Good afternoon, everyone. Welcome to the next session with Bicycle. I'm Ami Fadia, biotech analyst here at Needham, and it's my pleasure to be hosting Alethia Young, who's the CFO of the company. Alethia, thank you for being with us today. I'd really like you to kick us off with an overview of the company, the platform, and then we can dive into questions.
Yeah, thanks, Ami, for having us, and Needham for hosting this conference. Very happy to be here today. You know, Bicycle Therapeutics is a company that's based in Cambridge, Massachusetts, and in Cambridge, United Kingdom. The base of the technology is founded on Nobel Prize-winning science, which effectively, the science was driven out of kind of enhancements and improvements within the world of antibodies, ironically. You know, there's like kind of a scenario where, you know, small molecules provide some utility in different ways and antibodies do in others. The progression was from Sir Gregory Winter, who's one of the founders and a Nobel Prize winner for some of this work, kind of improving and enhancing upon, you know, a modality that could behave like an antibody being much smaller, right?
That's what these synthetic peptides essentially are that we now have the privilege of developing and, you know, known as Bicycle Therapeutics. Of course, it's called Bicycle because they sort of look like little bicycles, wheels, mind you. That's where the name came from. Again, like it's a platform where it's a delivery vehicle, for lack of a better word. I mean, we can deliver toxin conjugates, we can deliver radionuclides, or the isotope itself, we can deliver IO. There's a lot of things it can deliver. It's the easiest way to think about it, but you know, the linker and the technology that we're using is inherently smaller.
It is more precise and allows us to kind of get in and out of systemic exposure faster, which usually can lead to, you know, usually better outcomes for patients and lower toxicity profiles while achieving similar efficacy is the key point here. That is the technology. You know, if you go and kind of think about how we're utilizing the technology, we're utilizing the technology right now, lead, meaning the assets that we're developing are in oncology. Though the platform can be used in other, you know, other disease types. We have collaborations where we do that, and I can mention that in a second. You know, focusing on oncology, our lead program is called Zelanectide. It was previously known as BT-8009, so some people may know it as that on the phone. You know, essentially it is a nectin-4 targeting agent.
We're currently in phase two, phase three of the study, right? We're developing it out there. Our lead indication right now in that study is bladder, and it's being studied in first and second-line bladder. We also are leveraging Zelanectide, BT-8009, in other indications that we talk about with kind of using a genetic amplification marker that I'm sure you'll get into throughout this discussion, where we're looking to kind of achieve robust efficacy in breast and lung. Expand the aperture for nectin-4 beyond just bladder, which I think has been something that many people are trying to do. We think we are, you know, we're in phase one work of that, but we're very encouraged because it's the same asset effectively.
We have a very robust set of safety for Zelanectide with dosing over 400+ patients right now, and obviously have shown clinical activity and robust safety enhancements and benefits. We have another asset in oncology that's BT-8009. It's first in class, novel target for most people, EphB4. It's been something that's been difficult for antibodies to target because it leads to thrombotic risk. We've not seen that. We've shown activity in bladder in second-line, you know, response rates that look very good with a four on them. That is pretty exciting. We also are doing a lot of work in radionuclide space, where we're sort of starting to build our own capabilities there.
We have collaborations with Bayer and Novartis, each of them two targets, but we also are looking to kind of go and strategically think about building out what we'd like to think of as a next generation in radionuclides, where you're going after targets beyond the ones that just people talk about, and you're able to leverage any isotope. You know, we have a lot of different things that we have going on, again, all in oncology, going a little bit out of there to the collaborations. We have some collaborations with Genentech and Bayer and Novartis and Ionis. Ionis is more of a neuro collaboration. Again, it's a way to leverage, you know, what we're thinking about here in a different modality because we can't do it all. The platform can do a lot, but we can't do it all as a company.
We have to be very focused. You know, I think important in this landscape that we have to highlight is, you know, as of the end of the year, we have $879 million in capital cash runway out into the second half of the year. Obviously, lots of opportunities to think about that now in light of what's going on in the world that we live in. You know, we feel very good about that because we are able to prosecute, leverage the platform, and move forward with our goals. I think that's a unique position for a small-cap biotech to be in this era right now that we're living in. I think that probably covers everything at its highest level. Maybe you want to just dive into questions unless you think I missed something there.
No, I think that was quite broad and overarching. Let's jump into Zelanectide. I kind of want to maybe go back to the data that you guys had shared at the JP Morgan meeting earlier this year for Duravelo-1 in second-line plus urothelial cancer. Could you sort of address the debate around that data set that maybe started late last year and how the additional update you provided sort of, you know, went on to at least address that debate?
I mean, I think what you're referring to is in December when we presented data around the San Antonio Breast Cancer meeting, there were seven unconfirmed responses, right? In history, a lot of our responses have indeed confirmed. I do think that people wanted assurance that that could be potentially the case. Because we had viewed this as a top-line update, it was not like we were going to provide a spider plot or something. I think without the marriage of those two things, people assumed the worst and that these all may not respond. The response rate would be significantly lower than what was seen with like an enfortumab. In a similar enfortumab study, EV-302 cohort K, you know, the response rate was around 62%. I think that's what people were trying to get at, right?
You know, we provide like a top-level update, but because of the unconfirmed, if you just assume they all do not confirm, the number gets really low. That data cut was in September because the scans were done a little bit like at almost like a two-month interval. We had not intended to do this, but based on like how the stock behaved and also how, you know, just the questions and the feedback we were getting, we did a data cut in January, right before JP Morgan, right? We would have probably otherwise done a data cut a little bit later and prepared to go to something like an ASCO because the deadlines for ASCO are in late January. Instead, we wanted to do a data cut and see where we were at with the amount of unconfirmed responses.
Lo and behold, we basically, we now have information on almost all the patients effectively. There's one still that remains, but we also attached a spider plot in the JP Morgan deck itself that we presented where it kind of shows where everybody's at. I think marrying those two, that number one that you look at right now with the 20 people that study that we're talking about, you have, you know, a response rate and all the people, 13 of them right now, 65%, the confirmed rate is 10 at 50%. You can see that, you know, obviously with the two of the people they progressed, right? You have one patient right now who was a CR, who, you know, we haven't said what happened to that patient, but obviously much more, you know, that's probably much more granular than seven people, right?
I think people are now able to understand. One of the other interesting factors in this update was that our ECOG-2 status was 46%. So 46% of people had ECOG-2 status, where those patients, you know, behave from what we're learning from physicians coming out of meetings like ASCO GU quite differently. It's also a population that hasn't particularly been studied with enfortumab . I think, you know, there was a little bit of debate, like the response rate's lower, is that because the people were sicker? We always kind of know how that age-old debate goes in the world of Wall Street. You know, people like kind of want to see it before they can believe it. You know, again, I think those were kind of the core conversations.
I mean, on the safety front, again, it's like small numbers, so it's a little bit tricky. Some people have talked about, you know, the peripheral neuropathy, all grades slightly higher. And I think it's hard to tease out because you back out one patient and a number would have probably been something that probably no one would have bothered about. The grade three or higher still remain, you know, kind of very pretty low in my review, right? And lower than what you see with enfortumab. I think the conversations from the feedback we've gotten from investors is a lot around, was around this whole like the efficacy part of it, right? I mean, safety, you're adding a drug, you have people who are sicker, and it's the law of small numbers. It's kind of hard to tease that out.
I think we'll get, we're going to have obviously an opportunity in the second half of the year at dose selection with the phase two part of this, you know, study, Duravelo-2, to kind of get a feel. You know, we would assume right now, based on what the blind information suggests, that there won't be as many ECOG-2 patients. I think that may be a better barometer in thinking about how the drug will perform. I mean, I think we've done what, you know, we've shown and discussed what we can with a 20-person data set and frame, and, you know, I would encourage anybody to listen to this, you know, do the checks and talk to doctors about these people and see, but a lot of people will characterize these people as different.
You know, obviously we have a pretty important milestone coming up in the second half of the year, where you're getting 60 people in cohort one at two doses, mind you, that's a 30 and 30, and then at cohort two, which is the second line. You are also going to get an opportunity to see or understand the profile of this drug there as well. I'm sure we'll talk about the expectations into that later.
Yeah, yeah, let's put that aside for a second. I kind of wanted to just, you know, look at kind of the data that we've seen so far for Zelanectide and, you know, kind of really sort of talk about the emerging clinical profile that we're seeing here. You know, what we also saw in kind of the second-line setting, it certainly seems to be safer than what we have in the market so far. It seems like patients who are sicker also tend to do well on the drug. Can you kind of talk about sort of how that translates into the overall clinical profile of the drug? You know, right now we've kind of focused on the overall response rate. That's great, but ultimately it's, you know, how long can a patient be on drug that matters and the overall clinical profile.
Maybe, you know, where do you see the profile sort of evolving to?
Yeah, I mean, interesting question. I think really what you hope is that the people who with a drug that's safer potentially, you know, you hope that it's used first, right? I think, you know, the ultimate goal is that we would want, we would hope that people would try to use this medicine if the profile still holds up first, right? Because you are seeing with early trends, the duration of response when we looked at second line, you know, was 11 months versus probably what enfortumab showed, which is about seven. I think we believe that people are able to stay on the drug longer because they're able to tolerate it better. You know, that's kind of response rate in a way is effectively kind of a biomarker of early activity, but the name of the game is progression-free survival and ultimately survival.
The longer people stay on the medicine, since we know nectin-4 is an active target, I think is important. Like, you know, we still are very focused on the first line and how to, you know, drive that profile and hopefully gain share there, right? I think it's interesting with what we saw in the first-line ECOG-2 patients with so many of them being sick, but still getting a response. I mean, we're not, that's not the plan right now, the segment that, you know, it's saying, hey, we're going to run the study just only on that. But it is an interesting like finding, you know, as the profile for Zelanectide continues to build and emerge, is that seemingly people who are sick also can take this and get a pretty decent response rate, right? Because this is a population as studied before.
You know, in second line, I mean, data look pretty similar to what we saw with Padcev. Safety looked, in our view, neuropathy and skin better, especially all grade and grade three events. That was a monotherapy. You know, I think that that's kind of how we see the profile emerging, right? We still think, you know, currently probably enfortumab has about 50% share in the first line in the U.S., right? There still is more opportunity. I mean, I'm sure they'll continue to work hard and get more share, but like, you know, we do still think there's some potential opportunity for another, you know, molecule to come along that's potentially more, you know, more safe and hopefully people can tolerate better and stay on it longer.
Yeah, yeah, no, we'd also sort of conducted a physician survey recently and, you know, that sort of the feedback there was that the DOX profile or kind of the overall tolerability profile of Padcev seems to be limiting its use and it seems to be kind of, you know, that 50% range. Really, again, neuropathy and rash were the two most commonly cited reasons. I'm curious kind of, you know, you mentioned that, you know, it could grow over time, but I'm just curious if you guys have done any market research to sort of understand how the treatment landscape is evolving, particularly in first line. You know, as you think about completing kind of Duravelo-2 study, you know, how does the market evolve over the next year or two in the U.S. as well as in Europe?
Yeah, I mean, you know, I kind of referred to like, you know, what the claims would tell you. I mean, it's also what if you listen to the other company, you can what they're kind of implying, you know, that in first line is 50% or so. I mean, I'm sure that'll continue to build. It'll be very interesting to see over this year how that share continues to grow. You know, obviously there's significantly a lot of that shares come from chemo. You know, certainly that tracks and makes sense. In second line, I mean, second line's really fragmented. It's like kind of hard to, you know, I still think it's patients are more beat up. It's still an opportunity for us, potentially safer medicine.
Also, you know, it's again like it's one where it's not as consolidated as what you saw in first line. Europe, you know, I think our claims research and stuff suggests maybe the share for enfortumab is in the teens, you know, but like that's just what our work and estimations show. It makes sense anecdotally because reimbursement obviously usually takes longer in Europe, right? You have to go country by country, and so it's going to take a little bit of time. You know, it's a great medicine, so I'm sure, you know, share will get taken there as well. I think again, like for us, like we're very aware of that, that this is a very big market. You're talking in the U.S., 25,000 people, you know, that are first line, you know, metastatic bladder cancer patients a year.
I mean, you know, this is in it right now, you're at 50%. There's still an opportunity for another player to come along and get a reasonable piece and portion of, you know, the addressable market opportunity, especially if you think the profile is differentiated, right? Like the advocacy certainly has to be as good as the safety we believe, you know, has to give us a clear advantage. I think over time, right, as the profile emerges between PFS and OS, you know, then you hopefully that our medicine will, you know, continue to yield, you know, kind of stand out from there, right? But that's essentially how we look at it. You know, I think you think about where we're at in opportunity. I mean, I've not seen many markets where one drug just always is there for the next 10 years.
Usually, you know, even ones like PD-1s, you know, others have come along or you look at people like, you know, like kind of the Acalabrutinib and the Ibrutinib, you know, where there was a clear storyline of, you know, a medicine that was very, very good with Ibrutinib, right? Obviously had some cardiac signal and Acalabrutinib came along and actually had a little bit lower signal of that and was able to take some share. I mean, that's basically what, you know, the kind of information that we look at still corroborates. That's why we're, you know, obviously moving forward.
Yeah, I mean, one of the other things that our market research sort of seemed to indicate was, you know, I mean, a big majority of the physicians sort of indicated that they would rather use Zelanectide over Padcev in first line. You know, the market share kind of ranged all the way, you know, from 50%-90% simply because of kind of the overall sort of safety profile. I don't know if, you know, efficacy was sort of the big driver there as well. I guess I'm just curious kind of what you think about how the, you know, where the patients are being treated currently. You know, I'm sort of just surprised to see that if, you know, that physicians aren't replacing chemo with whatever other option that they get, right?
That must have something to do with kind of where the patients are treated and how comfortable physicians are with managing the safety profile. Maybe if you can sort of talk to some of those dynamics as well.
Yeah, I mean, I think from survey work we did, like it was like 65% is probably about the community, right? Which I mean, tracks with what other historical oncology medicines have told you, right? That when in the real world, the use is biased towards like, you know, my wonderful hometown, Hickory, North Carolina, where there's probably not an academic facility until you go another 100 mi or actually 50 mi. You know, I mean, there's clearly a biasing factor to that in the U.S with any oncology medicine. This one's no different. I think, you know, in the community, sometimes proximity to like supportive care becomes a matter, right? So like, you know, you have chemotherapy and people know how that works, right? And the side effects have been around forever.
When new medicines, you know, that have different side effect profiles, like whether it be skin or ocular, sometimes, you know, the referrals and stuff are a little bit more tedious if you're in the community, right? Because it's just, it's not like you're just going down the hallway and you're at Stanford or something or you're from Mass General, right? It's a little bit more onerous in managing it. I think that's the feedback that, you know, we've heard from many different physicians, right, who are kind of in the community is like, well, this is the efficacy and everything's great, but, you know, if we get a safety event, sometimes it can be just hard to manage, right?
Because it just takes time and it's, you know, getting all the things lined up is just not as like a seamless wonder as if, you know, if you have a robust academic center where everything is like probably in the same building or at least in the same campus. It is not an insurmountable challenge, but, you know, it certainly is one that, you know, I think when medicines can, if they're, you know, the grading, because again, it's a lot, I mean, drugs are going to have side effects, unfortunately, but when it's the grading of the side effects, if the grade three is up when they require more significant intervention, and then in the cases are more complicated, where I think that really starts to distinguish itself.
That's one of the things we've seen with our medicine, whether it be in neuropathy or skin or ocular, the grade three events are quite low, right? I think that continues to be something that people are encouraged by when we talk to physicians that this, yeah, I mean, yes, we would like fewer side effects. Thank you, right? That's pretty obvious, especially if the medicine on a response rate basis looks similar, right?
Yeah, yeah. Is sort of, you know, I'm kind of just trying to think about like a couple of years down the line and, you know, once your drug is also on the market, how do you see the treatment landscape evolving in first line, second line, you know, understanding that you are pursuing both first and second lines? How do you sort of see that landscape evolve? Which patients will get Zelanectide in later lines of therapy versus first line?
I mean, like I said, a lot of our focus is on first line and like thinking that the most safe, in fact, the most safe medicine should be used first so you can use it for the longest so patients don't progress, right? That's the name of the game. I mean, yeah, we think that like that's we've seen that, like I said, with I referenced, you know, kind of one example. There's other examples of more safe medicines with similar equivalent efficacy, you know, being able to kind of drive share for the exact reasons that we've talked about, which are the fact that, you know, there's not only it's community physicians, you know, they're treating and sometimes that kind of stuff matters when all things are equal, right?
That's, I mean, we continue to see, like, you know, nectin-4 is going to be the dominant kind of, I think, modality. I mean, you know, the way to treat in first line, I think chemo will probably continue to lose share for many reasons over time, right? Because, I mean, the efficacy difference that you see with survival with Padcev is just so different, right? I mean, that and over time, I think, you know, and that's why we are moving expeditiously toward the finish line is because, you know, people get used to side effects over time, right? You know, but like right now, they're probably still a little bit new. We're, you know, people are working through that.
Second line, I, you know, I think again, it's interesting because you have a, like a so many people now are being treated with MMAE in first line that like, you know, would you want to use MMAE in second line? I don't know, right? Maybe. You know, I think if the premise of what the Zelanectide profile holds up is that, safety with people who are progressed probably is more important than even in the first. I think like I've referenced before, the fragmentation of second line, we think it's potentially driven by some of the antibody toxicity and it's just kind of, you know, it's just kind of there's not one definitive winner, right? Like, you know, in a world of efficacy, it looks pretty similar.
I mean, that profile held up, you would think that, well, you know, we probably should be able to like get some share there. But again, like I said, our focus is going to be in the first line probably for explicitly for this reason I'm getting at is that like, I think there needs to be more, you know, evidence and research around using another MMAE after, right? I think that's what physicians are want is based on the feedback we're hearing.
Yeah, okay. I want to talk about the data updates that we'll get from Zelanectide this year. Can you maybe, you know, you already sort of gave us a cut in the second line patient population a little earlier than you were anticipating in January. What is sort of the next update there and when might we get that?
Okay, yeah, first line. First line, I mean, essentially we were hoping to try to, our initial premise was to like have the same medical meeting. I think, you know, we may still have it at a medical meeting, but it's not going to be very different than what you saw. Data cut will not be a different date. It'll be the same date. You know, maybe there's something else to add, you know, but like pretty much information you'll see is the information you'll see. Because again, our focus is on Duravelo-2 and moving toward the finish line. You know, taking extra data cuts, it's a lot to kind of do. You know, I would say, you know, what we want to get this information out to the medical community, we think it's important.
You want to be in a form where it can be in a poster because remember, it's not been in a poster presentation at a medical meeting yet, even though we've discussed it twice. That is why I said it was a little bit of change of plans. We, you know, we took a little risk because we put like, you know, the spiders and some fairly detailed charts and information in our presentation deck when we talked about this in January. We will see how that comes out for us on that front as far as the medical meeting. Second line, I think, you know, we kind of also, I would say as a company, want to make sure that we're providing like complete and robust updates when we are, right?
You know, there's probably a hope that, you know, you show second line if the data are all kind of done. The big focus on second line for people right now is PFS, right? We just have to see where we line up with that. I mean, the response rates, all the people are done, right? Effectively, more or less, right? I think, you know, the feedback we get is, well, what's PFS look like in second line? That'd be the first look. I think what else do we—oh, dose selection is in the second.
Maybe before you go to dose selection. Just in second line, what is sort of the bogey there and how much of an improvement would you want to see?
I mean, I don't know. I think the bogey is like whatever Padcev showed, probably something in the five months range. You know, I don't think it's over. I mean, it's not how much over. Like I said, our focus is very much first line. You know, I would say that's probably where if you look at their data, that's what data tells you. I mean, like I've said multiple times here, our premise is to be similar on efficacy, right? And have an enhanced safety profile. We'll see how that holds up and we'll, you know, we'll see when the data mature and get us to the PFS finish line, or at least being able to take a median PFS.
Okay, okay.
Dose selection?
Dose selection.
That whole thing called dose selection, yeah. I think to be clear, because we've talked about this at other conferences with investors, second half of the year, it's cohort one and cohort two, which is the first and second line part of the study. There are two doses in each and obviously a comparator, which is chemo and avelumab maintenance. We will have information on the first two doses, I mean, for both cohorts. The chemo will be blinded still. Also, the moving pieces is that we will be going and talk to the FDA, but we only need one scan to talk to the FDA. We're taking basically on the learnings that we're all getting from the market over the past six, seven months. You know, things need to be baked in the oven before they're presented and disclosed to the street.
We probably will not be updating the response rate at that time because there'll be a lot of unconfirmed responses. We will wait for all those responses to be confirmed. Nothing particularly new. We've said it in the past couple of months multiple times. You know, I think what would be the takeaway is like, well, we would be saying what dose and that we're moving forward. In a world, an environment that we're at right now, that's important, especially saying there've been conversations and discussions with the agency. I think that's where you'll get. We would look in 2026, probably that'd be at a medical meeting with the completed, you know, data that's confirmed, right? Because it doesn't seem like it would do us any favors to put unconfirmed responses out if there are a lot of them.
The reality is we need to get as fast to the FDA as we can to keep the progress of a medical study going. Waiting for another scan when it's not even necessarily needed perhaps is something that we, you know, I think we just are like, we've got to kind of move aggressively and as efficiently as possible.
Remind me, how often are you doing the scans in the study?
The study, I think it's like every month, I believe.
It is every month.
I think so.
Yeah, I believe you've been doing it every month.
It was every eight weeks and the Duravelo-1 portion of the first line. That's why. It was less frequent.
It was less frequent in Duravelo-1. Here it's every month. You're going to get that cut. You're going to discuss with the FDA. You'll maybe announce to the street what doses you're testing. Obviously I can understand that you want to kind of see a second scan before you report out any kind of response rate information. From a timing perspective, you wouldn't be able to get all the second scans in before the end of this year.
I mean.
From a timing perspective, it's just.
It's just like we're not going to. Look, we'll put it out when everybody has two scans. Full stop. Because that's what the market tells us is that's what they need. We're not going to be like, oh, well, 70% of the scans are done. Let's put it out. No. When 100% of the scans are done, we will discuss it. I mean, we have the luxury of this because we don't need to raise money because we have $880 million in the bank right now. You know, if we, but like we've tried to help people and a lot orient people to if we are moving forward, right? Meaning we have a dose and that we're moving forward. We've tried to explain to people what that bar means, right? Like efficacy that looks, it has to look very competitive, right?
The safety has to have some sort of advantage because this is a significant portion to move into the phase three and then it's a large spend, right? The data will have to hold up. We've tried to help people think about what that would mean in the world of where we're not giving a response rate in the second half of the year.
Okay. Will you share any safety data at that point?
No.
Okay. No safety, nothing except that.
At that meeting, we will discuss everything related to the clinical profile for Duravelo-2, right? And probably, I mean, look, things can change, but that's the plan right now is that we will talk about dose selection and what dose and that we're moving forward. Everything else will be in a comprehensive update. I think as a communications philosophy, we're in a place where when things are baked in the oven, it's best to show them then. That includes safety, right? Because you could show three months more, it's four months of safety and somebody's like, well, neuropathy comes at seven months. Okay. Great. Then we'll just wait. You know, we'll show, I think, everything, you know, when it's all baked in the oven.
You know, it's like also like we have a lot of patients dosed so far in between first and second line, right? You know the street wants to know and understand, but we just think it's more important at this point, especially just in this environment to give like complete fulsome updates where you can, you don't have to squint. You're not confused. The data is what it is. You know, that's where we're at. That's what we're trying, you know, we're really, you know, aspiring to do. It's not always easy, but that's what we're aspiring to do.
No, I completely agree. This is not a market environment to have data that's not fully baked in. No pushback there. Okay. Maybe let's switch gears in the couple of minutes that we have on sort of the breast and lung cancer sort of programs. Maybe kind of talk to us about where you are on both of those and maybe more broadly, how is your approach that different from what, you know, sort of the competition has done?
Yeah. I mean, I guess just to orient everybody. I'm just talking about we are using, so we are, we are going after this, how's the best way to start? The way we think about breast and lung and all other tumor types for Nectin-4, where clearly there's expression and activity. What the dilemma has been is that what people have shown early is like including our own data and our all-comer study in Duravelo-1 is that just used based on protein expression. It's pretty low. It's like in the teens, right? I mean, you know, our competitors showed that. We've showed that. You know, that response rate is going to be one that, you know, that's probably not going to be enough, right?
We've been doing work and we were working with our kind of academic collaborators at the University of Bonn in Germany on this concept, kind of nectin-4 gene amplification, where if you look across like the Cancer Genome Atlas number one, the frequencies in breast and lung of gene amplification are like 20%-30%. This is effectively based on like the amplification correlates with enhanced membranous nectin-4 expression in breast. As the cancer metastasizes, you see these gene amplification copies go up, right? That in its own right in a way becomes like a type of a signature.
We had early data that we presented also at San Antonio Breast that got lost in the shuffle that showed, you know, in our own data in the all-comers and triple negative, we showed like 13%, but then in the nectin-4 amplified, it was 57%. We showed a similar trend in lung where in the all-comers, it was 9%. You know, in the nectin-4 amplified, it was 40%. These were based on retrospective, right? What we've been working on is this throughout 2024.
What we really wanted to focus on is number one, like we've got to open up Duravelo-1 and dose more people here so that we can understand the frequency of the amplification signal in its own right is indeed 20%-30% like The Cancer Genome Atlas says or is it something different? We have to prepare ourselves to start perspectively defined studies, which that's called Duravelo-3 and Duravelo-4. If you look on clinicaltrials.gov, Duravelo-3 is on clinicaltrials.gov, which I didn't know was still being updated, but it's wonderful that it is. You know, we did execute across that. We said in the first quarter of 2025 that we would start that study. That's starting the perspective.
You're going to have a combination of the retrospective work that's been underway for a little bit of time that we reopened last year, and then these prospective studies, which will start throughout the year, obviously. We haven't given guidance on when to expect data there because again, it's the same philosophy that we want to make sure there's enough data that people can understand and interpret. You want enough time, right? Because maybe response rate, but maybe you need to understand the duration of that response, right? These are things that you have to think about because these opportunities are not particularly small in so much that you think about the breast and the lung opportunities for metastatic gene amp, the two of them together are about 55,000 people or so.
It's a big number, you know, when you mark that in comparison to 25,000 for first line metastatic bladder. It's something that we're really excited about because I think it presents a potential first-in-class opportunity for us, which is something that is always like where you want to be. You know, you don't want to be behind, right? You can if you're better, but being first is always great. We think, you know, we're really excited about kind of executing against this work over this year. We have the capital to do it. You know, hopefully soon, you know, at some point we'll talk about when we'll be prepared to kind of think about, you know, sharing what we've learned. Again, it's very much driven by, like I just said, Duravelo-3 just started, right?
Like we want to have enough people, you know, and enough time that people can make conclusions, right? Because the earlier data was early. It was like, you know, it was a handful of patients in each. This we hope to, you know, be more of a more fulsome update. You know, obviously the aspiration is to replicate the signal that we saw. I think if we do, I think we have something that, you know, could be a potential, you know, standout or potential breakthrough.
In terms of a wholesome update, how do you characterize that? Is that, I don't know, a certain number of patients having gone through two scans so that you can have sort of good visibility into response rates or is it slightly longer duration of follow-up as well?
I mean, the response rate is important. You know, I think, you know, it's like you look at what even just our data says like 13 and going to 50 or something. I mean, that's a significant improvement. You look at others in the teens, I mean, you know, if you can hopefully replicate, I think sometimes even our experts are like if you're in the 30s, you know, when you're starting to break out there, that's very exciting. I think we have to see that. You know, durability is always a little bit of like something you got to think about, especially in like later line patients where there's other medicines. Like you want to understand, you know, how that durability, like the duration of the response holds up, right? You know, it's something that we constantly think about.
We're watching it and we're looking at other, you know, data sets that are coming out and how many people and what's the appropriate time. We, you know, our investors talk to, we get a lot of feedback from our investors on this stuff. We're not really, we're not at a place we're going to say what the number is and how many. It's just that we want to make sure that it's a fulsome update where it can be, you know, clearly interpreted. I think response rate's a piece of that. The duration of response could be a potential piece of that as well in this population. Safety with enough time period. You know, again, we've dosed, you know, 400 plus people between first and second line. You know, you start to think you understand what the safety may look like.
Again, we, you know, you want to make sure. So that's kind of how to think about those updates. Again, it's a program. Those are two programs we're very excited about.
Yep. Maybe just one other question on this topic. That is just around kind of the gene amplification work. How well has this been studied in general in the industry? How kind of validated in your view is sort of this 20%-30% of patients have that type of gene amplification? Maybe related.
I mean.
Yeah. Let me pause here. Go ahead.
I was going to probably forget some of your questions.
Yes. Yes. Go ahead.
We're talking about gene, the Atlas amplification itself. Like genome is important to, you know, understand and that's what it tells you is a signal. That's why we're going back and reopen Duravelo-2. I mean, sorry, Duravelo-1 and lung and breast to see. Because again, if it looks in 20%-30% there and, you know, X amount of people, then, you know, you probably kind of have what you have. How well is understanding? Something we've been working on and we worked on it. We've been working also with the University of Bonn. You'll see the published papers, Niklas Klümper and his teams. One of them came out last year. I mean, that was looking at amplification within enfortumab itself, which showed there was a delineation in the signal.
It's, you know, it's something that I think is early biology for maybe like the community, but the biology has kind of been building over time to understand this amplification kind of marker and signature and more work. I think as we go throughout this year, I think more work probably will be done by others to, you know, investigate because obviously we're talking about it a lot now and starting studies and the feedback and stuff we get from, you know, people that, you know, are investigators, potential physicians, potential investigators is a lot of intrigue. Because it's really anytime that you can find a signature that can enhance potential response in cancer, that is the name of the game. I think there'll probably be more work done as we go through. Obviously we're doing our own work.
I assume if it just turns out to be something, you know, I think this will probably get more kind of recognition in the academic landscape. You know, we'll see how it goes.
Okay. Maybe in the last minute or so that we have, I kind of wanted to just touch upon the radionuclide program that you guys have and what is the next set of updates that we can expect perhaps this year?
Yeah, that's a good one. I mean, we want to talk about that too. We've said that we'll have more data, imaging data on MT1-MMP, which is one of the indications that we had. You know, we're still on like the imaging with our collaborators, DKFZ. We've also said with EphA2 imaging, we'll have some updates in the second half of the year. I mean, those are kind of the two key pieces. We've said that we are moving toward a Bicycle-sponsored clinical study in 2026 that still remains on track. You know, we're obviously wanting to be isotope agnostic. We're doing different work and things there to, you know, gain access to supply. You know, certainly still these programs moving forward, we're very excited about them and the updates that will come from those two.
Like I said, we're not really going to be going after the typical targets. We'll be trying to go after tumor antigen targets that we know well and ones that have not been prosecuted in this manner with radionuclides. That's probably it with us to see the one-minute warning.
Okay. Yes, indeed. Maybe this is a good time to close. Thank you so much, Alethia, for taking the time to do this. Thanks to all our listeners as well.
All right. Thank you so much.
All right.