Ladies and gentlemen, and welcome to today's Black Diamond Therapeutics webcast to discuss initial Phase II data for BDTX-1535 in patients with recurrent EGFR mutated non-small cell lung cancer. To begin today's webcast, I'd like to hand things over to the CEO of Black Diamond Therapeutics, Mark Velleca. Good morning, everyone. This is Mark Velleca, Chief Executive Officer of Black Diamond Therapeutics. Welcome to our webcast. We are excited to share promising initial Phase II data of BDTX-1535 in patients with EGFR mutant non-small cell lung cancer in the recurrent setting. This morning, we issued a press release on these encouraging results, and our slide presentation will be available on our website at the conclusion of this call. Here is our disclaimer slide as we will be making forward-looking statements. Let's start with today's agenda. We are fortunate to be joined by two experts in the field of non-small cell lung cancer, Dr. Christine Lovly from Vanderbilt University and Dr. Danny Nguyen from City of Hope. We greatly appreciate them taking the time to share their perspectives on the non-small cell lung cancer, EGFR mutation landscape and unmet need for patients, as well as the implications of today's BDTX-1535 update, and of course, we will hear a presentation of the initial Phase II data from our Chief Medical Officer, Dr. Sergey Yurasov. To remind you of the profile of 1535, here is a brief description: 1535 is a fourth-generation EGFR inhibitor designed to address a broad spectrum of classical mutations, non-classical mutations or NCMs, and the C797S resistance mutation. The molecule is selective versus wild-type EGFR, providing a wide therapeutic window and is covalent and brain penetrant. Next, I would like to take a few moments to talk about what we learned from these initial Phase II data and where we are headed after today's update. We have selected 200 mg as the dose for pivotal development. As you will hear from Sergey, we continue to see favorable tolerability at this Phase II update, with no new safety signals observed. Regarding efficacy, at the 200 milligram dose, the preliminary objective response rate was 42% in a well-defined patient population, comprised of 19 patients with known EGFR resistance mutations. We are very pleased to see durability of approximately eight months or greater in the first three patients with responses, and 14 of 19 patients remaining on therapy. We also learned that post-osimertinib, most patients in the recurrent setting become resistant via PACC mutations, an important subset of NCMs, or via C797S. So we now have two clear priorities in front of us. One, we look forward to sharing data with regulatory authorities to discuss potential paths to registration, and we plan to provide an update on our registration path in the first quarter of 2025. Two, we continue to focus on enrollment in our first-line cohort. Indeed, we look forward to reporting initial data for BDTX-1535 in the frontline setting in the first quarter of 2025. As we reported at ESMO earlier this month, there remains significant unmet need for newly diagnosed non-small cell lung cancer patients with non-classical EGFR mutations. We believe that the safety and efficacy data that we are reporting today in the recurrent setting bode well for the clinical activity we expect to see in the frontline setting. Overall, we are very pleased with where we are with our BDTX-1535 development program. We continue to believe that there is tremendous potential for a well-tolerated oral therapy that addresses a broad range of EGFR mutations to benefit patients across multiple lines of therapy. I would now like to introduce Dr. Christine Lovly from Vanderbilt University to discuss the evolving EGFR mutational landscape in patients with non-small cell lung cancer. Dr. Lovly will also comment on the diversity of mutations that were actionable by BDTX-1535 in our Phase II trial. Hello, my name is Christine Lovly. I'm a medical oncologist and thoracic physician scientist at Vanderbilt University Medical Center in Nashville, Tennessee. I'm excited to talk to you today about EGFR mutations in lung cancer and the expanding spectrum of drugs we have available to treat patients with EGFR mutant lung cancer. It's been 20 years since the initial discovery of EGFR mutations in lung cancer, and we have learned a wealth about how to treat patients with EGFR mutant lung cancer. Still a long way to go, but we'll start with a little bit of history of EGFR mutant lung cancer. The initial discovery of these mutants activating kinase domain mutations in 2004, and since that time, we have evolved this very complex landscape of multiple different mutations, the so-called classical mutations, exon 19 deletion and L858R, and non-classical mutations, which I'll get into on the next slides. Concomitant with multiple different EGFR mutations, we've had multiple different lines of EGFR small molecule inhibitors, or what we call tyrosine kinase inhibitors. From the earliest drugs, the first generations, erlotinib and gefitinib, which were wild-type selective inhibitors, to second generation, afatinib and dacomitinib, to third generation, osimertinib, and now to currently fourth-generation drugs like the Black Diamond compound, BDTX-1535, which we'll be talking about today. Going back to the non-classical mutations in EGFR mutant lung cancer, this is a very diverse and complicated field, and what you can see on this slide, primarily on the left, this is a schematic of the EGFR tyrosine kinase domain, and all these little lollipops, as we call them, represent the complex array of mutations that are possible within the EGFR kinase domain. While we initially thought in this field twenty years ago that it was as simple as exon 19 deletion and L858R, what we have come to learn over time is that there are multiple different mutations possible, encompassing the entire EGFR kinase domain, even outside the EGFR kinase domain. We will not talk about those mutations today. We will focus on the EGFR kinase domains, because this field is incredibly complicated, in and of itself, complicated and nuanced, yet so exciting to see it continue to move forward. If you look at the little lollipops here, the black lollipops are the classical mutations, the exon 19 deletion and the L858R, and the blue are what we consider the non-classical or atypical. I prefer the phrase non-classical over atypical, but you will see both in the literature. What you can tell is there are actually more blue lollipops than there are black. The non-classical mutations are less common than the classical mutations, but there's more of them, and we need to think about, as we take a nuanced, precision-based approach to the treatment of patients with EGFR mutant lung cancer, not just any EGFR mutation, but which specific EGFR mutation, and where is that mutation occurring in the EGFR gene, the resultant EGFR protein, and how is that affecting structure-function relationships and drug sensitivity? One class of EGFR mutations that are the non-classical group are the so-called PACC mutations. This is one of the most common and most important structural class of non-classical EGFR mutations. PACC mutations comprise more than thirty unique EGFR mutations in the EGFR kinase domain, which have been shown to have decreased sensitivity to our current drug, osimertinib, a third-generation EGFR TKI. This is a pivotal paper that was published in Nature in 2021. Together with cysteine 797 S, which is a resistance mutation that can occur when patients with the classical EGFR mutations are treated with the drug osimertinib, the PACC mutations plus C797S comprise about 20% of all recurrent EGFR mutant non-small cell lung cancer, so quite a significant percentage of patients with EGFR mutant lung cancer. What we do expect is that those patients who have the C797S osimertinib resistance mutation and the PACC non-classical mutations will continue to retain EGFR oncogene addiction, meaning they retain sensitivity to the EGFR kinase domain. This is a lot of information contained within this one slide, but the major take-home messages here are that there are multiple EGFR mutations that are possible within the EGFR kinase domain, that they have different sensitivities or degrees of sensitivity to different EGFR tyrosine kinase inhibitors that we have in our existing and emerging clinical portfolio, and that we need to take a nuanced approach to best treat our patients with EGFR mutant lung cancer. Thinking about the 1535 data that you're about to see, this is data from a Phase II clinical trial, a pivotal trial, and what I'm showing you here is just the spectrum of mutations that are possible. This is about 22 patients that are shown here, and what you can first see, without even getting into the granularity of which mutations and which patients is, there was a lot of different mutations detected, concordant with the data on the previous slide, that there are multiple different mutations possible within the EGFR kinase domain. So we need to move away from this old dogma, EGFR mutation present, absent, yes, no, to which specific EGFR mutation? How does that mutation or even compound mutations, which are seen here, where a patient can have more than one EGFR mutation in the tyrosine kinase domain, how does that affect drug sensitivity? To drill down a little bit deeper into the 1535 data, there were 10 patients who had the C797S resistance mutation. That is a mutation that occurs when patients develop resistance to the drug osimertinib. So these patients had at least two different EGFR mutations, a classical mutation like L858R, plus the C797S resistance mutation. There were nine patients that had a PACC mutation. These are the non-classical mutations that have decreased sensitivity to osimertinib, at least in vitro, that has been shown. And there were three patients with other non-PACC, non-classical mutations. Again, the take-home message here is that we need to take a very precise, nuanced approach to understanding the spectrum of EGFR mutations that are present in patients with EGFR mutant lung cancer. A major take-home message for everyone who's listening to this is, this is not an academic enterprise. This is actually data that we are collecting every day in the care of our patients. For a standard clinical care for patients with lung cancer, it is standard now to get full exonic sequencing of the EGFR gene. So these mutations are being detected in our patients every single day, and it is important that we take a nuanced, structural-based approach to identify the mutations and direct those patients with the specific mutations they have in their tumor to the best available therapy for them. Thank you. Thank you, Dr. Lovly, for your thoughtful commentary on the EGFR mutation landscape and the relevance to our patient population. Let's now turn our attention to our Phase II results. As a reminder, our Phase II trial included Cohort 1 and 2, which enrolled patients who progressed after prior osimertinib therapy. This will be the focus of today's update. Cohort 1 is for patients with non-classical mutations or NCMs, and Cohort 2 is for patients with a C797S resistance mutation, who may also have NCMs. Cohort 3 is enrolling treatment-naive patients with NCMs, and we expect to disclose initial clinical data results from Cohort 3 in the first quarter of 2025. Our first data analysis on June fifteenth assessed safety, PK, and tolerability to support pivotal dose selection of 1535. It included the first 40 patients enrolled in Cohort 1 and Cohort 2, who were randomized to receive 100 versus 200 milligram dose, 20 patients each. We selected the 200 milligram dose for pivotal clinical development based primarily on the favorable tolerability profile. It is consistent with approved EGFR TKI class of drugs with mild to moderate treatment-related adverse events of rash, diarrhea, stomatitis, and paronychia, which can be successfully managed with standard supportive care. Importantly, there were no cases of grade 3 or 4 diarrhea. We also note an absence of off-target side effects, such as liver enzyme elevations and QTc prolongation. Reflecting the well-tolerated profile, only one of 20 patients discontinued 1535, only four of 20 patients with dose reduced, and no patients discontinued due to rash, diarrhea, stomatitis, or paronychia. The next slide shows the second Phase II data cut on August seventeenth, which was done to assess preliminary efficacy and included 27 patients dosed at 200 mg, an addition of 7 patients since the June cut. These 27 patients have advanced refractory lung cancer. For context, these patients typically receive chemotherapy, and the majority of them relapse or die within six months. Let's walk through baseline characteristics. Approximately one quarter had brain metastasis and a third had visceral disease, both of which indicate poor prognosis. Most patients had some restriction of their physical activity, as evidenced by ECOG Performance Status 1. Patients were split 56% and 44% between Cohorts 1 and 2, and split 52% and 44% between second-line patients and third-line patients. There was one patient with greater than two lines of prior therapy, which was a protocol violation. Next slide shows the patient flow diagram. Starting with 27 patients, three patients were found to have exclusion criteria mutations, and two patients received more than one prior EGFR-targeted therapy. In the per-protocol population of 22 patients, the preliminary objective response rate was 36%. 19 of these patients had known on-target EGFR resistance mutations, either PACC non-classical and/or C797S. The preliminary response rate in this well-defined population was 42%. Let's now look at clinical activity in these 19 patients. Here is the waterfall plot. 8 of 19 patients met the criteria of response with more than 30% target lesion reduction, with several deep responses. There is a similar number of responses in Cohort 1 and Cohort 2. To the far right is a patient with a complete response that we will talk more about in a few minutes. Another nine patients achieved stable disease, and only one patient experienced progressive disease. Next, we will turn to the durability of response. Here is the swimmer plot, which shows that 14 of the 19 patients remain on therapy, an early sign of promise and durability. Meantime, a follow-up for all these patients was 4.7 months, and it is encouraging to see that the first three responders all had partial responses lasting approximately eight months or longer. Three of the eight patients who reached the PR their first scan are awaiting their second scan for confirmation of response and are ongoing.... Let's now talk more about the patient with a complete response, who is third from the top on the swim plot. This is a very compelling case, as we do not commonly see CRs in the recurrent setting. This patient had two non-classical mutations and had previously received osimertinib for eight months, followed by second-line chemotherapy for only two months before progressing and coming onto our study. They have extensive disease affecting the chest, the abdomen, and the brain. They tolerated therapy very well, and on the first scan, they had disappearance of the target lesion in the abdomen and then ultimately converted to a complete response on the fifth scan, which included disappearance of pleural and mesenteric tumors, as well as disappearance of two brain metastases. This patient remains on therapy at approximately eight months and is awaiting a confirmatory scan for their CR. Next, we show examples of circulating tumor DNA reduction for the first three patients with partial response. These data show near complete clearance of both the variant allele fractions and ctDNA, which has been reported to be an early predictor of a PFS benefit. So, here is the slide that Dr. Lovly showed you earlier, but with the addition of patient responses. Dr. Lovly discussed the broad mutation profiles that were present across the 19 patients, including the C797S acquired resistance mutation, PACC, non-classical, classical and compound mutations. The green bars identify the patients who were responders and comprise the 42% response rate. It is striking to see that radiographic responses are achieved across a broad spectrum of mutational profiles present in relapsed refractory lung cancer. Summarizing the data that I have shown you today, we conducted PK safety and tolerability assessment and selected the 200 milligram dose for pivotal clinical development. BDTX-1535 is a well-tolerated EGFR TKI oral therapy with manageable adverse events commonly seen with osimertinib. Our initial efficacy assessment revealed a 42% response rate in a well-defined patient population, with 14 of 19 patients remaining on therapy, demonstrating promise and durability. As Mark outlined earlier, next steps for us include seeking regulatory feedback on potential registrational path forward, which we expect in the first quarter of 2025. We believe that the safety and efficacy that we're reporting today in the recurrent setting bode well for the clinical activity we expect to see in patients with non-classical mutations in the frontline setting, and we look forward to reporting those data in the first quarter of next year. Now, I would like to introduce Dr. Danny Nguyen from City of Hope, who's going to discuss the current treatment paradigm in EGFR mutant non-small cell lung cancer and the potential for 1535 to address unmet needs for these patients. Thank you. Hi, my name is Danny Nguyen, and I am a practicing medical oncologist in the community, working at City of Hope, in California. And I frequently treat EGFR mutated lung cancer patients, here in this community. For these patients, I typically like to classify the EGFR patients into three broad categories. You have the classical EGFR mutations, which includes the exon 19 deletion patients, as well as the L858R mutations. And then you have the non-classical mutations, which also includes the PACC mutations, and then you have the EGFR exon 20 insertion mutations, who are not listed here. We're gonna focus here on the classical mutations as well as the non-classical mutations. As you see here, first-line treatment options for classical mutated patients includes the newly approved amivantamab plus lazertinib, as well as osimertinib, plus or minus a platinum doublet, and then for the non-classical mutations, you do have osimertinib being used a lot, even though it doesn't have that approval, and then afatinib for three specific mutations, and then you also have chemotherapy as well in this setting. What patients get in the second and third-line setting typically will be dependent on what they get in the first line, but in general, a lot of patients in the second line will get some form of chemotherapy, usually a platinum doublet, and in the third line, they'll usually get a docetaxel-based regimen. Historically, these regimens have a pretty mediocre response rates, about 30%, with the platinum doublet and about 10% with the docetaxel regimen. Next slide. We've learned over the past several years that, when patients progress, there's many different ways that they can progress in the EGFR setting. One of the mechanisms is via EGFR-dependent mechanisms. Specifically, a common one that we come across is the C797S mutation, for which we do not have any approved therapy options for right now. As well as picking up other additional non-classical mutations. And again, we don't really have anything approved in this setting as well. Outside of what has already been listed in terms of the chemotherapy options that we have. Next slide. So that's where Black Diamond comes into play with BDTX-1535. It's a fourth-generation oral EGFR TKI that is well-tolerated and targeted for these specific mutations. And it's being tested in the second and third-line setting, and as you see here, with some promising initial results. My experience with the drug, patients seem to tolerate it very well. The side effect profile seems to be very much in line with other approved oral EGFR TKIs, and so far, we haven't really seen anything any unique safety signals at this point. Next slide. In addition to the recurrent setting, Black Diamond has an ongoing Phase II cohort in newly diagnosed non-small cell lung cancer patients with non-classical mutations. As you heard from Dr. Lovly, this is a large patient population that really is underserved with the current treatment options that we have available right now. At this point, you know, we can do better with when compared to the treatment options that we have so far. I think this is where BDTX-1535 can fill the gap by providing a treatment option that has a good side effect profile as well as promising efficacy in the CNS. Thank you. Thank you, Dr. Nguyen. I would also like to thank all of our investigators, patients, and caregivers for their participation in our trial. We are very grateful for your engagement. Before going to Q&A, I'd like to offer a couple of closing thoughts. First, we believe that BDTX-1535 is favorably positioned versus a number of chemo-based combination regimens that are becoming available to patients with non-small cell lung cancer. BDTX-1535 is a well-tolerated oral therapy taken once daily. Patients do not need frequent IV infusions that can be associated with significant side effects. The success of osimertinib in treating patients in the front line and adjuvant settings tells us that patients value quality of life. Of course, patients expect efficacy as well, and we believe that BDTX-1535 can deliver robust clinical activity across a broad range of mutations and multiple lines of therapy. And second, we believe that there are multiple opportunities that lie ahead of us as we advance 1535. Today, we reported promising data in the recurrent setting for patients with EGFR resistance mutations, and we are moving quickly into the front-line setting for patients with EGFR non-classical mutations. And we look forward to presenting initial Phase II data from these frontline patients in the first quarter of next year. As we presented at ESMO earlier this month, there is also a significant opportunity to benefit newly diagnosed patients with the L858R mutation, which is approximately 40% of the overall osimertinib market. And finally, we believe that BDTX-1535 also has the potential to benefit patients in the adjuvant and post-adjuvant setting. With that, we'll move to Q&A. Thank you. Thank you. We will now begin the questions and answer session. Please unmute your line when I announce your name, and our first question coming from the line of Joe Catanzaro with Piper Sandler. Great. Thanks, guys. Appreciate the data here. Really interesting. Maybe first question, I know we could figure it out by looking at the slides, but can you say what the response rate was for patients in Cohort 1 who didn't have a classical mutation? And when you speak about the read-through, the frontline setting, are these the patients that we should focus on, or are there other populations here that you think are relevant to that potential read-through into frontline? Thanks, and I have maybe one follow-up. Joe, just wanna make sure I understand your question. You're talking about patients without a classical mutation or with a classical mutation? Yeah, correct. Without. Without a classical, yep. Yeah. I think Sergey can comment on the waterfall plot and answer your question, and then Liz can maybe address the relevance of that patient population for the first line- Yeah. -cohort. Thank you for your question. Yes, we did see responses in patients who have non-classical mutations without coexpression of a classical mutation, and as you, if you look at the waterfall plot, yes, it is a very broad- ... patient population with multiple mutations and combinations thereof. But if you can, in the middle of it, you can see there are patients actually with a singular non-classical mutations that had a confirmed partial response. Yeah. Yeah, and we know that, I mean, these non-classical mutations are frequently expressed in newly diagnosed patients, even the absence of a classical oncogenic driver mutation, including L858R and exon nineteen deletion. So we were quite pleased in this recurrent setting to present with three responses in such patients. So we had, seven patients who presented, with PACC non-classical mutations in the absence of a classical mutation, and we were able to capture responses in three of those patients. So I think this bodes well for what we expect to see in the frontline setting. Thanks. That's helpful. And if I could ask, maybe I guess, a somewhat related follow-up. Wondering if you have any updated thinking around non-PACC, non-classical mutations. If I understood correctly, those three patients that were excluded from the efficacy analysis were excluded because they had non-PACC mutations, without C797S, if I understand that correctly. And if you do have any updated thinking on those specific mutations, does that change maybe the frontline patients that you are enrolling into that Cohort 3? Yeah. Thanks, Joe. Liz can address that question- Yeah. particularly those three patients. Yeah, no, again, great point, and so I maybe I'll start by describing in the recurrent setting for EGFR mutated lung cancer, following progression osimertinib therapy, we most frequently observe either PACC, the PACC classification of non-classical mutations, or C797S, as this really represents those which are most insensitive to osimertinib therapy. And so in this patient population, post osimertinib, we see these PACC and C797S mutations either accumulated or acquired, with progression. Now, if we look at other mutations that may be also frequently presented in the newly diagnosed setting, there are PACC mutations there, but there are other categories of non-classical mutations that are non-PACC. Now, an example of such a mutation is L861Q. L861Q being a mutation which we know to be sensitive to osimertinib. And so in the recurrent setting, for patients who present with mutations, these osimertinib-sensitive mutations, such as L861Q, and who progress following osimertinib treatment without the acquisition of a secondary drug resistance mutation in EGFR, we really just don't expect those tumors to continue to be driven by EGFR. Their resistance is likely to be off target, and would not expect those patients to show sensitivity to 1535. Now, in the newly diagnosed setting, these are oncogenic driver mutations. These patients have not been exposed to prior EGFR TKI, and so we would expect BDTX-1535 to be able to act on PACC mutations, plus other structure-function categories of non-classical mutations, including the L861Q mutation. Again, that group of mutations, the collective group of non-classical mutations in newly diagnosed patients, represents 23% of the EGFR mutation space in lung cancer. Okay, great. That's helpful. I will drop off. Thanks for taking my questions. Thanks, Joe. Thank you. Now our next question coming from the line of Brad Canino with Stifel Nicolaus. Please proceed, Michel, with your question. Hi, good morning. Thank you, and congrats on the Phase II update. Two from me here. I guess first on the data. For the dose reductions, which are running around 20%, what dose are patients reduced to from 200 mg? And what is your confidence that that lower dose remains active, and patients can remain on that reduced dose without stopping? Yes, thank you. Thank you for that question. Very important one. So our step-down schedule, just to answer specifically, is down to 150. And now to take a broader look, as you know, dose reduction is part of management of the EGFR TKI class of drugs. And the patients that we had dose reduce, in fact, tend to have higher exposures. So I think from that perspective, when you think about efficacy in these patients, we do not believe it should be compromised in any way. And so that's why dose reduction in conjunction with standard supportive care measures result in the fact that these patients can continue, as you can see on the swimmer plot, on our drug without discontinuation for a very long period of time. No patients discontinued due to rash, diarrhea, stomatitis, or paronychia in our trial. Great, and then second, just looking forward, anything you can say about the potential size of the 1 Q frontline cohort, especially relative to the size of the cohort analysis that you provided today? Thanks. Yeah, thanks, Brad. Mark, I'll take that one. We haven't guided to specific patient numbers, but we obviously would want to have a sizable number of patients in the first quarter for that update. So something similar to what we're reporting here today. ...Any other questions, Brad? All set. Thank you. Thank you. Thank you. Our next question coming from the line of Marc Frahm with TD Cowen. Hi, thanks for taking my questions. I know going forward, we're very much focused on 200 mg, since that's been selected as go forward dose. But, can you speak to the dose response that you did see with, you know, in that randomized dose selection period? Are you referring to the 200 mg cohort? Yeah, right, you selected 200 mg, but there was a lower dose, you know, in the initial dose selection period there. Just can you speak to the kind of dose response that was seen there and, you know, and helped select the 200 to really the right dose to go forward with? Yeah, absolutely. We haven't reported specific response rate for a 100 mg, though we have seen responses at that dose, and Sergey can speak to our experience with a 100 mg in Phase I. The dose selection was based primarily, as Sergey said, on PK and tolerability. But Sergey, if you wanna remind, Mark and others on 100 mg experience in Phase I. Thank you, Mark, for the question. As you may recall, when we presented almost a year ago, our Phase I data, in fact, we had patient who responded at a 100-milligram dose, and they had multiple sites of the disease. Now, when we approach dose optimization, which led us to select the 200-milligram dose for the pivotal development, we focus on optimal risk-benefit. And that's what I think the key in understanding this data set. When we look at 200-milligram dose, we're seeing very robust responses across the spectrum of mutations as described, as well as we've seen a very good tolerability. Based, as I just mentioned, no discontinuations due to the most common untargeted effects of rash, diarrhea, stomatitis, and paronychia. Maybe I'll just conclude, remind folks that the one hundred milligram cohort was done to satisfy Project Optimus. Okay. Thanks, that's helpful. And then maybe looking forward to the regulatory piece, just, you know, I know the FDA has been kind of sending messages of, you know, preferring randomized trials in a lot of settings, but they've also continued to allow some single-arm approvals in targeted, in the targeted therapy space. Just lay out your thoughts there on kind of where this population falls on that spectrum, and what you would hope is the outcome when you do speak with the FDA. Thanks. Yeah, I'll take that. We do look forward to sharing these data with the agency, and we will be able to provide an update to everyone in the first quarter on that feedback. We believe that all paths to approval are open to us, including single-arm designs. Okay, thank you. Thank you. And our next question coming from the line of Farzin Haque with Jefferies. Hi, good morning. Thank you for taking my question. Just following up on the registrational question, like, is there potential - like, what is the bar that FDA will look for in order to approve, for example, a single-arm trial? I think Sergey can comment on the, you know, existing bar for chemo in the second line setting. Sergey? Yes. Thank you for the question, so I think, you know, for the majority of these patients, chemotherapy remains a commonly used regimen, and what we know for chemotherapy, that response rate can range from the high twenties, sometimes even 30% to 13% for docetaxel. There is a range from high twenties to low teens that you can see response rate with the chemotherapy. Got it. And then will you have an updated cut of the data, basically to take down confirmed responses before you meet with the regulators? And can we see the data, I guess, by this year, maybe? We will be sharing updated data with regulators, and we will also prepare to present these data at a medical meeting in 2025. Got it. Thank you so much. Thank you. And our next question coming from the line of Robert Driscoll with Wedbush. Thanks, guys, and congrats on the data here. I'm just wondering if you're collecting any data here on resistance to BDTX-1535 and kind of in responding patients, whether that might be different for the C797S or the mix or the, or the kind of non-classical mutations alone, or if there's maybe something you've seen in preclinically? Yeah, Robert, I'll allow Liz to answer that question. Yeah. So we don't, we haven't really systematically looked at this in this particular patient population. I think it's an interesting point. We do not know what the acquired resistance mechanisms to BDTX-1535 might be following a prolonged course of therapy. As we've learned from the experiences of other EGFR inhibitors, patients who progress following a prolonged period of time, greater than a year, may develop either on-target or off-target resistance mechanisms, but we do not know what those are for BDTX-1535. Great. And then just of the three patients that were excluded for having kind of those that subsequently identified non-EGFR mutations, could you tell us what they were? Yeah , I mean, I can say that. So for the three patients who were excluded, based on alterations which were not allowed according to our protocol, these were a MET amplification, a RET fusion, and a T790M mutation in a patient following an afatinib treatment. Got it. Thanks very much, guys. Thank you, Robert. Thank you, and our last question, our Laura Prendergast with Raymond James. Hey, guys. Congrats on the data. Two quick ones for me. First, can you discuss, you know, it seems like you've got quite a few patients who did have a progressive disease event, but they still remain on therapy. If you could just, you know, comment on those patients. And then, you know, similarly to the Phase I cut, you know, there appears to be a strong response in the L858R patient population. Can you elaborate on why you think this is? Thank you. So, let me just talk first about patients continuing on drug beyond progression, and then, my colleague, Liz, can answer your biology question on L858R. So it's an important point, as you see, that some of these patients met definition of a progressive disease based on the RECIST criteria, which is an increase in the size of the lesion. But as Mark pointed out in his introduction, quality of life is very important for these patients. And so the patients, actually, or their physicians, opted for a patient to stay on treatment for two main reasons: because they think that there is ongoing clinical benefit, so control of the disease, as well as, of course, tolerability is the other side of it. And that's why you see there are patients on the swimmer plot who did, in fact, had a PD, but still have an arrow attached to it because they opted to continue treatment. And so I'll pass it on to Liz to talk about L858R. Yeah. Thank you, Laura, for the question, and I think we're very encouraged with what we see for BDTX-1535 activity in the L858R patient population following osimertinib treatment. As you'll see in this study, we had five patients presenting with L858R mutations in our cohort, and we achieved responses in three out of those five patients. Interestingly, all of these patients presented with co-expression of a non-classical mutation, either a PACC mutation or another non-classical mutation. We expect BDTX-1535 to perform very well in the L858R patient population, even considering this in the newly diagnosed setting. And that's because BDTX-1535 is designed to be highly potent to target that specific mutation, more potent than osimertinib against the L858R mutation. Also, we know, and as we presented at the ESMO conference, about a week ago, we know that L858R tumors at diagnosis frequently present with co-expressed non-classical mutations. Those co-expressed non-classical mutations are insensitive to osimertinib, but they're sensitive to 1535, and we see evidence in this trial that we're able to action in that setting. Thank you. Thanks, Laura. Operator, I think we can wrap up. Thank you. Ladies and gentlemen, that concludes our Q&A session for today. Thank you all for joining us today. We appreciate your time and consideration. This ends today's webcast, and you may now disconnect.