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 touchtone 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 Investors section of the Bicycle website. I would now like to turn the conference over to Stephanie Yao, Senior Vice President, Investor Relations and Corporate Communications. Please go ahead. Thank you. Good morning, everyone, and thank you for joining today's call to discuss the first human imaging data for our Bicycle Radionuclide Conjugates and our radiopharmaceutical strategy. I'm Stephanie Yao, SVP of Investor Relations and Corporate Communications. Joining me this morning are our CEO, Dr. Kevin Lee; our Chief Financial Officer, Alethia Young; our Chief Technology Officer, Dr. Michael Skynner, and our Chief Product and Supply Chain Officer, Mike Hannay. Before we get to the presentation, I want to make you aware of our forward-looking statement disclaimer. And now I'd like to turn the call over to Kevin. Thank you, Stephanie, and thank you to everyone for joining us this morning. We're excited to review the first human imaging data for our Bicycle Radionuclide Conjugate or BRC, targeting the MT1-MMP, a novel tumor antigen that is overexpressed in many cancers. We will also discuss our strategy to develop differentiated radiopharmaceuticals. Here is the agenda for today's call. After I make some opening remarks, I'll hand over to Mike Skinner to review the first human imaging data for our radiopharmaceutical strategy. Then we'll move into Q&A with Alethia, Mike Skinner, Mike Hannay, and myself. Next slide, please. At Bicycle Therapeutics, we are using our novel platform to pioneer a new and differentiated class of medicines. Our focus is in oncology, where we have multiple therapies in clinical development. However, through our various partnerships, our platform has also shown potential in many disease areas. We recently shared updated clinical data for our molecules at ESMO, with additional data updates to come before the end of the year. So far, our molecules have been studied in more than 450 patients and are showing promising antitumor activity with emerging differentiated safety profiles compared to other drug conjugate approaches. Today, we will discuss our progress in using our platform to develop differentiated radiopharmaceutical medicines. Next slide, please. Since our founding, our goal at Bicycle has been to leverage the power of our platform in areas where we can have the most impact for patients. Over the years, we have built a robust pipeline of therapies to treat cancer, from targeted therapies to immune oncology and now radiopharmaceuticals. Our internal radiopharmaceutical programs build on what we've learned from our long-standing collaborations with leaders in this field. Today, we are excited to share the results of an important first step for us in this area, the first human imaging data for our first internal Bicycle Radionuclide Conjugate program. I will now hand over to Mike Skinner to further discuss our radiopharmaceuticals work and our strategy. Over to you, Mike. Thank you, Kevin. Let's move to slide six, please. I'm Dr. Michael Skinner, Chief Technology Officer at Bicycle. I'll be walking you through the first human imaging data for our BRC-targeted MT1-MMP, generated by the team at the German Cancer Consortium. But first, I'll give an overview of what we believe are our platform's unique capabilities to develop radiopharmaceuticals and our strategy. Next slide, please. At Bicycle Therapeutics, we are harnessing the power of bicyclic peptides to develop molecules that can precisely and selectively deliver payloads to tumors, using an array of diverse biological targets of interest. Our Bicycle platform is based on the work of Nobel Prize winner, Sir Greg Winter, widely considered the godfather of antibody therapeutics. Seeking to improve on antibodies, Greg discovered how to mimic the targeting part of an antibody, the paratope, with chemically synthesized, constrained, bicyclic peptides, which we call Bicycles. When appropriately formatted together or in concert with other chemical constructs, these Bicycle molecules allow us to selectively deliver toxins into tumors, to activate immune cells within the tumor, or, as in the case of radiopharmaceuticals, to deliver radioisotopes to tumors. A key attribute of the platform that enables our work in radiopharmaceuticals is an ability to target hard-to-drug oncology antigens. These Bicycle binders have high affinity for the designated target, are highly selective and exhibit attractive but tunable drug-like properties. Of course, it's also critical to be able to join these Bicycle molecules to suitable carriers or chelator cages that are used to deliver a range of different isotopes without changing the targeting affinity of the Bicycle molecule to the target. Next slide, please. There are two approved radiopharm therapies, Pluvicto, targeting PSMA, and Lutathera, targeting SSTR2. What unites these two successes is that the ligands used to deliver the isotopes are derived from peptides. Many other companies are pursuing programs to these same targets, as there is a shortage of peptide leads to other targets and limited mechanisms to generate new ones. With the Bicycle platform, we've solved this problem, as we can create new peptide-based ligands for targets which don't have natural peptide start points. Since our founding, we've been building a deep proprietary library of Bicycle molecules to a wide diversity of different targets, which we can now mine using machine learning tools. We've used these Bicycle molecules to obtain detailed structural information using techniques such as Cryo-EM, and more recently, by applying artificial intelligence, so we can accelerate and continue to generate new structures to new targets. This slide highlights some of the structures we now have in our database. Since our inaugural R&D Day last December, we've added 10 more structures to our collection. Next slide, please. For those of you familiar with Bicycle, you've heard us talk about the Bicycle advantage and how the properties of our Bicycle molecules are well-aligned for use as radiopharmaceuticals. Specifically, they have a low molecular weight, high selectivity, and high affinity for their intended target. As you can see from the time course in preclinical species, they rapidly extravasate and flood the body and tumor within 10 minutes of administration, driven by their small molecule-like pharmacokinetics. Then, as they are peptides, they're rapidly cleared by the renal route of elimination over the next 50 minutes, but are retained in the tumor, where they persist, in part due to their slow target off rate. When applied to the radiopharmaceutical space, we believe our Bicycle Radionuclide Conjugates, or BRCs, have broad potential medical application as both diagnostics and therapeutics. Next slide, please. We're taking a three-pronged approach to our radiopharmaceutical strategy. Firstly, a key cornerstone of our approach has been partnering with industry and academic leaders in the field to build our understanding and deepen our knowledge base. We are proud to collaborate with Novartis and Bayer, the only companies to date with approved radiopharmaceutical therapies, to use our Bicycle platform to discover and develop new potential therapies in this space. And we're very lucky to have a group of distinguished oncology advisors at our disposal to help us navigate the development of our internal radiopharmaceutical pipeline. Secondly, we intend to pursue novel targets by first intent. We believe we can make a greater difference to patients by developing innovative new therapies to help patients live longer and to live well. Through the use of early human imaging agents, we can understand and de-risk novel targets, allowing tumor and non-tumor distribution to be profiled to evaluate tumor pharmacokinetics, as well as profile potential patient populations across a range of tumor types. Finally, we believe one of the great strengths of our technology platform is the ability to pair our Bicycle molecules with any isotope. We intend to study our BRC with a range of isotopes and select the one which best aligns with the target biology and indication. To do this, we plan to partner with various isotope suppliers, the first being Eckert & Ziegler. Next slide, please. MT1-MMP is our first radiopharmaceutical target. We believe it to be an attractive novel target with first-in-class potential. As you can see from the table in the slide, it's expressed across multiple high-value solid tumors with significant unmet need, while having low expression in normal tissue. On the right-hand side of the slide is a preclinical imaging study conducted with an early MT1-targeted Bicycle molecule. The image is generated with gallium-68 labeled MT1 and taken about one hour after dosing. Notice the distribution, with high uptake in the tumor, low uptake in healthy tissues, and clearance through the renal route of elimination. This is a typical profile we aim to generate prior to imaging with BRCs in humans. Next slide, please. I'm extremely proud to share the first human imaging data for a Bicycle radionuclide conjugate targeting MT1-MMP. This was presented yesterday at the European Association of Nuclear Medicine Congress by the German Cancer Consortium and is representative of other images from other patients using our MT1 targeted BRC. Here, we see a series of scans of a sixty-five-year-old male, diagnosed with advanced pulmonary adenocarcinoma of the left lower lobe and lymph nodes. This is confirmed by endobronchial biopsy ultrasound. The cancer. This cancer is the most common type of non-small cell lung cancer. On the left, the patient received FDG-PET/CT imaging, and two weeks later, MT1-MMP PET/CT imaging, up to one hour post-injection of the Gallium-68 labeled BRC tracer. The imaging was conducted under a form of compassionate use according to local regulations. Both PET scans revealed multiple mediastinal lymph node metastases and bone metastases in the sternum. MT1-MMP-specific PET imaging demonstrated tracer uptake in the primary tumor, as indicated by the arrow, as well as in both lymph nodes and bone metastases, consistent with the FDG-PET/CT findings. The MT1-specific tracer showed renal excretion, with all other organs only showing a negligible tracer uptake. Great imaging contrast was also observed at early time points. These initial data clearly demonstrate the feasibility of using the bicyclic tracer to visualize MT1-MMP-expressing primary tumors and metastases. Importantly, these data validate the role of this target in this disease and also clearly highlight the translatability of Bicycle molecules as potential radioimaging agents and radiotherapeutics from preclinical species and into the clinic. Investigations to assess the potential of BRCs for clinical use are ongoing. Next slide, please. Building on the positive human imaging data, our next aim is to develop an MT1-targeting theranostic. Here, our aim is to conduct iterative design, make test cycles, looking to improve drug-like properties such as affinity, as shown in the graph on the top left. This activity is enabled by structural determinations, as shown in the lower panel on the left. The overarching aim of this phase of the work is to improve the tumor-to-kidney ratio of our BRCs. As you can see in preclinical images on the right of the slide, generated with an Indium-111 imaging isotope, the animal on the left is dosed with a molecule similar to the one used to prepare the human imaging agent used by the German Cancer Consortium to generate the first human imaging data. While the image on the right side is an example of an advanced molecule that we've optimized for high tumor uptake and low kidney retention, which is the profile we intend to take into IND-enabling work with the ambition to progress into human clinical studies. Next slide, please. We're also delighted to announce today that our second BRC target is Ephrin A2, a target we know a lot about, and again, a target with first-in-class potential. Ephrin A2 is expressed in a wide range of high-value cancers with significant unmet need, as shown in the table, and our internal data suggests that Ephrin A2 expression increases with disease severity and progression. We've already selected a human imaging module based on its tumor uptake, low background staining, and renal route of elimination, and expect to progress this into human imaging in twenty twenty-five. Next slide, please. So what's next? For MT1, we were moving a theranostic BRC into IND-enabling studies. For ephrin A2-targeting BRCs, we intend to take a similar approach, i.e., to first develop an imaging agent and then develop a theranostic. We're on track to have an ephrin A2 molecule ready for human imaging in twenty twenty-five. As we progress our work in radiopharmaceuticals, we will continue to leverage the deep expertise of our clinical advisory board to help guide the optimal positioning of our BRC portfolio. Next slide, please. In summary, today, we've shown the first human imaging of an MT1-targeted drug conjugate, which demonstrates the potentially high value of MT1-MMP as a therapeutic target in oncology. We've also shown here and in previous releases that the Bicycle platform is well suited for radioisotope delivery. We can create new Bicycle binders to novel targets, regardless of whether they have natural peptide start points or not, tune their properties for optimal therapeutic effect, and compare them with any isotope, allowing us to remain isotope-agnostic. As for next steps, in twenty twenty-five, expect a further update on the imaging data set around the middle of the year, and for our first BRC molecules, we plan for them to enter Bicycle-sponsored clinical trials in twenty twenty-six. Thank you very much. Kevin, back to you. Thanks, Mike. We'll now begin the Q&A portion of our call. Mike Skinner, our CFO, Alethia Young, our Chief Product and Supply Chain Officer, Mike Hannay, and myself are here to take your questions. Operator, first question, please. The first question comes from Jay Olson with Oppenheimer. Please go ahead. Oh, hey, congrats on all the progress, and thank you for providing this update. We had a few questions. Maybe to start off, could you please talk about the expression level of MT1 in the kidney and how that impacts the tumor-to-kidney ratio? Hey, Jay. It's good to hear from you, and thanks for the, the question. As you can tell, we're pretty excited about this data. We think it's really exciting and looking forward to build on it. So with MT1 expression in the kidney, there is low to no expression of MT1 in the kidney. Okay, great. Thank you. And then maybe a big-picture question. Can you talk about your selection for the isotope for your BRC programs, and what are some of the key parameters that will factor into your decision around the isotope? ... Yeah, that's a really important question. I'm gonna hand that one over to Mike Skinner to answer. Hi, Jay. Yeah, I mean, our approach here is to remain isotope agnostic, and we feel it best to match the isotope with a particular tumor type, and the properties of the drug target. Clearly, different targets are expressed to different extents through a tumor, that may be expressed more homogeneously or less homogeneously, have different rates of internalization. And we believe those parameters together dictate which isotope that we need to use, and we'll determine that empirically. Okay, great. And if I could please ask one more question about the selection of FAP as a second BRC target. Can you talk about any learnings from your BTC program that can accelerate the clinical development of your BRC programs? And maybe the tumor indications that you're looking at for FAP, and then would you consider using the FAP radio imaging agent for your BTC program? These are really good questions. So, I think it's quite plausible that the EphA2 imaging agent may have value in whatever we do in the EphA2 space, including with 5528. We haven't disclosed exactly which target, which tumors we will pursue with a radionuclide conjugate. What was the middle question, Jay? I missed that one. Learnings from your BTC program? Oh, yeah, sure. I mean, we've lots of learnings. Obviously, we feel we are, you know, absolute leaders in the Ephrin A2 space. I think we have, you know, little to no competition in the space. We've now dosed more than 100 patients with 5528, and there are lots of learnings around target expression, and how that relates to 5528 activity, and we've published on some of that. What we need to do in the radio conjugate space is see if the same rules apply, and that's something that we'll do in due course. Okay, great. Thank you again for the update, and thanks for taking all the questions. Thanks, Jay. Thank you. The next question comes from Li Watsek with Cantor. Please go ahead. Good morning, team, and thanks for taking my questions. Maybe just a couple from me. For MT1, just curious if you can share some information on the imaging data in other histologies that you might have looked at, and whether you have seen any heterogeneous uptake across different tumor types? Up to now, the work that we've done has been consistent, and we see that, you know, we see good activity in MT1 expressing tumors, so no heterogeneity today. Okay, and then in terms of the work that you've done, for the Bicycle binders, just curious, aside from the chemical optimizations that obviously you spend a lot of time on, have you looked at other components, including the chelator and the linker, and whether you would need different chelators, maybe for different isotopes? That's a great question. I'll let Mike Skinner answer that. Yeah. I mean, in contrast to toxin conjugates, there's less work done on the linker system. But the question is a good one, in that you need to match the chelator to the isotope that you use within the cage. So we've done optimization around the combination of different isotopes with different chelator cages to get to the compounds we've described in the presentation. Thanks. Anything else, Li? No, thanks for the questions. Appreciate it. The next question comes from Tara Bancroft with TD Cowen. Please go ahead. Hi. Good morning. My first question, I just want to quickly follow up on Jay's question from earlier, but I want to confirm for the EphA2 asset, do you plan to continue to take both the BRC and BTC forward? And what would the relative advantage of each be if you view them as having separate utility? Good question, Tara. You know, we absolutely do want to take both assets forward. I think the space in the Ephrin A2 is wide open. It's a high-value target, which is widely expressed across many tumor types. There are gonna be certain areas where one approach makes more sense than another approach. For example, we know that certain tumors, for example, are insensitive to MMAE, and that's where you might want to deploy a radio conjugate. So, we're actually very excited about moving two assets in the same space forward. We think that's gonna be really exciting for patients and to the field. Okay, thanks. And then if I may, the other question that I had was more general. So, you know, there's a lot of emerging supply issues that are occurring in the space as a whole. I see that you've selected Eckert & Ziegler for your manufacturing. You know, we've spoken to them, and they have told us a lot on logistics. You know, it's extremely important because the half-life and the shelf life of the product. But can you tell us more about how you expect to weather these supply challenges with your partners, either existing and future? Yeah, I mean, I'm gonna ask Mike Hannay to chime in. But I think the key message here is we are not gonna limit ourselves to one supplier and one radioisotope. We think that's a major advantage. We think it gives us a level of flexibility that perhaps others don't have. Anything to add, Mike? No, thanks, Kevin. I think the key thing is we undertook a very structured selection, looking at the capability, capacity and quality of the suppliers. And as you've spoken to Eckert & Ziegler before, you'll recognize that they are very competent, very capable of what they're doing, but we've also been looking for capacity in the future. We've seen that there are more companies investing in radiopharmaceuticals, both in isotope supply and in the radiopharmaceutical manufacturer. And we'll continue to monitor the market and move as we need to, to support products as they enter the clinical phase. Thanks, Tara. Thanks so much. The next question comes from Gregory Renza with RBC Capital. Please go ahead. Great. Hey, hey, Kevin and Bicycle team, congrats on the progress and the updates, and thanks for taking my questions. Maybe, Kevin, just sticking with a broader team and a broader theme, and as we're certainly seeing a great deal of strategic activity and a great deal of white space with radiopharm, I'm just curious if you could riff a little bit about, you know, kind of what's up for grabs for Bicycle. We appreciate the approach of isotope agnostic as well as the novel target. But how do you see it ultimately playing out, and where is Bicycle's niche and ultimate role? And then I've got some follow-ups. Thanks. Thanks for the question, Greg. If I understand it correctly, I think you're alluding to the fact that we, you know, we're very active in the toxin conjugate space. We're very proud of what we're doing and what we're seeing in that space, and we think we, you know, we have a very promising future, as we continue to do more in that area. We see the addition of radioconjugates as a natural progression. As I've already said to Tara, I don't think there's, you know, it's ever going to be one size fits all, and having multiple approaches and flexibility is gonna be great for the patient, and that's what we're very focused on. I hope that answers your question. Yeah, sure. It sure helps. And maybe as you and Mike have mentioned, the Bayer and Novartis collaborations, just curious how that work has helped to inform these internal pipeline efforts with these programs that you're discussing today. And then lastly, maybe it's for Alethia, but as we think about resource allocation and the mention of advancing INDs and into clinic, just curious if you could talk a bit about how we should think about the spend and the trajectory and what the levels of investments could entail over time. Thanks so much. Thanks, Greg. So, I'm gonna ask Mike to actually answer your first question, and then Alethia after. Yeah. Hi, Greg. I mean, I think, I mean, your question around how we've informed our strategy, I mean, rather than maybe reflecting on Novartis and Bayer, both of which are very strong collaborations making excellent progress, which we signed eighteen months ago. Maybe a more recent reflection, having just come back from the EANM conference, where we sat through a lot of presentations, which were really chasing down three major targets, so PSMA, SSTR2, and FAP, with the content of probably six out of ten or more talks about at that meeting. I think our strategy of how we're going to play to win here is very much coming forward with novel targets. So the properties of the molecules combine with our ability to drug future targets outside of those three very competitive areas. I think that's how we intend to play to win in this space. I think that is informing our strategy. Thanks, Mike, and Alethia, if you want to take that last question from Greg. Greg, do you mind repeating the question? Yeah, Alethia. Hey, yeah, just as far as your cash and just your thinking about resource allocation, as you talk about, you know, a building leg of the stool here, any thoughts on potential r amps and spend and investment? Great. Look, you know, we raised capital early this year, $555 million. And a lot of the things were to really invest in the future that we have with all the platforms. We kind of were mindful of all these potential scenarios and progress that we could have, including radiopharm, when we did with that raise as well. We feel pretty good about where we're positioned. We've said that we have cash until the second half of 2027, and that, you know, we obviously, that entails some movement, forward movement with these programs as well. Fantastic. Thank you. Thanks, Greg. The next question comes from Kelly Shi with Jefferies. Please go ahead. Congrats on the progress. Thank you for taking my questions. Maybe a follow-up on the EphA2 BRC program. Just curious what kind of a clinical profile you target to achieve compared to BTC program? And if the Bicycle molecule part actually in the same design sequence between two programs? And I have a follow-up. The EphA2 molecule, the Bicycle molecule, is essentially the same. I think that speaks to the power of the platform and the ability to flex the payload. I think I've already kind of answered your question on, you know, how we're gonna deploy the Ephrin different molecules. We think there is plenty of space for two molecules in the Ephrin space. You know, one way to think about it is tumors which are sensitive to the various payloads, and that's obviously something that we'll look at carefully. So, you know, we haven't ruled out also the idea that, you know, using them in combination at some point might be an interesting thing to do. So I think what we're developing is a portfolio of molecules, which I've said for forever, to be honest, that I think are, you know, are really taking us, hopefully, to be leaders in the solid tumor space, that we can use in a flexible and interchangeable manner for the benefit of patients. And that, as I say, is what we're very focused on. So I think you had a follow-up question, Kelly. Yeah, thank you very much. And also, in the mouse model you just presented data with, it showed a very high level of a BRC internalization. And how does this high level of internalization change the biodistribution, the clearance? That's like a general question to BRC. Thank you. That is early imaging data. As we showed with the MT1, we can modify the parameters to essentially eliminate any accumulation in the kidney. I don't know if you want to add, Mike. Yeah. I mean, internalization is quite a topical area in the field, to be honest. And, you know, some isotopes probably require internalization for action. Some of the more locally acting short path range isotopes. The longer path range isotopes probably are less dependent on internalization. There's some really nice work... Again, we heard this at the recent conference on SSTR2, where antagonists which bind to that target and don't trigger internalization, have activity, as well as agonists that are to internalize. But it depends on the target. But broadly speaking, what you would expect is internalization to lead to a greater tumor retention. Thank you very much. Thanks, Kelly. The next question comes from Maxwell Skor with Morgan Stanley. Please go ahead. Great. Thank you for taking my question. I was just wondering if there's any way to kind of quantify these data, or should we expect more quantitative data at the next update, specifically FDG uptake versus your MT1 BRC? And also, aside from the payload, is there a difference between your MT1-MMP BRC and BT1718? Thank you. Thanks, Max. To answer your first question. In this case, we are using a different Bicycle compared to the one that's in 1718. In response to your second, your first question, these data are generated by DKFZ, and we don't have, these are not our studies. We're very grateful for the work that DKFZ has done. When we do our own internal work, then yeah, there'll be much more in terms of quantification. Okay. Thank you. Thank you. The next question comes from Jonathan Chang with Leerink Partners. Please go ahead. Hi, guys. Thanks for taking the questions. First question, how do the MT1-MMP and EphA2 binders used in the radio program differ from the previous ones used in the Bicycle Toxin Conjugate programs? And what's the hypothesis that the clinical profile for the radio programs will be better than the Bicycle programs going after the same target? And then second question, can you give us an update on the latest and greatest with the Novartis and Bayer collaborations? Thank you. Thanks, Jonathan. To answer your first question, as I've already said, the effector binders are essentially the same. With MT1, we're using a different binder, which actually is much. It had a different scaffold. We use the same scaffold in this particular radio imaging work. As we use a TATA scaffold, which is the same as the scaffold in the 5528 and 8009. You know, in terms of the question, I think the question, to paraphrase it, was how do we think the radio is gonna be different than the toxin work and the results? I assume you're talking about 1718. Just as a reminder, that was a prototype molecule using a very old toxin linker system, whereas in this situation, we're gonna be using a much more contemporary linker and a radioisotope. So I expect the results will be very different in nature. I think, and Novartis and Bayer, of course, we're not really at liberty to give any real details of the progress regarding the progress we're making. Mike has already said we're very pleased with the progress we're making, and I think that's all I can say at this point, but thanks for the question. Got it. Thank you. The next question comes from Peter Lawson with Barclays. Please go ahead. ... Great. Thanks for taking my questions. Just as we think about the current radiopharmaceuticals, I mean, that must be focused around prostate and PNET. Do you think that your platform's gonna be able to move the industry beyond prostate and PNET? And then I've got some, a couple of follow-ups. I think by what we've already said, Peter, that's a kind of a statement of intent. The only targets that we're not going to pursue are those that are already, you know, being pursued. We're interested in, and our platform allows us to go into completely, you know, blue sky into targets that perhaps others are currently unable to. And that's where we see the real opportunity and how we're going to maximize our advantage. Got you. And then the radiopharmaceuticals that you're thinking about choosing, are there particular radiopharmaceuticals that work better with a Bicycle peptide? Kind of, if you can kind of talk through where there's a great overlap between your peptides and unmet need. I mean, the quick, the short answer to that question is, I think we've already displayed and shown across multiple Bicycle molecules that we, you know, we're agnostic, whether it's indium, radium, lutetium, lead. So we think that's a huge advantage, you know, to be locked into a payload and then design everything around the payload is one way of doing things. The other way of doing things is say, what is the best possible molecule you can generate and then take that one forward. And we're very much in the latter camp than the former camp. Okay. And then as you think about costs, are there additional costs for manufacturing versus existing radiopharmaceuticals, or do you have a potential advantage as you scale up? We haven't discussed the cost because of Bicycles, other than to say that they are low. I think that's all I want to say today. We think that will ultimately give us a significant advantage, but I don't want to go into the details of specific costs at this stage. Okay. Thank you so much. Thanks, Peter. Appreciate it. Thank you. The next question comes from Rajan Sharma with Goldman Sachs. Please go ahead. Hi. Thanks for taking my question. Just in terms of strategy, you mentioned that partnerships will remain sort of a key part of the BRC strategy. So how should we think about that going forward? Is that likely to be platform-based partnerships as you have with Bayer and Novartis, or would that be potentially on a target or an asset-specific basis? And then I have a follow-up. Yeah, I mean, we have the existing relationships with Bayer and Novartis, and, you know, we're very pleased with the progress we're making. I think it's a really healthy exchange of information that both parties are benefiting from. You know, when we talk about collaborations, there's those types of strategic collaborations, and then there's the collaborations that, you know, have been very valuable to us and we're very excited about and that's the work that we do with DKFZ and other groups. And so, you know, not all partnerships are pharma type, you know, upfront and milestones type partnerships. I think where we're gonna focus much more in the future are those partnerships that enable us to move our molecule, our own wholly owned molecules forward as quickly as possible. You know, we've talked about and you've seen the benefits of the DKFZ collaboration today. We've mentioned the Kettering relationship. I think you can expect more of those types of interactions moving forward as we build our own wholly owned internal pipeline. Okay, perfect. That's very clear, and then just the second question. At your R&D Day last year, you highlighted CD38 as a potential target or potential BRC, and there was some imaging data that you shared on the day that looked quite interesting. Just wondering if you have any updates there in terms of timelines or any further developments since you last updated us? I mean, not really. Only that that's one of, you know, a whole host of potential targets that we, you know, have access to. You know, Mike, in his presentation we've just done, indicated the range of peptide binders that we now have structurally enabled, and we are very excited by. The two targets we've chosen to move forward, initially, MT1 and Ephrin A2, are targets which we believe we're already, you know, industry leaders on. And what we want to do is really double down on that leadership and, you know, maximize the opportunity and maximize the benefits to patients. So that's all I can say at this moment. Okay, thank you. Thanks, Rajan. The next question comes from Amy Fadia with Needham. Please go ahead. Thanks. Good morning, everyone, and congrats on the progress. A couple of quick questions from me. You talked about your library of new targets, where you know, there's no endogenous peptide ligands. Can you talk about what criteria do you use to determine if a particular target is interesting, in terms of its you know, expression on tumor versus normal cells? And then just you know, are there certain tumor types where a BRC approach is more appropriate than a BTC approach? And then maybe my third question is, for MT1, you mentioned that there was negligible uptake in other organs, but can you maybe quantify that and talk about potentially maybe at higher doses, is there any, you know, sort of, targets, in terms of organs that we should watch from a safety perspective? Thank you. Yeah. Yeah, let me start with the third, the last question, because I think that's, there may be a misconception. MT1 is a target that's actually expressed extremely low levels in adult tissue. And we don't see any MT1-dependent uptake into any tissue other than in the tumor. In terms of your first question, the library of new targets and how we select targets, you know, that's largely around, as you mentioned, around expression in normal tissue versus tumor tissue. And whether it's a BTC approach or a BRC approach, to some extent, that will be dependent on the expression profile of that target in healthy tissue versus tumor tissue. And then the second question around BRCs and BTCs. I mean, the classic view on this is, you know, for example, in colorectal cancer, we're pretty confident that the tumor is insensitive to MMAE, so a BRC approach may make more sense there. Obviously, as we develop our pipeline and we learn more about individual tumors and their select sensitivity to different types of payload, and, you know, we're not limited to MMAE and radionuclides. That will dictate the approach or approaches that we take to tackle a given tumor type. Anything to add, Mike? Yeah, no, I think there was a piece in there around sort of what makes a good target for a radioconjugate versus a toxin conjugate. And I think there is a greater sensitivity to off-target effects with a radioconjugate. I think if you look at the work with Pluvicto, where they have a particular issue with salivary gland toxicity, it shows you that the tissues are very unlikely to be resistant to a radio payload, where certain tissues will be resistant to a drug conjugate. So you probably broadly need a cleaner profile. Thank you. Thank you. The next question comes from Reni Benjamin with JMP Securities. Please go ahead. Hey, good morning, guys. Thanks for squeezing me in. A couple of questions. One, I'm sure Mike already mentioned this, but how many patients have been treated to date for imaging? And, you know, as we think about, you know, sort of the clearance from the body across these patients that have been treated, how long does it take to clear the isotope from the body, especially the kidneys? And how does it compare to, you know, to call it other imaging agents that have been out there, or even approved radioconjugates that are out there? And then a final question, as we think about mid-2025, what kind of additional data might we be on the lookout for? Great questions, Ren, as always. Firstly, we, I think we guided that we'd have data in a handful of patients. These are not our data. DKFZ are conducting the work, so we can't be precise on exactly how many patients have been tested or how many they intend to test. These are their studies. We're very grateful for them sharing this image and allowing us to use the image. The clearance from the body, total clearance from the body, is not something that they explored in any detail yet. That's work that we will do. And mid-2025, I think you'll see a lot more imaging data across a range of different tumor types. So that's all we can share at the moment. Great. Thanks for taking the questions. Thank you. The next question comes from Lee Xun with H.C. Wainwright. Please go ahead. Hello, this is Lee Xun for RK. My question is, can you remind us of the previous clinical development efforts, targeting the MT1-MMP? And what is the general challenges with this target? Thanks. Thanks, Lee. As I mentioned, the 1718 molecule is our prototype molecule. We actually undertook a collaboration with CRUK to explore that molecule. It's a first generation linker toxin system using a DM1 toxin, a hindered val-cit, which the industry has moved away from. As you'd expect, using that type of system, you see a range of toxicities which are well described for the DM1 field. CRUK is still doing some, I think, quite interesting work on that molecule, understanding more and actually generating data to help us understand more about the tumor penetration of Bicycles, et cetera. I don't think this is a... This is or was ever a particularly developable molecule, and I think we've been pretty clear on that. What it's allowed us to do is think about that target, MT1, which we see is a very high-value target in a more holistic way, hence the work that we've done in the radiopharm space and the molecules that we're now bringing forward. Thank you. The next question comes from Kalpit Patel with B. Riley Securities. Please go ahead. Yeah. Hey, good morning, and thanks for taking the questions. A couple from us. First, for the human imaging data, curious if you have quantified the tumor to kidney ratio in terms of dosimetry. It looks like the kidney uptake is retained out to one hour in that image. And second, do you have any preclinical data that supports that BRCs have longer retention times in tumors compared to other peptide-based RLTs? Thanks, Kalpit. I'm gonna ask Mike to answer those questions. Yeah, I mean, the molecule we use for the human imaging work, in the slide deck, I think we refer to it. It's an early molecule, a tool molecule, so we're not looking in that imaging study to optimize for tumor-to-kidney ratio. That's the second part where we develop the theranostic piece, where we tune the drug-like properties, and if you look in the slide deck, I think it's slide 13, you'll see a good example of the molecule used or a similar molecule used for the human imaging versus the theranostic, which is a very different profile, where we do optimize for tumor retention and low kidney retention. Thanks, Kalpit. The next question comes from Tony Butler with Rodman & Renshaw. Please go ahead. Good morning. This is Tausif Hasan on for Tony. Thank you for squeezing us in. It's apparent that tumor uptake happens with Bicycle-based assets, but you know, not every metastasis, smaller ones in certain lymph node disease, can be occult to, you know, imaging techniques. With this in mind, and based on your knowledge about bicyclic peptides, what can you share with us about the tissue penetration abilities with both BRCs and BTCs? The other question may involve some guesswork, and I apologize for that. But given the differences between an auristatin-based payload and a radio payload, how may one expect, you know, the adverse events with a radio-based bicyclic peptide versus what we have seen with BTCs? Thank you. You were breaking up. It was quite challenging to hear the question, but I think Mike caught the question. I think, I think I caught question one, Tony. So, I mean, I think the first thing to say is that, you know, when they biopsy the lymph nodes in that human image, they were both cancerous and MT1 positive. So we had very good concordance in that study between the FDG, CT, PET scan and the gallium work. I think the broader piece here is that, around penetration. So, penetration of the tumor is driven by fundamental pharmacokinetic properties. So the volume of distribution of our molecules is equivalent to extracellular fluid, which would mean that you would expect and predict that these would extravasate almost instantaneously and fully, fully penetrate the tumor in a very short period of time. And effectively, that's, that's what we see. I think if you look at the video that or the frames from the video we showed early on, that talks to Bicycle Advantages, you can see in those images that within ten minutes we see Bicycles flood the body, and within the hour, we see restriction to the renal elimination, and very importantly, retention in that tumor. I think you asked a second question, but I didn't catch it. I don't know if you want to try again? Yeah, sure. Let's see. Can you hear me better now? Yeah, yeah, better now. Okay, that's great. So the second question involves... may involve some guesswork. Given the differences between an auristatin-based payload and a radio-based payload, how may one expect the sort of adverse events with a Bicycle BRC versus what you have seen with BTC assets? Yeah. No, okay. So, I mean, I think what we've learned about toxin conjugates is that the Bicycle, because of its greater selectivity compared to an ADC, because of its shorter half-life compared to an ADC, systemic half-life, not intratumoral half-life. We think that the Bicycle per se is a very clean molecule. The toxicities that we see with BT5528 and BT8009 are essentially mediated by the free MMAE, which is released by the linker. And I think as we put at R&D Day last year, we've now got a new set of linker systems, which we think will be even better tolerated. So if we're working in a radionuclide conjugate space with essentially an uncleavable linker, I would expect the profiles could be potentially cleaner. But as you say, that's pure guesswork at this point in time. But thanks for the question. I appreciate your response. Thanks. Thank you. The last question comes from Chiara Montironi with Kempen. Please go ahead. Hello, this is Chiara Montironi from Kempen. Thanks a lot for taking my question, and congratulations on the update. I just wanted to follow up on the target, EphA2. You always show to be very mindful about choosing the target, and I just wanted to know a bit more if you can elaborate how you went about choosing the two targets. So if I understood correctly, EphA2 was about deliver another type of payload to tissues other than the epithelial. And why would you choose the metalloprotease, and why not Nectin-4, for example, and is it because, for example, you have a competitor or... Yeah, any color you can give is really appreciated. Thank you. Thanks, Chiara. I, again, I'm struggling to hear you a bit, but I think I got the question: Why did we choose MT1 and Ephrin A2 as our first targets? So as I've said, I think these targets both represent very novel targets where we've a long-established history, where I think we're already leaders in the field. And I think the opportunities presented by both targets is actually very significant. I hear you, you asked the question around Nectin-4 and other targets. Of course, these are targets that are well within our reach, and I wouldn't rule out that these are not these are. Let me ask too many negatives there. I think these are targets that we, we'd absolutely consider and do continue to consider as potential opportunities for us. Thank you. If I can follow up, which advantage will the radiopharmaceutical targeting MT1-MMP give you compared to a Bicycle Toxin Conjugate? So why did you choose, again, this target? So, I'm struggling to hear, but I think the question is MT1 as a target and for radiopharmaceuticals. It really is very selectively expressed in the tumor compared to normal tissue, in our analysis. I wouldn't rule out that we might well consider a toxin conjugate. We haven't said we're not going to do that. I think the opportunities are there. The first molecule, DM1, gave us a great deal of information that's really been helpful for how we think about MT1. And as we've learned about other linker payload systems, I think the opportunities are very apparent. Right now we're focused on the radioconjugate, but of course it's relatively trivial for us to develop a toxin conjugate when we decide we want to do that. Got it. Thank you so much. Thank you. All right, well, thank you for joining us this morning. A replay of this call and webcast will be available on our company website. Please reach out to ir@bicycletx.com with any questions. Have a good day.