe that based on what we see today that it's highly likely that there'll be other cohorts moving forward into Part 2 of Phase 2.

Okay. Great. Thanks. Also I have follow-up. So in UPS, have you observed the correlation between AXL expression level and the depth of response?

Yeah, so we -- for the part -- all the UPS patients we've enrolled in Part 1 in Phase 1 and Phase 2 were -- had a TmPS of 70% or more. And so we've seen these patients responding to treatment; at least 50% of them responded and had a PR. So it's -- the correlation is that it is -- I mean patients that have a TmPS of 70% are responding.

More broadly in sarcoma, we've seen that correlation, that the response comes at around 70% TmPS. Now we did not, in Phase 1, if you recall, enrolled patients between 50% and 70% TmPS. And so as part of Phase 2 Part 1, we wanted to explore those patients. Unfortunately, we were only able to enroll two of these patients, so far. All the rest have a TmPS of 70% or more.

I will say -- just to add to Philippe's comments. One of the very positive things for us about UPS is not only are the patients who are AXL-positive, they usually generally have a very high level of AXL positivity or AXL expression, but also most UPS patients -- 70% to 80% of them -- are AXL-high. And so it's a very good population for us to be studying further.

Great. Thanks.

Kaveri Pohlman, BTIG.

Good afternoon and thanks for taking my questions. My first question is regarding the PD-1 combinations. Can you provide any color on your development strategy there, because I believe these combinations or PD-1 therapy -- monotherapy itself is not really approved for sarcoma?

Thank you for the question, Kaveri, and good afternoon. Yeah. So, in general -- I'll hand this over to Philippe for a more substantial answer. But the general color, I believe that we saw -- as we saw a very little, if any, benefit from the PD-1 in the sarcoma population.

So I believe unless things change, our development strategy will be to move forward in monotherapy and certainly in the two cohorts that we're moving forward.

I don't have much more to add to that. I think we didn't see a benefit in adding the PD-1 to BA3011 in sarcoma. And I think that we were generally -- we were expecting that but wanted to confirm it. And so going forward, we'll focus on the monotherapy in sarcoma -- let me stress that -- because it may be different. And we expect it to be somewhat different in non-small cell lung cancer and melanoma.

Got it. And regarding the TmPS score for AXL and ROR2, I believe one of your previous slide decks suggested lower TmPS score for ROR2 compared to AXL. Why is it that ROR2, with the same payload, allows you to build in much lower toxicity?

Yeah. So it's not just about the payload; it's also about the level of expression of AXL and ROR2 on the membrane of the tumors where we are testing. And right now, what we are doing for ROR2, because we have less information than we have for AXL, where we went with the broad TmPS score of 1% or more, for a couple of reasons.

One is the fact that we've seen a PR in head and neck patient in Phase 1 that was at 18% TmPS score. Therefore, we could have chosen 10% of the threshold, but we might as well go up 1% and see if we can derive benefit for those patients. I think it's important for the Part 1 of these studies to really define what the cut-off is going to be for ROR2 and AXL going forward into registration studies.

And I also think that, to Philippe's comments, it's important for us to be able to characterize the response relative to AXL or ROR2 expression with the regulatory agencies. It's very, very important for us to do that.

It was more definitive in AXL. It seemed very much more clear to us that high AXL expression responded and low AXL expression didn't. As Philippe alluded to, those head and neck patients with 18% ROR2 positivity, a TmPS of 18%, and they responded very, very well. So we're trying to characterize the relationship between ROR2 expression and response.

Yeah. And I'll add something else, which I think is not disclosed -- hasn't been disclosed so far. The patient that got mentioned, melanoma ROR2, that just had a complete response to TmPS was 30%, right? So it's below that 50% threshold that we have seen for AXL in sarcoma. And so it continues for -- it makes sense for us to go broad and then narrow it down should we need to do that.

Makes sense. Thank you.

Tony Butler, ROTH Capital.

Thanks very much. I have actually a few questions. Perhaps I could just ask them all upfront. It may help a little bit.

So one of the questions is, is there any evidence that other markers, for example MDM2 amplification or CDK4 amplification, correlated with response rate? That's question one.

Number two is, the spider plots you show are really quite impressive. But I wanted to make sure, did all of the patients who are observed on those spider plots, did they receive at least two scans or were there patients which only have had one scan with a second for follow-up? That's question two.

Question three -- and my apologies. You stated it; I just didn't capture it. Again, what were the number of patients in Phase 1 on UPS that did respond? Was that just one patient or was it two? And I thank you for taking those questions.

Thank you, Tony. And I'll answer your last question first and then kick it over to Philippe to get into more detail -- the first two questions. And in Phase 1, we saw two AXL-positive UPS patients, both of whom responded -- two of two.

That's great. Thank you.

At the RP2D of 1.8 milligram per kilogram. So what was your first question again? I'm sorry.

Yeah, sorry. So other markers -- so for example, MDM2 amplification, CDK4 amplification. And I'm just trying to see if, in fact, there was any correlation to other genetic -- let's just call it genetic abnormalities. Thanks.

Yeah, this is data we'll be able to report once we have the full cohorts enrolled. We've gathered -- we're gathering the information, and we haven't analyzed it just yet. We'll be waiting for the full cohorts to do that. And then we'll report on it. And if we see any correlation, we'll make sure to highlight them for you.

And the second question was relative to scans in the spider plots?

Yeah, so scans in the spider plots -- the scans you're seeing are -- you will note for instance that in osteosarcoma, you have seven patients for the progression-free survival for Phase 1 and 2, but you only have six patients shown.

The reason is the seventh patient has not -- had 12 weeks yet and has not had a first scan yet, either. But it's captured in the PFS. Patient being censored, but it's obviously not shown on the spider plot because we have not -- the patient is undergoing treatment, and we don't have a first scan yet.

Yeah, but Philippe also -- thank you for that. It's great. But also were all patients -- they have, other than the one you mentioned -- have one scan or do some have two scans?

Yeah, so most have two scans. But if you don't see a second -- for instance, in the osteosarcoma part, there's one line that's overlapping and that -- between two patients. And one of these two patients only has one scan so far. Patient is ongoing, waiting for the second scan.

And the other patient has four scans. Is that -- that you're talking about, right? So all the way from one scan to four scans in this patient population. Did I answer your question?

Thank you very -- yeah, you did. Absolutely did. Thanks very much.

And again, we'll update this -- as these patients continue, we'll update this on the Q2 call with how these patients are progressing and what -- for their scans and further information at that time as well. But what we see here is very, very encouraging in a very difficult-to-treat patient population.

Yeah. I understand it's preliminary and very early, but I have to ask. And I'm grateful for the follow-up.

Yeah. Understood. Of course. Thank you, Tony.

(Operator Instructions) Arthur He, H.C. Wainwright.

Hey, good afternoon, everyone. This is Arthur from H.C. Wainwright. Most of my question has been answered. I just want to follow-up on the LMS cohorts. For those 17 patients, is there any patient -- get the dose reduction or all seven patients received the Phase 2 reduction -- dose levels?

So all patients started with a Phase 2 dose of 1.8 milligram per kilogram, and some patient had to have dose reduction. I don't have the exact number in front of me, but I can follow-up and let you know what that number is. But some patients had to have dose reduction because of some AEs that sometimes were related or not related to treatment. But we have a few patients that require a dose reduction, yes.

Thanks for that color. And I switch gear to the 3021 in myeloma. Could you give us more color on the ROR2 score for the patient enrolling the Phase 2 study? How that compared to the score for the patient -- has a complete response in the Phase 1?

Yeah. So if you recall that -- so the patient here, I just mentioned the TmPS score for the melanoma patient that has complete response in Phase 2 is 30%.

In Phase 1, we were not able to determine what the score of that patient was, because there were some malignant staining that precluded us from seeing the entire surface of the cell. We saw ROR2 staining but we couldn't give it a score. And so right now what we know is that one of the two CRs had a TmPS of 30%. The other one, we don't have the score.

I just would like to add, as we talked about when we were in our prepared remarks, we're very excited about this program. This is -- really highly unusual to see two ROR2-positive patients both having complete responses.

There have been some operational difficulties. And around the idea that it requires an invasive biopsy to get in and at a positivity rate of 10%, physicians in the states are seeing many more negative biopsies to positive which then deters them. So moving to a liquid biopsy, I think, will help us operationalize this in a very, very good way. And we're really excited about the potential here.

Awesome. I'm looking forward to -- the liquid biopsy asset. Thank you.

Thank you. And I'm currently showing no further questions at this time. I would like to hand the conference back over to management for any closing remarks.

Well, thank you. And thanks, everyone, for your questions and attention today. We're very excited about the year ahead, and we're --

I think -- I don't know if -- I think we might have lost Jay there, but just thank you very much for your attention. And we look forward to continuing to update everybody as we move through the quarters. And we're in a very, very exciting time with our clinical programs with lots of inflection points coming up. And we're very, very excited about the future. Look forward to continuing to update you on our progress. Thank you.

Thanks, Scott. (multiple speakers) for a second. Thanks, everyone.

Ladies and gentlemen, thank you for participating in today's conference. You may now disconnect. Everyone, have a wonderful day.