Hello, and welcome to Vir Biotechnology's T-Cell Engagers Investor Conference Call. As a reminder, this conference call is being recorded. At this time, all participants are in a listen-only mode, and after the speaker's presentation, there will be a question-and-answer session. I will now turn the call over to Rich Lepke, Senior Director, Investor Relations. You may begin, Mr. Lepke. Thank you, Operator, and hello, everyone. Welcome to Vir Biotechnology's PRO-XTEN Masked T-cell Engager Investor Event Conference Call. Before we begin, I'd like to remind everyone that some of the statements we are making today are forward-looking statements under applicable securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance, or achievements to differ significantly from those expressed or implied by such forward-looking statements. These risks and uncertainties and risks associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including Forms 10-K, 10-Q, and 8-K. Joining me on today's call from Vir Biotechnology are Dr. Marianne De Backer, our Chief Executive Officer, Dr. Mark Eisner, our Chief Medical Officer, Dr. Mika Derynck, our Executive Vice President of Oncology, and Jason O'Byrne, our Chief Financial Officer. We are also honored to be joined today by two renowned key opinion leaders in the field of oncology, Doctors Josep Tabernero and Johann de Bono. Let me briefly outline today's agenda. Marianne will start with opening remarks on Vir's cancer modalities and the PRO-XTEN platform. Mika will then provide an update on the phase I data for VIR-5818, a dual Masked T-cell engager targeting a variety of HER2-expressing solid tumors. We're pleased to then have Dr. Josep Tabernero join us to offer his perspective on the data and potential of this modality in HER2-expressing cancers. Mika will then return to present the phase I data for VIR-5500, a dual Masked T-cell engager targeting PSMA in metastatic castration-resistant prostate cancer. Dr. Johann de Bono will then offer his perspective on the data and the activity seen to date in these patients. Finally, Marianne will provide closing remarks before we open the call for questions. Please note that due to scheduling constraints, Dr. Tabernero will not be available for the Q&A portion of today's call. However, Dr. de Bono will remain with us to address any questions related to the clinical data and perspective shared during the presentation. With that, I'll now turn the call over to our CEO, Marianne. Please go ahead. Thank you, Rich, and good early morning, everyone. We appreciate your participation in today's call, which marks an exciting milestone for Vir Biotechnology. We are driven by a bold vision, harnessing the power of the immune system to transform patients' lives. Today, I'm thrilled to share with you the progress we've made in bringing this vision to life, specifically in our oncology program. The data we'll present today represent a significant step forward in our mission to develop innovative immune-powered therapies for people living with cancer. Our in-licensed PRO-XTEN Masked T-Cell Engager platform is driving our oncology strategy. Let me highlight our most advanced assets and their potential to redefine cancer immunotherapy. VIR-5818 is the only Masked HER2-targeted T-Cell Engager in development and has shown broad activity and a promising safety profile across HER2-expressing tumors. At early efficacious doses, we're seeing tumor shrinkage in 50% of the patients, with responses deepening as we increase the dose, and we have observed a low incidence of grade 3 or higher treatment-related adverse events. We've observed minimal CRS, only grade 1 and 2, with no grade 3. Our second clinical stage asset, VIR-5500, is the only dual Masked PSMA-targeted T-cell engager in development. We believe it has the potential to be the best-in-class treatment due to its therapeutic index. All patients have shown PSA declines, with 58% achieving PSA 50 response, and we have significant room to further escalate the dose. Importantly, unlike VIR-5818, we've seen no grade 3 CRS and very low levels of grade 3 or higher treatment-related adverse events. We also believe the long half-life of VIR-5500 will enable every three-week dosing, which could significantly improve patient convenience, particularly in early lines of prostate cancer therapy. Looking ahead, we're excited about VIR-5525, our EGFR-targeted T-cell engager, which represents an opportunity to pursue multiple high-value indications. We plan to initiate phase I studies in the first half of 2025. A key advantage of our platform is that our Maskeds are universal. We can apply them to new targets without the need to titrate and tailor each Masked, accelerating our pipeline expansion. Moreover, the learnings from our initial clinical study allow for more rapid dose escalation in future programs. Underpinning all of this is our robust estimated cash and investment position of approximately $1.1 billion as of January 1st, which allows us to pursue our programs with the urgency they deserve while maintaining financial discipline. Next, we'll explore how our oncology programs are translating this innovative approach into reality. I'd like to take a moment to place our oncology programs in the broader context of our portfolio. Vir Biotechnology is uniquely positioned to harness the power of the immune system in both infectious diseases and oncology, two fields with immense potential for transforming patient care. In our infectious disease portfolio, we're working to rapidly advance to our Hepatitis Delta registrational ECLIPSE program in the first half of 2025. I also want to briefly mention our Hepatitis B program, where we are pursuing a functional cure. It's important to note that further development will only proceed with a partner. Alnylam has the right to opt in on Elebsiran, with that decision to be confirmed. I'll expand on our capital deployment priorities later in the presentation. Turning to oncology, the landscape, despite numerous advances, still presents substantial challenges. Many patients with metastatic solid tumors face limited treatment options, drug resistance, and debilitating side effects. It's these persistent unmet needs that drive our ambition to take on cancer. To address these challenges, we're advancing a portfolio of Masked T-Cell Engagers leveraging the innovative PRO-XTEN platform. In time, we aim to build on this foundation, leveraging our in-house capabilities in antibody discovery and protein engineering to further expand our T-Cell Engager pipeline with new and novel targets. It's important to understand both the promise and the challenges of this technology. T-Cell Engagers have shown compelling activity and the potential for long-term responses in cancer treatment. As you can see on the left, T-Cell Engagers work by facilitating T-Cell engagement and tumor cell killing. They act as a bridge, forming an immunological synapse between T cells and tumor cells expressing a specific tumor-associated antigen. This interaction triggers a powerful cascade of events. It activates T cells, leading to tumor cell killing while stimulating a robust cytokine release. This cytokine response further activates and recruits additional T cells to the tumor site. The mechanism allows for potent T cell activation against cancer cells, which can potentially lead to deep and durable tumor control, a key promise of T-Cell Engager technology. However, unmasked T-Cell Engagers face a significant challenge, as illustrated on the right side of the slide. They don't differentiate between tumor cells and normal cells that may also express the target antigen. This lack of selectivity can lead to systemic toxicity, such as cytokine release syndrome, and can lead to the destruction of healthy cells expressing the tumor antigen, limiting both the safety profile and the therapeutic index of these drugs. This challenge has been a major hurdle in the development of T-cell engagers for solid tumors, leading to a narrow therapeutic window and inability to dose these agents high enough to drive deep tumor responses. This is where the PRO-XTEN technology comes in. Our approach is designed to preferentially unmask and activate T-cell engagers in the tumor microenvironment, addressing this fundamental limitation. On the right, you can see how our dual masking strategy works in healthy tissue. By masking both the tumor binding and the T cell binding domains, we significantly reduce interactions with normal cells. This dual masking limits binding and reduces T cell-mediated cytotoxicity in healthy tissues, dramatically improving tolerability. A critical activation happens, though, in the tumor microenvironment, as illustrated on the left. Here, tumor-associated proteases selectively cleave the masks, activating our T cell engager. Once unmasked, it can bind both tumor cells and T cells, promoting targeted cancer cell killing. Importantly, any unmasked molecule that doesn't immediately bind is rapidly eliminated, further minimizing off-tumor toxicity. This selective activation is the key to the PRO-XTEN platform's promise. Building on this foundation, our goal is ambitious yet focused: achieving long-term, durable responses across a broad spectrum of solid tumors. The powerful PRO-XTEN technology offers this potential and allows us to differentiate our T cell engagers in several critical ways. First, our approach involves masking both the tumor-associated antigen and the CD3 binding domains. This dual masking strategy is designed to maximize the therapeutic index. Second, we anticipate lower toxicity compared to both unmasked and single-masked T cell engagers. Third, our data demonstrate a longer half-life, supporting the potential for every three-week dosing. Fourth, it's important to note that our masking technology has been clinically validated. This isn't just a theoretical advantage. We're seeing real-world evidence of its benefits in our clinical trial. And lastly, our universal dual masking platform has the potential to accelerate clinical development into new targets. We believe our unique dual mask assets could enable us to redefine the standard of care in multiple solid tumor indications across lines of therapy. By potentially offering improved safety, convenience, and efficacy, we aim to make a significant impact on patient outcomes in areas of high unmet medical need. I would now like to turn the presentation over to Dr. Mika Derynck, our Executive Vice President and Head of Oncology. Mika will dive deeper into our clinical data, starting with VIR-5818. Mika, over to you. Thank you, Marianne. I'm excited to share with you today some compelling data on VIR-5818, which we believe demonstrates the significant potential of the PRO-XTEN platform. I'd like to start with a case study that illustrates the transformative potential of VIR-5818. This slide shows a remarkable journey of a HER2-positive breast cancer patient who had exhausted multiple lines of therapy, including in HER2. At baseline, this patient presented with extensive ulcerated chest wall lesions that invaded throughout her skin and back. Having undergone nine prior lines of therapy, this case underscores the treatment-resistant nature of her disease. After the very first dose, on day one, within one to three days, the patient noted increased redness and induration along with tumor pain, indicating an intense initial inflammatory response to the drug. By the end of cycle one, the pain resolved, and just after three weeks of treatment, we observed significant regression of her tumor lesions on her chest and back. Her tumor ulcerations also started scabbing over and healing. Over the next few cycles, the patient continued to have a dramatic response. By week 12, cycle four, she had a transformative result, leading to near-complete normalization of her chest wall and back. She also showed a 52% tumor shrinkage of her target lesions. This level of response is rarely observed in such a late-line setting and is quite impressive. It demonstrates the potential power of immune-directed treatments when they are well tolerated. It's also a unique opportunity to visually see the drug in action and observe the initial pro-inflammatory nature of the drug's activity, which eventually resulted in the near-complete eradication of her tumors. The patient tolerated the treatment well, experiencing only the initial tumor pain. Notably, there was no evidence of elevated cytokines. This case provides an excellent visual example of proof of mechanism for VIR-5818 and showcases its potential to deliver significant clinical benefit that can make a real difference in patients' lives. Now, let's dive into the details of our phase I study for VIR-5818. Our dose escalation strategy has been deliberately conservative, aligning with health authority expectations given the safety concerns observed with our unmasked T-cell engagers. This cautious approach was particularly important given that VIR-5818 was the first PRO-XTEN masked T-cell engager to enter the clinic. We started at an extremely low dose of one microgram per kg and have gradually escalated to 200 micrograms per kg, followed by step-up dosing cohorts. We're now evaluating a top dose of 1,000 micrograms per kg and 800 micrograms per kg Q3W. Of note, a historic unmasked HER2 T-cell engager has shown grade 4 CRS at just 0.5 micrograms per kg and could not escalate to doses to show any evidence of anti-tumor activity or radiological responses. This showcases how masking can dramatically extend the therapeutic index. In parallel, we're also exploring Q3W dosing, which may offer greater convenience for patients, in particular in earlier lines of treatment. It's important to note the breadth of our patient population. We've enrolled 79 patients to date across multiple indications. These patients have HER2 IHC 2+ to 3+, HER2 amplification, or HER2 mutant tumors. Now, let's examine VIR-5818's pharmacokinetics. The left graph illustrates pharmacokinetics during step-up dosing. The masked drug exhibits dose-dependent linear pharmacokinetics. At higher doses, we have observed small amounts of the unmasked molecule in circulation. This low level of the unmasked drug was predicted by our preclinical models, demonstrating minimal peripheral unmasking and is consistent with a minimal cytokine release syndrome that we have observed. On the right, we see linear and dose-proportional PK with an overall half-life of five to six days, which supports a dosing frequency of three weeks or more. This is a major advantage as we develop this drug for patients in earlier lines of treatment, where convenience and quality of life considerations become increasingly important. This observed profile could significantly improve patient experience compliance, especially in long-term treatment settings. Now, let's examine the patient population enrolled in this study. It's a diverse and heavily pretreated group of patients who have exhausted all available standard of care treatments. Approximately 62% of our patients have received over three lines of therapy, and about 25% have undergone more than five lines. Many have had prior HER2-targeted therapy, representing the most resistant type of tumors with a very high unmet need. Our study includes a wide variety of tumor types, including patients with liver metastases. Liver metastases are often resistant to immunotherapies. Overall, this heterogeneous patient population represents some of the most challenging cases in oncology and resistance to treatment. Now, let's turn to VIR-5818's safety profile, which is impressive, particularly regarding CRS. Only 16.5% of patients experience grade 3 or higher treatment-related adverse events, which is impressively low compared to other T-cell engagers. Crucially, we observed an overall low rate of CRS, primarily grade 1, which is just fever managed with antipyretics, and no grade 3 or higher CRS events, even without mandatory pretreatment steroids. Regarding pneumonitis, most cases were grade 1, asymptomatic and often not requiring intervention. grade 2 cases were generally reversible and manageable with steroids, allowing for re-challenge without any sequelae. The majority of cases occur in patients with lung metastases, suggesting tumor flare may play a role. This profile differs significantly from ADC-induced lung injury, which is often irreversible and requires discontinuation. There were only two grade 3 pneumonitis cases, one successfully managed with corticosteroids, and a second patient with extensive lung metastases who had rapidly progressing disease throughout the lung in the first weeks of dosing, confounding the picture. Importantly, we observed no other grade 3 or higher safety signals, including cardiotoxicity, liver toxicity, or colitis. Dose escalation continues as we haven't yet reached the maximum tolerated dose. The graph on the right demonstrates the benefit of our masking technology. Even at doses up to 1,000 micrograms per kg, we're seeing very low levels of IL-6. This is all consistent with a minimal CRS overall and no high-grade CRS. This contrasts sharply with unmasked HER2 T-cell engagers, GBR 1302, where severe CRS has been observed at doses as low as 0.5 micrograms per kg, with grade 4 CRS and sky-high IL-6 up to 10,000 pg/mL, as seen with the red dotted line. In the coming slides, you'll see enriched responses and tumor shrinkage at doses of 400 micrograms per kg and higher. This favorable safety profile, particularly the minimal CRS without widespread steroid use, suggests VIR-5818 has the potential for a very wide therapeutic index not afforded by unmasked T-cell engagers. With this in mind, let's now turn our attention to the efficacy data we've observed with VIR-5818, which are very encouraging, especially considering the heavily pretreated nature of our patient population. This waterfall plot shows the best change in sum of the longest diameters from baseline for patients treated at doses of 400 micrograms per kg and above. What's striking is that 50% are having some tumor shrinkage across multiple indications, and we have a disease control rate of 65%, which is impressive given that this is a very late-line population that often shows progression with the first tumor assessment. We've observed RECIST-defined responses in four out of these 20 patients, with dose escalation still ongoing. We've also seen additional responses at lower doses, which aren't reflected in this waterfall. We are also seeing a dose-response relationship with more and deeper responses at higher doses. This is particularly exciting as we continue dose escalation in both weekly and Q3W regimens. Remarkably, we're observing responses in patients who have received up to nine prior lines of therapy, including the breast cancer patient I highlighted earlier. This speaks to the potential of VIR-5818 to provide benefit even in patients who've exhausted all treatment options. As we continue to escalate the dose and gather more data, we're optimistic about the possibility for even deeper responses and characterizing this in a more homogeneous patient population. Now, I'd like to focus on a particularly exciting subset of our data, the results we're seeing in HER2-positive colorectal cancer patients. This group represents an area of significant unmet need, and our findings here are especially encouraging. At doses of 400 micrograms per kg and above, we're observing compelling results. A confirmed partial response rate of 33%, two out of six patients. One of those patients has been on study for greater than two years, with a duration of response of greater than 18 months. CEA is a tumor biomarker reflecting tumor burden, and here we're seeing a 100% response rate for patients who had a CEA biomarker. We are also seeing an impressive disease control rate of 83%. Notably, we've seen an additional colorectal cancer patient with a 40% tumor shrinkage at a dose of 200 micrograms per kg. Importantly, all of these patients had microsatellite stable tumors, a population historically resistant to immunotherapy. Approximately 6% of metastatic colorectal patients are HER2-positive, which is typically a poor prognostic and resistant tumor type. These results, while early, are particularly encouraging given the challenging nature of this patient population and the possibility for accelerated development. In addition to the clinical responses we've observed, we're also gathering compelling molecular evidence that supports VIR-5818's anti-tumor activity. Let's turn our attention to the circulating tumor DNA, or ctDNA, which can provide a more sensitive measure of treatment effect. This waterfall plot shows a percentage change in ctDNA from baseline for patients treated with our step-up dosing regimen. Each bar represents an individual patient with the dose levels indicated below. There are several points that I'd like to highlight. One, we're seeing a 54% molecular response rate defined as greater than 50% decline in overall ctDNA levels and an impressive 31% with 100% molecular response. Two, these responses are observed across various dose levels and in both HER2-positive and HER2-low patients, suggesting broad applicability. Three, ctDNA analysis may provide complementary information to imaging-based assessments, potentially offering additional insights into treatment effects and changes in tumor burden. This is particularly valuable in cases where tumor inflammation might mask early signs of efficacy in imaging studies. Finally, there's emerging evidence that ctDNA can be a biomarker for monotherapy immunotherapy activity in numerous cancer types, and in some cases, ctDNA responses can be associated with overall survival and be a better predictor than tumor shrinkage. Moving forward, we're now collecting ctDNA in all patients. This will provide us with an even more comprehensive picture of VIR-5818's activity over time and may help guide our dosing and treatment strategies. As we conclude our discussion for VIR-5818, I'd like to highlight how this program is validating the PRO-XTEN platform and informing our broader strategy. We recognize that HER2 is a highly competitive field, yet we believe our dual mask technology offers a differentiated approach to this disease. The data we've presented is very encouraging. At efficacious doses, we're seeing a wide therapeutic index in a heavily pretreated population. We've observed a 33% response rate in heavily pretreated colorectal cancer patients, which could possibly open an accelerated regulatory pathway. Our ctDNA and tumor biomarker data provides additional insights complementing our RECIST findings. VIR-5818 has provided convincing proof of concept of our platform. We're seeing evidence of unmasking with anti-tumor activity coupled with unprecedented tolerability, no grade 3 or higher CRS, and only 16% grade 3 or higher treatment-related adverse events overall. This safety profile is particularly striking when compared to unmasked T-cell engagers or current standard of care therapies, which often see much higher rates of severe adverse events. The universal nature of our masking technology means that these learnings apply across our entire platform. This has allowed us to more rapidly dose escalate in our VIR-5500 PSMA targeted program and will inform the development of future targets. To that end, we're continuing dose escalation both weekly and every three-week regimens, pushing the boundaries of what's possible with T-cell engagers in solid tumors. Additionally, we're exploring combination therapy with PD-1 inhibitors with enrollment ongoing. The potential that we're seeing with VIR-5818 is truly exciting. To provide an external perspective, I'm pleased to introduce Dr. Josep Tabernero, a key opinion leader, director of the Vall d'Hebron Institute of Oncology, and an investigator on this study. Dr. Tabernero, the floor is yours. Thank you, Mika. I'm pleased to share my perspective on VIR-5818 and its potential impact on HER2-targeted therapies across various cancers. Let me start with a compelling case study, a 57-year-old male with HER2 IHC3+ colorectal cancer who had progressed through six prior lines of therapy, including HER2-targeted agents. HER2-positive colorectal cancer represents a high unmet need because patients develop resistance to HER2-targeted therapies, and this heavily pretreated patient would typically be particularly resistant to additional therapies. Starting at a relatively low dose cohort of 60 micrograms per kg, he showed a dramatic 90% CEA tumor marker response in the first cycle. He continued with radiographic stable disease, and as he was able to dose escalate per protocol, we observed initial tumor shrinkage. But when he escalated to 600 micrograms per kg, he achieved a partial confirmed response about a year after starting the treatment. This response has been sustained for over 18 months, which is quite extraordinary for this indication and treatment history. As of the last data cutoff, he continues on study with his response maintained, and importantly, his tumor is microsatellite stable, which typically resists immune therapies. What is equally impressive is the drug's tolerability. The patient has experienced minimal adverse events over two years of treatment, and what we have heard, he has been able to go back to work, get married, and have an excellent quality of life for an otherwise end-stage terminal illness. Moving to the overall data set, this is a heavily pretreated and heterogeneous population. The safety profile is noteworthy. Previous attempts at developing HER2 T-cell engagers without masks were probably toxic with grade 3, 4 CRS, even with prophylactic steroids. In contrast, VIR-5818 has shown minimal CRS, mostly grade 1, without mandatory steroid use. This double mask approach represents a significant advance for T-cell directed therapies. We have observed pneumonitis, but it's primarily low-grade. The majority of cases were grade 1, which means it's asymptomatic and found incidental on CT scans. Many of these patients did not require additional treatment and could continue on study. The few grade 2 cases were manageable and reversible with steroid treatment, and most grade 1, 2 cases followed with patient returning without major issues. Many of the grade 2 events have been associated with concurrent lung metastasis, possibly indicating a strong inflammatory response to the tumor. And unlike ADCs induced ILD, which tend to be more serious and irreversible, this profile has been manageable. There were two grade 3 plus related adverse events, which were manageable or had rapid progression of the disease in the lung. Other related adverse events, such as tumor flare, are expected given the mechanism of action, and in some patients, this flare has later resolved in tumor shrinkage. The aggregated data suggests that much of the tumor flare has now been mitigated with the step-up dosing. Importantly, there were no reported adverse events for liver or cardiac toxicities, nor were there original signals for colitis, which are typically concerns with HER2 and/or other immune agents. Efficacy data shows responses and a good response across multiple tumor types, which is impressive, given that this is a heavily treated population, later line population that has exhausted all standard of care. This has the potential to address an unmet need in particular tumors, including colorectal cancer, endometrial, and pancreatic cancers, a major advance for solid tumor T-cell engagers. Monotherapy T-cell engagers can cause pseudoprogression, where tumor shrinkage may not be the only indicator of anti-tumor activity. I am very encouraged to see biomarker responses and, in particular, ctDNA responses in the liquid biopsies, even in patients that have progressive disease as their rare response, which may indeed be pseudoprogression due to tumor inflammation, which we have seen on this study. This indicates to me that radiographic tumor size decrease may underestimate the totality of the clinical benefit seen with this drug. I look forward to seeing how these signals evolve in more homogeneous expansion cohorts at higher doses. The activity in colorectal cancer is particularly exciting. The activity seen in the microsatellite stable patients is very encouraging and could potentially lead to an accelerated approval. Overall, I see clinical validation of the masking platform and also look forward to the other PRO-XTEN pipeline candidates, such as EGFR. In conclusion, while these data are early data, I'm very encouraged by what I have seen with VIR-5818. The combination of durable responses, manageable safety profile, and potential for use both as a monotherapy and in combination across multiple lines of therapy suggests that this could be a significant advancement in HER2-positive cancer treatment. Thank you very much, and I'll now hand it back to Mika for further discussion. Thank you, Dr. Tabernero, for those insightful comments. Your perspective on the unique case study and the broader implications of our VIR-5818 data is invaluable as we continue to advance this program. Now, I'm excited to shift our focus to another promising asset in our pipeline, VIR-5500, our PSMA-targeted dual-masked T-cell engager for prostate cancer. Let's dive into our phase I study for VIR-5500. This study design was built on the learnings from our VIR-5818 program, allowing us to move more rapidly and efficiently in our dose escalation. On the left, you'll see our weekly dosing regimen. We're currently at step-up dosing of 300, 600, and 1,000 micrograms per kg. This is a significant acceleration of dose escalation, reflecting our confidence in the safety of our PRO-XTEN programs. On the right, you can see that we're also exploring a Q3 week dosing schedule. This could potentially offer greater convenience for patients while maintaining efficacy. We're currently evaluating doses stepping up from 500 to 2,000 micrograms per kg in this regimen. Now, let's take a closer look at the patient population. As you can see, we've enrolled a heavily pretreated group of patients that are both resistant to hormonal and chemotherapies. The median age is 69. On average, these patients have undergone four prior lines of therapy. 94% of patients have received prior chemotherapy. 22% of our patients have previously received PSMA radioligand therapy. We have one patient who has previously been treated with a CD3 T-cell engager. In terms of disease burden, all of our patients have significant metastatic disease. 100% of participants have bone metastases. Over 50% also have lymph node metastases. This is a population with high unmet need. Traditional therapies often fall short here, and prognoses are very poor. That's why any activity we see in this group is particularly meaningful. Now, let's look at VIR-5500 pharmacokinetics. The left graph illustrates the pharmacokinetics in a single patient who showed any measurable fully unmasked T-cell engager or TCE. It's important to note that in 13 out of 14 evaluable participants, no unmasked TCE was detectable above the assay's lower limit of quantification. In this one patient, the unmasked TCE only becomes detectable after two cycles, demonstrating a nominal level of unmasking in the periphery. The right graph shows first dose pharmacokinetics across all dose levels. We observe a linear dose proportional relationship with a half-life of 8-10 days, potentially enabling Q3 week dosing or less frequent dosing. This potential for extended dosing intervals is particularly advantageous as we consider moving to earlier lines of treatment. Prostate cancer in earlier stages is often managed as a chronic disease, with patients requiring treatment for months to years. So, coming to the clinic less often is really important for patients. Looking at the left side of this slide, we're seeing a very well-tolerated profile overall. Importantly, we've observed no dose-limiting toxicities to date. The majority of treatment-related adverse events have been low-grade, with only a single grade 1 adverse event of a laboratory elevation of AST without a grade 1 ALT increase, indicating that this is unlikely specific to liver toxicity or related to CRS. Notably, we've seen no adverse events of ICANS or hearing loss, suggesting superior protection of our double mask compared to other PSMA-targeted therapies. Moving to the right side, we see data on CRS. What's immediately striking is the low overall incidence of CRS, with only a small percentage of patients experiencing grade 1 or 2 events, and we've observed no grade 3 or higher CRS events at any dose level. Even more impressively, at our highest dose level, we've seen no CRS events at all. This is an unprecedented CRS profile, in particular without the use of prophylactic steroids or anti-IL-6 medications, and as you'll see in subsequent slides, this is at early but efficacious doses. As we continue to dose escalate, we'll monitor closely these safety parameters. However, the data we've seen so far gives us confidence in the potential of VIR-5500 to offer a best-in-class therapeutic index among PSMA-targeted therapies and other T-cell engagers. Now, I'm excited to share with you our efficacy data for VIR-5500, which we believe demonstrates significant promise in treating metastatic castration-resistant prostate cancer. While early, these results are truly remarkable. Every single patient, 100% of the cohort reflected here, experienced a PSA decline. Looking closer at the magnitude of responses, 58% of patients, or seven out of 12, achieved a PSA 50 response, meaning their PSA levels decreased by 50% or more. We've also observed a PSA 90 response in one patient. These are promising early response signals, especially considering the heavily pretreated nature of our patient population and at very low doses. Notably, there's no correlation between anti-tumor activity and CRS. The graph only shows three participants experiencing low-grade CRS with no relationship with PSA response. Moreover, we observed no IL-6 elevations, which are a hallmark of severe CRS. The fact that we're seeing these responses with such a favorable safety profile suggests that we have significant headroom to continue dose escalation, which could lead to even more deeper and more durable responses. As we move forward, we'll be closely monitoring not just PSA responses, but also radiographic responses and, crucially, the durability of these responses. Now, let's examine this graph showing the longitudinal PSA responses. This chart illustrates PSA changes from baseline over time for patients across different dose levels. As mentioned, we're seeing confirmed PSA 50 responses in seven out of 12 patients, or 58% of the cohort. We're also observing a trend towards increased durability for certain patients. Additionally, we see a PSA 90 response in one patient, which is particularly encouraging at this early stage of dose escalation. Note the call-out for a patient who paused treatment due to an unrelated infection resulting in a non-durable response. These data suggest a large therapeutic index for VIR-5500 with early efficacy, with minimal CRS and toxicity without the need for prophylactic steroids. We have a lot of room to increase dosing to achieve deeper or more durable responses. We already have hints that we are on the low end of the therapeutic window with a case of a patient with deep radiographic and PSA response that Dr. de Bono will highlight. Let's contextualize our VIR-5500 data within the landscape of other PSMA-targeted T-cell engagers in development for prostate cancer. We do not have head-to-head data, and cross-trial comparisons are inherently limited and may suggest similarities or differences in outcomes that may not be reflected in the actual results of any head-to-head studies due to differences in study design, patient populations, subject characteristics, and other factors. However, we believe cross-trial comparisons can provide valuable insights into the potential differentiation of our approach. Looking at the far right of the graph, you'll see VIR-5500 safety profile of our dual-masked approach. Only 25% of patients experienced grade 1 or 2 CRS. Importantly, we've seen no grade 3 or higher CRS events. grade 3 or higher treatment-related adverse events were observed in just 10% of patients, which is just one patient with an asymptomatic laboratory event. Notably, we've achieved the safety profile without prophylactic corticosteroids. This contrasts with other T-cell engager programs, both unmasked and single masked, which often require steroid pre-medication to manage CRS and other toxicities. The unmasked and single masked T-cell engager programs represented here show significantly higher rates of CRS and treatment-related grade 3 or higher adverse events, with some reporting CRS rates over 90% and meaningful percentages of high-grade CRS. We believe our differentiated safety profile is a direct result of our dual masking approach. What's particularly exciting is that we're seeing this favorable safety profile while also observing promising efficacy signals. This suggests that we have significant room for further dose escalation with the goal of achieving a best-in-class therapeutic index. Now, let's consider our efficacy in the context of evolving PSMA-targeted therapies. Our current phase I data shows a PSA 50 response rate of 58% and a PSA 90 rate of 8%, encouraging results, especially given that we're still in the early dose escalation stages. Again, while we do not have head-to-head data, we believe we have a lot of room to move with our current safety profile relative to other levels of CRS and the use of prophylactic steroids in competitive programs. We believe that there is significant opportunity for further optimization in both our weekly and Q3 week dosing schedules. Our favorable safety profile with no high-grade CRS and no need for prophylactic steroids gives us confidence to explore higher doses and potentially establish a best-in-class therapeutic index. As we continue to dose escalate, we're keenly focused on accelerating VIR-5500 development to get this important modality to patients as quickly as possible. As we conclude our discussion of VIR-5500, let's consider its potential positioning across different stages of prostate cancer, highlighting how our dual masked approach is driving its differentiated profile. In the late line metastatic castration-resistant setting, we've already shown clear initial activity in heavily pretreated patients. For early line treatment, three factors stand out. One, VIR-5500's long half-life supports every three-week dosing, which is crucially important for patients in that early line setting. Two, the safety profile without prophylactic medications. Corticosteroids can be very problematic in this early setting where patients have more options and less tolerance for side effects. Three, the dual masking approach may allow us to reach higher doses with a much wider therapeutic index, which could translate to improved efficacy with better tolerability compared to single masked or unmasked T-cell engagers. Looking ahead, we see opportunities in non-metastatic and hormone-sensitive prostate cancer. Our dual masking approach may provide a competitive edge here, enabling both monotherapy and combination strategies. Overall, VIR-5500 shows broad promise across the prostate cancer landscape. We believe its promising efficacy and safety profile position it as a potential best-in-class therapy from late to early line treatment. Now, to provide further insights into our findings, I'd like to introduce Dr. Johann de Bono, who will present one of his patients on the study and offer his expert perspective on the data we've discussed. Johann, over to you. Hello, my name is Professor de Bono. I am Professor of Cancer Medicine at the Royal Marsden and the Institute of Cancer Research in London. And I want to thank you for the opportunity to discuss these really exciting early results with this dual-masked bispecific tumor-targeting antibody targeting PSMA and CD3. The double masking here is really key since we are seeing significant anti-tumor activity in the absence of any major concerns regarding cytokine release syndrome or CRS, which is of huge importance to this class of novel drugs. Let me start, first of all, by sharing a case from my own experience giving this agent to my patients in my trials unit that I really believe illustrates the huge potential of this novel IMP. Can I please see the next slide of my case? This is a 73-year-old man who had exhausted most available standard therapies, including darolutamide, the RRP, and two chemotherapies, including docetaxel and cabazitaxel. He had high burden disease with a large number of bone mets, more than 20, and a high PSA that was rapidly rising at almost 1,000. His PSA was 959 at baseline. He then went on to this IMP phase I trial and received step-up doses of 200, 300, and then 400 micrograms per kilogram and tolerated the treatments very well without requiring any steroids or anti-IL-6 pretreatment to manage any CRS. He really had minimal toxicity. In fact, we also saw impressive and significant rapid PSA fall of more than 90%, now sustained for multiple months of follow-up. Importantly, on whole body magnetic resonance imaging, which I would argue based on our publications is actually the best way to monitor tumor response in bone, we have seen significant anti-tumor activity with essentially liquefaction of his hypercellular cancer and the eradication of tumor with a major increase in the ADC, what I would call the apparent diffusion coefficient, which basically measures water movement in the cancer, showing a major increase in water movement from the back cellular limited water movement pre-therapy, the hypercellular tumor, to a lot of water movement in the cancer, indicating tumor liquefaction and tumor kill after therapy. In my experience, this really means major anti-tumor response in keeping with the more than 90% PSA fall. This drug in this gentleman has had impressive anti-tumor activity. Now, critically, with this dual-masked BiTE, from a safety perspective, this gentleman has experienced only grade 1 mild, minimal really, hypotension. Importantly, what we're seeing, and this gentleman had this, was a significant flare-up of lower back pain, grade 1 and manageable with analgesics. This to me indicates that this agent is having a significant impact on the immune T-cell response against his cancer and is probably, in my opinion, an on-target effect. Importantly, we are collecting quality of life data in this trial. In this gentleman, we have now seen a major reduction in pain symptoms in keeping with the observed anti-tumor activity we have seen with this dual-masked BiTE. I know this is a single case, but it really demonstrates the potential of this IMP VIR-5500 to elicit deep biochemical and clinical responses in patients with really advanced high burden, you know, tumor burden, prostate cancer, with this major PSA decline, imaging changes on whole body MRI, and symptomatic improvement. When you look at the overall trial data set, not just my patient, but overall, I'm really impressed by several aspects of this new IMP VIR-5500, particularly, one, the safety profile is hugely encouraging. I've developed multiple similar drugs, and the slow rate of CRS that we're seeing is very important because it will allow higher dose intensification with this agent, which will maximize anti-tumor activity, importantly avoiding the use of steroids or anti-IL-6 pre-therapy, and in particular, steroids really worry me because these can really fuel tumor growth as well as cause side effects. Importantly, we're seeing PSA decreases in multiple patients, so that is really supportive of the fact this drug has significant tumor activity, and also with some of these other agents, we have seen other toxicities such as hearing loss or hypoacusis, xerostomia, liver toxicity due to PSMA binding of the agent away from the tumor, and this actually is a major issue for other BiTEs that are not double masked like this BiTE. Now, because this, you know, is not being seen to date, although it's early days, I guess we'll have to get more data with higher doses, it would indicate really in principle that this drug is primarily being activated and unmasked at the tumor site. I do believe there is considerable room for further dose escalation, and I am confident we're going to continue to see a dose response by increasing dose of this novel agent. But if, as we are seeing, this dual masking approach continues to pay dividends in terms of safety with little to no evidence of peripheral unmasking, I think we'll have a broad therapeutic index with more anti-tumor activity, even in this heavily pretreated population of patients who have exhausted all other therapy options. So that's really all, you know, the durability of response that we're seeing so far is encouraging, but we need more data for sure. But really, the trends we're seeing so far with increasing doses make me hopeful and be confident that this agent, you know, with its longer half-life of eight to 10 days that will support three-weekly dosing, you know, is very promising for this population of patients. So thank you for your attention. I think I've covered most of the bases. And with that, I would like to now hand over to Marianne. Thank you. Thank you, Dr. Tabernero and Dr. de Bono for sharing your valuable insights with us today. We truly value your expert contributions to this discussion. As we conclude, I'd like to highlight the key takeaways from today's presentation. First and foremost, we've clinically validated the universal dual masking PRO-XTEN platform. Our data indicates a potentially best-in-class therapeutic index with minimal CRS and few grade 3 or higher treatment-related adverse events across programs. We're seeing clear efficacy signals in both our HER2 and PSMA programs, even in heavily pretreated patients. Importantly, we believe we have significant headroom for further dose escalation, which could lead to even stronger efficacy. Our T-cell engagers demonstrate a differentiated pharmacokinetic profile with the possibility for every three-week dosing. And finally, the universal nature of our masking approach enables rapid development of new targets, as evidenced by our upcoming EGFR program. These achievements highlight the PRO-XTEN platform's potential to redefine solid tumor treatment with our masked T-cell engager approach. Looking ahead, we have several key catalysts on the horizon. For Hepatitis Delta, we are initiating our ECLIPSE registrational program in the first half of 2025. For our oncology portfolio, we'll start first inpatient dosing with our EGFR dual-masked T-cell engager in the first half of 2025. In chronic Hepatitis B, we'll share 24-week functional cure data from our MARCH Part B study in the second quarter. These milestones underscore the potential of our pipeline across both infectious diseases and oncology. All our efforts are underscored by a strong financial position with an estimated $1.1 billion in cash and investments as of January 1st, 2025. Over the past year or more, we have taken numerous steps to right-size our cost structure. After applying strict financial discipline and portfolio prioritization during our 2025 planning process, we are pleased to share that we have secured a cash runway extending into mid-2027. Our capital allocation priorities are clear and strategic. We are accelerating investment in two main areas. First, our hepatitis delta program. Following the compelling data we presented at AASLD 2024, we're moving forward with our registrational phase III ECLIPSE studies. Second, our masked T-cell engager programs. We're prioritizing dose escalation for VIR-5500 and VIR-5818 and initiation of the phase I study for VIR-5525. For our chronic hepatitis B program, we look forward to sharing functional cure data from our MARCH Part B study in the second quarter of 2025. As mentioned, future advancement of this program will be contingent on securing a worldwide development and commercialization partner. VIR will not proceed in HBV alone. We're evaluating the best path forward to maximize the value of this important asset. Through a focused approach to capital allocation and strategic partnerships, we believe we can drive significant value creation while extending our cash runway. As we wrap up today, I want to emphasize how far VIR has come. We've evolved from a company that developed a lifesaving therapeutic antibody for COVID-19 to one that's now working to address higher unmet needs in both hepatitis and cancer. This evolution leverages our unique antibody identification and AI-powered engineering capabilities both across infectious diseases and oncology. By applying our core strengths to these areas, we're building a broader, more robust pipeline while staying true to our mission of harnessing the immune system to transform patient care. Our dual-masked T-cell engager technology isn't just another incremental step. It's a fundamental rethinking of how we can possibly make immunotherapy safer and more effective. The early data we've shared today, particularly the encouraging efficacy signals at early doses, suggest we're on the right track. But what really excites me is the potential impacts on patients. Whether it's someone battling hepatitis delta or a cancer patient who has exhausted standard of care, our goal is to offer new hope and better outcomes. We're not there yet. We have a lot of work ahead. But with five clinical programs now underway and a robust pipeline behind them, we are positioned to make a real difference in areas of significant unmet need. In closing, I want to express my sincere gratitude to our study participants, investigators, team members, and investors. Your contributions drive our mission to transform patient care. With that, I'll turn the call back over to Rich to begin the Q&A session. Thank you, Marianne. This concludes our prepared remarks, and we will now start the Q&A section. Please limit your questions to two per person so that we can get to all of our covering analysts. I'll turn it over to you, operator. Thank you. We will now begin our analyst Q&A session. For our analysts, please press star one on your telephone keypad to indicate you would like to join the queue if you have not done so already. Please ensure your line is not on mute when called upon. One moment, please, while we pull for questions. Your first question comes from the line of Paul Choi with Goldman Sachs. Your line is open. Hi. Thank you. Happy New Year, everyone, and congratulations on the data. It looks like the licensing deal with Sanofi has the potential to pay off nicely here. My first question is on 5818, and I was wondering if you could comment on if you're seeing any responses in patients who are RAS mutant. That's historically a limitation of HER2 therapy, particularly in colorectal cancer, but just I was wondering if you've seen any responses in patients who are RAS mutant. And just does that give you any clarity on what tumor type you'd want to focus on initially as your lead indication there? And second, for 5500, can you maybe comment on your development plans in earlier lines, maybe potentially the pre-taxane setting? Just thoughts on what the timing and strategy there might be. Thank you very much. Thank you, Paul, for your questions. I will ask Dr. Derynck to address them. Yeah, thank you for the question. So for 5818, in terms of RAS mutants, we have not yet done the analysis to see which patients are RAS mutants. But I think it's important to note that the mechanism of action of T-cell engagers is they use HER2 as an address in order to cause that T-cell killing. So regardless of what's driving the tumor in terms of oncogenic mutations, these things should work regardless of that status, as long as there's HER2 expression, is really the major question that you're talking about. It is true, though, that for EGFR inhibitors, there is a higher rate of HER2 expression that occurs. And so for patients who've been pretreated with EGFR inhibitors, there might be an enrichment for HER2 positivity. And of course, EGFR inhibitors tend to not be used in the HER2 mutant patient population. In terms of your 5500 question, in terms of going into earlier lines of treatment, particularly in pre-taxane patients, we think that there is a significant opportunity and differentiation with our drug in that we have a superior safety profile, which we think is a result of the dual masking. We only have a 25% CRS rate, grade one and two. And also, we do not use, at least for now, we're not using pretreatment corticosteroids. Corticosteroids is actually very problematic for patients if you have to give it routinely. And so that is a significant advantage that we don't need to use that. In terms of also scheduling, we are evaluating a Q3 week dosing. Our half-life is eight to 10 days, which really affords that less frequent dosing. This is so crucially important for patients in that early line setting where prostate cancer is more of a chronic disease, and so having to not go to the clinic every week is particularly advantageous, so overall, we think that the opportunity in the early line setting is there. We are currently, in our current protocol, have the opportunity to combine with other agents such as androgen receptor pathway inhibitors, as well as other standard of care options that will get us into the earlier line setting. We're also allowing, with a new amendment that's been approved, to have patients with earlier lines of setting definitely in the pre-taxane space, and we believe that the drug actually will work better in the early line setting, given that the immune systems tend to be much more robust in that early line setting. Thank you very much. The next question comes from Roanna Ruiz with Leerink Partners. Your line is open. Hi. Morning, everyone. Just adding on to the prior question, I was curious if you could give more granularity on the subsequent dose escalation plans that you have across your PSMA and HER2 programs. And secondly, I was particularly curious which specific doses and schedules you might want to test and how much Q3 week data do you have at this point? Thank you, Roanna. Mika. Please go ahead. Yeah. In terms of more granularity of our HER2 and PSMA plans, for HER2, we're focusing more on the Q3 week dosing at this point. And we're currently at 800 micrograms per kg. We do believe that we have some room to move with that drug, but we haven't reached the MTD. And so it's unclear yet what that ceiling would be for the HER2 space. For PSMA, we believe that we're very early in our dose escalation stage with just really very minimal toxicities, and as I mentioned in the presentation, we only have one grade three related event, and that's a laboratory finding, so there's really very little toxicity. Again, we're not using prophylactic steroids, and we have a very low grade CRS rate, so we believe that we're still in the early stages for dose escalation for the PSMA drug. Then, in particular, regarding to which doses we want to test and at the Q3 week dosing schedule, for HER2, we are, again, as I mentioned, we're focusing really on the Q3 week dosing primarily. We do believe that the Q3 week is significantly advantageous. Our early data suggests that it is similarly well tolerated. There doesn't appear to be any resensitization with that extra holiday that you have between the three weeks, and as well, we've seen responses at the Q3 week with the HER2 agents. And so we do believe that it's still early, but we do believe it's similarly efficacious, but much more convenient in dosing. And there might be an advantage of giving the immune system a holiday between those three weeks because weekly intense T-cell activation may not be necessarily good for your immune system. So overall, the focus has been on the Q3 week. We just started for the PSMA drug the Q3 week dosing, and we don't yet have data on that. But we're also very encouraged because of that superior half-life of 8 to 10 days, really affords that Q3 week dosing with the possibility of even less frequent dosing, which would be really advantageous in the earlier line setting. Super helpful. Thanks. The next question comes from Gena Wang with Barclays. Your line is open. Thank you. Congrats on great data. I have two questions. One is more technical. One is clinical data. So the technical question is regarding your dual masking component, the XPAT proteins. Can you give a little bit more color regarding the molecular weight? And are these two components, the molecular weight, identical? And also for the two candidates? And then second, the clinical data questions, maybe slide 30, when we look at the 300, 600, 1,000 microgram per kg QW versus 2, 3, 400 microgram per kg, we did not see too much dose response. I know it is small patient numbers, and it's too early. So maybe any thoughts there? And I'll follow up, Mika, where you just comment, would that be the similar dose you will carry forward with Q3 week dosing? So regarding the technical question on the dual masking, so I'm not quite sure if you mean on both sides of the mask or between the two molecules, but on both sides of the molecules, it's slightly longer on the CD3 binding side versus what's on the tumor antigen binding side. And that's true for both molecules, both the PSMA and the HER2. And the molecular weight overall, we don't have the exact molecular weight. It's slightly smaller than an antibody, but it is around 150 or so kilodaltons is my belief. But I would need to go back and check the actual molecular weight. With regards to the clinical data of looking at those different dose levels for VIR-5500, the 400 microgram per kg top dose versus 1,000 microgram per kg top dose, I think you're right in terms of that the data is still pretty small. We only have a few patients per cohort at this point. And so it's really likely that we're going to get more robust understanding of dose response when we get to higher doses, which we do believe we have a lot of room to move on that dose escalation. And as well, we do think that we're looking at 2,000 micrograms per kg at the Q3 week dose level right now. And so we still need to generate that data. And we'll continue to dose escalate even beyond 2,000, which we think we have the room to do, so. But I also would like to ask Dr. de B ono whether he wants to talk about dose response and the experience with T-cell engagers in general. I mean, ours is really early, but perhaps he can give us some of his experience with other T-cell engagers. Yes, of course, Mika. I think a few things to say is that we have, with these agents seen at higher doses, have more anti-tumor activity. So we would be very hopeful that with dose escalation, the PSMA CD3 dual mask compound will have more anti-tumor activity. And I'm actually quite confident of that. And I want to again say that we have a lot of evidence, published and unpublished, that the earlier you go in this disease, and these are obviously very late-stage subjects, heavily pretreated. But as we'll go earlier, particularly into the pre-chemo space, I am confident that these tumors will be more responsive to this kind of therapy. We've shown that before with other T-cell engager trials. Perhaps the most important thing with this agent is that we're seeing minimal, if any, CRS and IL-6 release with this dual masking in the light of substantial anti-tumor activity, as you see in my patient, 90% PSA fall, tumor liquefaction on MRI scan, and resolution of his PSMA PET tumor detection. This is really quite a major advance because we have never really had any doubt that these drugs work. With the other T-cell engagers, which had impressive responses before, but before it was the CRS that was limiting drug development. The fact that this dual masking has minimized CRS is a huge advance, as Josep Tabernero said in his talk as well. Thank you very much. The next question comes from Mike Ulz of Morgan Stanley. Your line is open. Hi. Good morning. This is Rohit on for Mike. Thanks for taking our questions. For VIR-5818, is there a bar that you think you need to hit on efficacy for colorectal cancer? And then secondly, when can we expect to see higher dose data for both programs? Thank you. So for VIR-5818, in terms of what we would need in terms of response rate for colorectal, we believe that in HER2 and tucatinib and the trastuzumab and that, they have an overall response rate of around 38%, if I recall correctly. And so we are currently around 33%. But what is very likely is that we would initiate and post standard of care treatment. And so the bar there is much, much lower. So for drugs like ramucirumab, which have single-digit overall response rate, we believe a 33% response rate would enable an accelerated development, accelerated regulatory path for us. In particular, given that this is a biomarker-driven patient population historically, the health authorities have been very favorable in looking at patient population with a high unmet need, and so we think we're already there. Our data is still with small numbers, and so we clearly need to generate more data in order to confirm that response, and then the other thing that I would also add in terms of overall efficacy is that we talked about the ctDNA preliminary data that we have across a subset of patients, and the ctDNA response rate, we have a 54% molecular response and a 31% with 100% molecular response for ctDNA, and we know that tumor shrinkage can't capture all of the activity for T-cell engagers and TCRs in that they can cause some pseudoprogression, and so tumor shrinkage may be masked. We're encouraged by that molecular ctDNA data because that's across a number of doses and as well as in HER2 low across multiple indications. We're now collecting ctDNA as mandatory for all patients. The collective information that we're going to have with a few more patients in colorectal as well as other indications with both RECIST and ctDNA will be well-positioned to make any future decisions for further development. In terms of seeing additional data for these programs, we're not yet committed to disclose anything as of yet. We certainly would like to update with significant amounts of data that we will have for both programs. Right now, given that we're still in dose escalation, it's really very difficult to know when that next milestone will be. Thank you. The next question comes from Eric Joseph with J.P. Morgan. Your line is open. Hi. Good morning. Thanks for taking the questions. Just one each on the two TCEs. On 5818, I'm wondering whether there's any observable relationship between depth of response either by RECIST or ctDNA that tracks with the intensity of HER2 expression and whether looking forward, you might focus the scope of qualifying tumors by HER2 status. And then on 5500, just as you look to just looking forward with further dose evaluation, I guess maybe just can you speak to the rationale to the weekly titration scheme within each dose cohort? And just given the tolerability that you're seeing so far, being highly favorable, any plans to sort of dispense with that and start with the intended maintenance dose? Thanks. Oh, well, so I'll start with the first question. In terms of relationship with RECIST and ctDNA relative to the HER2 expression, unfortunately, early on in our dose escalation, we did not mandate ctDNA collection. So we only have about 11 or 12 patients or so worth of data, and that's across a number of doses. It's really difficult to correlate with all the other RECIST data. Right now, we don't have a ton of that data. What I can say in terms of the RECIST data itself with HER2 expression, we are seeing better, higher rates of tumor shrinkage with HER2 positivity. There is a trend there for that. We are still in dose escalation. Our prediction based upon preclinical data is that we do need to achieve higher doses in order to see a HER2 low response. But having said that, the ctDNA, as I mentioned, we have a HER2 positive or sorry, a HER2 low breast cancer patient with a ctDNA molecular response. And as I mentioned earlier, ctDNA may be a more sensitive measure of tumor anti-tumor activity than RECIST with this modality of immunotherapy due to pseudoprogression that can occur. So we really need to sort of, one, evaluate more ctDNA patients as well as get to higher doses in order to understand whether there is a dose response question. And then for your 5500 question, wasn't quite clear. Can you repeat that question again? Sure. It probably actually applies to both molecules. There's a titration scheme, a weekly titration scheme, right, for each dose cohort. Just given the tolerability profile, particularly favorable in colorectal excuse me, in prostate cancer, is there an opportunity, do you think, as you dose escalate to dispense with that titration scheme and just start with, I guess, the final dose that you'd intend to transition to the three-weekly dose interval? Yeah. Yeah. So we are currently using the BOIN method in terms of dose escalation. And I think the issue really is it would be a major amendment to the study to change the design of our dose escalation criteria. And so we can be more aggressive in our dose escalation as approved by our safety committee that approves both clearance of cohorts and dose escalation. And we have been very aggressive in our dose escalation. We've significantly went from 30 to 2,000 micrograms per kg in six cohorts. So we're rapidly dose escalating. But T-cell engagers can be very toxic. And we think our double mask has really shown that superior safety profile that allows us to be more aggressive. But we have to sort of balance what we have in the protocol. Okay. Great. Thanks for taking the questions. Thank you. The next question is from Alec Stranahan with Bank of America. Your line is open. Hey, guys. Good morning. I want to offer my congrats on the good data as well. Two questions from me, both on 5500. Maybe first, could you talk a bit about the one patient with the grade 3 AST increase? Was there anything unique about this patient or maybe something in the step dosing or somewhere else that could be driving this for that patient? Secondly, just on the steroid prophylaxis, it looks like this could stifle the TCE activity if done for too long from what we've seen from some of your competitors. So I appreciate that the prophylactic steroids were not given in your studies, but curious whether rescue steroids are still allowed, say, for managing the low-grade CRS and whether any patients receive this to date. Thank you. Yeah. So with your first question, the one grade 3 AST increase, as I recall, that patient does not have any concurrent ALT increase. It's unclear what that is. And so that's all I can really comment on that right now. In terms of steroid use, we do believe that, as Dr. de Bono had mentioned, that corticosteroids can fuel tumor growth. So we clearly agree that to try to avoid prophylactic use as much as possible is essential. So we're trying to prioritize that lack of use as well. In terms of managing low-grade CRS, as the investigators are getting more comfortable, and I'll ask Dr. de Bono to comment on this, the low-grade CRS such as fever can be managed by antipyretics generally. When you get to grade 2 CRS, I think most investigators have been trying to use steroids to sort of quench that, which is really kind of unavoidable because you don't want to necessarily have that to progress to grade 3 CRS. Some investigators try to use tocilizumab instead of going there, but typically, they give both just because of the potential severity that could happen with that. Now, having said that, I would say those comments were really more for 818. The 5500 CRS has been really, really very manageable. But I'll have Dr. de Bono comment on steroid use and his experience. Thank you, Mika. I think there are major concerns with steroid use in prostate cancer. Clearly, there is the concern of immune suppression, which would limit the activity of this class of agents. But more importantly, the laboratory of Charles Sawyers and others have raised concerns that steroids can fuel tumor growth. And indeed, in some of these tumors, we get androgen receptor mutations that actually are activated by glucocorticoids that are given as therapeutics. So basically, the therapeutic steroids fuel prostate cancer growth. So giving steroids generally for prostate cancer specifically is not a good thing. And probably it's not a good thing broadly across other cancers too. But specifically in prostate cancer, it really is a concern. We have probably done at least a dozen different T-cell engager trials in my unit. I think it's a fair statement that this agent, this IMP, has been the one with the least number of IMP-related CRS events that we have seen to date. So it would appear to me that this dual masking genuinely is working, and we have been very stringent in calling any grade 1 pyrexia temperature increase a CRS. Really, I think it's fair to say that my colleagues at Amunix have been very diligent in making us call these pyrexias CRS. But I am very confident that so far, steroid use or any kind of therapy to manage this CRS has not been necessary across the trial, which kind of really is quite unusual and was arguably the most important thing that we needed for this class of drugs, which has really limited their developme nt. Great. Thank you. The next question comes from Phil Nadeau with TD Cowen. Your line is open. Good morning. Marianne. C ongratulations on the data. Two questions from us as well. First, on 5818, could you talk in a little bit more detail about what you saw in the 13 patients with breast cancer? I think you had one case study, but we're asking more broadly, what are you seeing in breast cancer, and what are the next steps there? The second for 5500, were you able to discern any predictors of response among the patients? For example, was there any correlation of response with treatment with a prior PSMA agent, or is it simply too early to discern those factors? Thanks. Yeah, so for 5818, in terms of the breast cancer patient cohorts, we had both HER2 positive and HER2 low patients. And we had very few HER2 high patients enrolled in the study, and a bunch of those were at lower doses. Given just the heterogeneity in terms of those patients as well as the dose range, it's really hard to make a call on trend for efficacy or whatnot other than that spectacular response that we saw at a high-dose in a HER2-positive breast cancer patient. So we really need to generate more data in a homogeneous breast cancer patient in order to really understand what the activity is. In terms of the 5500 question, in terms of predictors of response, I think it's still really too early to say. We did have patients with prior PSMA radioligand therapy, but those patients were treated at the low-dose cohorts. And so, again, really hard to say that there's any predictors of efficacy or resistance. That's very helpful. Thanks again, and congrats on the data. Thank you. That is all the time we have for questions. I'll turn the call back over to Rich. Thank you, everyone, for your interest and participation. We appreciate your support and look forward to providing you future updates on our progress. So thank you, operator. This now concludes the call. Thank you. This concludes today's conference call. Thank you for joining. You may now disconnect.