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Good morning, and welcome to CASIA Therapeutics Corporate Update Call. All participants are currently in a listen-only mode. Following the prepared remarks, we'll open the line for questions. Please note that today's call is being recorded. Before we begin, I would like to direct your attention to the forward-looking statements disclaimer displayed on the screen. We encourage you to review this information, which applies to the statements made during today's presentation. I would now like to turn the call over to Dr. John Friend, Chief Executive Officer. All right. Good morning, everybody, and thank you for joining us today. On behalf of Cozy Therapeutics, I appreciate your time to participate in today's investor call. I'm joined today by our Chief Scientist, Professor Sudha Rao. Together, we'll provide a corporate and clinical update following several recent announcements across the PECS-ALCID program, including our emerging data in triple negative breast cancer, our planned expansion into HR positive HER2-negative breast cancer, and our colorectal cancer program. More importantly, we want to use today's call to connect these developments and provide some perspective on what we believe are emerging clinical and translational data and telling us about PACS and how that is shaping our development strategy going forward. With that, let's get started. So, today we're going to provide an update about Paxalysib, an investment framework. Then we're gonna go into the new data with regard to triple negative breast, our program in HR positive, early stage triple negative breasts, but also PMMR colorectal cancer. We're gonna talk a little bit more as far as the clinical trial expansions and then recap and then summary next steps. The next slide. So as you know, Paxilisib or Paxilizib is our lead stage asset. This is an oral, once-a-day, blood-brain-penetrant small molecule. It is a pan-dual PI3K mTOR inhibitor with epigenetic and immunomodulatory activity. This is a Genentech molecule that we've been in development and work in development across glioblastoma, neuro-oncology, pediatric brain cancer, but now especially transitioning and providing a really solid stake in the ground in terms of development in breast cancer as well as now colorectal cancer. Let's discuss the formulation. This is an oral once a day. It is a key mechanism in terms of immunotherapy resistance as well at the ability to cross the blood-brain barrier. A couple of the key sort of differentiating features. We talked about the mechanism of action. This hits all the major isoforms. It is a traditional dual PI3K mTOR inhibitor with some additive clinical benefits that we'll be talking to in significant detail. IPY, as you see here. As I mentioned, the initial development strategy for PAX was in a glioblastoma. We put several other shots on goal in terms of pediatric brain cancer, but also brain metastasis patients. We've dosed over 550 patients to date, so we have a really solid handle from a safety and tolerability. After several years working with Professor Sudha Rao in terms of understanding how PACS could work even outside of brain cancer, but in particular breast cancer, we launched a Phase 1B trial in Stage 4 triple negative breast last year. The trial schema you see here on the next slide, this is a Phase 2B multi-center open label randomized trial, evaluating PACS in combination with standard of care. So standard of care in stage 4 triple negative breast consists of checkpoint inhibitor, pembrolizumab, plus chemo. So we are adding PACS as an add-on therapy to the standard of care. So we are evaluating PACs at very low doses. So PACS at 15 milligram and PACS at 30 milligram in combination with standard of care in stage four triple negative breast frontline setting. You see in terms of total enrollment target is 36 patients, and we'll be providing some updates as far as the preliminary updates on the first few patients. Primary and secondary endpoints are what you would expect in the phase one study being safety and tolerability in this new combination, but also importantly would be secondary end points, which are biomarkers that Sudha will be talking about at some length today, but also the typical response rates, radiographic response rates progression-free survival, and overall survival. The next slide. Today, the data updates that we will be discussing are aligned with our recent press releases over the past few days, and we'll be providing updates on six patients' dose with Pax, or Paxilisib, in the upfront stage 4 triple negative breast setting, whereby all six patients, we have shown drastic immune restoration. By immune restoration, we mean the ability to see drastic reductions in terminally exhausted CD8 T cells, which we'll talk about more, but also in all six patients showing the ability to target these previously untargetable circulating tumor cell clusters, and we'll talk more about those. In addition to radiographic responses, where we show 100% clinical benefit response, CBR, or clinical benefit, response is a characterization of a drug in terms of all patients having a complete response, partial response, or stable disease. And we'll talk more about each of these six patients. We're also going to look at one particular patient who had a complete metabolic response and look at her over time, her scans, and layer that on with her biomarkers, i.e. her response in terms of reductions in terminally exhausted T-cells, as well as reductions in these metastatic seeders, these circulating tumor cell clusters. We're super excited to also provide updates as far as our expansion into HR-positive HER2-negative breast cancer, early-stage triple-negator breast, as well as MFFP-MMR colorectal cancer. And we'll talk more about that patient population as well. We're not going to focus on the commercial viability and the market potential. We all know these are huge market potentials. going to focus on the science as well as the data because we believe that's what we've been focusing on for the past several years and we believe, that will add tremendous value to both our, you know, our patients but also our shareholders. The next slide, we'll be talking and I'll ask Professor Suda Rao to go through the next few slides and then we'll jump into additional data as well as the expansion. So, Sudha, would you review this slide, please? So, one of the key highlights or focuses of our clinical trial has been a longitudinal liquid biopsy analysis in our clinical predictive facilities where we've been able to monitor, for one of first times, both the CTC clusters and the terminally exhausted T cells in the blood in real time and dynamically. And importantly, these are the seeders of metastases that standard of care immunotherapy or chemotherapy cannot target. Now, the key take-home message of the slide, and I've been in this field for more than a decade, is that this represents one of the first times clinically that we are able to dual target both the CTC clusters and the terminally exhausted T cells. So if I can draw you to the slide, to the panel one, in baseline, you see these are patients with high metastatic burden. The black dots represent the CCC clusters. What is quite exciting here is that in six out of our six patients, within a few weeks of treatment, we see a dramatic reduction in these CTC clusters. If I can then draw you to panel three, what we see simultaneously in the same blood within one to three weeks of treatment is a reduction in the terminally exhausted T-cells. So these are the exhausted T cells that immunotherapy cannot touch. Importantly, the total T cell pool remains the same. We are not killing the T cells. Instead, what we're observing for one of the first times is selective rewiring of these terminally exhausted T cells to distinct phenotypes. Next slide, please. What we're observant of is that the T cell pools are not killable. What we are observing here, importantly, is that we see, firstly, an increase in the affected T cells, these are the killer cells. which are required to attack the tumor. Secondly, what we're observing is an increase in cancer immune immunity, which means that the cancer cells themselves become visible to the immune system. But thirdly, we see increase in immune memory, suggesting that we're likely to have durable, sustained responses. Next slide, please. This is an example, really, to show the depth at which we were able to undertake a multimodal analysis using one of our patients who's had complete response as an example. Now, the clear take-home message of this slide is that our early efficacy readouts with our liquid biopsy analysis indeed is able to predict what we observe in our radiographic or metabolic scans. So, if I can draw you to the left of the the slide. At baseline, the patient has a high metastatic burden. In parallel to that, the patient had a high CTC cluster burden, a high T-cell exhaustion burden. With a few drops of blood, we're able to look at the patient's own immune system, and the patient-owned immune system is poor at this stage. Within two weeks of our treatment, there's a reduction in CTC clusters, reduction in terminally exhausted T cells, and the patient's immune system starts to get restored. Within four months, the patient starts to have complete response as far as the metabolic scans are observed. Within subsequent blood analysis, thepatient then ultimately has no CTC clusters visible at all, and an immune system is completely restored. And as of August, the patient is of complete response. So this is the depth at which we've been able to undertake a multimodal liquid analysis. And importantly, this is giving us a real insight of the mode of action as we move forward into the patient responses. Thanks, Suda. Great overview. Again, And these early signals are super exciting and we'll be expecting and anticipating this longitudinal biomarker assay across all the future enrolled patients, but also across our expansions into the other indications. So the next slide shows our individual patient responses. So you see here listed all six patients, whereby we have two patients at 15 milligram and four patients that have been dosed at 30 milligram. You can see within the 15 milligram, we have one patient with a partial response and one patient with stable disease. And then within the 30 milligram, We have three patients with partial responses and then the one patient with a complete metabolic response that Sudha just took you through. As one would expect with a stage four triple negative breast patient population trial, that these patients have a number of target lesions, so their radiographic tumor burden, as well as, as you saw, their blood burden in terms of circling tumor cell clusters is pretty extensive, whereby the target lesions can be soft tissue, they can be organs, they Can be bone, and they can also be CNS or brain target lesiones, as Well, as You can see, patients are showing some nice early preliminary responses to all of these. The time to response also, I'll bring you to that far column on the right. We're seeing at the earliest radiographic assessment, so at approximately three months, we're showing some radiographic responses, right? So in terms of, as Suda walked you through, the circulating tumor cell cluster reductions, but also drastic reductions in terminally exhausted T cells, that this could also be playing a part in terms OF the radiographic responses that we're seeing here. The next slide, again, we look at all adverse events, grade three or higher are automatically considered serious adverse events. And so this is as of August 1st, looking at serious adverse effects. We have no Paxalicib-related serious adverse events. Remember, this is in combination with immunotherapy and chemo. So we do have a number of adverse events that, as you see listed here, the ones unrelated to Pax are related to chemo or immunotherapy in particular, pembrolizumab. But, you know, importantly is that we've not shown any sort of grade three or grade four stomatitis mucositis. So we're very, very encouraged with the dose selection. Remember, we're using 15 and 30 milligram once a day in this combination. That's quite a bit different than what we've used in the glioblastoma trials and as well as the weight-based assessments in pediatric brain cancer, whereby that target dose is around 60 milligram once a day. So with this lower dose that's been able to target the epigenetic as well as our own immune microenvironment, that this dose is more effective at the lower at 15 and 30 than we would expect at the 60 milligram. So very exciting from a safety and tolerability perspective. The next slide. This is just a quick summary. From a clinical perspective, we've shown selective reinvigoration, i.e. all patients showing drastic reductions in terminally exhausted T cells with a median at approximately three weeks of about half, so about 51% reduction. But also importantly, as Professor Sudha Rao had mentioned, that the total number of T cells remains the same. So it isn't like we're selectively reducing these dysfunctional T-cells that they're being reprogrammed or rewired. On top of that, looking at the metastatic seeders, these circulating tumor cell clusters that we know PEMBRO, chemo, and others can't touch, that they have no effect. They do well with the highly progressing and proliferating cancer cells, but in terms of these fairly dormant cells and clusters, they have no effect, and you can see here we show a drastic reduction and disruptive effect in these CTC clusters. The next slide. So, excitingly, we have not been resting on our laurels. We've obviously been pushing in terms of understanding how PAX works in stage 4 triple negative breast, but also we've been evaluating other potential opportunities for PAX because we believe this not just being a PI3K mTOR inhibitor with, you know, kinase inhibition. We are strongly believers that Pax adds something very unique and different on top of being a kinase PI3K inhibitor. And with that, the three that you see here in terms of HR positive, HER2 negative, early stage triple negative breast, as well as colorectal cancer were top on our list to evaluate. As you'll see as we go through the next couple of slides from an IP perspective, We fully ring-fenced all of these, and we're aggressively moving across the board into these programs. Sudha, the next few slides, would you go into the data, preclinical data, please? So, importantly, as John has mentioned, innovation has been backed up by compelling new data, which has really further strengthened our IP position and, importantly, has unlocked new avenues for differentiation and biomarker discovery in terms of clinical utility. In terms of the HR-positive situation, importantly, we've done head-to-head benchmarking experiments comparing GED-I with other PI3K-M2 and PI3M inhibitors. And importantly, what we have found is something very unexpected, that this is not a class effect. So just to take you one step back, I did my PhD in this area, but to target the entire disease aspect of the PI3-M3 pathway, you need to target the canonical, which is the cytoplasmic enzymatic traditional activity, but you also need to importantly target the non-canonical pathway, which is the nuclear epigenetic resistance pathway. It's the nuclear epidemic resistance pathway, which is critical if you want to target resistance and metastasis. And what we found for the first time is that PAX is superior at targeting the nuclear epigenetic axis. DEDA actually enriches for this nuclear epogenetic axis, and importantly, we know why PAX is unique. The features that PAX has to allow it to cross the blood-brain barrier, importantly, have been hijacked to allow IT to now also be superior at crossing the nuclear pool and disrupt this nuclear epygenetic axis and importantly what we've done is we've developed a novel biomarker to detect this nuclear epigenetic axis. We've developed our own tissue IHC test as well as a blood test. And what's really exciting here is that using hundreds of patients that we've profiled bioinformatically, we show that those patients who are enriched in this nuclear-epigenetic switch are the ones who have poor survival in the context of the HR-positive situation, which means that we can go ahead into a clinical trial where we're able to enrich for certain patient populations. Next slide, please. So this is really our early data to show that when we benchmark together versus PACS, side-by-side comparison in terms of targeting the primary tumor activity, they're identical. Where PACS is unique is that it's able to target the seeders of metastases, and the metastatic burden. Importantly, our extensive preclinical work has shown that we see no toxicity, no decrease in body weight. We have a blinded pathologist who has shown there is no evidence of any stomatitis or any hyperglycemia in any of our preclINICAL models. Next slide, please. What is really exciting here is that a trial at the moment is in stage 14 BC. What we've shown for the first time is that we believe we can advance now to an early stage 2, 3B setting. What we've shown for the first time here is that PAX is able to significantly inhibit local, regional, and distal metastases, either in combination with chemotherapy or as a triple with immunotherapy as well for the 1st time. Importantly, we understand the biomarkers towards this that we believe that we can use for further stratification and liquid biopsy analysis as we move into a stage 2, 3B setting. Next slide, please. This is pretty exciting here. This shows that for the first time in a PMMR CRC setting, Paxilisib is able to work as a monotherapy, suggesting it's not able to work in the same fashion in every disease setting. As you know, PMMR-CRC is a major unmet need. There's few therapeutic options globally, and immunotherapy doesn't work. And what we show for the first time is that Paxilisib in our preclinical models that we have developed works as a monotherapy, but importantly, it's further inhibited when you combine it with immunotherapy. Importantly, we've developed our own liquid biopsy analysis here where we can monitor the fetus of metastases in PMMR-CRC for the first time, allowing us to advance, again, with a very precision medicine approach into a clinical trial situation. Next slide. As you can imagine, as we said on the slides, all of this has been provisional patents across all three of these indications and a number of other provisional patents that we're expecting to file here over the next six or nine months on top of that, just to fully ring fence how we believe PACS is working across these indications. But these sorts of preclinical programs, both in vitro, in vivo, and ex vivo blood samples coming from a number of these patient population indications are great unless you can, you know, they're not fantastic unless you can create that and move into clinical trials, and that's what you see here on this slide. So, we are imminently expanding our ongoing PACS ABC clinical trial in stage 4 triple negative breast to incorporate the far left, looking at PACS in combination with fulvestrant plus palbociclin or CDK4-6 and pretreated HR-positive HER2-negative. We'll be evaluating PACs, as you see, in those doses of 15 and 30 milligram once a day on top of standard of care for these patients, which is Fulvestrant plus CDK4-6. And we're also going to be including an in-study comparator, so looking at Fulvestrant as your in-Study comparitor. So we're very, very excited and be moving forward, and we'll talk about next steps and when to anticipate patients in full enrollment in the next couple slides. On top of that, also evaluating PACS in the adjuvant setting, right, in earlier stage triple negative breast. So this is additive, as Sudha had mentioned, on top of the stage four evaluation. So, this is adding Pax to standard of care, which is pembrolizumab plus capecitabine and other chemotherapy in high-risk residual disease stage 2B, stage 3. So very, very excited. And again, same dosing evaluating Pax at these lower 15 and 30 milligram doses. Lastly, but not less importantly, would be evaluating Pax in MSS-PMMR colorectal cancer. And as Tudor had mentioned, this is a huge unmet need. The majority of advanced metastatic colorextal patients are not responsive to immunotherapy, have not been shown to be responsive to immune therapy. And as you've seen, Pax works a little bit differently, as one would expect, but we're really understanding and moving it forward from a science, but understanding how we can be beneficial for these patients. And so we'll be evaluating PAX both as monotherapy as well as additive with PAX plus pembrolizumab, as you saw with the previous slides. On top of that, this will also have an in-study comparator with standard of care. The PMMR colorectal is actually going to be a standalone phase two trial that we are initiating and expect to have first patient in in the first quarter of next year next slide recap um so we're extremely excited within the stage four triple negative breast patient population where we've shown um you know the bench to bedside translation of of the extensive pre-clinical program that we've developed here over the last few years whereby pax has been able to show with the additive to standard of care ability to drastically reduce terminally exhausted CD8 T cells, right, those cytotoxic cells that are out there searching and killing cancer, as well as the ability of all patients showing drastic reductions in circulating tumor cell clusters, these metastatic seeders that we know have not been effectively targeted with immunotherapy, other target therapies, but also chemo. And then on top of that, some preliminary radiographic responses across all patients with one complete response, four partial responses, and one stable disease. We're very excited now with the financing also to be moving forward in terms of the trials you saw in that last slide. The next slide, please. So again, as we bring the presentation portion of today's call to a close, I want to leave you with a few takeaways. So first, PAX is a molecule with a substantial clinical foundation. Again, as we mentioned, more than 550 adult and pediatric patients have now been treated across a multiple of clinical programs, giving us a significant body of experience with its safety, tolerability, and pharmacology. What has changed and what I think is particularly important is our understanding of what this molecule may be capable of doing. The emerging clinical and translational data that we've talked about today suggest Paxalicid activity may extend beyond conventional PI3K mTOR pathway inhibition. We're now seeing evidence across several dimensions of cancer biology, including tumor control, treatment resistance, immune exhaustion, and metastatic dissemination. That evolving understanding is directly driving the expansion of our development strategy. In triple negative breast, we'll continue to build on the clinical and translational findings we've discussed today. We're expanding into HR-positive HER2-negative breast cancer, where treatment-resistant represents a significant unmet need. And in PMMR colorectal cancer, we're taking this biology into a setting where the overwhelming majority of patients historically derive little to no benefit from immunotherapy. At the same time, we continue to advance our CNS programs, including our discussions regarding anglioblastoma, other pediatric brain cancers, but all the other neuroscience programs on top of this. So when you look at this slide, I think it's an important point to not simply the number of programs. It is that each of these programs gives us an opportunity to test a different dimension of the biology we are seeing with PACS and potentially translate the biology into meaningful clinical benefit for patients. And with the capital from our recent financing, we now have the resources to execute on that strategy. With that, I believe we can open up to questions. Thank you. We'll now be conducting a question and answer session. If you'd like to ask a question today, you may press star 1 from your telephone keypad and a confirmation tone to indicate your line is in the question queue. You may press start 2 if you'd like to withdraw your question from the queue. For participants using speaker equipment, It may be necessary to pick up your handset before pressing the star keys. One moment, please, while we poll for questions. One second, that's star one. Thank you. Thank you, our first question comes from the line of Kambiz Yazdi with BTIG. Please receive your questions. Morning, theme. Congratulations on the TNBC data and HACS development expansion. Three questions for me this morning on the different indications. First, Paxilisib's therapeutic effect may extend beyond the cytoplasmic PI3K mTOR inhibition. Can you help us understand the mechanistic basis for that hypothesis? What specifically about Pax's biology enables the CDC cluster disruption and the T cell exhaustion reversal you're observing in TNBC? Second question. Oh, sorry, I'll let you answer, and then I'll ask the two follow-ups. Yeah, let's do that, Kavis. Yeah, thank you for that question. Sudha, would you mind, let us take each one and then go from there. Yes. Yeah, thanks for the question. So what we know is that with the PR3K mTL pathway, there's two aspects to target the entire pathway. So we've known this for a long time. One is the cytoplasmic enzymatic pathway, and the second is there's an independent nuclear PI3K mTL pathway, which we call the non-canonical pathway, which mediates the epigenetic mechanism. So what we found is that initially, which we didn't expect, is that PaxLutic was superior at targeting this nuclear epigenetics axis of the nuclear complex. So we went and did extensive structural analysis, computational analysis, you name it. We did experiments around it. And what we found was that Paxilisib, the size of the Paxilizib allows it to penetrate the nuclear pool. But importantly, all of the features, its structural features that allow it to cross the blood-brain barrier seem to have been utilized to allow it also cross the nuclear poor, which is pretty exciting. And so by doing so, it is able to then disrupt the nuclear complex and then prevent the resistance axis. So we've done extensive analysis in patient-derived samples, in cell lines, and it's evolving. We're actually going to present this work at the San Antonio Breast as well, because it's a very, very novel area that is opening up in terms of this PR3K-N2 axis that we wouldn't have anticipated. And we've also ring-fenced this in terms of IP, but also it's allowed us to develop our own biomarker as we move into any clinical trials as well, which is pretty exciting. And following up on that, which was my second question, Suda, you mentioned you've identified a biomarkER for this nuclear genetic access, and that applies to HR-positive or to negative patients. Maybe, Suta or John, will you be looking to enrich for these patients in the three-arm expansion. I'll jump in, Suda, and then you also talk, obviously, from an IP perspective. I think it's important that we obviously have fully ring-fenced that. Yes, I believe that that opportunity for us to enrich the ongoing, well, the soon-to-be ongoing clinical trial and expansion into HR-positive will be extremely important. As I mentioned, you know, we'll be enrolling a number of patients across all of those, so a minimum of 18 per arm across all three of those arms. So we will have extensive data, right? This will be the first time evaluating PACS in combination with Fulvestrin plus CDK4-6. And then the potential of utilizing this novel biomarker to potentially show responders or super responders or very deep, durable responders will then enrich accordingly with the next trial. But yes, I don't know, Sudha, if you have any other comments. No, I mean, just to say that it's incredible that we actually have a standard tissue ISC test so we can stratify patients, but also we have a liquid biopsy test that we can monitor as we go as well to understand the efficacy. And we know already that 40% of patients in terms of large numbers of bioinformatic analysis that we've done, the ones that have this switch are the ones which are associated with poor survival in HR-positive, so there's a large percentage that we'll be capturing, so enriching for that population, which is very important in this space. Great. Thank you so much. And my last question, what gives the team conviction to advance to phase two and collect electoral cancer specifically? What is it about Pax's mechanism that you believe is reprogramming immune visibility in these tumors? Great question. Suda, take that, please. So this is incredible, actually. We wouldn't have anticipated it. So what we're finding, we've actually developed our own preclinical PMMR CRC model. And also we have access to, importantly, patient-derived samples as well. And what we're finding is that within the PMMR situation, that PAX is able to rewire these cancer cells, this unique subset of cancer cells. I can't say too much because we're actually trying to ring fencing this in terms of IP as well. But we've identified a unique metastatic cancer cells that become immune visible by PAX. And that immune visibility then allows then the immunotherapy to work more effectively. It's a brand-new mechanism that we've identified. We're actually in the process of ring-fencing VIP in this space. That's a great question, Kambiz. I'll just add to what Suda had mentioned in terms of our conviction. So as we mentioned, we've shown extensive both in vitro, in vivo, ex vivo, And now clinical data showing PAX in combination with PEMBRO, at least in stage four triple negative breaths, is, you know, A, you know, safe and tolerated, but also showing clinical activity across both biomarkers and radiographically from that perspective. We have extensive safety and tolerability with PAX's monotherapy across a wide range of indications. So in terms of moving forward with the proposed schema that we put a few slides ago, we feel very, very comfortable and highly encouraged that we'll be able to, A, enroll these third line patients, which is a huge, huge unmet need. Although we've had some movement in terms of recently approved agents over the past couple of years in the third line setting, really nothing is moving the needle in terms OF, you know, the resistance, but also the progression of these patients. So in terms Of moving into phase two, we feel highly, highly confident from a safety tolerability but also hopefully and potentially some clinical benefits across the board thank you so much i'll hop back in the queue thanks companies great questions the next questions are from the line of chad messer with lake street capital should see your questions oh great thanks for taking my question and and congrats on the data and the and the financing um I am just really fascinated by the emerging data on mechanism here, this epigenetic reprogramming. The idea that you can reverse T cell exhaustion is so incredibly powerful. Do you have any evidence that this effect kind of outlasts some level of therapeutic dosing, that we've truly reversed something in T cells? or perhaps it is just something that requires a constant, you know, constant effect from the drug. I mean, either way, fascinating. I'm just wondering if you've looked at that. Okay, I'll start, and then, John, maybe you can finish off the thing. So it is incredibly exciting. I think I've been in this field. I'm an epigeneticist and an immunologist, and to have a terminally exhausted T cells are what importantly that immunotherapy cannot touch and I have not seen any treatments clinically so far that have been able to convert those terminally exhaustive T cells to a form which are called progenitor exhausted T cells that immunotherapy can work and we're able to do that. The fact that we're able to do that. And the fact that we've got immune memory, now that's the bit that is pretty exciting. The immune memory suggests that we have got durable responses, but that would also mean that the responses are going to be lasting. So I think really in terms of your question, in terms of the dosing, really the trials will tell us. I mean, that's a power of a longitudinal analysis, The fact that we were able to be sampling every three weeks in these patients, and we're going to really get a handle on what represents stable disease, what represents responsiveness, what what represents not responsiveness and whether the generation of immune memory happens or not. And that's going to be really give us a handle as we advance into phase two and so forth in terms of what that would mean like in dosing. So the fact that we can rewire these thermally exhausted T cells, but the fact that we're generating immune memory is pretty exciting, I think. You hear the passion as well as the excitement in our voice, too, because this is something that we haven't seen or even thought was possible, and now not just from a preclinical and ex vivo blood samples, but also showing in a clinical trial. I share that excitement with you, Chad. But I too, obviously, looking at across all these other expansions, will obviously be employing and looking at all these patients at regular time points, approximately every three weeks in terms of blood work. Because the bottom line is, would I love to see 100% responses? Of course. Do I think it's realistic with stage four triple negative breast or third line advanced metastatic CRC? No, but that's where us assessing both tissue but also blood that we'll be able to identify why, where, can we pre-identify why these, you know, are these patients starting to progress before the scans, right? Scans take usually three, six months. These blood, you know, these blood samples and our longitudinal biomarker, we may be able to show earlier these super responders and then obviously then to be able to enrich and look at why they were and understanding not, you know, from a molecular, from a single cell, from a protein level, why they're progressing, or why they are showing tremendous responses. But no, it's a fantastic question, and I would expect we'll have additional, I know we'll have additional data throughout this year and well into 2027. And as Sudha mentioned, you know, that's why the target enrollment is 36, right? We need to show, so we'll add 18 patients at 15, 18 patients that 30 milligram, and we can pivot based off if we're showing a dose response, we can add more patients or, you know, convert patients to whatever that optimized dose is along the way. No, I mean, truly the implications of the work you're doing here are fascinating. And if this is half as good in the real world as it's starting to look on paper, it's truly game-changing. Maybe just one more sort of practical near-term kind of follow-up here. On the, if I'm, you know, just reading through some of your filings, the Series A warrants are triggered by a data readout that is expected second half of 27. I just want to confirm, I believe it's 12 patients and six months of PFS. Can you just explain what the exact trigger is there for that quote top line readout? Because I don't think it's all the patients, right? No, it's not. So it's triggered with at least 12 patients with essentially it's PFS6, right, so it's patients with at last data associated with six months progression-free survival. And so we would expect, based off the enrollment strategy, but also expansion of the trial, which actually we are looking to expand outside of Australia, expect to have the first country up and running in the next two and a half months. But we'll have, so that trigger is based off of 12 patients with at least progression-free survival up to about six months, which is essentially PFS6. we will have obviously a part of that will also be safety and tolerability i will also point out that that those are triggered at a premium to uh the the the deal price right so it's at a 15 premium on top of the 1550 closing price and then the next tranches in a similar fashion it's the 12 patients with pfs6 in the hr positive or two negative and we've announced that we expect to have that trial up and running and first patient enrolled by the end of this year, and full enrollment of both the HR positive and the CRC trial, full enrollment by the end of 2027. And then that second with the HR positive, again, is even at a higher premium. That's premium based at a 25% premium. All right. Yeah, thanks for the clarification there. And again, a Fascinating stuff, and congrats on the data so far. I know we're running out of time here. I do appreciate everybody. I don't know if we have a final question or if we should just go into closing. We actually do have a Final Question. That's coming from the line of John Newman with Canaccord Genuity. Please go ahead with your question. Perfect. Hey, guys. Thanks for taking my question. Congratulations to the team. clinical data as well as the financing two quick questions one is I think you you've talked a lot about this non canonical pathway in terms of the mechanism of action in triple negative best breast cancer for your molecules could you talk a bit about your biomarker strategy there and then quick quick additional question is in terms the dates are positive for true negative study, will you be allowing dosing for your molecule beyond progression? Thank you. Suda, would you take the first one, and I'll take the second one? Yes, yes. Yes, I mean, in terms of the non-canonical pathway, yes, we've got our biomarker. We've got the tissue and the liquid test that we have. We're also continuing to develop our biomarker strategy in this area. You'll see much more coming out in the following months. But I think that the idea that we've uncovered the importance of the non-canonical pathway, I think it's going to open up the entire field. But I also think it has allowed us to understand why Pax is going to be superior, we believe, in the HR positive setting in terms of the metastatic burden? Yeah, John, great question. From our perspective with the trial, we would expect that once patients have progressed on this triple combination, right, Pax plus Fulvestrant plus Palvo, CDK4-6, that more than likely most providers, at least based on who we've been talking to in terms of principal investigators and key opinion leaders, they're a little hesitant in terms of continuing therapy once they've progressed on the triple combination of PA3K mTOR plus Palvo plus fulvestrin. But I think it's something that we'll take on an individual patient-by-patient basis, whether we need to do, you know, like an expanded access for those particular patients and provide PAX as a compassionate use. Beyond that, if the providers think that that would be added value, if they're having some sort of added value that we believe that Pax is providing for those patients. Okay, great, thank you. Thanks, John. All right, I believe we're over time, Rob, if I remember. So I'm just gonna go into my closing remarks, is that okay? Yes, please go ahead. All right great. So let me close today by putting this discussion into perspective. For more than two decades, PI3K drug development is largely focused on one objective, directly inhibiting tumor growth. That remains an important part of Paxilis' activity, but our emerging clinical and translational data that we've talked to today really suggest the opportunity may go beyond inhibition and be considerably broader. You know, now across over 550 patients treated to state, we've established a substantial clinical safety and tolerability database. What we're now beginning to see is evidence that PACS may influence several fundamental drivers of cancer progression, right? Direct tumor control, cancer reprogram, immune restoration, and metastatic biology. In triple negative breast, we're seeing highly encouraging clinical activity accompanied by striking biological activity and changes, including reductions in these terminally exhausted CD8 positive T cells, as well as these metastatics, these circulating tumor cell clusters. Importantly, these changes are occurring within weeks of treatment initiation, and we're beginning to see how that biology may extend beyond triple negative breast. In our HR-positive HER2-negative breast cancer program, built around PAX's inherent PI3K mTOR inhibitory properties, but importantly, PAX has potential to reverse treatment resistance and resensitize these tumors to establish therapies. In MSS, PMMR, colorectal cancer, we're pursuing a different but related challenge, and that would be reprogramming an immunologically resistant tumor environment to potentially make immunotherapy more effective. So the opportunity we see today is no longer one drug in one indication. It's one molecule, multiple clinical programs, and a differentiated biological platform with each program supported by its own scientific rationale and intellectual property strategy. Following our recent financing, we now have the resources to advance and importantly complete all of these programs in parallel. We expect the first HR-positive breast cancer patient enrolled by year-end, colorectal cancer enrollment to begin first quarter of 2027, and additional clinical and translational data later this year and well into 2027 and beyond. That gives us multiple meaningful clinical catalysts heading into 2026. And importantly, multiple opportunities to determine just how broadly the biology we're seeing with PACS can translate into clinical and patient benefit. Thank you for your time and wishing you a safe and enjoyable holiday weekend coming up. Ladies and gentlemen, thank you for Your Participation. This now concludes today's teleconference. You may disconnect your lines at this time.