Earnings Transcript for BCEL - Q4 Fiscal Year 2021

Operator: Thanks for standing by. Welcome to the Atreca Fourth Quarter and Full Year Financial Results Conference Call. At this time, all participants on in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. [Operator Instructions] I'll now hand the conference to your speaker today, Alex Gray, Head of Investor Relations. Please go ahead.

Alex Gray: Thank you, operator, and thank you to those joining us today. We pleased to hosting a year-end conference call and webcast, including updated data from our ongoing Phase 1b trial of ATRC-101. Joining me for prepared remarks are John Orwin, CEO; and Dr. Jonathan Benjamin, Senior Vice President of Clinical Research. Also on the line are Dr. Tito Serafini, Chief Strategy Officer and Founder; and Herb Cross CFO will each be available during the Q&A session. For those joining by phone, I'd note that presenting slides as part of today's program, which can be viewed by the webcast posted to the events and presentation section of our Investor Relations website ir.atreca.com. An archived replay of today's webcast and the accompanying slides will be available on our IR sites, following the live session. During today's call, we will make forward-looking statement based on current expectations. These statements are subject to a number of significant risks and uncertainty, and our actual results may differ materially. For a description of risks and factors could affect our future financial results and business, please refer the disclosure in the accompanying slide on our most recent forms 10-K and 10-Q and the reports that we may file on Form 8-K with the Securities and Exchange Commission. All our statements are made as of today, March 3rd, 2022, based on information currently available to us. We can give no assurance these statements will prove to be correct. We undertake no duty to update these statements except as required by law. I'll now turn it over to John Orwin. John?

John Orwin: Thank you, Alex. Before discussing the agenda, I'd like to briefly address the purpose of this call. Based on the ATRC-101 trial results we begun to see and its impact on our clinical strategy, we are providing updated data along with our year-end earnings. We will continue to provide enrollment updates in our earnings reports going forward, but we do not yet plan to host regular quarterly conference calls and future data presentations will be timed around key clinical milestones. We expect to present a further update in the second half of the year. On today's call, Jonathan will present data from the ATRC-101 monotherapy and pembrolizumab combination cohorts in our ongoing Phase 1b trial evaluating ATRC-101 participants with select some solid tumor cancers, followed by an update on our clinical strategy on 101. I will then discuss our financials and upcoming milestones before opening the line for Q&A. Top line summary is that ATRC-101 is demonstrating antitumor activity in participants with ATRC-101 target expression, including responses by resist, both as monotherapy and combination with pembrolizumab. And it was well tolerated for all doses and dosing frequencies evaluated. So, for each of the major points in turn, the primary objective of the Phase 1b study is to evaluate safety. We are pleased to share that the ATRC-101 so far has been well tolerated in both monotherapy and in combination including at the highest dose study of 30 milligrams per kilograms administrated with 101 at the two week and a once every three week dosing schedule. As a reminder, ATRC-101 targets novel ribonucleoprotein complex and will continue to see significant association between target expression and anti-tumor activity. We now validated this platform derived targets as well as the diagnostic for participant selection, which we are proceeding integrating into the trial protocol. Furthermore, we're excited to report that in heterogeneous and heavily pretreated persistent group receiving responses and stable disease with reduction in tumor burden across multiple cancer types in participants treated with monotherapy and in combination therapy. We believe that this data shown that our first clinical candidates active validate the ability of our platform to identify potentially valuable therapeutic antibodies, recognizing novel targets in oncology. I'll turn it over to Jonathan Benjamin to discuss the data.

Dr. Jonathan Benjamin: Thanks, John, and thank you to everyone for joining the call today. Before we discuss this data, I will review the trial design, the baseline characteristics of participants treated and the analysis. As a reminder, and as shown on Slide 6, this is a basket trial with multiple ongoing and planned expansion cohorts. Trial began with ATRC-101 administered as monotherapy every three weeks for Q3W. Dose escalation portion was completed last year with no dose limiting toxicity serve in any cohort. Today, we will be presenting data from a larger number of participants enrolled in the Q3W cohort, and from the every two weeks or Q3W monotherapy cohort as well as the pembrolizumab combination cohort. Participant's enrollment is ongoing at 30 milligrams per kilogram in the Q3W monotherapy and combination cohorts and at 10 milligrams per kilogram in the Q3W monotherapy cohort. We have treated participants at five dose levels, ranging from 0.3 to 30 milligrams per kilogram. Most of our analyses, however, we will be focusing on participants who received 3, 10 or 30 milligrams per kilogram of ATRC-101, which we view to be more pharmacological developments in the 0.3, and 1 milligram per kilogram doses. Now, I'd like to review intelligible indications for the study. For monotherapy enrollment is limited to participants with tumor types displaying greater than 50% immunoreactivity to ATRC-101 in preclinical studies. Those tumor types are listed on the slide. Enrollment in the pembrolizumab combination cohort is limited to patients that have progressed on or after treatments with an anti-PD-1 or anti-PDL-1 agents or that stable disease, but the treating physician has determined that the participant needs additional treatments. We plan to share additional eligible for monotherapy that have tumor types and the combination cohort is expanded to include those in pembrolizumab is an improved therapy and also displayed greater than 30% immunoreactivity to ATRC-101 in the preclinical studies. These indications are also listed on the slide. Under the adjusted of the trial is determine the safety and tolerability of ATRC-101 when administered is monotherapy or in combination with key additional objective of determining a recommended dose expansion, measuring initial clinical activity, and characterizing predictive and pharmacodynamic biomarkers in blood and in tumors. As we've previously discussed, as shown on the bottom of the slide, we're also evaluating a separate combination cohort with pegylated liposomal doxorubicin based on the growing understanding of the potential mechanistic synergy of tumor therapies with ATRC-101. In the preclinical model, doxorubicin increases target expression in tumors which we believe will contribute to the clinical activity of the combination. On Slide 7 is an overview of the baseline characteristics for participants enrolled in both monotherapy arm and in the combination arm. As of the data cutoff date of February 15, 2022, 47 participants have enrolled overall. 36 from a Q3W dosing schedule, 8 on the Q2W dosing schedule and 3 in the combination arm. As you can see, the median age of participants was 58 years with most having an ECOG performance status of 1. Nearly half of participants had colorectal cancer which is not surprising given the scale of unmet needs in modification. We've recently instructed our clinical sites to prioritize enrollments of patients with other tumor types so that we can get a more complete profile ATRC-101 from its dose stage trial. Finally, as the slide title indicates, participants enrolled in this study trial for the most part can be heavily pretreated with a median of five prior lines of therapy that half of participants received at least one prior line of checkpoint inhibitor therapy. As a reminder, prior exposure to anti-PD-1 or anti-PD-L1 is in eligibility requirements for the pembrolizumab combination. In this presentation, we will be reviewing safety and response data entering overall response and target lesion responses. For the sake of clarity, we want you to find the person analysis on Slide 8. Gaining with the safety steps our 47 total participants received at least one dose of the study drug, 36 were valuable for H-score in a pre-treatment tumor biopsy. As a reminder, H-score is a composite score, target expression and captures the proportion of self-esteem as well as the intensity about standing. Definitely of the 47 total participants in the safety set, 38 were administered doses of at least 3 milligrams per kilogram. Although, there may be some activity on lower doses as we've said, we believe that it is more relevant to focus on the higher doses to the efficacy of the doses. Of to 38 participants treated at those dose levels, we currently have post 8 point radiograph of tumor region assessments for 32. Those 32, we also have H-score assessments for 25 participants. But we're in the final row on this chart as of the data cut off gain 1 of the 25 participants for tumor region and H-score assessments do not have their overall response status entered into the database thus the response in H-score set only includes only 24 participants. Please note that both the H-score responses only participants who may have that data in the future because they're still in treatments or their biopsy assays pending. Also note that, in certain features, such as in waterfall and spider plots participants in monotherapy and combination cohorts are grouped together. However, in time to hedge analysis, it is necessary to restrict the analysis to uniformly-treated participants. Moving to Slide 9, ATRC-101 continues to be well-tolerated with no dose limiting toxicities observed in the safety set of 47 treated participants. Off the adverse events observed, there remains no pattern to suggest the particular toxicity profile, nor were their relationship between incidents or severity of adverse events results or incidents of adverse events with target expression. There were 2 grade three adverse events considered by study investigators as possibly related to treatments for adding a small intestinal obstruction. No participants have to come off study due to toxicity or required a dose reduction. Slide 10 is a waterfall thought of 32 participants in the target lesion assessment set. Including the three participants enrolled in the combination cohort, indicated by cross patch bars, participants in the Q2W monotherapy cohort are indicated by the check bars. Looking at the three participants on the far right of the plot, we are pleased that a melanoma participants enrolled in the combination cohort achieved a complete response. Non-small cell lung cancer patients enrolled in the Q2W monotherapy cohort achieved a partial response. Other participants treated with monotherapy achieved stable disease with reduction in tumor burden, including one participant still on study with 29% reduction in tumor burden. Of note, this slide includes all participants involved at a relevant dose level, regardless of target expression. Activity observed, however, was related to target expression, as shown on Slide 11. Here, we have the chart on the left, showing the significant association between target expression and response in the trial, which includes data from the response to H-score of 24 valuable participants. Spot demonstrates that target expression is significantly higher in participants who experienced complete response, partial response for stable disease at their best radiographic tumor assessments versus those who have progressive disease. We placed a horizontal line corresponding to an H-score 50 to indicate an analytic threshold that defines low target expressors and high target expressors and to compare outcomes for these groups. On the right is a bar chart in numerating stable disease or better responses in a low target expressors participants shown in light blue versus high target expressors participants in dark blue, delineating these populations as we have demonstrated significant differences in outcome between these two groups. I'd also like to note that if the 36 total participants enrolled thus far and that were valuable for target expression, there was an equal split between those with screen scores above 50, and those with scores below 50. This distribution is roughly in line with our expectations to look at some preclinical analyses. And we have not yet enrolled enough participants to generalize conclusions about target expression patterns in any specific tumor types. As we previously stated, the target expression diagnostic has now been validated and we expect to be able to screen participants based on target expression in future cohorts within this trial. On Slide 12, when we apply the same color schemes to identify high and low target experssors to the waterfall plot previously shown on Slide 10. We can see clearly that participants with significant tumor growth on the left side of the slide were predominantly low target experssors, and the two participants who experienced resist responses and shown on the right of the slide were both high target experssors. Moving to Slide 13, and because our next area of focus will be to enrich participants based on target expression. We've removed low target experssors from the charts. Bars are now colored according to tumor type. As you can see, we've observed activity as defined by tumor burden reduction in multiple tumor types including melanoma, non-small cell lung, colorectal, breast and ovarian cancers. Although, it's still too early to narrow our focus, we are particularly intrigued by the potential of ATRC-101 in non-small cell lung cancer and melanoma. In the appendix of this presentation and provided for your reference, is a waterfall chart, bringing participants enrolled at the lower dose levels regardless of target expression. On Slide 14, it's a spider plot and Kaplan-Meier curve showing time to progression. Here our participants with target H-score of less than 50, showing that low target expressors and its progress on treatment and shorter durations of therapy and participants with target H-score of greater than or equal to 50. Shown on Slide 15, I target expressors or more likely to have tumor reduction in the first response assessment onward and remained on therapy longer. Shown on the right, there was a statistically significant difference in time to progression. As a reminder, the Kaplan-Meier curves limited to participants treated in the monotherapy Q3W cohorts. Here the median times progression in the low target expression group is 41.5 days compared with 94.5 days in the highest expression group. Also note that the previously referenced participants who achieve CR, PR and the 29% tumor reduction all remain unsteady. On Slide 16 by the treatment history and represented to CT scans from the participants with the confirmed complete response reported in the combination cohort. And this is the only target expressing participant treated with combination therapy for whom, we presently have response data. Participants is a 78-year old female, who is diagnosed with BRAF mutated metastatic melanoma and progress first on anti-PD-L1 therapy and then on combination to dabrafenib and trametinib before being enrolled in this study. As the CT scan show a supraclavicular left-sided nodal legion present at the time of screening have largely disappeared by the week 7 scan. By the week 13 scan, the lesion was undetectable. This pattern was also served in other targets and non-target patients. We're excited to see such a robust response in the first target expressing participants treated with combination therapy. Particularly given that 78 years old, this participants will be ineligible for the majority of clinical trials on oncology. Attribution in a single-arm combination trial can be challenging, but there are a few points that give us confidence that ATRC-101 contributed to the response of service. First is the evidence of monotherapy activity including in a participants with acral melanoma. Second, this participants with a high target expresser. And third, tumor types of roles in the combination cohort including melanoma rarely respond to anti-PD-1 monotherapy having after having progressed and prior PD-1 therapy. However, it still early is encouraging to see the first target expressed participants fusion with combination achieved a complete response. Now, moving to the data summary in next steps beginning on Slide 18, we are encouraged by the results observed thus far in Phase 1b trial ATRC-101. Summary 101 continues to pivot antitumor activity associated with target expression and was well tolerated at all the testing with no dose limiting toxicities observed and no treatment discontinuation due to adverse events. High target expression training defined as a screening H-score of 50 or above delineated with better outcomes. Finally, we were gratified that trial participant chooses CR and remained on study in the combination cohort. And another participant chooses PR and remained home study in the monotherapy cohort. Overall 13 of 19 valuable participants with high or unknown target expression treated with ATRC-101 in doses of 3, 10 or 30 milligrams per kilogram achieve stable disease or better in the heterogeneous and heavily pretreated group of participants. Slide 19 is an outline of the next steps for 101. First, the target expression assay now at CAP-CLIA validation and basically part of the data presented today, we expect to begin selecting participants based on target expression in the second quarter of this year. During FDA review of the modified protocol, people continue to enroll participants at 30 milligrams per kilogram of ATRC-101 monotherapy in order to obtain additional information on efficacy and biomarkers and to further inform our clinical strategy. On the anti-PD-1 competition side, enrollment is underway in the 30 milligrams per kilogram combination cohort. We plan to report additional data from both the monotherapy and combination cohorts later this year. Likely in the fall, once we've enrolled a sufficient number of target expression participants to provide a substantial update. In the interim, we will continue to provide enrollment updates in our quarterly earnings reports. As previously mentioned, we're also evaluating separate combination on with pegylated liposomal doxorubicin pending completion and review of the Q2W monotherapy cohorts. I will now turn it back over to John to discuss our financial and upcoming milestone. John?

John Orwin: Thank you, Jonathan. Finally, on Slide 21 with a summary of our financials and upcoming milestones, 2021 was a productive year for the advancement of our pipeline and we are pleased to announce that, we will be hosting a pre-clinically focused R&D Day on April 5, during which we'll be discussing our EphA2 program as well as several other previously undisclosed antibodies against new targets in antibody drug conjugate, T-cell engager and other weaponized formats, in addition to our non-oncology program. As Jonathan mentioned, we plan to present additional data from both monotherapy and combination cohorts and provide an update on clinical strategy for the second half of the year. We expect to soon be able to select participants based on target H-score. And the timing of our update would be driven by the piece of enrollment of additional target expressors. Finally, we had $148.1 million of cash and cash equivalents and investments as of December 31, 2021, which provide this runway into the first half of 2020. That concludes today's prepared remarks. We'd like to thank our trial participants and their families as well as investigators and research staff at our clinical site. Thanks again to everyone, who joined the conference call and webcast today. With that operator could you please open the line for Q&A?

Operator: [Operator Instructions] Our first question comes from line of Stephen Willey from Stifel. You may begin.

Stephen Willey: Yes. Thanks for taking my questions and congrats on the data. I was just curious, I know that you talked about having a particular interest, I guess in non-small cell in melanoma. And I was wondering if you could maybe tell us what proportion of those tumor types in the refractory setting meet that threshold level of H-score cut off? And then I guess second to that, curious if you've looked at H-score longitudinally in terms of just trying to understand the stability of target expression overtime during the course of treatment?

John Orwin: Great. Jonathan?

Dr. Jonathan Benjamin: Yes, excellent question. So the first question about distribution of H-score in melanoma and non-small cell lung cancer. As I indicated, we are still working with a somewhat small sample size. So, I would rather not go too much into that at this point. I think we need to see more data. And in terms of the stability of the target overtime, it is something that is actively being explored. As we mentioned in pre-clinical model that can be modulation and target level like chemotherapy, whether or not that is durable overtime is unknown to us. But we are actively analyzing that very question.

John Orwin: And I think with our diagnostic strategy, we will be collecting both archival as well as fresh tissue biopsies and maybe able to look at those pair examples, and further leads for target expression.

Stephen Willey: Okay. And then maybe, just lastly, I guess when you look at the differences in activity that's been observed between the high and low target expressors. I think there's a bar chart on Slide 11 the right hand panel. Do we know what proportion of those patients who have extracted clinical benefit and have an H-score greater than 50 receives the 30 mg per kg dose?

John Orwin: So you're saying in terms of…

Stephen Willey: So in terms of the fixed stable…

John Orwin:

.:

Operator: Our next question comes from the line of Philip Nadeau from Cowen. You may begin.

Philip Nadeau: Thanks also for taking the question and congrats on the activity. A few questions on the patients from us. First on the CR patient with melanoma, what was the prior response to nivolumab in that patient to-date progress immediately? Or was there a pure CR to the first round of PD-1 treatment?

John Orwin: The patient progressed after approximately nine months. The precise best response is a little bit unclear, but there was not a lot of measurable disease at treatment initiation and then patient progressed to nine months timeframe.

Dr. Jonathan Benjamin: And they have received -- they've been treated with both a PD-1 as well as the BRAF/MEK inhibitor combination.

Philip Nadeau: You mentioned in your prepared remarks, it's very rare that this response on retrieving with PD-1 and melanoma post-progression. Do you have that response rate data handy? How often does it happen?

John Orwin: There are various levels of evidence here and there are analyses on this topic. So, there are a range of numbers that have been provided depending how it's been defined, but I can summarize in one way by saying just look at the guidelines. The guidelines -- the antigen guidance et cetera, that it's not recommended to retreat in this setting. But I would say that if there are bona fide response and we're not talking about treatment beyond professional, so primary therapy, I would say that's it's in the probably the single digits.

Philip Nadeau: And then in terms of the PR and CR, I apologize, if I missed this if you said it. Are those patients still in response? And just now, what was the duration of those responses?

Dr. Jonathan Benjamin: The CR, the PR, and the colorectal cancer patients to 29% reduction remain on treatment, they remain on study.

Philip Nadeau: And then the last question on the PR non-small cell lung cancer patient, what were their prior lines of therapy?

Dr. Jonathan Benjamin: They have plenty prior lines of therapies including a platinum date as well as another microtubule taxol on experimental trial with pembrolizumab actually did have a trial of pembrolizumab monotherapy.

Operator: Our next question will come from the line of John Newman from Canaccord. You may begin.

John Newman: Thanks for taking my questions and really interesting response data here. Thanks for sharing it with us. Wondering if, I may have missed this, I apologize. Just curious, if you have disclosed the dose level, where you saw the response for non-small cell lung cancer as monotherapy as well as the combination where you saw the complete response?

John Orwin: Yes, for the non-small cell lung cancer patients that was in the Q3 week dosing frequency of 30 milligrams per kilogram. For the melanoma patients who have a complete response to the combination it was 10 milligrams per kilogram of ATRC-101.

John Newman: Also, just had two quick additional questions. Just curious as to what type of H-score cut off you're considering as you begin enrolling based on target expression in the second quarter?

John Orwin: So we are making proposals to the regulators. So I believe that subject and negotiation. We can't be firm on it but that analytical threshold is where we're starting. That's due impart access because of the response data as in the overall responses. FD, CR, PR versus TD, but also when you look at the lesion response, percentage reduction, because as you know, stable disease can be heterogeneous with disease rose up to 20% or disease reduction up to 30%. So we really tried to focus on a cut off that would minimize those with the huge growth more towards tumor reduction.

John Newman: And one more if I could sneak it in. Just curious, if you have any rough idea on timing for data from the back through chemotherapy combination trial with 101?

Dr. Jonathan Benjamin: Maybe I apologize if I was not clear about this. John has not started enrolling. We plan to wait until we complete the every two weeks monotherapy dosing and evaluate those results. We've not started enrolling although the protocol is activated.

Operator: Our next question comes from Roger Song from Jefferies. You may proceed.

Roger Song: Congrats for the data and thank you for taking a question. The first one maybe just to clarify, Jonathan, if I misheard that, so how many patients on the monotherapy at the highest the dose 30 mg per kg with the high H-score greater than 50?

Dr. Jonathan Benjamin: I think we have a lot of different analysis sets and overall though, I think we're seeing that Roger, and I apologize the total number is 30 plus. But in terms of what we presented today, we are roughly, we are presenting approximately presentations overall for H-score.

Roger Song: Yes. Okay. That's fine. So, thank you. And then, so for those patients, they have the H-score. Do we know the median prior for those patients because overall you have like around five prime median among those 12 patient with the H-score what is the prime median?

Dr. Jonathan Benjamin: Yes. So it's a great question, Roger. And we are looking at that. I can only tell you that, within a relatively small data set, we are seeing typically that there is, that if we split the groups, the median number of prior lines is slightly higher in the H-score greater than or equal to 50 groups, slightly higher. So, it's still small numbers and I think we're not ready to say that, that is a group phenomenon yet.

Roger Song: Got it. That's helpful. Okay. Maybe just the last one from us is the, in terms of the next step, and you will share with us the additional data in second half. Given your focusing on those high-dose 3, 10 and 30, would you be able to also determine the RP to be kind of moving forward directed dose from those three doses?

Dr. Jonathan Benjamin: Yes. That's also a great question in terms of the dose for expansion. As we said, we have not seen any safety signals. We don't believe that higher doses would in some way mitigate any active. So, for the time being, we are going with the highest tolerated dose, which in this case is the highest tested dose. Now that doesn't necessarily mean that that is a committed dose for all future stages of development. But moving forward, we will probably use the highest dose that is tolerated.

John Orwin: So, we could take into consideration the Q2 schedule, which is also highest dose, which is 30 mg per kg.

Roger Song: Yes, that's right. Got it. Okay, thank you. Thank you for taking all the questions.

Operator: Our next question will come from line of Tony Butler from ROTH Capital. You may begin.

Tony Butler: Jonathan, really two questions. One is, even if it's anecdotal, do you have any evidence that the tumor size had an effect such that bulk tumor, let's say, a large tumor responded less well than a small tumor? That's question one, by the way. And then second, and there's, you didn't allude to or at least I didn't hear any translational data. But was there any substantial difference that you know of either A from biopsies on CDA and/or in serum, especially at 30 in responding patients even in stable disease patients?

Dr. Jonathan Benjamin: So, we have had actually look at lesion by region, as well as overall tumor burden, impact and being sort of short-term outcomes of response, and we have not seen a difference. So patients with lower tumor burden as well as with higher tumor burden that seems to be impacting the outcome. But it remains to be seen because certainly the precedents and ontology including with immunotherapy, it's a larger than tumor less likely in the overall durability response. Second question was on sort of the biomarkers whether from serum for tumor. And we're continued to analyze that, including flow cytometry, both lymphoid and myeloid populations, continue to record cytokines. And when you mentioned the CDA T cells in the tumor, pre inverse, we will present that data, we're not ready to present that data yet for digital in short-term.

Tony Butler: There's no question. But could I ask, at least from, I'm sorry, to press it more. But at least from what you're seeing, are you encouraged by what you're seeing? Such that you don't want to complete that data set and think that it's really correlative to what the patients may be experiencing?

Dr. Jonathan Benjamin: I think that we are encouraged that the data, at some level support the mechanistic model that has been proposed and aligned with what we presented last July.

Operator: Our next question comes from the line of Joel Beatty from Baird. You may begin.

Joel Beatty: The first question is. Can you speak to kind of broadly, if you saw a dose response in the data. Now, looking at the activity in beyond just the responses ever seen in the one patient with 30 milligrams and the other patient with 10 milligrams?

Dr. Jonathan Benjamin: We're seeing overall dose response. The numbers are too small and 3, 10 and 30 groups say that there's a fair dose response. I think once we have a larger group of target positive patients treated with comparable or that we'll be able to really make a statement. We've never really thought that there, we've always thought that there could be a good response of lower doses, but that they would just probably occur with greater frequency and higher doses, but be more patients with high in resource.

Joel Beatty: And maybe one more question. Could you share any potential to present data and decision from this trial and upcoming medical conferences?

Dr. John Orwin: We are certainly eager to share this data with the broader medical community in the world. Moving forward as we've done in the past, probably a future act of [indiscernible]. We may present there 50 all one of the conferences that we find very interesting to attend and to participate into that that's why highlight that one.

Operator: Our next question comes from the line of Joe Pantginis from H.C. Wainwright. You may begin.

Joe Pantginis: My question may be too early, but I wanted to link it also to some of your earlier comments today. When you look at the spider plots on Slide 15, I was just curious. First, do you have any overall observations because there seems to be a bit of variability with regard to the especially over 50 expressors the H-score on the slopes of the curves and the different inflection points? Do you have any additional observations from these patients you wanted to share? And then linking to the earlier comments, I just wanted to make sure I heard you correctly. Going forward in the future, you'll be able to then generate more data to say maybe some of the rapid progressors in the over 50 might be loss of target?

John Orwin: Going first to the heterogeneity of the spider plus. I think we believe that we believe target is necessary, but not sufficient for ATRC-101 activity. We believe that this is a heterogeneous group of patients, some are different prior for tumor kinetics or tumor kinetics going into the trial and we would expect that variability in spider plots. So one thing that I am encouraged by that few set of participants who have at least the 5% reduction in overall tumor burden, they seem to be relatively stable. But again, the follow-up is short. So, don't want to get too far ahead of that. And I apologize. There was I think the third part of your question.

Joe Pantginis: More of a follow-up on, either for these patients or patients that you enroll later on that some of the say rapid progressors, even over 50, that you'd be able to assess the loss of target to your earlier comments?

John Orwin: Yes, so it's a great question. And again, I'm going to refer back to some of the preclinical mechanistic studies that we've been covering today to talk, but we believe that ATRC-101 initiates an immune response that ultimately involve the adaptive immune system and is not strictly require persistent expression of ATRC-101 in order to try to be active, we believe that is accurate will lead to tumor cell death and finding products or responses that can ultimately lead to tumor control. So of course, we are going to be looking at patients we have not only on study biopsies, but we have end of treatment biopsies, where we would like to be able to understand, if there is resistance that emerges, what are the molecular mechanisms, what are the phenotypes of the escaping tumor cells.

Operator: And our next question comes from I know Kumar Raja from Brookline Capital. You may begin. You may begin.

Kumar Raja: Thanks for taking my questions and congratulations on the data. So with regard to the H-score, you touched on this a little bit. In terms of different histologies, are there specific histologies where you are seeing high score in some population?

Dr. Jonathan Benjamin: Yes. Again, I apologize. I'm just not comfortable making any broad statements about the types of target expression patterns in this limited number of patients. I really think we need do a larger prevalence screen and that is actually ongoing -- excuse me, determined, what the distributions are and especially given these relatively broad definitions of cancer type. And of course, everyone is drilling down some more molecularly defined or immunologically defined cancers. We imagine that there may be the variations within tumor types according to those other markers. So, more to come on this, but suffice to say that we are continuing to enroll unselected patients and we get a little bit more prevalent data that way. And with our eligibility screen, we will also be able to determine quite a bit on distribution of H-scores.

John Orwin: I think it's fair to say now that we've treated, a larger number of patients that, what we have observed in terms of target expressions, not inconsistent with what we initially assumed based on the preclinical observations and what a lot of histology work that we've done previously, right, it's about 50% overall for all the patients that we've treated. I think there is just not enough patients of any one indication to really be able to make meaningful distinctions between.

Dr. Jonathan Benjamin: Thanks John. And the analysis that we have presented where we've looked at H-score, it's been a 50-50 split, exactly.

John Orwin: There's a little variability due to small numbers.

Kumar Raja: Okay. So, when you are planning enrollment expansion, so that probably will end up with about 50% screen failure rate?

Dr. Jonathan Benjamin: Screen failure based on target expression.

John Orwin: Yes, there obviously other things that contribute to it, like patient failing screening. But on average, we are seeing about 50% of patients exhibiting target expression.

Kumar Raja: Okay. And finally with regard to the EphA2 target, when can we expect to have update on that?

John Orwin: So, as I mentioned at the offset, we are planning our R&D Day for April 5. And at that time, we expect to be able to present a lot of new information related to the entire pipeline. But in particular, our EphA2 program, which I think is what you're referring to.

Operator: Thank you. I'm not showing any further questions in the queue. I'd like to turn the call back over to John for any closing remarks.

John Orwin: Great. Well, thanks everyone for joining our call today and all the terrific questions. And we look forward to providing additional updates on ATRC-101 program as well as our preclinical research programs in the future. Great day.

Operator: This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone have a great day.