Atreca, Inc.

Good day and thank you for standing by. Welcome to the TRICA fourth quarter and four-year financial results conference call. At this time, all participants are in listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you need to press star one on your telephone. If you require any further assistance, please press star zero. I want to hand the conference over to your speaker today, Alex Gray, Head of Investor Relations. Please go ahead.

Thank you, operator, and thank you to those joining us today. We are pleased to be hosting a year-end conference call and webcast, including updated data from our ongoing Phase 1B trial of ATRC 101. Joining me for the repair 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 Atreka founder, and Herb Cross, CFO. We'll each be available during the Q&A sessions. those joining by phone, I'd note that we are presenting slides as part of today's program, which can be viewed via the webcast posted to the events and presentations section of our Investor Relations website at ir.atraca.com. An archived replay of today's webcast and the accompanying slides will be available on our IR site following the live presentation. During today's call, we make forward-looking statements based on current expectations. These statements are subject to a number of significant risks and uncertainties, and our actual results may differ materially. the disclosure in the accompanying slides, 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 3, 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 Orwell. John?

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've begun to see and their impact on our clinical strategy, we're 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 of 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 first-in-human phase 1b trial, evaluating ATRC-101 in participants with select solid tumor cancers, followed by an update on our clinical strategy for 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 anti-tumor activity in participants with ATRC-101 target expression, including responses by resist, both as monotherapy and in combination with numberless meth. And it was well tolerated at all doses and dosing frequencies evaluated. So from each of the major points in turn, the primary objective of the Phase 1B study is to evaluate safety, We're pleased to share that the ATRC-101 so far has been well tolerated in both monotherapy and the combination arm, including at the highest dose study of 30 milligrams per kilogram administered both on a once-every-two-week and a once-every-three-week dosing schedule. As a reminder, ATRC-101 targets a novel ribonucleoprotein complex, and we continue to see significant association between target expression and anti-tumor activity. We have now validated this platform-derived target, as well as a diagnostic for participant selection, which we are proceeding with integrating into the trial protocol. Furthermore, we're excited to report that in this heterogeneous and heavily pre-treated participant group, we are seeing responses and stable beliefs with reduction in tumor burden across multiple cancer types in participants treated with monotherapy and combination therapy. We believe that these data, showing that our first clinical candidate acted, validate the ability of our platform to identify potentially valuable therapeutic antibodies, recognizing novel targets in oncology. I'll turn it over to Jonathan to discuss the data.

Thanks, John. And thank you to everyone joining the call today. Before we discuss the data, I will review the trial design the baseline characteristics of participants treated, and the analysis. As a reminder, and as shown on slide six, this is a basket trial with multiple ongoing and planned expansion cohorts. The trial began with ATRC 101 administered as monotherapy every three weeks, or Q3W. The dose escalation portion was completed last year with no dose-limiting toxicity observed 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-week dosing, or Q2W monotherapy cohort, as well as the Pembrolizumab combination cohort. Participant enrollment is ongoing at 30 milligrams per kilogram in the Q3W monotherapy and combination cohorts and at 10 milligrams per kilogram in the Q2W 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 three, 10, or 30 milligrams per kilogram of ATRC-101, which we view to be more pharmacologically relevant in the 0.3 and one milligram per kilogram doses. Now, I'd like to review the eligible 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 treatment with an anti-PD-1 or anti-PD-L1 agent, or have had stable disease but the treatment physician has determined that the participant needs additional treatment. Compared to the indications eligible for monotherapy, the set of tumor types in the combination cohort is expanded to include those in which Pembrolizumab is an approved therapy, and also displayed greater than 30% immunoreactivity to ATRC-101 in preclinical studies. These indications are also listed on the slide. The primary objective of the trial is to determine the safety and tolerability of ATRC-101 when administered as monotherapy or in combination, with key additional objectives of determining a recommended dose for extension, measuring initial clinical activity, and characterizing predicted and pharmacodynamic biomarkers in blood and in tumors. As we've previously discussed and shown on the bottom of this slide, we're also evaluating a separate combination cohort, the pegylated liposomal doxorubicin, based on the growing understanding of the potential mechanistic synergy of chemotherapy with ATRC-101, In a preclinical model, Dr. Rubison increases target expression in tumors, which we believe could contribute to the clinical activity of the combination. On slide seven is an overview of the baseline characteristics for participants enrolled in both monotherapy arms and in the combination arm. As of the data cutoff date of February 15, 2022, 47 participants had enrolled overall, 36 on the Q3W dosing schedule, eight on the Q2W dosing schedule, and three in the combination arm. As you can see, the median age of participants was 58 years, with most having an ECOG performance status of one. Nearly half of participants had colorectal cancer, which is not surprising given the scale of unmet need in that indication. We've recently instructed our clinical sites to prioritize enrollment of patients with other tumor types so that we can get a more complete profile of ATRC-101 from this early stage trial. Finally, as the slide title indicates, participants enrolled in this study have, for the most part, been heavily pretreated with a median of five prior lines of therapy, About 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 an eligibility requirement for the temporalism mask combination. In this presentation, we will be reviewing safety and response data, including overall response and target lesion response, For the sake of clarity, we want to define the pertinent analysis sets on slide 8. Beginning with the safety sets are 47 total participants who received at least one dose of the study drug. 36 were evaluable for H-score in a pretreatment tumor biopsy. As a reminder, H-score is a composite score. Target expression that captures the proportion of cells that stain as well as the intensity of that staining. Separately, of the 47 total participants in the safety set, 38 were administered doses of at least three milligrams per kilogram. Although there may be some activity of lower doses, as we've said, we believe that it is more relevant to focus on the higher doses for the efficacy of the substance. Of the 38 participants treated at those dose levels, We currently have post-baseline radiographic tumor lesion assessments for 32. Those 32, we also have age score assessments for 25 participants. A word on the final row of this chart. Of the data cutoff dates, one of the 25 participants with tumor lesion and age score assessments did not have their overall response status entered into the database. Thus, the response and age score set includes only 24 participants. Please note that both the age score and response sets omit participants who may have that data in the future because, for instance, they're still on treatments or their biopsy assay is pending. Also note that in certain figures, such as in waterfall and spider blots, participants in monotherapy and combination cohorts are grouped together. However, in time to event analysis, it is necessary to restrict the analysis to uniformly treated participants. Moving to slide nine, ATRC 101 continues to be well tolerated, with no dose-limiting toxicities observed in the safety set of 47 treated participants. Of the adverse events observed, there remains no pattern to suggest a particular toxicity profile. nor were there relationships between incidence or severity of adverse events with dose or incidence of adverse events with target expression. There were two grade three adverse events considered by study investigators as possibly related to treatments, a headache and a small intestinal obstruction. No participants had to come off study due to toxicity or require a dose reduction. Slide 10 is a waterfall plot of 32 participants in the target lesion assessment set, including the three participants enrolled in the combination cohort, indicated by cross-hatched bars. Participants in the Q2W monotherapy cohort are indicated by the checkered bars. Looking at the three participants on the far right of the plot, we are pleased that a melanoma participant Enrolled in the combination cohort achieved a complete response. Non-small cell lung cancer patients enrolled in the Q3W 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. Of note, this slide includes all participants enrolled 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 and H-score set Plot demonstrates that target expression is significantly higher in participants who experience complete response, partial response, or stable disease at their best radiographic tumor assessment versus those who have progressive disease. We placed a horizontal line corresponding to an H score of 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 enumerating stable disease or better responses in low-target expressing participants, shown in light blue, versus high-target expressing participants in dark blue. Delineating these populations as we have demonstrates significant differences in outcome, these two groups. I'd also like to note that of the 36 total participants enrolled thus far and that were valuable for target expression, there was an equal split between those with screening scores above 50 and those with scores below 50. This distribution is roughly in line with our expectations that were based on 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 applied the same color scheme to identify high and low target expressors 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 plot were predominantly low target expressors, and the two participants who experienced resist responses and shown on the far right of the plot were both high target expressors. 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 expressors 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 cancer. 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 including participants enrolled at the lower dose levels, regardless of target expression. On slide 14 is a spider plot, the Kaplan-Meier curve showing time to progression. Here are participants with target age scores of less than 50, showing that low target expressors tended to progress on treatment and had shorter durations of therapy than participants with target age scores of greater than or equal to 50, shown on slide 15. high-target expressors were more likely to have tumor reduction from the first response assessment onward and remained on therapy longer. As 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 time to progression in the low-target expressing groups 41.5 days, compared with 94.5 days in the high expressive group. Also note that the previously referenced participants who achieved CR, PR, and the 29% tumor reduction all remain unstudied. On slide 16 are the treatment history and representative CT complete response reported in the combination cohort. In fact, this is the only target expressing participant treated with combination therapy for whom we presently have response data. Participant is a 78-year-old female who was diagnosed with BRAF-mutated metastatic melanoma and progressed first on anti-PD-1 therapy and then on combination, Degrafinib and Tremetinib before being enrolled in this study. As the CT scans show, a supraclavicular left-sided nodal lesion present at the time of screening had largely disappeared by the week seven scan. By the week 13 scan, the lesion was undetectable. This pattern was also observed in other target and non-target lesions. We are excited to see such a robust response in the first target particularly given that at 78 years old, this participant would be ineligible for the majority of clinical trials in 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 observed. First is the evidence of monotherapy activity, including in a participant with atrial melanoma. Second, this participant was a high target expressor. And third, tumor types involved in the combination cohort, including melanoma, rarely respond to anti-PD-1 monotherapy after having progressed on prior anti-PD-1 therapy. While it is still early, it is encouraging to see the first target expressing participant treated with combination achieve a complete response. Now, moving to the data summary and next steps, beginning on slide 18. We are encouraged by the results observed thus far in the Phase 1B trial of ATRC 101. Summary 101 continues to exhibit anti-tumor activity associated with target expression and was well-tolerated at all doses tested. with no dose-limiting toxicities observed and no treatment discontinuation due to adverse events. High-target expression of screening, defined as a screening each score 50 or above, delineated a group with better outcomes. Finally, we were gratified that a trial participant achieved a CR and remained on study in the combination cohorts, And another participant achieved a PR and remains on study in the monotherapy cohort. Overall, 13 of 19 evaluable participants with high or unknown target expression treated with APRC 101 at doses of 310 or 30 milligrams per kilogram achieved stable disease or better in this heterogeneous and heavily pretreated group of participants. On slide 19 is now a line of the next steps for 101. First, the target expression assay now has cap-clear validation, and based in part on 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, we will continue to enroll participants at 30 milligrams per kilogram of ATIC-101 monotherapy in order to obtain additional information on efficacy and biomarkers and to further inform our clinical strategy. On the anti-PD-1 combination 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 expressing 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 are also evaluating a separate combination on the pegylated liposomal doxorubicin, pending completion and review of the Q2W monotherapy cohorts. I will now turn it back over to John to discuss our financials and upcoming milestones. John?

Thank you, Jonathan. Finally, on slide 21, the 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 preclinically focused R&D day on April 5th, during which we will be discussing our FA2 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 programs. As Jonathan mentioned, we plan to present additional data from both monotherapy and combination cohorts and provide an update on clinical strategy in the second half of the year. We expect to soon be able to select participants based on target age score, and the timing of our update will be driven by the pace of enrollment of additional target expectors. Finally, we had $148.1 million in cash, cash equivalent and investments as of December 31st, 2021, which we believe provides us runway in 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?

As a reminder, to ask a question, you will need to press star one on your telephone. And to withdraw your question, just press the pound key. Please sign by or compile the Q&A roster. Our first question will come from Stephen Willie from Stifel. You may begin.

Yeah, thanks for taking the 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 melanoma. 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 cutoff. 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 over time during the course of treatment.

Great, Jonathan? Yes, excellent question. So the first question about distribution of age scores in melanoma and non-small cell lung cancer. As I indicated, we're 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 over time, it is something that is actively being explored. As we mentioned in the preclinical model, there can be modulation in target levels by chemotherapy. Whether or not that is durable over time is unknown to us, but we are actively analyzing that very question.

And I think with our diagnostic strategy, you know, we'll be collecting both archival as well as fresh tissue biopsies, and we may be able to look at those paired samples and further elucidate quality of target expression.

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, right-hand panel. Do we know what proportion of those patients who've extracted clinical benefit and have an age score of greater than 50 receive the 30 mg per kg dose?

So you're saying in terms of So in terms of the six patients with stable disease. Patients with stable disease on slide 11 in the bar graph. To be honest, I have a number in my head, and I haven't used the number, but I think it's approximately eight.

Okay. Very helpful. Thanks for taking the questions, and congrats again.

Thanks, Steve. Thanks.

Our next question is from . Good afternoon.

Thanks also for taking our question. 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? Did they progress immediately or was there a PR or CR to the first round of PD-1 treatment?

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 the patient progressed at the nine-month timeframe. You mentioned it's very... Sorry.

And they had received, they had been treated with both a PD-1 as well as a BRAF MEK inhibitor combination.

Right, right, yeah. No, it's very interesting. And you mentioned in your prepared remarks it's very rare that there's a response on re-treatment with PD-1 in melanoma post-progression. Do you know what that, do you have that response rate data handy? Okay. How often does it happen?

Well, you know, there are various levels of evidence here, and there have been meta-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 if you just look at the guidelines, the guidelines that the NTTN guidelines, et cetera, that it's not recommended to retreat in this setting. But I would say that if there are bona fide responses, and we're not talking about treatment beyond progression, so it's primary therapy, I would say that it's in probably the single digits. Got it. Okay, that's really helpful.

That's very helpful. Then in terms of the PR and CR treatment, I apologize if I missed this, if you said it. Are those patients still in response? And if not, what was the duration of those responses?

The CR, the PR, and the colorectal cancer patients, the 29% reduction remain on treatment. They remain on the study.

Perfect. Okay. And then last question on that, the PR non-small cell patients. lung cancer patient, what were their prior runs of therapy?

They had plenty of prior lines of therapy, including a platinum-based Douglas, as well as another microtubule, I believe it was Taxol, on an experimental trial with etezolizumab, and actually did have a trial of Temporalism admonitherapy.

Perfect. Thank you. That's very interesting, and congrats again on the activity. Thanks, John.

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

Hi, gentlemen. 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.

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

Thank you. Also just had two quick additional questions. Just curious as to what type of H score cutoff you're considering as you begin enrolling based on target expression in the second quarter?

So we are making proposals to the regulators on this. And so I believe that since it's subject to negotiation, you know, we can't be firm on it. But that analytical threshold of 50 is where we are starting. That's due in part not just because of the response data as in the overall response of FD, the CRPR versus PD, but also when we look at the lesion responses, so the percent reduction, because as you know, stable disease can be heterogeneous with disease growth up to 20% or disease reduction up to 30%. So we really try to focus on cutoff that would minimize those with disease growth more towards tumor reduction.

Okay, great. And just one more if I could sneak it in. Just curious if you have any rough idea on timing for data from the Dr. Rubison chemotherapy combination trial with 101. Thanks.

So maybe I apologize for I apologize if I was not clear about this. Data has not started enrolling. We plan to wait until we complete the every two-week monotherapy dosing and evaluate those results, and we'll take it from there. But we've not started enrolling, although the protocol includes that cohort. We just have not activated that cohort yet.

Okay, great.

Thank you. Our next question will come from Roger Song from Jefferies. You may begin.

Great. Congrats for the data, and thank you for taking your question. The first one, maybe just to clarify, Jonathan, if I misheard that. So how many patients on the monotherapy at the highest dose, 30 meg per kick, with the high-edge skull?

You know, I think we have a lot of different analyses sets and overall though, I think we're seeing, you know, Roger, I apologize, the total number didn't plus, but in terms of what we presented today, you know, we're representing approximately 10 patients overall with high age score.

Yeah. Okay. That's fine. So thank you. All right. And then, so for those 12 patients, they have the high age score. Do we know the median prior for those patients? Because overall, you have like around five prior medians. among those tele-patient with the highest score, what is the prime median?

Yeah. So it's a great question, Roger, and we are looking at that. I can only tell you that with a relatively small data set, we are seeing typically that if we split the groups, the median number of prior lines is slightly higher in the H4 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 real phenomenon yet.

Got it. Yeah, that's helpful. Okay, maybe just the last one from us is in terms of the next step, you will share with us the additional data in second half. Given you're focusing on those high dose 3, 10, and 30, would you be able to also determine the RP2D kind of moving forward, select the dose from those three doses?

Yeah, that's also a great question in terms of the dose for expansion. As we said, we have not seen any safety We don't believe that higher doses would in some way mitigate any activity. So for the time being, we are going with the highest tolerated dose, which in this case is the highest tested dose. Now, it 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.

And we could take into consideration the Q2 week schedule, which is also the highest dose, which is 30 mgs per case.

Yeah, that's right. Got it. Okay, great. Thank you. Thank you for taking all the questions. Thank you, Roger.

Our next question will come from the line of Tony Butler from Roth Capital. You may begin.

Yes, thanks. 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 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 CD8s and or in the serum, especially at 30 in the responding patients, even at stable disease patients?

Okay. So we have actually looked at lesion by lesion as well as overall tumor burden impact and the sort of short-term outcomes of response. And we have not seen a difference. So patients with lower tumor burden as well as those with higher tumor burden. We're definitely looking to be impacting the outcome, but it remains to be seen because certainly the precedence in oncology, including with immunotherapy, right, is that the larger the tumor, the less likely. the overall, at least, durability of the response. Second question was on the biomarkers, whether from serum or a tumor. And we're continuing to analyze that, including flow cytometry, both of the lymphoid and myeloid populations. We're continuing to look at cytokines and what you mentioned, the CDAP cells in the tumor pre and post. We will present that data. We're not ready to present that data yet, but it is forthcoming.

Yeah, there's no question. But could I ask, at least from, and 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 know, you want to complete that data set and think that it's really correlative to what the patients may be experiencing?

Yeah, I think that we are encouraged that the data at some level supports the mechanistic model that has been proposed and seems to align with what we presented last July.

Thanks very much.

Thank you, John. Our next question comes from Joel Beattie from Bayer.

You may begin. Hi. Thanks for taking my questions, and congrats on the responses. The first question is, can you speak to, you know, kind of broadly if you saw a dose response in the data, looking at the activity, you know, maybe beyond just the responses that we're seeing in the one patient with 30 milligrams and the other patient with the 10 milligrams?

If we're seeing an overall dose response, you know, the numbers are too small in the 3, 10, and 30 group to say that there's a clear dose response. I think once we have a larger group of target positive patients treated with comparable or same dose, then 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 with lower doses. but that they would just probably occur with greater frequency with higher doses, but we just need more patients with high age scores.

Got it. I appreciate that. Maybe one more question. Could you share any potential to present data on this agent from this trial at upcoming medical conferences?

We are certainly eager to share this data with the broader medical community, and we will do so moving forward as we've done in the past. Probably a future ASCO, more this year's ASCO. Great, thank you. Yeah. I mean, we may present, there's, you know, SIFTI is always one of the conferences that we fund. very interesting to attend and to participate in, so that's a highlight there as well.

Our next question comes from Joe from H.C. Wainwright. You may begin.

Hi, guys. Good afternoon. Thanks for taking the questions, and thanks for the update today. So 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 scores, you know, 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 or rapid progressors in the over 50 might be loss of target?

Okay, so going first to the heterogeneity of the spider plots, you know, I think we believe that, I'll just say that we believe target is, necessary but not sufficient for ATRC 101 activity. We believe that this is a heterogeneous group of patients, some with different prior tumor kinetics or tumor kinetics going into the trial. We would expect that variability in the spider plots. One thing that I'm encouraged by is that it seems that participants who have at least a 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, a third part of your question.

More of a follow-up on, you know, either for these patients or, you know, patients that you enroll later on that, you know, some of the, say, rapid progressors, even over 50, that you'd be able to assess the loss of targets. To answer some of your earlier comments, yeah.

Yeah, so it's a great question, and again, I'm going to refer back to some of the preclinical mechanistic studies that we didn't cover in today's talk, but we believe that HRC-101 initiates an immune response that ultimately involves the adaptive immune system and is not strictly require persistent expression of ATRC-101 in order for the drug to be active. We believe that it actually will lead to tumor cell death and lose advantage in priming for other T cell 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?

Got it. Thank you very much.

And our next question comes from Kumar Raja from Brookline Capital.

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

Yeah.

Again, I 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 to do a larger, have a larger prevalence screen, and that is actually ongoing to determine what the distributions are, and especially given that these are relatively broad definitions of cancer types, and of course everyone is drilling down to more molecularly defined or immunokinetically defined cancers, we imagine that there may be the variation within tumor types according to those other markers. So more to come on this, but suffice it to say that we are continuing to enroll unselected patients, and we'll get a little bit more prevalence data that way. And with our eligibility screen, we'll also be able to determine quite a bit on the distribution of age scores.

I think it's fair to say, though, now that we've treated a larger number of patients, that what we've observed in terms of target expression is not inconsistent. It's about 50% overall for all the patients that we've treated. I think there's just not enough patients of any one indication to really be able to make meaningful distinctions between.

Thanks, John. In the analysis that we presented where we looked at age score, it's been a 50-50 split, exactly. There's a little variability due to small numbers.

Okay, so when you are planning the enrollment expansion, so the assumption is that probably you will end up with about 50% screen failure rate?

Screen failure based on target expression.

Yeah.

There are obviously other things that contribute to patient failure screening. patients exhibiting target expression.

Okay. And finally, with regard to the EPHA to target, when can we expect an update on that?

So as I mentioned at the outset, we're planning our R&D day for April 5th. And at that time, we expect to be able to present a lot of new information related to the entire FA2 program, which I think is what you're referring to.

Thank you so much. Thank you.

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.

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

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