Good afternoon, welcome to Theseus Pharmaceuticals Investor Event. As a brief reminder, all participants are currently in a listen-only mode. Following formal remarks, we will open the call up for questions. I would now like to turn the conference over to Brad Dahms, Chief Financial Officer at Theseus. Please proceed. Thank you, operator. Good afternoon, everyone. Welcome to Theseus's Investor Event, where we will discuss initial dose escalation data from our phase I/II clinical trial of THE-630 for patients with advanced GIST. This afternoon, we issued a press release outlining these results. The press release and the presentation we will reference during today's event can be found on the Investors and Media section of Theseus's website at theseusrx.com. As a reminder, this call is being recorded, and a replay will also be archived on the company's website for 90 days. At this time, I would like to remind listeners that during this call, we may make forward-looking statements and ask that you refer to our SEC filings available at sec.gov for a discussion of potential risks and uncertainties. Please also refer to the disclaimer on Slide 2. All information presented on this call is current as of today or the data cut-off date with respects to our initial data. Theseus undertakes no duty to update this information unless required by law. As you can see on Slide 3, joining me to present today are Tim Clackson, Chief Executive Officer, and David Kerstein, Chief Medical Officer. Following the prepared remarks, William Shakespeare, Co-founder and President of Research and Development, Victor Rivera, Co-founder and Chief Scientific Officer, and I will be available for the Q&A session. Looking at Slide 4, the agenda for today's call will begin with an introduction from Tim, followed by an overview of the initial dose escalation results from the ongoing phase I/II dose escalation and dose expansion trial of THE-630, led by Dave. Tim will then return for closing remarks before we open up the call for Q&A. With that, I will now turn the call over to Tim. Thank you, Brad. Thank you all for joining today's call. We are excited to present to you today the first clinical data from our phase I/II study, evaluating THE-630 in late-stage GIST patients who have developed resistance to earlier lines of therapy. Moving to Slide 6, GIST represents one of the major unmet needs and opportunities in targeted oncology. GIST is a disease that is overwhelmingly driven by KIT mutations, and KIT remains the driver through multiple lines of treatment, as evidenced by the emergence of secondary KIT mutations following treatment with imatinib, the approved therapy in the frontline. GIST has a high level of mutational heterogeneity in these later lines of therapy. This makes the disease very difficult to control with a KIT inhibitor that does not inhibit all activating and resistance mutations. We believe that pan-variant inhibition could drive a truly meaningful improvement in patient outcomes and presents a significant commercial opportunity as well, particularly in earlier lines, where with a pan-variant inhibitor, you could drive substantial durations of therapy. As you can see on the right part of the slide, in KIT-driven GIST, the disease is initiated by an activating mutation found in either exon 9 or 11, shown in gray. Following treatment, two different types of resistance mutations emerge, either in exons 13 and 14, shown in blue, or in exons 17 and 18, shown in green. It is imperative to hit all KIT mutations found in patients to combat treatment resistance and drive meaningful clinical benefit. Turning to Slide 7, current standards of care in KIT-driven GIST are unfortunately inadequate, particularly following frontline treatment with imatinib. As shown here, subsequent lines of therapy are associated with very low response rates and a median PFS in the range of six months. Without treatment, progression occurs in about one month. Importantly, as patients move through these lines of treatment, they experience continued evolution of complex mutational profiles that render the disease more difficult to treat. This includes recently discovered compound mutations, that is, two resistance mutations in the same gene following treatment with ripretinib in the fourth line. Therefore, it is critical to deploy an effective pan-variant inhibitor early in treatment, which is why our strategy is to get to the second line as soon as possible. Slide 8 analyzes this heterogeneity in more detail. This chart shows the mutational diversity and frequency that occur even in second-line patients following treatment with imatinib. Roughly half of the mutations occur in exons 13 or 14, most commonly the V654A mutation, with the other half occurring in exon 17 or 18. This clearly illustrates that success in the second line will require potent activity against both families of mutations. The recent clinical data from the phase III INTRIGUE trial emphasized this fact. ripretinib and sunitinib both showed a median PFS of around eight months in the second-line all-comers population. However, in the ripretinib arm, patients with only exon 13 or 14 mutations had substantially lower median PFS of four months. Conversely, sunitinib patients with only exon 17 or 18 resistance mutations had a much lower benefit, with a PFS of only 1.5 months. These data demonstrate that the liabilities of mutational coverage of each drug limit their efficacy, and that a pan-variant inhibitor could dramatically improve patient outcomes. Moving to Slide 9. At Theseus, we have for many years used our predictive resistance assay, or PRA, to characterize the mutational coverage of TKIs. As you can see here, we have used the PRA to analyze the mutational profile of existing KIT inhibitors. We compared IC 50s to the clinical average drug concentration, or Cavg, represented by the horizontal black lines. This analysis predicts that none of the currently available therapies will be able to effectively inhibit both classes of resistance mutations. For example, ripretinib is predicted to have deficiencies in exons 13 and 14, represented by blue mutations above the line. Conversely, sunitinib is seen to have deficiencies in exons 17 and 18, where those IC 50s, in green, are above the line. This is exactly what was borne out in the intrigue subgroup analysis mentioned on the previous slide. For THE-630, this analysis predicts that as we dose escalate in patients, specific mutations will be inhibited at exposures starting at around 10 nanomolar, with some mutations requiring higher exposures than others. At an exposure of 100 nanomolar, which we project to reach in cohort 8 of the ongoing trial, this analysis predicts that THE-630 should demonstrate activity against all major classes of resistance mutations. Moving to Slide 10. In the preliminary data set today, we set out to address three important questions related to the activity of THE-630 in GIST. First, are we seeing safety and PK that is supportive of once-daily dosing and continued dose escalation towards our 100 nanomolar target for pan-variant inhibition? Second, are we seeing reductions in ctDNA for individual resistance mutations at doses consistent with the preclinical data from the PRA? Importantly, are we seeing evidence of activity on both classes of resistance mutations as we step up the PK exposure ladder? Finally, are we seeing this translate into early clinical benefit? In this late-stage patient population, responses are rare, so we would be looking for evidence of stable disease and evidence that this correlates with drug exposure and mutational effects. With that background, I will now turn the call over to Dave to review the clinical data. Thank you, Tim. We will begin on Slide 12. Here, we depict the design of the ongoing first-in-human phase I/II trial, evaluating THE-630 in patients with advanced GIST. This study consists of a phase I dose escalation and a phase II dose expansion into three cohorts defined by prior therapy, spanning from 2nd line to 5th line plus. The focus of today's call will be on the ongoing dose escalation portion of the study. The patient population enrolled in the phase I are 3rd line or later, having received prior therapy with imatinib and at least one other TKI. Important evaluations in the study include disease assessment by modified RECIST and a circulating tumor DNA analysis conducted using the Guardant360 platform. On Slide 13, we provide more details on the phase I portion of the trial, which utilizes a standard 3 + 3 dose- escalation design. The starting dose level was 3 milligrams once daily, and we have thus far evaluated doses up to 27 milligrams in cohort 7. The protocol defines dose increases of up to 100% until certain tolerability criteria are met, as listed on the slide, at which point dose level increases of up to 50% are to be implemented. Interpatient dose escalation is allowed. The focus of today's presentation, based on an April 21st data cutoff, is on the 23 patients enrolled in cohorts 1 through 6, spanning 3 milligrams to 18 milligrams. At the time of data cutoff, two additional patients were enrolled in cohort 7, with the DLT observation period ongoing. Both patients have subsequently cleared the DLT observation period without experiencing a DLT, and a third patient has recently initiated treatment in this cohort. The study population in cohorts 1 through 6, as shown on Slide 14, consists of patients with heavily pretreated GIST. All patients had KIT-activating mutation. The median age was 59, consistent with expectations for this patient population. All patients, but one, had ECOG performance status 0 or 1. Patients had a median of four prior therapies, with a range of 2% to 8. 70% of received four or more prior TKIs, with all patients having previously received treatment with imatinib and sunitinib, and 65% also having previously received regorafenib and ripretinib. Slide 15 shows the progress of the dose escalation cohorts. In cohort 1, at 3 milligrams, two patients experienced a Grade 2 or greater treatment-related hypertension adverse event. This triggered a change to dose escalations of up to 50% from the prior cohort. Treatment-related hypertension has not been reported in subsequent cohorts. In cohort 2, at 4 milligrams, 1 DLT was observed, a Grade 5 myocardial infarction. This event occurred in a 64-year-old female patient with 8 prior lines of therapy, hyperlipidemia, and ECOG performance status of 2 at baseline. On cycle 1, day 1, this patient had approximately 1 nanomolar average plasma concentration of THE-630. After four doses of study drug, the patient was hospitalized on study day 5 for adverse events assessed as not related to the study drug. On study day 6, the patient experienced myocardial infarction and subsequently died. The event was considered a DLT, as the relationship to treatment with THE-630 could not be incontrovertibly ruled out. On this basis, the cohort was expanded per study protocol. No additional DLTs were observed in cohort 2 expansion patients, and no additional DLTs or cardiac ischemic adverse events have been observed in subsequent cohorts to date, which have yielded significantly higher exposures. Slide 16 presents the overall safety profile of THE-630 to date, which is supportive of further dose escalation. The table shows adverse events occurring in greater than or equal to 10% of patients. 65% of patients have had treatment-related adverse events of any grade. The most common treatment-related adverse event were fatigue, AST elevation, diarrhea, nausea, dry mouth, and dyspnea. Most treatment-related adverse events were grade 1 or 2. Of 89 reported, five were grade 3 or higher, three of which occurred in cohorts 1 and 2. There was no dose relationship when looking at these higher grade events. Overall, the safety profile is consistent with expectations based on drugs in the class and preclinical data for THE-630. The DLT previously described in cohort 2 was the only DLT and the only treatment-related serious adverse event reported to date. An MTD has not been reached, and dose escalation continues. Slide 17 shows the emerging pharmacokinetic profile of THE-630 through cohort 6, which is consistent with once daily dosing. On the left, the concentration time curves for THE-630 at steady state are displayed by dose. We observed a 3-fold to 6-fold accumulation between single dose and steady state plasma exposure. On the right, we've plotted mean average concentration versus dose of THE-630, with once daily oral dosing demonstrating approximately linear pharmacokinetics from 3 milligrams to 18 milligrams, with an R squared value of 0.88. The mean steady state average concentration at 18 milligrams was 48 nanomolar. Assuming consistent linearity with what has been observed in cohorts 1 through 6, we predict that a 40 milligram dose would yield our target exposure of a 100 nanomolar average concentration. On Slide 18, we illustrate the clinical activity of THE-630 in a swimmer plot showing time on treatment by dose. We are encouraged by preliminary data that demonstrate prolonged stable disease at the higher doses tested. Patients are grouped according to starting dose cohort in descending order from 3 milligrams to 18 milligrams, with the number of prior TKIs noted for each patient. The blue swim bars indicate patients with stable disease as best response, and open bars indicate progressive disease at first scan or patients who are not evaluable. Black circles indicate stable disease at a given time point, while black triangles indicate progressive disease. A dose-dependent increase in stable disease can be observed, with eight of nine evaluable patients treated at 9 milligrams and above, having achieved stable disease as best response, of which six remain on study at the time of data cutoff, as indicated by the blue triangle. For patients with sufficient follow-up, we're seeing evidence of prolonged stable disease, particularly at doses of 9 milligrams and above. Of note, you can see a patient initially treated at 4 milligrams with treatment duration of over eight months. On Slide 19, an analysis of ctDNA data shows that reductions in all major classes of activating and resistance mutations in KIT were observed following treatment with THE-630. The waterfall plot captures the best full change in mutant allele frequency compared to baseline, with decreases in frequency for a given variant appearing as bars below the line and increases indicated by bars above the line. The detected variants are grouped by exon, with gray indicating the activating mutations in exons 9 and 11, blue indicating ATP binding pocket resistance mutations in exons 13 and 14, and green indicating activation loop resistance mutations in exon 17. The patient in which these variants were detected is depicted at the bottom of the figure, color-coded by dose. Multiple bars are shown for patients who had multiple mutations detected. In this analysis, we observed KIT mutations in 16 of 19 patients with pre- and post-baseline samples. Five of these patients had more than one detectable resistance mutation, with a range of 2 to 6. At lower doses, reductions in mutant allele frequency for activating mutations found in exons 9 and 11, as well as exon 17 resistance mutations, were observed. This is consistent with our PRA predictions, where the activating mutations and certain exon 17 mutations, such as those at the D820 position, are expected to require a lower exposure for activity. At higher doses tested, we started to see reductions in resistance mutations in exons 13 and 14, including the most common resistance mutation, V654A, again, consistent with our PRA predictions. V654A was detected in the ctDNA of five patients at different doses, and there was a clear dose response, where increases in V654A were observed at lower doses, and a strong reduction was observed in a patient at 18 milligrams. We also observed a strong reduction in the T670I gatekeeper mutation in exon 14 in this patient. This emerging evidence of activity against both classes of resistance mutations is encouraging, as it is essential to have potent activity in both to yield meaningful clinical benefit in second-line and later GIST. Slide 20 couples the ctDNA data with the swimmer plot. Patients are grouped according to starting dose cohort in descending order from 3 milligrams to 18 milligrams. On the left, we've summarized the ctDNA data from the preceding slide, with arrows indicating whether there was an increase or decrease from baseline for a given mutation by exon on a patient-by-patient basis. This view clearly illustrates the parallel emergence of increased frequency of ctDNA reduction, including both classes of resistance mutations and increased frequency of stable disease at higher doses. For example, in all six patients in cohort four through six, with KIT mutations detected at baseline, reductions in all KIT mutant variants were observed, including activating mutations in, detected in exons 9 and 11, and resistance mutations detected in exons 13, 14, and 17. Notably, these doses are only at most providing 50% of our target exposure. We are excited by these initial results. The emerging molecular data and evidence of disease stabilization in a population that, without treatment, would on average progress within approximately one month, gives us confidence that we are on the right track as we continue to dose escalate THE-630. On the next slide, we'll highlight two of these patient cases. Patient 4 in cohort 2, with an exon 17 mutation detected in ctDNA, and patient 17 in cohort 5, with an exon 13 V654A mutation identified in tumor tissue at baseline, but notably no mutations detected in ctDNA. On slide 21, we focus on two patient cases that are representative of each class of resistance mutations. On the top, we highlight a patient from cohort 2, a heavily pretreated, 6th-line patient with an exon 17 resistance mutation, who started treatment at 4 milligrams. This patient was treated for over eight months with THE-630. The patient had a 12% decrease in target lesions, maintained stable disease at 24 weeks, and had a reduction in mutant allele frequency for both the exon 11 and exon 17 mutations detected at baseline. This patient ultimately increased dose to 9 milligrams before discontinuing therapy. On the bottom, we highlight a patient from cohort 5, treated at 12 milligrams. This patient had two lines of prior therapy and a V654A mutation detected on pre-treatment biopsy, but no mutations detected in ctDNA. This patient had approximately a 10% decrease in target lesions and maintained stable disease at approximately six months and remains on treatment, having recently escalated to 18 milligrams. Moving to slide 22. In conclusion, THE-630 has an encouraging safety profile to date. A PK profile consistent with once daily oral dosing and approximate linearity from 3 milligrams to 18 milligrams, which supports continued dose escalation towards our 100 nanomolar target exposure. Despite being at exposures of, at most, half of those expected to deliver pan-variant KIT activity, we are encouraged to observe ctDNA reductions in activating mutations across both classes of resistance mutations, consistent with preclinical predictions from the PRA, as well as evidence of disease stabilization in a heavily pretreated patient population. Considering all of this, we continue dose escalation towards the target exposure, which we predict from our PRA, will deliver pan-variant activity against all major classes of KIT activating and resistance mutations. With that, I turn the call back to Tim. Thank you, Dave. Moving to slide 24. An important question going into this data readout was whether the preclinical predictions from our PRA regarding mutational coverage would translate into effects in patients. On this slide, we have replotted the data from our PRA on the left, presenting the individual PRA IC50 s for each mutant and overlaid the clinical drug exposures that we observed in each cohort. This allows us to compare the clinical ctDNA effects on individual mutations with our preclinical predictions. As you can see from the three boxes on the right, we have clear evidence that we are observing the expected mutational reductions at the dose levels predicted in our preclinical work. At the lower end of our exposure, we would expect certain mutations in exons 17 and 18, such as those at the D820 position, to be affected. As shown in the first box, that's exactly what we've seen. At higher exposures, we would expect activity against exons 13 and 14 to emerge, and this is particularly apparent in our analysis of V654A, which was detected in the ctDNA of five different patients at different doses, and for which there was a clear dose response that lined up with the PRA predictions. Finally, we would expect the T670I gatekeeper mutation in exon 14 to be knocked down at a higher exposure, which is consistent with what we saw in one patient at an 18 mg dose. We believe this is robust mechanistic evidence that supports our goal of achieving pan-variant inhibition and continued platform de-risking. Turning to slide 25. We believe these first data on THE-630 provide important answers for all three of the questions that we posed at the beginning of this presentation, and put us on the road to success in developing a pan-variant KIT inhibitor for patients with GIST. First, with regards to safety and pharmacokinetics, we have shown that THE-630 has an expected and predictable safety profile, and PK consistent with once daily oral dosing that supports continued dose escalation towards our 100 nanomolar target. Second, we have shown proof of mechanism via evidence of reductions in ctDNA for both major classes of resistance mutations, and importantly, that those reductions are consistent with preclinical predictions from the PRA. Finally, we are encouraged to see that already, these data point to evidence of patient benefit, as demonstrated by stable disease in 8 of 9 patients treated in the higher dose cohorts. To wrap up, on slide 26, these first data form the foundation for our clinical development program for THE-630. We have seen an encouraging safety and PK profile supportive of continued dose escalation and clinical ctDNA reductions in line with our PRA predictions, leading to evidence of stable disease. Currently, we are dosing patients in cohort 7, with the aim of achieving the 100 nanomolar target exposure in cohort 8. In the fourth quarter of this year, we plan to report data from these remaining cohorts, including initial backfilled patients, plus additional data from the currently enrolled cohorts. The subsequent stage of clinical development will evaluate our recommended phase II dose in expansion cohorts of this current trial, in which we aim to fully characterize the activity of THE-630 in various lines of therapy, most importantly, in second-line. We aim to select our recommended phase II dose and begin these expansion cohorts in the first half of next year. These data will then lead to pivotal trials in which we plan to prioritize the development of THE-630 in second-line GIST, where there is the greatest potential for patient benefit, and in fifth-line patients, who represent an urgent and significant medical need. Beyond THE-630, we believe this data set further validates the PRA and our capability at Theseus to discover and develop pan-variant TKIs that have the potential to dramatically improve patient outcomes in targeted oncology by outsmarting cancer resistance. This concludes our prepared remarks. Operator, you may now open the call for questions. Thank you. Ladies and gentlemen, to ask the questions, please press star one one on your telephone. You will then hear a message advising your hand is raised, and then wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Li Watsek with Cantor Fitzgerald. Your line is open. Hi, good afternoon. Thanks for taking my questions and congrats on these initial data. Very exciting. First, looking at the reduced allele frequency observations, can you talk about what your PRA had predicted specifically and how this aligned with what you saw in the trial, especially given the number of different mutations listed here? Based on this consistency, what's giving you increased confidence heading into dose 8? Thanks, Li. Let me begin to answer that question, and then I may ask some of my colleagues to elaborate. I think the data that we've shown today, we feel is certainly in line with what we had predicted from our preclinical PRA work. I think the slide that we showed towards the end of the presentation, exemplifies that, where not only were we seeing effects at the doses generally that we would have predicted, but also that there was a dose response apparent in each of the two cases where we have multiple ends. We feel that that lines up well. With regard to your question on how that portends an eventual cohort 8, I think that bolsters our confidence that the predictions would continue to play out as we move to 100 nanomolar, and we would be looking for stronger and eventually more longitudinal effects on the mutations. Thanks. I know stable disease is considered a positive outcome here in light of the patient population at these dose levels, but can you talk about how you're starting to think about durability and expectations starting to fit into what you'd view as positive here, both from the data you reported today as well as the target dose? Then, you know, just help us by setting the stage for what's expected in this very heavily pretreated patient population. Thank you again. Thanks. I think, to answer that, I'll hand off to Dave, our CMO. I think part of the answer is really thinking about what's the best reference population for this late-stage patient population in terms of expectations of durability. Thanks, Tim, and thanks for the question. First, I think important to point out that, in the absence of treatment, second line and beyond, patients will progress within four weeks to six weeks. We know this from the placebo arms of the randomized trial, cabozantinib, regorafenib, and ripretinib. This was a heavily pretreated population. The all patients were third line plus, 65% of the population had all four prior approved therapies, were fifth line. Starting to see the, well, the emergence of, first, a dose response, as we got to higher doses, at the lower doses, seeing progressive disease at the first scan, and then as we got to higher doses, starting to see the emergence of stable disease, and then prolonged stable disease in those patients who had long enough follow-up, to either four months, or six months, is encouraging, from the perspective of activity, you know, clearly matching up with the dose response to, from the ctDNA perspective. Important to highlight, this is at most, 50% of our target exposure. Even seeing that, meaningful clinical activity. lower at these doses, portends well for, what we could expect to see at target. Thank you. Thank you. Please stand by for our next question. Our next question comes from the line of Andrew Berens with SVB. Sir, your line is open. It looks like we lost Andrew. Please stand by for our next question. Our next question comes from the line of Bradley Canino with Stifel. Your line is open. Hey, good afternoon, and nice to see this translational step. Maybe the biggest congrats on condensing all the technical details in the slides. You probably covered this in the deck, but to try to tie some of this early PD effect to the clinical effect, you had that one outlier patient in the lower dose cohorts with the N822K mutation that had a durable stable disease response. Can you tie that to what Cavg in the PRA hit in IC50 s for that mutation? Did this patient obtain an exposure level that matched or exceeded that Cavg? Brad, thank you for that question. Multifaceted question and, an important one. Firstly, it's obviously gratifying to see durable, stable disease like that in a pretreated patient. We did break out a little bit of the experience of that patient in terms of the serial scans on the anecdote slide, I forget the number. But let me pass your PK question on the exposure in that patient over to Dave, and then ask Vic, our CSO, to talk a little bit about our ctDNA experience in that patient. Thanks, Tim. As you can see from the PK slide 17 cohorts for the 4 milligram cohort, had about on average a 10 nanomolar steady-state C.av. That could put into context the, you know, the exposure that that patient was seeing, and maybe that can elucidate the PRA data. Yep. Again, thanks for that question. I think we're pleased to say overall, we've certainly seen as we highlighted in several examples, the PRA being predictive of the dose response required to inhibit specific mutations. I think you point out one of maybe two notable examples where we started seeing ctDNA decreases, even though we weren't at our target, PRA-predicted concentration. I think that could possibly be due to the fact that these resistance mutations exist in the context of different activating mutations. We don't have a precise PRA number for every mutation, but so far, again, it seems like we've erred on the side, at least in those examples, of being able to see ctDNA decreases and the one patient you mentioned, seem to be of durable benefit, with what might be predicted based on the specific mutation looked at as a partial inhibition. Appreciate those comments. Maybe another follow-up on this, because your PRA always suggested you'd most likely see the initial PD and activity in the exon 17 and 18 patients, and at higher exposures, you'd start to kick off the exon 13 and 14. When I look at slide 18 and 19, you do have an 18 mg patient with exon 13 and 14, including the V654A, and the drug pushed that to undetectable after treatment, yet the patient still progressed on the first scan. I guess, what do you think explains this discordant effect? And are there any other details on that patient you have that could explain the progression? Thank you. Thanks, Brad. Yeah, you've zeroed in on a really interesting case. Let me ask Dave to elaborate on the background for that patient. Thanks, Brad, for the question. In fact, yes, we didn't highlight this in the presentation, but it's in the footnote. That patient had a pretty complex mutational profile. In addition to the exon 13 and exon 14 mutations that we show as decreasing in this, in the waterfall figure, the patient also had alterations in PIK3CA, PDGFRA, FGFR1, MYC, and HER2. This is a pretty complex patient, and those other resistance mechanisms or alterations could explain the progression in this patient. Brad, I would just add that I think this is consistent with the way we've tried to articulate the role, the interpretation of ctDNA reductions of mutations, in that we view those as necessary, but not sufficient to translate into clinical benefit. We know that there may be other things going on in a patient, either KIT related or unrelated, but we know that if we are showing that the molecule can, so to speak, walk the walk from a KIT PD point of view, then we are validating that primary mechanism of activity. Very helpful. Thank you, congrats again. Thanks. Thank you. Please stand by for our next question. Our next question comes from the line of Andrew Berens with SVB. Your line is open. Hi. Thanks, thanks for the call, guys. Congrats on the first clinical data. Wondering if you have any ctDNA data on the patients that progressed while they were on the study. Did they progress because their baseline genetic mutational pattern was not suppressed enough with the doses they were being treated? Did the tumor actually mutate to a different genetic pattern? Then I have another question on the grade 5 adverse event after that one. Sure. In general, we don't yet have all of the longitudinal data we need to answer that question on whether we see additional mutations kind of explaining the outcomes. In some cases, for example, we did start to see in the later stages of the exemplified patient with the N822 mutation, had 8 months, we did start to see 1 other mutation come out, but it's really difficult to tie that in with any particular outcome. That'll certainly be something that we look for as we get more mature data with more Ns and can really look at trends. Okay. happy to. And, uh- Go ahead on the grade five. Yeah. I know you gave some clinical background on the patient, but just a couple other questions on that. Besides hyperlipidemia, did she have any additional risk factors? I think you said she had an asymptomatic PE at baseline. Was that actually being treated with anticoagulants? That's right. It was being treated? Yep. Could you clarify, she was being treated with anticoagulants? She was, yeah. It was, she was being treated with anticoagulants when they detected it on the screening scan. Okay. Okay. Then when she was on THE-630, did she become hypertensive? She did not. You know, overall, we don't see strong evidence for a causal link between this event and THE-630, particularly given the lack of emergence of additional events at much higher exposures. We point out, of course, that there's a very low exposure for this patient, 1, the anti-MI event at cycle 1, day 1. But as you note, heavily pre-treated patient with hyperlipidemia and the asymptomatic PE at baseline there. Just a question, isn't a patient on coagulation like that, I mean, wouldn't that be somebody that would generally be screened out of a clinical trial program? No, this, for an asymptomatic PE that was incidental, that wasn't an exclusion criteria, wouldn't traditionally necessarily be as long as other criteria are met. Patient wasn't at all symptomatic, again, from the subsequent segmental PE that was that was identified. Okay. Thanks, and congrats again. Thanks, Andy. Thank you. Please stand by for our next question. Our next question comes from the line of Maury Raycroft with Jefferies. Your line is open. Hi, congrats on seeing your PRA data translate in the initial data update here, and thanks for taking my questions. You highlighted that the two patients that were intra-dose escalated, did you see deepening on ctDNA in these patients when you increased the dose? Just wondering if any additional patients were dose escalated, and what is your criteria for dose escalating? Thanks, Maury, for those questions. Let me first update to go through the criteria and timing for intrapatient dose escalation decisions. I'll ask Vic to comment on your ctDNA question, although, we'll comment that we don't really have that experience yet with longitudinal ctDNA to, to properly evaluate. Dave? Got it. Sure. Thanks, Maury. The criteria for dose, intrapatient dose escalation were essentially that the higher dose had been shown to be safe, meaning had passed the DLT observation period, as we dose escalated, and that the patient to be escalated, was tolerating their current dose without any need for dose reduction, and then made it through to the final PK draw, which was the beginning of cycle three. Regarding the longitudinal question, Again, as Tim mentioned, we haven't looked at it in depth and don't really have enough patient data to comment precisely. I could certainly say that anecdotally, we've seen both examples of a dose escalation where the allele frequency was further increased, it decreased, it was increased, and the opposite, but it's really a very small end. Sorry, I neglected to answer your other question, which was, are there dose escalated patients in this data set? The answer is yes. For instance, that patient who was on for over eight months started at 4 milligrams, had ultimately dose escalated to 9 milligrams. The patients at 12 milligrams, starting at 12 milligrams and 9 milligrams, who remain on study, have dose escalated to 18 milligrams. Got it. Thanks for taking that question. For slide 17, the exposure versus dose curve, it seems like you could be seeing some plateauing in the Cavg going from 12 mg to 18 mg. I'm also seeing that in the 12 mg dose in the mean steady figure on the left side, it has higher error bars. Just checking whether you're seeing some plateauing or if anything unique was happening with the 12 mg dose. Yeah. Thanks, Maury. That's an important question and understandable one based on those numerically similar mean Cavg for cohorts 5 and 6, and the variability in cohort 5. We, we don't really see that as indicating anything along the lines of plateauing. Let me, let me ask Dave to go into that in a bit more detail. Sure. Thanks, Maury, for the question. You know, right to point out and hone in on the variability we saw in cohort five, which is a clear outlier here. Even within that data, if you look at the overall trend of the data, we see approximate linearity with a high R squared of 0.88. So we're quite confident that based on this data, it projects to still being on the right track of 100 nanomole Cavg being achieved at by 40 milligrams, which is consistent, of course, with the guidance we've given. Yeah, just a note about aside from that outlier cohort, the other cohorts have been quite in line in terms of variability with other TKIs, both within the GIST and non-GIST space. We're quite comfortable with this data and the linearity that it appears to show. Got it. Okay. Congrats again. Thank you. As a reminder, ladies and gentlemen, that's star one one to ask the question. Please stand by for our next question. Our next question comes from the line of Ami Fadia with Needham & Company. Your line is open. Hi, good afternoon. Congrats on the nice translation data here. I wanted to know if, you know, these data sort of give you enough confidence that you will be able to achieve the 100 nanomolar level, as you go up in dose, to 40 milligram from there. If you could maybe help understand if, say, for example, on slide number 18, for patient number 16, who eventually started to see progression in disease, do you have ctDNA data for that patient at that time point, to see what mutations might have sort of developed at that time point? Thanks, Ami. Regarding your first question on the how we see this giving us confidence to get to 100 nanomole, I think we do overall see this as supportive of continued dose escalation. Both from the PK point of view, from the safety and tolerability point of view, as well as seeing that there's a nice tie-in with the emerging, if you like, PD data from ctDNA and clinical benefit. All of that seems to be lining up quite nicely and pointing to both the feasibility and the promise of getting to 100 nanomole, which, as you see, we're projecting in cohort A. Regarding the specific question on the patient who discontinued, and whether we have any ctDNA correlative information on that, I think Vic kind of addressed that earlier, that we don't really feel as if we have enough strength or depth of data to be able to interpret any one particular set of mutational changes. In many cases, we don't actually have, you know, sometimes the DNA, in later times, is we don't, we weren't able to get it. At this point, that's why we really wanted to focus on what is the initial effect of a given dose on ctDNA, reflected by best response mean allele reduction, and really tie that in to understanding the initial effect on the disease, as opposed to trying to extrapolate what might be going on as patients fail. Unfortunately, as we mentioned, it looks as if many of these patients do have complex backgrounds in addition to the KIT mutation. Thank you. Just one other quick question. It was mentioned that there were five grade 3 or greater adverse events in groups 1 and 2. I presume that the fourth one was the grade 5 event. What was the fifth one? Yes, I'll let Dave go into that. It is, the information is on that slide, but in a very small footnote. Dave can elaborate on that. Yeah. That's right. I'm now... The safety slide 16. As you rightly point out, overall, we saw 5 grade 3 or greater treatment-related events. Three are shown in the slide itself, given the frequency overall of certain events. The 4th was the grade 5 MI, and then the 5th, not depicted because of the lower frequency of overall, was a grade 3 asymptomatic ALT elevation. Thank you. Thank you. I'm showing no further questions in the queue. I will now like to turn the call back over to Tim for closing remarks. Thank you all for joining us today and for your interest in Theseus. We look forward to giving additional updates on THE-630 and our pipeline of oncology therapies in the future. Thank you, and have a good evening. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.