BioAtla, Inc. Q2 FY2022 Earnings Call

Hello and welcome to the BioAtla Second Quarter 2022 Earnings Call. All participants will be in listen-only mode. After today's presentation, there will be an opportunity to ask questions. Please note today's event is being recorded. I now would like to turn the conference over to your host today, Bruce Mackle. Bruce Mackle, please go ahead.

Thank you, operator, and good afternoon everyone. With me today on the phone from BioAtla are Dr. Jay Short, Chairman, CEO and Co-Founder; Scott Smith, President; Philippe Martin, Chief of Clinical Development and Operations; Sheri Lydick, Senior Vice President, Commercial Strategy; and Richard Waldron, Chief Financial Officer. Earlier this afternoon BioAtla released financial results and a business update for the quarter ended June 30, 2022. A copy of the press release is available on the Company's website. Before we begin, I'd like to remind everyone that statements made during this conference call will include forward-looking statements including but not limited to statements regarding BioAtla's business plans and prospects, financial and operating performance and expectations, operating costs and expenses, product pipeline, clinical trial and regulatory timing and associated resource requirements, its programs and potential partnerships and the advancement of its CAB technology and product candidates. These statements are subject to various risks, assumptions and uncertainties that can cause actual results to differ materially and are described in the filings made with the SEC, including the most recent quarterly report on Form 10-Q. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today, August 9, 2022. And BioAtla disclaims any obligation to update such statements to reflect future information, events or circumstances, except as required by law. With that, I'd like to turn the call over to Jay Short. Jay?

Thank you, Bruce. Thanks to everyone for joining us for our second quarter 2022 BioAtla earnings call. The broad applicability of BioAtla's CAB technology has allowed us to continue advancing the development of our innovative clinical and preclinical programs. The second quarter was marked by strong execution with promising results across five potentially registration enabling ongoing Phase 2 trials for our two latest stage CAB-ADC product candidates, Mecbotamab vedotin or BA3011 and Ozuriftabmab vedotin or BA3021 across multiple solid tumor types for these first-in-class therapeutic candidates. But before I go any further, I'd like to remind everyone that additional details related to what we are going to present are available on our website as part of our updated company presentation that may be helpful to you. We have several additional upcoming catalysts this year for both our lead assets, including important results to be covered in today's discussion. We previously shared interim data on our BA3011 Phase 2 sarcoma study and we now look forward to enrolling multiple sarcoma subtypes into part 2 of that study. Further, on today's call, we will discuss new results for additional sarcoma subtypes, an important initial interim data for the non-small cell lung cancer study for BA3011. Our Phase 2 BA3021 study is also continued to advance and we anticipate an interim update for non-small cell lung cancer in the fourth quarter. We also expect that our successful validation of the liquid biopsy will accelerate the melanoma study for an enrollment update later this year. In addition, we are actively screening in our head and neck study with the first patient anticipated to be dosed shortly. Our Phase 1/2 basket trial for our CAB-CTLA-4 antibody, BA3071, is currently ongoing with the first patient dose completed. We also remain on track for our pre-IND meeting and IND filing for our dual CAB bispecific antibody, EpCAM CD3 or BA3182 this year. We are pleased with our cumulative results that continue to support both the efficacy and safety for more differentiated proprietary CAB platform thus far in 2022. And I believe we are well positioned to continue with strong execution. Most importantly, we are excited to share the updates of our ongoing clinical programs with you today, in particular, observations from our Phase 2 non-small cell lung cancer study with our lead asset BA3011. With that, I would now like to turn the call over to Philippe for additional details. Philippe?

Thank you, Jay, and good afternoon everyone. I would like to provide initial interim observations on Part 1 of our Phase 2 study in non-small cell lung cancer and an update on Part 1 of our Phase 2 study in sarcoma. First, I will go over our preliminary data in non-small cell lung cancer and start with a brief introduction of the study design. Our ongoing potentially registration and labeling Phase 2 trial of BA3011 is designed to evaluate the efficacy and safety of BA3011 monotherapy and in combination with nivolumab in AXL expression patients with refractory non-small cell lung cancer that have failed either ALK, EGFR or PD-1 inhibitors. We do not restrict the number of prior lines of therapy or restrict any particular type of non-small cell lung cancer and have enrolled patients with either non-squamous or squamous cell carcinoma. Therefore, the interim data will be presented accordingly. There are two parts to the non-small cell lung cancer Phase 2 portion of the trial. And Part 1 interim analysis will be conducted up to 20 and up to 40 patients at the potential to be followed through at least three months. Our predefined go criteria for the interim analysis is to achieve an overall response rate of approximately 20%. As of the data cut-off of July 16, 2022, we've enrolled 15 patients with nine efficacy evaluable patients. Four patients are currently on treatment, but don't have yet the opportunity to be followed for three months. And two additional patients were not deemed efficacy evaluable. Importantly, 12 patients are PD-1 failure patients and have failed on average 2.5 prior lines of systemic therapies for metastatic disease. Of the nine evaluable patients, seven were diagnosed with squamous adenocarcinoma and two were squamous cell carcinoma patients. So far we've observed a total of one complete response and two partial responses, for a combined objective response rate of 33%. All responses were observed in the non-squamous group, representing an ORR of 43% or three out of seven patients. Four out of seven of these non-squamous patients were administered BA3011 monotherapy, while three received BA3011 in combination with nivolumab. The two partial responses were observed in the non-squamous monotherapy group, representing an ORR of 50% for this group and the complete response was observed in the non-squamous combination group representing an ORR of 33% for this group. Of the two evaluable patients in the squamous cohort, we have not yet observed a response with either BA3011 monotherapy or BA3011 in combination with nivolumab. All patients enrolled were AXL-positive with a 1% cut-off; the rate of AXL positivity in the non-small cell lung cancer population continues to be high. We estimate to be approximately 35% for the non-squamous population and approximately 30% for the squamous population, based on over 200 non-small cell lung cancer patients tested so far for AXL expression. As of the latest safety data cut-off, the safety and tolerability profile from the Phase 2 non-small cell lung cancer study continues to be differentiated from other MMAE diseases. No new signals have been identified from Phase 1, no treatment-related death, and very few Grade 3-4 AEs were reported. To put this data into perspective, notwithstanding the preliminary nature of the small sample size of our data set, the efficacy observed in this study, and particularly the efficacy observed for the BA3011 monotherapy non-squamous and BA3011 monotherapy for non-squamous and squamous combined, is so far highly competitive in this PD-1 refractory population and supportive of moving forward to the registrational part of this study. We are continuing to enroll patients in Part 1, to help us better define which population and which treatment cohort or cohorts we will be advancing to the registrational part of the study. We've now close to 20 patients enrolled in Part 1 of the study. We anticipate we will be able to present interim results of approximately 20 patients in the fourth quarter of this year. I will now present the sarcoma data. During our last quarterly call, we presented interim data from our ongoing Part 1 of the potentially registration enabling Phase 2 trial of BA3011, which was designed to evaluate the efficacy and safety of BA3011 in adult and adolescent patients with refractory soft tissue and bone sarcoma. We enrolled patients across seven different sarcoma subtypes to receive BA3011 monotherapy and across all sarcoma subtypes to receive BA3011 in combination with nivolumab, equally between CD20 positive and CD20 negative tumor expression. The purpose of Part 1 was to identify sarcoma subtypes that do not respond to BA3011 treatment and eliminate these subtypes for moving forward into Part 2 of this study. Predefined go/no-go criteria for the interim analysis determine 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 for subtype or progression-free survival rate of at least 40% at three months. Patients were selected based on AXL expression using TmPS of greater than or equal to 50% in each sarcoma subtype. These subtypes in soft tissue sarcoma included leiomyosarcoma, synovial sarcoma, liposarcoma, and other soft tissue sarcomas such as UPS. In bone sarcoma, the subtypes included osteosarcoma, Ewing sarcoma, and other bone sarcoma, which includes chordoma and chondrosarcoma. The interim results presented previously in UPS and osteosarcoma satisfied our predefined go criteria into Part 2 of the Phase 2 BA3011 study. The UPS and osteosarcoma are advancing as separate cohorts to registration studies. Additional details for these registration studies will become available following FDA written response. Today we are sharing data from additional cohorts based on an efficacy data cut-off of July 26, 2022. In liposarcoma, we've enrolled six patients and observed a PFS rate of 60%, which exceeded our predefined go criteria to Part 2 of Phase 2. These patients had progressed on two or more prior lines of systemic therapy. For context, recent studies have shown that for the earlier first and second-line metastatic liposarcoma patients, the PFS rate for placebo at three months is around 30% and approximately 50% for eribulin and trabectedin. In synovial sarcoma, we've enrolled five patients. These patients have progressed on three or more lines of systemic therapy. The PFS rate at three months was 50%, which also exceeded our predefined go criteria to Part 2 of Phase 2. For context, the PFS rate for pazopanib at three months is 49% for the year-on-year first and second line patients with metastatic synovial sarcoma. With regards to the safety profile across sarcoma subtypes, BA3011 continues to be generally safe and well tolerated with a Phase 2 safety profile consistent with the profile observed in Phase 1. We are currently evaluating the clinical and commercial opportunities for these subtypes, and we will decide on the path forward in the near future. We are continuing to enroll patients in the Ewing sarcoma cohort and the bone other second cohort, mostly made of chordoma and chondrosarcoma. Thank you for your attention. Sheri will now highlight the significant unmet need and commercial opportunity in non-small cell lung cancer. Sheri?

Thank you, Philippe, and good afternoon everyone. Lung cancer is the second most common cancer and the leading cause of cancer-related mortality worldwide, with 80% to 85% classified as non-small cell lung cancer. Upon further breakdown, the non-squamous subtype accounts for approximately 75%, while squamous cell accounts for the remaining 25% of non-small cell lung cancer cases. There are over 540,000 people in the U.S. living with lung cancer and approximately 200,000 newly diagnosed patients per year, the majority of which are diagnosed with advanced or metastatic disease. The introduction of targeted therapies and checkpoint inhibitors in the past decade has improved the treatment landscape for patients with advanced or metastatic non-small cell lung cancer. Chemotherapy plus immune checkpoint inhibitors has become standard of care in the first-line setting for patients with metastatic disease. Despite advances in first-line care, a majority of patients eventually progress and experience worsening outcomes after each line of subsequent therapy. There are limited options for these patients who have progressed on immune checkpoint inhibitors, and available treatments in the second line setting and beyond have reported overall objective response rates of 10% to 20%. While the data Philippe just shared indicate that our early observations are encouraging, particularly when we think about this multi-refractory non-small cell lung cancer population, we believe that BA3011 has the potential to fill a significant unmet medical need for these patients. Turning to the commercial opportunity, non-small cell lung cancer is one of the largest oncology therapy markets, valued at approximately 20 billion in 2020 in major markets and projected to grow 9% annually, reaching 48 billion by 2030. We estimate that there are approximately 40,000 to 50,000 AXL positive non-small cell lung cancer patients per year in the U.S. and over 100,000 per year worldwide. We estimate that this represents a significant global commercial opportunity of approximately $2.5 billion to $3 billion. With respect to sarcoma, we remain energized about the continued opportunity for BA3011 in soft tissue and primary bone sarcomas. Even when considering only UPS and osteosarcoma, given the significant unmet medical need and lack of approved treatments for these patients. Combined, there are approximately 5,000 to 7,000 AXL positive addressable UPS and osteosarcoma patients per year in the U.S. and over 12,000 globally, which we estimate to be a worldwide commercial opportunity of up to $1 billion. Taken together, our preliminary observations in non-small cell lung cancer and our Phase 2 sarcoma study data, our lead CAB-ADC asset BA3011 has the potential to be a best-in-class therapeutic treatment for patients who have failed frontline regimens with an estimated total global commercial opportunity of approximately $4 billion. We are excited for the upcoming near-term catalysts this year in our BA3011 program, and for the potential of this asset to fill significant unmet needs for refractory patients across a variety of cancers. Now, I would like to turn the call over to Scott Smith, President of BioAtla, to provide an overview and update on other ongoing clinical programs. Scott?

Thank you, Sheri, and good afternoon everyone. Before I review our key operational updates from the quarter, I want to share my excitement around the preliminary observations from Part 1 of our Phase 2 non-small cell lung study. Given the significant unmet medical need and commercial opportunity in refractory non-small cell lung, we are very excited to see an early signal in the non-squamous population, albeit with a small number of evaluable patients to date. Preliminary observations in the non-squamous cohort validate the signal observed from our Phase 1 study. We will wait for the full interim data analysis before making detailed study determinations, but we are thrilled to see a trend in a positive direction thus far, with BA3011 in this initial cohort. The early observations in Part 1 of our Phase 2 non-small cell lung study exceed our internal predefined go/no-go criteria, and we will begin preparations for discussions with the FDA for Part 2 of the study. In the interim, we will continue to enroll and dose patients in both subtypes and anticipate a full interim dataset of approximately 20 patients through multiple scans in the fourth quarter of this year. Traditionally, the non-small cell lung Phase 2 preliminary observations further strengthen BA3011 as a potential best-in-class therapeutic treatment for a variety of cancers, given the clinical outcomes from our other studies in sarcoma. As reported last quarter, the interim Phase 2 analysis at three months in AXL positive sarcomas demonstrated meaningful antitumor activity, and we met our predefined go-criteria for two very important sarcoma subtypes, UPS and osteosarcoma. As discussed earlier, we are very pleased to note the two additional cohorts, liposarcoma and synovial sarcoma, now qualify to move to Part 2 of the study based on our predefined criteria. We are currently evaluating the clinical and commercial opportunities for these subtypes and will decide on the path forward in the near future. With respect to UPS and osteosarcoma, we have submitted a request to the FDA for written feedback regarding the study design to support registration. For UPS, we have proposed a single-arm trial with overall response rate as the primary endpoint and a sample size of approximately 60 patients. For osteosarcoma, we have proposed a double-blind, randomized, placebo-controlled trial with progression-free survival as the primary endpoint in a sample size of approximately 120 patients. We anticipate written feedback in the coming weeks and will begin enrollment shortly thereafter. Now turning to our second lead CAB-ADC product candidate BA3021, a CAB-ADC. As a reminder, there are no other therapies targeting ROR2 in the clinic, so we have the potential to have the 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 partial responses in non-small cell lung, one partial response in head and neck cancer, and a complete response in a melanoma patient who remains in complete remission of treatment for over two years. To date, we have three Phase 2 trials ongoing with BA3021, and I'm happy to provide an update as to where we are with each, beginning with non-small cell lung. The non-small cell lung trial in refractory patients is enrolling as planned and currently dosing with an interim update of the preliminary cohort of up to 20 patients, followed by at least three months of therapy, anticipated in the second half of this year. Turning to the melanoma trial, which is being conducted in patients refractory to PD-1 therapy. As previously discussed, we ran into challenges with trial recruitment which we believe was due to lower working positivity rates than anticipated and challenges obtaining invasive tissue biopsies in these patients. However, after working on a liquid biopsy with our partner, we are happy to report that we now have a validated non-invasive liquid biopsy assay and that we are implementing this part of the study protocol this quarter. As a reminder, we previously mentioned that one melanoma patient enrolled in the Phase 2 as of last quarter achieved a complete response. Together with the complete response we observed in one patient in the Phase 1 study, we have two out of two ROR2-positive PD-1 refractory patients with a complete response, which is quite remarkable. We remain very excited about the potential of BA3021 in melanoma patients, particularly with potential acceleration of enrollment following validation and implementation of the liquid biopsy. The third Phase 2 study that we've initiated with BA3021 is in refractory patients with head and neck cancer, and the first patient is anticipated to be dosed very soon. To round out our CAB-ADC programs, we are supporting a multi-center investigator-initiated Phase 2 clinical trial of BA3011 or BA3021 in patients with platinum-resistant ovarian cancer. This trial is ongoing and to date, five patients have been dosed. Now I'd like to talk briefly about updates for our CAB-CTLA-4 antibody BA3071. The Phase 1/2 trial that will examine safety and tolerability of BA3071 of monotherapy and in combination with nivolumab is ongoing and the first patient has been dosed. We believe there is a tremendous unmet need and commercial opportunity for a safer and better-tolerated CTLA-4. Turning now to our preclinical pipeline, BioAtla has several candidates in lead optimizing phases that include CAB bispecific and second-generation ADC antibodies. We remain on track for a pre-IND meeting and IND filing for a CAB EpCAM CAB-CD3 bispecific antibody later this year, as well as for potential additional IND filings for preclinical next-generation CAB-ADC candidates and a second CAB bispecific in 2023. With that, I'd like to hand the call over to Rick to review the second quarter 2022 financials.

Thank you, Scott. As of June 30, 2022, we had $202.3 million in cash and cash equivalents compared to $245 million as of December 31, 2021. We expect cash and cash equivalents will be sufficient to fund planned operations including all ongoing CAB product development programs into the second half of 2024. As a reminder, we control all CAB product rights in the U.S., Europe, and Japan. Our business strategy includes advancing commercial preparations in key global markets, while exploring opportunities to extend our cash runway by generating upfront cash through the selective licensing of product rights in certain territories or collaborations with other biopharmaceutical companies, that could also provide development milestones and royalties upon regulatory approval and commercialization and create additional value for stockholders. For the second quarter ended June 30, 2022, we reported a net loss of $28.9 million compared to a net loss of $30.4 million in the same quarter of 2021. Research and development expenses increased from $14.9 million in Q2 of 2021 to $20.7 million in Q2 of 2022, primarily driven by expansion of our product development efforts, including clinical development for CAB-CTLA-4 and preclinical development of additional CAB candidates. 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 clinical programs. General and administrative expenses were $8.3 million for the second quarter of 2022 compared to $15.9 million for the same quarter of 2021. The $7.6 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 the development of our product candidates, advance our intellectual property portfolio, support focused pre-commercialization activities for our product candidate BA3011, and meet all requirements as a public company. Net cash used in operating activities for the six months ended June 30, 2022 was $42.1 million compared to net cash used in operating activities of $28.5 million for the same period in 2021. The increase in net cash used in operating activities for the first six months of 2022 is primarily due to an increase in research and development expense related to our program development efforts as compared to the first six months of 2021. And now back to Scott.

Thank you, Rick. We are very pleased with the progress we've made this year. And with the cash runway into the second half of 2024, we are well poised to reach several milestones and key inflection points with our innovative CAB assets. BioAtla will remain acutely focused on prioritizing the programs and indications that we view have the highest probability of therapeutic success and market potential to maximize value for our shareholders while being prudent with our strong balance sheet to ensure development and execution in support of our robust clinical and preclinical pipeline. We're very excited about the future of our innovative CAB antibodies and the potential impact on patients across multiple tumor types. BioAtla looks forward to creating long-term sustainable value in transformative cancer therapy. And with that, we will turn it back to the operator to take your questions.

Yes. Thank you. At this time, we'll begin the question-and-answer session. And the first question comes from Kelly Shi with Jefferies.

Congrats on the great progress and thank you for taking my questions. My first question is, so the - for the non-small cell lung cancer program, the AXL cut-off has been lowered to 1%. I'm just curious with this new cut-off, what percentage of the non-small cell lung cancer patients are eligible for the enrollment criteria? And also in the industry responders, how does the AXL expression level look? Are they fairly like a broader range of AXL level or more like high expressers? And also, I mean, even though it's a very small number, just curious whether you saw a trend, there is a correlation between the AXL level and the depth of the response. Thanks.

So Kelly, thank you very much for that question. The AXL part is; with AXL greater than 1%, is approximately 35% to 40% of non-small cell lung patients in the area that we're studying. The three patients, I don't know that we have disclosed the three patients that responded with their AXL positivity rates. But I'll ask Philippe if there is anything that we can report on that at this time or is that part of the bigger data set once we get that.

Okay, great. Sorry, go ahead.

Yes, I think it's too early to give you the disease control rate for these patients. All the responders are still on treatment and are still ongoing. And then we have a number of patients that are going through their first scan as well. So once we have all patients actually gone through two scans, we will be able to disclose that kind of information.

Hi, good afternoon, everyone. Congrats on the progress. I just want to follow-up on the lung cancer data. Could you give us about the disease control rate for these nine evaluable patients?

Yes. Thank you, Arthur, and again I'll ask Philippe to comment on the specifics here.

Yes, I think it's too early to give you the disease control rate for these patients. All the responders are still on treatment and are still ongoing. And then we have a number of patients that are going through their first scan as well. So once we have all patients actually gone through two scans, we will be able to disclose that kind of information.

Yes. Sorry, forgive me, three specific questions if I may. One, they're all related to the 3011 in NSCLC. The first is, was there a scan at three months, correct? And then the next scan, which you're discussing would be at six months. So could you just talk about the cadence of scans? That's question one. Number two is, do you have information or could you share that information on time to response? Would you have an idea about that the monotherapy and the combo, I just wondered if in fact the combo led to a time to response that was more rapid. And the third is, if you consider what duration one would like to see from a registration perspective, what might that be? Thanks very much.

So, thank you, Tony, for the questions. All give a sort of top line overview and I'll pass to Philippe to go into more detail with you. With these patients, they are getting scans at six weeks and 12 weeks. For example, in the three-month period and that six-week scan cadence continues as we move forward. I don't believe we can see or make any conclusions on time to response between mono and combo at this point in time, although I will ask Philippe to comment on that. But I think we saw responses on the first scan for these three all three patients, I believe, and again, I'll let Philippe correct me if I'm wrong there. And then in terms of duration of response, we'd like to see, I believe, sort of six months and the average regulatory response you would look for somewhere in that range. And I will say, when you take a look at the Phase 1 study in patients that responded, in line you see a very long duration of response in that one patient and you saw that in sarcoma as well. So again, Philippe do you want to address sort of the last two in a little more detail the time to response and the durability that we could obviously.

Yes. So, I think so - I agree that it is early to make any impact of determination, but I will say that the complete response was particularly fast, in the combination arm. And as for the third question, the duration of response would be best observed over six months.

Well, we’ll certainly say - Philippe, just want to make a quick comment. Philippe, and then you can certainly - again we want to wait till we see sort of the full 20 patient data set through multiple scans, but we saw responses in the non-squamous population and then so far as squamous population. So there is a clear differentiation; right. We had three responses, two on the complete in seven patients with non-squamous which is pretty remarkable response rate. So that's one characteristic. I don't know, Philippe, if you know if there is anything else about the patients that would help predict response.

No. So far we’ve enrolled patients that are all PD-1 carrier patients. I think generally speaking, the number of prior lines of therapy usually is a factor in how well or how quickly a patient can start treatment, so we will keep an eye on that. And all of the patients we've been also far are current or prior smokers, so that generally is a negative factor for these patients, but they all had the same similar baseline when I'm just looking. So nothing extremely different from patient to patient.

Thank you all for joining on the call. I think a quarter of real important progress for us on non-small cell lung, but also our progress in sarcoma. We want to continue to accelerate the clinical programs and we have more to report on, as we get into the Q3 call. Just again, thank you all very much for listening and very, very excited to continue these programs and continue to show this the differentiation we believe these CAB assets are going to have in the clinic. So thank you all for your attention.

Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect your lines.