Good morning and welcome to the Bicycle Therapeutics call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on your touch-tone phone. To withdraw your question, please press star, then two. Please note this event is being recorded. You may listen to a webcast replay of this call by going to the investor section of Bicycle's website. I would now like to turn the conference over to CEO Kevin Lee. Please go ahead. Thank you. Good morning from the San Antonio Breast Cancer Symposium, and thanks to everyone for joining today's call to discuss our program updates for zelenectide pevedotin. We're excited to review data updates for zelenectide pevedotin, discuss the role of Nectin-4 gene amplification and its importance in cancer, and outline our ambitious development strategy that we believe has the potential to position Bicycle as the leader in addressing Nectin-4 associated cancers. Next slide, please. Before we get to the presentation, I want to make you aware of our forward-looking statement disclaimer. Next slide. Today, I'm joined by members of my management team, our Chief Financial Officer, Alethia Young, our Chief Development Officer, Dr. Santiago Arroyo, and our Chief Strategy Officer and Head of Commercial, Jennifer Perry. I'm also excited to have two distinguished oncologists and members of our clinical advisory board join us this morning, Dr. Niklas Klümper from the University Hospital Bonn in Germany and Professor Sherene Loi from the Peter MacCallum Cancer Centre in Melbourne, Australia. Next slide. Here is the agenda for today's call. After I make some opening remarks, I'll hand over to Santiago to review the top line zelenectide pevedotin plus pembrolizumab combination data in first-line metastatic urothelial cancer. He will also provide an update on Duravelo- 2 enrollment timelines. Then Dr. Klümper will provide an update of Nectin-4 gene amplification, followed by Professor Loi, who will review the zelenectide monotherapy data in breast cancer patients and triple-negative breast cancer patients with Nectin-4 gene amplification. Santiago will then take us through top line zelenectide monotherapy data in non-small cell lung cancer patients with Nectin-4 gene amplification and our ambitious development strategy. Then we'll move into Q&A, for which Alethia and Jennifer will join us. Next slide, please. At Bicycle Therapeutics, we're using our novel platform to pioneer a new and differentiated class of medicines. Our current focus is in oncology, where we have multiple therapies in clinical development. However, through our various partnerships, our platform is showing potential in many disease areas. We currently have three bicycle molecules in clinical development for various cancers, with bicycle toxin conjugate zelenectide pevedotin being our most advanced. We also recently shared our first human imaging data from our novel radiopharmaceuticals program, and we are working to advance our bicycle radionuclide conjugates into the clinic. With our last financing round, we are well-financed and well-positioned to execute on our plans, including the ones which we will outline today. I'll now turn over to Santiago to provide an update on the progress we are making with zelenectide. Santiago? Thank you, Kevin. I am Dr. Santiago Arroyo, Chief Development Officer at Bicycle. In this section, I will provide a brief overview of zelenectide and Duravelo- 1 trial before discussing the first of our data updates, zelenectide and pembrolizumab combination data in first-line metastatic urothelial cancer, or mUC. I will also be providing an update on Duravelo- 2 enrollment and timelines. Next slide, please. Nectin-4 is a cell-adhesion molecule and is overexpressed in a number of solid tumor cancers, including bladder, lung, and breast cancers. We designed zelenectide pevedotin to target Nectin-4. It has a highly specific bicycle toxin conjugate that binds to Nectin-4 and selectively delivers MMAE to tumors expressing Nectin-4. Next slide. We have been studying zelenectide in various tumors in our phase I/II Duravelo- 1 trial. It is an open-label trial. The first involved dose escalation as shown on the left side of the slide, then dose expansion at the recommended phase II dose, as shown in the middle of the slide. Last December, at our end date, we shared data from patients enrolled in the dose escalation and dose expansion cohorts. We also announced the addition expansion cohorts shown on the right side of the slide and guided to sharing data from these cohorts this year. In September, at ESMO, we shared the first of these data updates, zelenectide monotherapy data in second-line plus EV-naïve mUC. Today, at the San Antonio Breast Cancer Symposium, we are sharing the rest of our updates. The top line data for zelenectide and pembrolizumab combination in first-line mUC, zelenectide monotherapy data in second-line plus breast cancer and TNBC, a poster containing full results, was presented yesterday, and Dr. Loi will momentarily present her highlights from them. We will also be presenting top line results from zelenectide monotherapy in second-line plus in NSCLC. We are planning to present more details for the mUC and NSCLC results at future medical meetings. Next slide. These are the top line results from the zelenectide pevedotin first-line cis-ineligible mUC cohort in combination with pembrolizumab. The response data are promising and in line with other therapies used to treat first-line mUC. Furthermore, the safety and tolerability profile continued to be differentiated from ADCs. In this cohort, 22 mUC patients who had not previously been treated and were not eligible to receive cisplatin chemotherapy were enrolled and treated with zelenectide at the recommended phase II dose of 5 mg/sqm weekly plus pembrolizumab 200 mg once every three weeks. The median age was 77 years old, and the majority of the patients were male. Half of the patients had ECOG performance score of two. As of September 13, 2024, data cut, 20 of the 22 enrolled patients were efficacy evaluable. 12 of those 20 had either partial or complete response, resulting in an overall response rate of 60%. Of the responses, five were confirmed and seven were unconfirmed. 15 patients remained on treatment at the time of this data cut. The safety and tolerability of zelenectide plus pembrolizumab were in line with what we saw in the second-line monotherapy and combination cohorts. Adverse events of clinical interest, such as peripheral neuropathy, skin reactions, and eye disorders, were primarily low-grade. There was only one report of grade 3 sensory peripheral neuropathy and one report of grade 3 rash. Both of them were transient and reverted to grade 1 upon dose interruption. Overall, we are very pleased with this top line data and look forward to presenting more detailed information at a future medical meeting. Next slide, please. As you know, we are currently conducting our phase II/III Duravelo- 2 registrational trial, evaluating zelenectide plus pembrolizumab versus chemotherapy in first-line mUC, cohort 1, and zelenectide monotherapy and in combination with Pembro in second-line mUC, cohort 2. In contrast to the open-label Duravelo- 1 trial that only included cis-ineligible patients, Duravelo- 2 includes both populations. We initiated Duravelo- 2 in the first quarter of this year, and we have been executing against our plan for site activation and enrollment. We have made great progress, and as of today, we have 140 sites active in 20 countries, including the U.S., and regulatory approval to conduct the trial in 26 countries. Enrollment has been progressing very well, with more than 140 patients enrolled to date. Given the impressive progress, I am pleased today to say that we expect to be in a position to report dose selection and top line data for both cohorts in the second half of 2025. Now I will turn over to Dr. Klümper to discuss Nectin-4 gene amplification. Thank you, Santiago. Hello, everyone. My name is Niklas Klümper. I'm a consultant for GU Oncology at the University Hospital Bonn in Germany, and I lead the translational neuro-oncology research group. My research focuses on drug development of drug conjugates and Nectin-4 gene expression, and as Kevin said, I'm also a member of Bicycle's Clinical Advisory Board. I'm pleased to provide an overview of Nectin-4 gene amplification as a promising biomarker to streamline drug development of anti-Nectin-4 therapies. Next slide, please. Gene amplification is a common mechanism by which cancer cells gain function. The more copies of a gene, typically the more protein that is expressed. It was actually Bicycle Therapeutics that first identified that the Nectin-4 gene sits on a commonly amplified chromosome in various solid cancers. The company has filed multiple patents around this observation. My colleagues and I recently published research at JCO that identified Nectin-4 gene amplification as a predictive biomarker for anti-Nectin-4 enfortumab vedotin response in metastatic urothelial cancer. Since zelenectide pevedotin also binds to Nectin-4, we hypothesized that Nectin-4 gene amplification may predict zelenectide pevedotin response and could serve as a biomarker for therapy stratification. Next slide, please. This slide is work done by Bicycle to examine the frequency of Nectin-4 gene amplification across entities using the Pan-Cancer TCGA data set. As you can see, Nectin-4 amplification is a frequent genomic event across many solid cancers. Notably, you can see that it is observed in over 20% of breast, bladder, and lung cancers. Next slide, please. In an independent breast cancer cohort, we were able to validate the high frequency of Nectin-4 gene amplification in breast cancer. If we look at the breast cancer subtypes, hormone receptor positive, HER2 negative, HER2 positive, and triple-negative breast cancer, Nectin-4 gene amplification, or polysomy, occurs in about 15% to 25%, with highest frequency observed in TNBC. Importantly, the graph on the right side shows an analysis of about 250 breast cancer samples and demonstrates that Nectin-4 gene amplification leads to significantly more Nectin-4 protein expression on the tumor membrane than in non-amplified tumor samples. Next slide, please. So what does this all mean? Well, our working hypothesis is that Nectin-4 gene amplification leads to stable and more Nectin-4 protein expression on the tumor cell membrane throughout metastatic spread. This results in more sites for Nectin-4 targeting agents, such as zelenectide pevedotin, which leads to a higher response. Therefore, Nectin-4 amplification might be a promising predictive biomarker for anti-Nectin-4 therapy drug development. In this context, it is well established for anti-HER2 drug conjugates that HER2 status closely correlates with therapy response across solid cancers. Given these findings, we have been working with Bicycle to understand the relevance of Nectin-4 gene amplification and the clinical activity of zelenectide pevedotin in breast and lung cancer. I will now turn it over to Sherene to take you through the breast cancer data. Thank you, Nicholas. Hi, everyone. I'm Professor Sherene Loi. I'm a medical oncologist specializing in breast cancer treatment, and I also am a group leader with research in genomics and drug development at the Peter MacCallum Cancer Center in Melbourne, Australia. I also chair the scientific committee of the International Breast Cancer Study Group based in Bern, Switzerland, which is the largest academic global breast cancer trial cooperative network. I'm also a member of the Bicycle Clinical Advisory Board. I'm pleased to share today the data from the Duravelo- 1 study for zelenectide pevedotin in breast cancer patients with Nectin-4 gene amplification, and these were presented at the San Antonio Breast Cancer Symposium yesterday. Next slide, please. So these are the demographics and clinical characteristics of the breast cancer patients enrolled in the study. 38 breast cancer patients were enrolled, 32 of which had triple-negative breast cancer. These patients that were enrolled into this phase I study were heavily pretreated with a median of six prior lines of therapy. Notably, nearly 100% of patients had received prior taxane, and around three-quarters of these patients had previously been treated with an ADC, the most common being sacituzumab govitecan, which has a topo-1 payload. The majority of these patients were treated with the recommended phase II dose of zelenectide pevedotin, which is 5 mg/sqm, and this was given weekly. Next slide, please. So these are the response data. It shows that breast cancer patients with Nectin-4 gene amplification, or polysomy, which is a copy number greater than six, experience a far higher response rate, objective response rate, to zelenectide pevedotin. In breast cancer, we saw a 62.5% objective overall response rate in patients with Nectin-4 amplification, or polysomy, versus 14.3% in the total efficacy available population. Specifically, in triple-negative breast cancer, the objective response rate in orange there was 57.1% versus 13.3% in all patients who were available for efficacy. Of note, the frequency of Nectin-4 amplification, which was performed in the study by FISH, is 30%, and this frequency has been confirmed in larger cohorts. This is a common genomic alteration in breast cancer. All three patients with triple-negative breast cancer with the amplification who responded to zelenectide had previously been treated with sacituzumab, and this is important as this has likely become first-line standard of care. There were zero responses in non-amplified or non-polysomic patients. Next slide, please. This slide shows the waterfall plots and the individual patient responses to zelenectide in this study, and as you can see, 100% of breast cancer patients who experienced the response had Nectin-4 gene amplification, or polysomy. Next slide, please. So this slide is the spider plot, which shows the duration of response to zelenectide. As you can see, the responses are considerably longer in patients with Nectin-4 amplification, or polysomy, and they seem to be very durable given the median lines of prior therapy in this population, including sacituzumab. These data are very encouraging, and of note, in triple-negative breast cancer, the median time to response in the second line is four months or less. Next slide, please. Importantly, this slide demonstrates the safety and tolerability of zelenectide in breast cancer. The data is consistent with other Duravelo- 1 cohorts in other tumor types, with most events being of low grade and a nature that oncologists should be able to manage. I'll just highlight a few relevant adverse events. One is alopecia, particularly for breast cancer patients, and at first sight seems that rates of complete alopecia are low. I'll also highlight here nausea, frequency is a little higher than expected, but this is as a result of antiemetics not being allowed in the dose escalation part, and we anticipate this should decrease in future studies with routine incorporation of antiemetics. Next slide, please. These are the adverse events of clinical interest with zelenectide, and this is also similar to other Duravelo- 1 cohorts. And you can see here relevant for breast cancer patients, the relatively low rate of peripheral neuropathy, given that most patients had prior taxane treatment and up to grade 1 baseline neuropathy was allowed, and the skin toxicity as well, which again differentiates potentially this agent from other agents targeting Nectin-4. For breast cancer patients, there's no ILD of note, which is important given that sacituzumab govitecan can have this significant problem, and also very little high-grade transaminitis, which bodes well for future combinations as well. Next slide, please. So in summary, there are important learnings from this data, even though it's a small number of patients. First of all, the data confirms that Nectin-4 amplification appears to be a common genomic event in breast cancer. As you can see, around a third of patients treated with triple-negative breast cancer had a gene amplification. And importantly, this amplification seems to be associated with significant response rates in triple-negative breast cancer patients who are still in need of new therapies. And importantly, there seem to be no responses in the non-amplified or non-polysomic patients, which is important for future biomarker selected populations. And also, as we have more and more relevant and interesting therapies in breast cancer, this identifies this as a biomarker-specific therapy and a new target for breast cancer patients. So despite this small study and this post-hoc analysis, I think this provides promising data for zelenectide's anti-tumor activity in breast cancer patients with Nectin-4 gene amplification. Thank you very much for your attention, and I'll now turn it over to Santiago. Thank you, Professor Loi. I will now share with you the top-line immunotherapy data in NSCLC patients with Nectin-4 gene amplification. Then I will discuss how this data informed our ambitious development strategy. Next slide. Similar to the breast cancer data, we found that NSCLC patients with Nectin-4 gene amplification showed an enhanced response to zelenectide. 40 previously treated patients with NSCLC were enrolled and treated with zelenectide monotherapy. We saw a 40% ORR in patients with Nectin-4 gene amplification versus 8.8% in the total evaluable population. Out of 19 patients tested for Nectin-4 gene amplification, none of the non-amplified patients responded, and as we've seen with the other data shared today, the safety and tolerability profile was in line with the data from Duravelo- 1 second-line monotherapy cohorts. More detailed information will be presented at a future medical meeting. Next slide. As the data we have presented today has emerged, we have been increasingly aware that we have a potentially unique opportunity to transform the lives of patients suffering from Nectin-4-associated cancers. Over the course of this year, we laid a robust foundation to enable zelenectide to be first-in-class in multiple Nectin-4 gene-amplified tumors. This was in addition to establishing zelenectide best-in-class potential in metastatic urothelial cancer. We also continue to build robust patent estate related to the use of Nectin-4 gene amplification and build our own CDx expertise to complement our selection strategy. Today, we are in a strong position to execute on our regulatory and clinical plans that you will see on the next slide. We are embarking on multiple studies that we believe can not only position Bicycle as a leader in addressing Nectin-4-associated cancers, but also potentially expedite zelenectide development. We have added two new cohorts to Duravelo- 1, one for breast and another for the lung, to help us continue to explore the anti-tumor activity that zelenectide may have in patients with Nectin-4 gene-amplified breast or lung cancer subtypes. These cohorts are currently enrolling. Duravelo- 2, our registrational trial for zelenectide in metastatic urothelial cancer, continues to enroll patients. As stated earlier, we plan to provide dose selection and top-line data for both cohorts in the second half of 2025. We are also starting a dedicated breast cancer trial called Duravelo- 3 that will only include patients with Nectin-4 gene amplification and study zelenectide in previously treated patients with HR-positive/ HER2-negative breast cancer, and TNBC. We plan to initiate this trial in the first half of 2025. Duravelo- 4, our dedicated lung cancer trial that will enroll only patients with Nectin-4 gene amplifications and include previously treated patients with squamous and non-squamous NSCLC. And lastly, we plan to study zelenectide in a multiple tumor trial called Duravelo- 5 that will enroll previously treated patients with a variety of cancers, all selected for Nectin-4 gene amplification. We plan to initiate Duravelo- 4 and Duravelo- 5 in the second half of next year. Next slide. Through our strategy, we believe Bicycle is uniquely positioned to potentially transform patient treatment across multiple Nectin-4-associated cancers. By selecting for Nectin-4 gene amplification status, we have the potential to help about 150,000 U.S. patients across various tumor types. This, in addition to the about 25,000 patients with metastatic urothelial cancer. We believe this represents a significant patient population who may be able to benefit from zelenectide. Next slide. In summary, to date, we have now dosed zelenectide in more than 325 patients across a spectrum of cancers. From this work, we believe that we are seeing a drug candidate that exhibits an improved and potentially beneficial tolerability profile compared to ADCs without any compromise in ORR and the early promise of potential enhanced durability. In metastatic urothelial cancer, we have initiated our ambitious Phase II/III pivotal study and are very pleased with our progress. Today, we have presented our first glimpse of zelenectide's potential in combination with a checkpoint inhibitor, and we are delighted that its promise as monotherapy seems to be maintained when in combination with CPI. We look forward to sharing those selection and top-line data from Duravelo- 2 cohorts in the second half of 2025. In addition, we now present a novel and potentially unique approach to the development of zelenectide pevedotin across Nectin-4-associated cancers using Nectin-4 gene amplification as a novel selection strategy. We believe we have created a strong leadership position and continue to build a robust patent estate. We believe Zelenectide has the potential to be best-in-class in metastatic urothelial cancer and first-in-class in other cancers, and that it is our duty to get Zelenectide to these patients as quickly as possible. We have also delivered on the updates we committed to providing this year, and we look forward to initiating our additional trials for Zelenectide next year. Thank you very much. Kevin, back to you. Thanks, Santiago. We'll now begin the Q&A portion of our call. Operator, first question, please. We will now begin the question-and-answer session. To ask a question, you may press star, then one on your touch-tone phone. If you're using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star and then two. Please limit yourself to one question and one follow-up. The first question comes from Li Watsek with Cantor. Please go ahead. Good morning. Congrats on the data. F irst on the front-line combo data in bladder cancer, I wonder if you can talk about how it stacks up against platinum-based chemo. And for the unconfirmed responses, would you be able to say if these patients are still on therapy? And then what's your confidence level that they'll be confirmed with a longer follow-up? Thanks. Hi, Lee. Thanks for the question. As we stated, we're going to give an update on the status of the study at a medical meeting, and then we'll provide more information at that time. Thank you. The next question comes from Jay Olson with Oppenheimer. Please go ahead. Oh, hey. Congrats on the progress, and thanks for providing this update. We have a multi-part question for the KOL on Nectin-4 gene amplification. Can you help us understand why Nectin-4 gene amplification is a better predictor of response compared to Nectin-4 protein expression? And also, can you use ctDNA for the Nectin-4 gene amplification test? And then as a follow-up, can you talk about Nectin-4 gene amplification as a prognostic factor? And is there any correlation between Nectin-4 gene amplification and PD-L1 expression levels or any other important biomarkers? Thank you. Thanks, Jay, for the question. I'm going to hand that over to Niklas. Yeah. Thank you for the question. So in urothelial cancer, we have shown that Nectin-4 amplification is a more stable and reliable biomarker compared to Nectin-4 protein expression, which often decreases during metastatic progression. Genomic biomarkers are easier to implement with clear-cut thresholds than immunohistochemistry and easier to incorporate into existing NGS panels to implement them for standard of care. We have seen in the EV-202 clinical development for tumor-agnostic in breast cancer and lung cancer and other tumors that there's a lack of association between Nectin-4 protein expression and EV response. Regarding your second question on ctDNA, so currently, there's no data out there which demonstrates that you can identify Nectin-4 amplification via ctDNA, so I cannot comment on this, and the third question was about prognostic value. So we've looked into that, published also in our JCO paper earlier this year for urothelial cancer. And at baseline in a non-EV treated cohort, Nectin-2 amplification had no prognostic impact. So it seems that Nectin-4 amplification is not leading to more aggressive phenotype. In breast cancer, we've looked into that as well. And it seems as well that Nectin-4-amplified tumors have not another worse prognostic outcome compared to the non-amplified setting. Thank you. Regarding overlap with other biomarkers such as PD-L1, we have no data out there to correlate this. Great. Thanks for taking all the questions. Thanks, Jay. Next question comes from Kelly Shi with Jefferies. Please go ahead. Congrats on the progress. For the Pembro and zelenectide combo, on the safety data table, it was measured at 27% all-grade peripheral neuropathy. The line below is sensory events. Just to confirm, this is not added, but it refers to the 27% PN actually sensory. Thank you. Kelly, could you repeat the question? I didn't quite catch the end of it. So the sensory events listed below peripheral neuropathy is not added, but it just referred to the 27% peripheral neuropathy. We saw 27% peripheral neuropathy in the study, if that answers your question. Yes, that's right. Thank you. On slide nine. Next question, please. The next question comes from Gregory Renza with RBC Capital. Please go ahead. Great. Good morning, Kevin and team. Congrats on the update today. Thanks for taking my question. Kevin, just maybe on the Zel/Pembro update and that cohort, just curious if you can talk a bit about Nectin-4 expression status and these populations, if you've checked those, and what the potential biomarker strategy would look like in bladder populations? Yeah. Thanks for the question. Others as well. Thanks so much. Yeah. Thanks for the question, Greg. In bladder, it's slightly different. The Nectin-4 is highly expressed across all patients. We don't believe that an amplification strategy is required given the strength of the data that we're presenting today. Obviously, in bladder, breast, and other indications, the expression levels are much lower, and an amplification strategy is warranted. And you can see the product of that approach there. We're very excited and happy about what we're seeing using amplification in breast and lung, but probably not required in bladder. And the next question comes from Tara Bancroft with TD Cowen. Please go ahead. Hi, good morning. So I have more of a kind of theoretical question. But considering that you have differential activity in expressors or non-expressors that you see here, what's your theory for how Padcev observed a couple of responses in IHC0 patients when they presented initial data at ASCO? Do you think in a larger data set that you would be able to achieve some responses as well? Or if not, why do you think that zelenectide would be different? And just a follow-up on that, can you clarify a bit more how amplification and polysomy would translate to expression by IHC? Would amplification be a super high H score or not? Thank you so much. So taking the last question first, we've shown that in the amplified breast population, we see high levels of membrane Nectin-4 expression. So we believe there is a correlation there. I don't really want to comment on other people's molecules. For us, we're very much focused on using amplification to select patients in indications beyond bladder cancer. Thank you. The next question comes from Maxwell Skor with Morgan Stanley. Please go ahead. Maxwell, your line is now live. Great. Sorry about that. Thank you for taking my question and congrats on the update. I have a clarification question. Did the KOL say that Nectin-4 protein expression decreases through the lines of treatment? So would you assume that a Nectin-4 targeting approach would have a greater impact at earlier lines of treatment? Are these clones potentially selected for or not selected for as you go through lines of treatment? Just trying to get a better understanding of where this could fit in the treatment paradigm. Thank you. Thanks, Max. I'm going to hand that over to Niklas, who's the expert on this and has done a lot of work around this. So, up to you, Niklas. Thanks for this question, so yes, for urothelial cancer, we published this in Clinical Cancer Research in 2023, and we've seen in a cohort of patients matched samples, primary tumor metastatic sample, that membrane Nectin-4 expression often decreases to the metastatic sample, so it seems to be that anti-Nectin-4 targeting therapies might be of higher efficacy in the primary tumor setting or in an earlier sequence. We don't have such data for breast cancer, but we want to look into that as well for breast cancer, but it seems to be like that Nectin-4 amplification is a very stable genomic event, and in patients with urothelial cancer, Nectin-4 amplification in a primary tumor is usually preserved also in the metastatic sample, so these are the patients who might have the best and longest benefit of anti-Nectin-4 targeting therapies. Thank you. And the next question comes from Peter Lawson with Barclays. Please go ahead. Hey. Thank you so much. So congrats on the data, r eally appreciate it, a nd congrats on the enrollment as well. I wonder if you provide any details around the enrollment, how it's going for first-line versus second-line, if you think this data helps kind of accelerate first-line over second-line enrollment? Thanks, Peter. That's a great question. I'm going to pass that on to Santiago. I mean, both cohorts are recruiting well. We are slightly more advanced in the second-line, but actually, both of them are doing well. We will do an interim analysis with both cohorts together, and as mentioned before, we will have results and hopefully the FDA feedback by the second half of the year. Got you a nd then just the other part of that question was just around whether you think the data kind of if you're already seeing kind of an uptick in first-line over the second-line? The investigators that we work with are very excited by what they're seeing in their studies, and clearly, these data are very supportive of the molecule's activity and safety, so I believe that it will obviously help, so yeah, I think that's fair to say. Thank you. Then the follow-up would just be around how much data we should expect to see in the second half. Santiago. We will be doing the interim analysis. As you recall, the interim analysis is once we reach 30 patients per cohort. So it will be a total of 150 patients. 30 of those will be treated with chemotherapy, and then 60 and 60 with combination hormonal therapy at two different doses. Perfect. Thank you so much, r eally appreciate it, c ongrats. The next question comes from Max Dahl with Goldman Sachs. Please go ahead. Hi, this is Max on behalf of Rajan Sharma. So we have a couple of questions. So first of all, are you likely to use a monotherapy approach in breast cancer and in other indications? Or is there a potential for combinations? That's the first one. Another one is, what's your latest level of confidence in the probability of Duravelo- 2 via Project Frontrunner? So this is from the FDA. Is there risk that changes at the FDA under the new leadership may impact Project Frontrunner and your prior expectations? And sorry, third one, if I may. How do you think about R&D cost evolution in 2025 given that there are going to be additional trials plus ongoing Duravelo- 2 trial? Thank you. Thanks, Max. So regarding we've seen great activity as a monotherapy. So we'll obviously push that hard. We will consider combinations, as you might expect us to. We really want to maximize the value for patients. And one of the great things about this molecule is its safety profile. So combining and Professor Loi has already alluded to that. Regarding your last two questions, I'm going to hand that over to Alethia. Great. Thanks. Hey, Max. You were talking about the regulatory environment. We can't speculate on what's going to happen there. We have great collaborative collegial relationships with the FDA, and we hope that we can expect that will continue, and then around the R&D cost, we've said when we raised capital earlier this year, and we raised $555 million gross, that we have a runway into the second half of 2027. Obviously, that factored in development of Duravelo- 2 and thinking about the progression of an amplification strategy and radiopharm and everything. So we're comfortable where we're at. We don't get direct guidance on how to think about R&D growth. Thank you. The next question comes from Ami Fadia with Needham. Please go ahead. Good morning. Congrats on all the progress, and thanks for taking my question. Just based on the data that you've seen so far, where do you see the differentiation for the product versus Padcev in breast and lung? Do you expect it to be sort of comparable on efficacy similar to what we're seeing in UC and the key differentiation coming from safety, which translates into durability? And then also just more broadly, if you sort of demonstrate a path forward in Nectin-4 expressing tumors, amplified tumors, is there a regulatory path to obtain approval across cancer types based on just Nectin-4 levels? Thank you. Let me hand the first question over to Alethia. There's a lot there to unpack, Ami. I might have to come back and ask you to repeat some of those questions. So if I understood the first part of what you were saying is it's talking a little bit about the differentiation potentially in breast and lung from the strategy we discussed today. Is that correct? Is that the first part of your question? Right. Yes. Great. So to answer that, just think about what we've shown today. And obviously, it's still very early. But when you look at Nectin-4 amplification versus the non-amplified patients in breast and lung, there were dramatic improvements in response rate, right? And this is what we showed in the slides today, and that's kind of the discussion at San Antonio that we're having around breast cancer. What we've also showed is differentiated safety is continuing to be a very strong trend here for us in line with what we've shown with bladder. So when you think about that, and as it relates to our other peers, we've seen clinical data that has not looked at Nectin-4 amplification, but the IHC and obviously the response rates have been a bit lower. We think that the strategy that we're pursuing here is differentiated as it relates to the exact strategy around Nectin-4 gene amplification. Maybe I'll toss it to Niklas to kind of round out anything I said there. Yes, thanks, Alethia, so in EV202, we've seen data at ASCO presented for the breast cancer and also lung cancer cohort, and in biomarker unselected populations also previously treated, there was an objective response rate of around 10% to 20%, which is in line with the efficacy of zelenectide in, for example, the breast cancer cohort in a biomarker unselected population, and we see that patients with zelenectide response are the ones with Nectin-4 amplification or polysomy, so with this strategy, it seems to be that we really have a very precise biomarker and a good rationale to move this strategy forward to have a larger benefit to the patients with Nectin-4 amplification on zelenectide, and this clearly differentiates to the other pipelines with Nectin-4 targeting therapies. Ami, could you repeat the other questions, please? There was just one other question, which was really, is there a path forward to a regulatory path forward to think about an approval in Nectin-4 amplified tumors irrespective of the cancer type? I'll hand that one to Santiago. Definitely. That's something that we are certainly looking at. We have evidence of responses in urothelial cancer. And now we have shown that we have strong evidence of response in breast cancer and lung cancer. So we will be exploring, as I mentioned before, not just breast and lung, but we will be exploring other cancer tumors with the idea of trying to seek potentially an approval in a basket of indications related to Nectin-4 amplification. Thanks, Ami. And the next question comes from Reni Benjamin with Citizens JMP. Please go ahead. Hey, good morning. Thanks for taking the questions and thanks for the data update. I might have missed this, Kevin, but can you talk a little bit about maybe the varying levels of gene amplification that you might be seeing? Is there a potential broader strategy to develop maybe even a new type of testing for this gene amplification? I guess where I'm kind of going with this is there were some non-responders within the gene amplified patients. Any learnings from those patients that might help maybe further refine patient selection as you move forward? Thanks. Thanks, Reni. I mean, taking the second question first, there is I think it would be unusual for every patient to respond. I think that there are always going to be some insensitivity to the payload, and that's something we'll study. I would point you to the fact that these are late-line patients on the whole. So we have to keep our open mind and judge the data as we receive it. In terms of the levels of amplification, there is a slide in the presentation that relates to that. Broadly speaking, we're seeing about 20% to 30% of the breast and lung populations having the amplification and then varying levels between 10% and 20% for many of the tumor types. So it's a common amplification across many tumors, and we believe it's very exciting for us. Do you think that there'll be a cutoff that you will establish kind of going forward, or did you see responders in those that had higher levels or not really? I think it's something that we will continue to explore. We have a battery of assays that we're applying as we explore this, all the various technology you might imagine we're applying, and we'll find the best, the one that's best suited for the broadest applications. Great. Thanks for taking the questions. Thank you. The next question comes from Swayampakula Ramakanth with H.C. Wainwright. Please go ahead. Thank you. My good friend Ren actually stole my question away. But just a quick one to Dr. Klümper. Based on your work on Padcev and in UC, how should we think about this drug in terms of gene amplification? It looks like it almost doubled the efficacy of Padcev in UC. I'm just trying to understand, can Padcev compete in these indications as well, which Bicycle is looking at? Thanks for the question. So as Kevin said earlier in the Q&A, urothelial cancer is the tumor type with the highest overall Nectin-4 expression. So there's also a lot of tumors with high membranous Nectin-4 expression in a non-amplified setting. We believe that Nectin-4 amplified tumors are the ones who have the best long-term benefit due to the fact that it seems to be that it's a stable event through augmented metastatic evolution. Regarding strategy in urothelial cancer, Kevin already answered this. Do you have another question for me? That's it. Thank you. Thanks. This concludes our question and answer session. I would like to turn the conference back over to Kevin Lee for any closing remarks. Thank you for joining us this morning. A replay of the call and webcast will be available on the company website. In the meantime, please reach out to Stephanie Yao, our SVP of Investor Relations and Corporate Communications for any questions. Many thanks for your attention and have a good day. Thank you. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.