Good afternoon, everyone. My name's Rajan Sharma. I'm part of the European research team at Goldman Sachs, and my coverage is Bicycle Therapeutics. Pleased that we have Alethia Young, who's the CFO of the company, with us this afternoon. Hi, Alethia. Thanks for taking the time. I guess just to maybe kick off as an introduction, could you just kind of give us an overview of the Bicycle platform? There might be some people who are less familiar than others.
Great. Thanks to Goldman for having us, and thanks to Rajan for hosting us. And thanks for you guys for tuning in, both in person and on the webcast. So to talk a little bit about Bicycle Therapeutics, we're a clinical stage company where our predominant focus right now is on oncology. We are a platform company, which our platform chemistry is based on Nobel Prize-winning science from Sir Greg Winter, who was the leader in modern-day antibody development, so assets like Humira and Keytruda. And so he has made it his work to also improve upon. Obviously, antibodies are incredible and have had incredible therapeutic benefit, but also to improve upon that profile. In a way, I like to think about it as like a Goldilocks scenario because we are a small synthetic constrained peptide.
What that affords us is that we're able to, we're basically 90% smaller than an antibody itself. This platform is a delivery tool, for lack of a better word. The small constrained peptide allows us to go into places where others can't go because it is too big. But we also have some of the benefit that small molecules have as far as its efficiency. When you broaden that out, it means that we have their synthetic-based molecules where we're able to really fine-tune based on disease and indication and everything that we're going after. What's really exciting about it is that because it's a delivery tool, if you think about delivery tools, there's like ADCs, there's RNA, there's antisense, there's our Bicycles. You're able to really fine-tune and modulate what the profile is for what disease you need.
And so that's been a big advantage for us, is that this small, precise kind of way that's excreted via the kidney, it affords us what we believe what we call the Bicycle Advantage, which is that we're able to, in clinical data so far, and we've had hundreds of patients with data now, where we see a safety profile that's starting to look differentiated. So in a way, we're able to do two things. One, when there's targets that are known and well-validated targets, and we'll talk about one of them, I'm sure, today, we're able to potentially improve upon the safety profile, the tolerability, which is ultimately important for cancer patients, especially when you have very efficacious therapies because at the end of the day, it is about patients' quality of life as well, and extending PFS and survival. We also have been able to target the undruggable.
I'm sure we'll talk about that asset as well. So that's really what the platform affords us, is kind of two very distinct ways to go and in very broad ways. So the platform applicability, we are focused on toxin conjugates, but we also have IO, and we also have a radionuclide platform as well. And so it's because it's a delivery tool, and all these things require delivery tools, for lack of a better word. Our lead asset is BT8009, which is a Nectin-4. It's in a phase II/III study right now. It's been dosed in hundreds of patients. And we're moving that large global phase II/III study around in the ambition of getting that completed, and then hopefully we'll be able to go to the finish line toward hopeful commercialization.
Now, that's in bladder cancer, but there are potential for other indications as well, we think with Nectin-4. And then we have BT5528, which is the first in class, I think an interesting case study on how to target the undruggable. And that we've dosed in hundreds of patients. We've seen that clinical activity. And we'll talk—and we've studied that in bladder, and we've looked at that also in ovarian. So we'll talk about how to move forward there as well. And then BT7480, which is a Nectin IO, CD137, another way of kind of a play on Nectin-4, but also kind of shows the breadth of the platform. And then we have a radionuclide platform, as we've talked about, where we're delivering via radionuclide. So we have a lot of catalysts.
I think the punchline is, if people ask, "Where are our milestones over the year?" They're all in the second half of the year. So effectively, we're about in the second half of the year. So we have a lot of catalysts, a lot of milestones for the company as we work through the rest of this year.
Okay. Perfect. That's a great intro. And I guess given we're coming off the back of ASCO, where you had some new data presented, maybe could you just kind of give us an overview of what was presented at ASCO? And then I guess specifically, what should investors be kind of most encouraged about from the presentation?
Yeah. I mean, we could always characterize ASCO as incremental because to some degree, what we showed is we showed why Bicycles have potentially an enhanced safety profile, and they've been able to be so precise. So it was a PK poster where this, again, was in hundreds of patients with 8009 and 5528. And we looked at like systemic half-life, which for our molecule is hours versus ADCs are days. So the whole poster was comparing a BTC, which is a Bicycle toxin conjugate, to an ADC, which is an antibody drug conjugate, but was based on our data that's been generated in the clinic, of course. And obviously, the ADC data, we all know that's like historical data. And so we've characterized, and we've done those experiments. We characterized the PK. So you're talking hours, half-life, systemic versus days for ADC.
But what's interesting is when you look at the exposure within the tumor, it's actually about the same time, which is days. So it shows that we're able to kind of systemically get out of the areas that you don't want to be in, but we hang out for a pretty long time in the tumor, which is actually the profile you want. That's translated into potential safety benefits that we've seen. I'm sure we'll dig more into that as well as we work through this. So that was kind of—that was very important. We also looked at the differentiation between conjugate and unconjugated MMAE, which gets a lot of discussion about what and who is doing the work there. So we also looked very supportive as well.
What I thought was really interesting is when you kind of overlay all the PK curves between 8009, 5528, the profile looks almost exactly the same, which clearly suggests Bicycles actually do almost the exact same thing, no matter if you're going after Nectin-4 or EphA2, but the platform looks very stable from a PK perspective.
Okay. And then maybe just moving on to BT8009, which is the urothelial asset that you talked about there. So you're in a phase III or potentially kind of registrational trial there. Maybe just if you outline the data that we've seen so far to kind of give you confidence that the phase III needed to be executed. And then secondly, just how you think about differentiation. Nectin-4 is obviously kind of a highly kind of concentrated field. There's a lot of people targeting it. There's a lot going on in the urothelial space.
Yeah. I mean, a lot of questions there and a lot of information unpacked, but I'll try to take it slowly so that we can all get through it and survive through it. So BT8009 is our Nectin-4. We presented data in R&D Day in December, which was the most recent data that we presented. And in that, we showed a 38% response rate and 26 evaluable patients at the time. There were obviously more patients that were kind of being dosed and were going through the cycle, going through their scan cycle. So when we update people in the second half of the year, you'll see more patients, probably like a handful more. And you'll see what happened to the patients who were on it with time. And so what was showed there is, well, 38% response rate.
It's about in line with what enfortumab showed in their phase I study, which was about 41%. Then we also looked at duration of response, which was still early in the study, and it was 11.1 months. And kind of the typical comparison on that is about 7 months for our competitor. So that was quite encouraging. And I think if that profile continues to hold up, that could be really differentiating. We're coming out of ASCO, and I'll try to weave in ASCO tidbits into this discussion since that's the spirit of things here. A lot of physicians found if the differentiation on duration of response was 20%, 30% higher, then maybe like the 7 months, that would be very encouraging. So that's mathematically 9 months.
So I think that could be interesting to people because the way the Bicycle Advantage works is that because it's potentially safer and more tolerable, you can take the drug for longer and at the right dose. So one might think the duration of response should be higher. And then over time, that should play out into PFS and OS benefits, we would hope, right? Because that's kind of if you stay on a drug and you know the target's active, usually that's what happens. And a lot of the challenges as to why people don't always get the exact clinical benefit they need is because of toxicity, and they have to either dose-reduce or they have to go off the drug for some period of time and maybe go back on or maybe not at all.
So that's an encouraging, I think, breadcrumb that a lot of people are looking forward to as far as in the clinical community for us to show. And then the safety we showed was very differentiated. When you think about Nectin-4, the kind of AEs of interest or the adverse events are peripheral neuropathy, which gets a lot of attention, ocular, skin, and hyperglycemia too, shockingly. And for physicians, these are different. This is our competitor profile, our Padcev. They've popped up. So our competitor has some degree of grade 3 of those toxicities, right? We had none which was in 113 patients in those effects. Now, at all grades that are lower, we did see some, but albeit the incidence was lower than what was seen with our competitor as well. So that was really encouraging.
It also helps to explain why it looks like our median dose intensity is about 90%, which we have not been shown by our competitors. So that's actually a really interesting set of information as to where this is kind of going. So second half of the year, we'll update that. We'll show more patients, and we'll talk about what happened with duration. I think that's an important up. But we've been very confident in the profile we have. And so that's why we obviously started a large phase II/III registration trial before that because we feel like that's enough evidence to show you that we do have something that's active. We know Nectin-4 is active. So that's a key piece of what you'll see there. And you were talking about kind of the differentiation. I think I did. Did I?
Okay. And then are you comfortable with did I say enough about the?
I guess the other question is that what is the ultimate differentiation in that? Do you think BT8009 wins out because of efficacy, is it safety, is it tolerability, or is it?
Well, I mean, I think we look at overall response rate as a biomarker, a short-term biomarker. And again, it shows if the drug is working or not. And it certainly is. And then we think that we're similar. But if people continue to take the drug, that's why duration of response and some of these are important. We would hope that that would play out to better PFS because we know Nectin-4 is a great target. So the longer you stay on it and at the right dose, hopefully you would continue to get benefit. That takes a while to play out, as we all know with PFS, especially and OS when things are really working. So that'll take time. But it's kind of all about the progression and the clues of things that you're seeing.
That's why I think the PK lining up with what the clinical safety has shown now is very encouraging for the academic and the community physicians as well and many people in the industry to see that like, "Okay, it's all starting to line up. You're telling us the progression is showing." So that's ultimately that. I think at the end of the day, you would think that if you go 100 years from now, you would hope that this hypothesis would be that the PFS and OS are better over time because people stay on the drug longer, right? And we know it's active, and so that's the case. And hopefully, people are getting the results they need.
But that's going to take time to play out because if you look at our Duravelo-2 study, the first endpoint, our accelerated endpoint, is overall response rate, which I would think about as the totality of all the information that'll be available at the time. So I think there's room to improve, and clinical benefit is something that gets thrown around a fair amount. But it is also the activity, efficacy, but it's also safety. But I think sometimes people get a little confused and just think that we're talking about having a more safe drug. I think. And I think that safety profile and tolerability will lead to advantages over the long term. We'll have to see where that goes.
Okay. Perfect. And then I guess you touched on the Duravelo trial. It's a relatively kind of innovative design that you have in place. Could you maybe just talk us through it? And obviously, the strategy not to go head to head with Padcev, it's still something that comes up in conversations.
Yeah. Well, okay. I'll talk about design. I'll talk about that if I don't remind me. Duravelo-2 is a phase II/III trial enrolling 300 sites around the world. We got alignment from the FDA before with the design that I'll talk about in a second, which is cohort one. It's a first-line trial. It has two doses that are being studied. And the comparator is avelumab and chemo and avelumab maintenance, avelumab, PD-L1. And so the primary accelerated endpoint is overall response rate. The secondary and the full approval in first line would be around PFS. And obviously, we're powered for survival because it's important to show. There's a cohort two, which is second line, which basically looks at the two doses that we've talked about. And we'll look to see if we can get response rate there.
Then we'll have to look to do if we want to confirm the signal there. But we need to have two separate parts of this trial for the contribution of components as well. But we also believe commercially there's opportunity and potential first and second line that shouldn't be. I think people think a lot about first line, but the reality is second line is still a very fragmented market where there's a reasonable opportunity to help patients for the better. So to roll that back up, which is your question, and I'll say that for the first part of the study, we're going to look at two doses. Obviously, while there's a comparator going on, we'll make a decision at some point about what dose that is.
So each arm has like 30 patients that will be the 5 milligrams per square meter weekly or 6.5 milligrams two weeks on, one week off. So we'll look at that and try to see if there's any benefits. The 6.5 dose has a little bit lower MMA than the 5 milligrams, but the efficacy has been seen to be about the same we hypothesized via modeling. So if all things were considered, I'm sure we would probably think about what's most convenient for patients, but we have to get to that milestone. When you think about the comparator, I think it's a regulatory question. There's a commercial question. As we evolve over time, I mean, it was approved and full approval in the United States and in Europe in December or so. So we'll have to see how that evolves. But it's certainly not exactly yet the standard of care.
The standard of care still remains chemo in the maintenance regimen, whether PD-L1 or PD-1 of choice you want to use. Now, over time, it'll evolve. It's not like we live in a vacuum or a box. We're very aware that the commercial around us is evolving. But I think there's a regulatory discussion to be had on what the standard of care and where the world's going is a commercial question, a.k.a. the future. So certainly, we spent a lot of time here on this conversation talking about how our data and what our confidence is on how this profile will emerge versus the leaders in the space as it stands today. We feel comfortable. So I think there is a way that this works out for both sides.
But we're going to take the comparator that we had discussions with the agency about and go forward with that. If this study was being run two years from now, I'm not sure if that would be the case, even though no one can ever speak for what the future holds. But right now, I think the world is still evolving. I thought what was interesting at ASCO as well from a lot of the conversations we had; it's a little bit more complicated in first line better than maybe what the world thought as far as making decisions about who goes on what and how do you manage this and manage this tolerability or kind of that. So I do think there's still some discussion. And it's still very interesting. Chemo and maintenance and a PD-L or a checkpoint maintenance regimen is still very. It's something people know.
I think when you get outside of academic communities, sometimes what people know in the community still is something that's comfortable, and it takes some time to get some transition. All that affords us the opportunity to get this trial rolling, hence why we started this. The trial started in the first quarter of 2024.
Okay. And then I guess the other question that comes up a lot, and it may be a frustrating one for you, but you're using the FDA's Project Front Runner as kind of aligned with that too to move to a registrational trial and to kind of get the approval. Obviously, we haven't seen any approvals come through that pathway to date. So it is an area that people are maybe a little bit concerned about, a little bit more kind of apprehension relative to a normal trial and approval. So could you maybe just walk us through that process and why you're confident that you are fully aligned?
Yeah. I mean, look, every question is a fair question. I mean, because you guys don't work at Bicycle. We do. So we have to answer the questions you have. Now, Project Front Runner, I mean, I think the reality is when the FDA puts out a guidance, they're probably pretty serious about it. And yeah, everything has to start somewhere. And there have to be people who are early adopters of things. Now, if it's a priority, then and we've had those conversations, it's something that we think that stands good on the guidance. It's just how it works. Now, to unpack this a little bit, which is the real crux of your question is, well, do you think you're taking some sort of shortcut to get where you need to be? Absolutely not.
What we're doing is that we've run a large-scale, well-thought-out phase I program that's looked at tons of doses and has generated response rate data that looks very comparable with, as we'll see in the second half of the year or not, how that starts to emerge on longer-term endpoints, maybe like duration and/or will safety continue to hold. I think that's a big piece. If you go back to Padcev label, there's a black box label for Stevens-Johnson. I do think there's opportunities to improve on clinical benefit. There just always are. Unfortunately, a black box affords that to some degree. It's not a silver bullet on this because certainly the drug is incredible on its efficacy, right? There is always room in clinical development, as we know if we operate companies, to improve on a drug's profile for patients.
Because I started with the comment I did in the beginning for an explicit reason is that we all get kind of hung up on the juice part of this, which is the efficacy. But when you're a patient and caring for someone, it's the tolerability when you're that first patient going through it, and you're the caregiver. And so there's always opportunities to improve. I know that Wall Street tends to think they have it in the bag and have it answered, but it's just not the case in the real world. And it's incumbent upon us to generate enough evidence and proof that we get this thing to the finish line in a way that's robust and gives the agency, the clinicians, and the patients the comfort they need. So it's always been a robust thing that we're doing.
So I don't really think it exactly matters whether it's Project Front Runner or not. And there's always been, if you think about it, there's been some successes on people trying to run earlier studies, and there've been some challenges. And a lot of it is the thoroughness and the depth of the clinical program that you're doing. And I think that's kind of what we've been trying to be very mindful of is to try to really have all the boxes checked. At the end of the day, the drug's profile has to, on a clinical benefit nature, be different somehow, right? Otherwise, it gets tougher, and you're probably heading toward more of a full approval. But I do think you don't know until you try.
That's what you have to do when we think that we have something like we have, which is a medicine that is more tolerable and better for patients over the long run. So if there's an opportunity set for us to move as fast as possible to get it to patients, we absolutely have to.
Okay. There's a lot to talk about. So just last one on 8009 to wrap up. In terms of data updates, you talked to them at the top of the conversation. What should we expect in the second half of the year?
Yeah. We talked about this. I think the updates will be throughout the second half of the year. It's hard to say that one will have all the updates because basically BT8009, 5528, BT7480, our radiopharm imaging data, they're all things that are going to come in the second half of the year. So it'll be hard to pack that into one nice little moment. And certainly, there's always aspirations for us to get important data out into the medical community as well. So we have to think about all the venues to do that. So you've got Duravelo-1, which is the study that was presented in December. There were multiple arms. There was a second line bladder arm, which we've updated, talked about. We'll show more patients and hopefully more duration on what's happened there or not.
And then also what we'll show is we have a first-line cohort over time that will read out 20 patients as far as Duravelo-1. Well, and that's BT8009 and Pembro. We probably hope they have some early data there later in the year. We've said that we have a breast, a lung cohort that's kind of ongoing where we've dosed more patients. We saw responses at the R&D Day. They were kind of like teens to low 20. We'll see what that looks like in more patients and hopefully think about what the path forward is there. I actually think for that update, the path forward is just as important as to update. So we'll have to make sure that and it's a rapidly evolving space. So we want to make sure that we really have been thoughtful there and are able to help investors understand.
BT5528, which we'll get to, we will be updating the data we presented at R&D Day. Kind of in a similar fashion to 8009, second line I was talking about. There was a cohort for ovarian. We'll look and see if we saw any activity there. With 5528, we saw a good response in the dose we were at, but we went to a higher dose. 7480, which is the IO molecule next in Nectin-4, we'll be talking about the entire escalation study upon completion, which is mostly for safety, but hopefully also to talk a little bit about what are the next steps. And then for the BRC, which is the Bicycle Radionuclide Platform or conjugation technology, we hope to have some early imaging data in the second half of the year as well.
That kind of we've talked about the first target, which is MT1-MMP, which is a novel target. So a lot of catalysts. We'll probably also be talking some life cycle things, some interesting stuff we're doing with the platform.
Okay. Just that point on 5528, obviously you talked about it being an undruggable target in the past, which is probably fair given the levels of attrition we've seen with EphA2. So what do you think it is about the platform that you have that has basically made that a druggable target now?
Well, I mean, it goes back to the Bicycle Advantage, which is the precision, specificity, and high affinity. I would probably argue the toxicity seen preclinically and clinically with using ADCs for this EphA2. Probably because the therapeutic window is pretty narrow. And if you don't cross across it in a very clean way, you're probably triggering. I mean, the vasculature is very impacted by EphA2, and it's almost everywhere. So you probably are trying to thread a very thin needle to put it in a non-precise way. And because we're much more precise and have the specificity and affinity in tunable PK, we're kind of able to thread the needle because we haven't seen any of the bleeding issues. And we've dosed in 100+ people as it stands today at multiple doses.
And actually, when you broaden it out, the safety profile looks ironically very similar to BT8009. We don't see a lot of neuropathy and the other things as well. So I think it's just this. The nature of this platform is just delivery is very unique, right? It kind of hits whatever euphemism you want to use, whether it be Goldilocks or whether you want to use thread in the needle. It gets you into places that have been harder where you have a narrow therapeutic window, which is always the inherent challenge. When I think you think about ADCs, it's like you're trying to hit that just right, right? And if you don't, you can have some unintended side effects as well, which can be limiting. And if you hit it too low, you're not going to get any efficacy.
Okay. Obviously, you're investigating that in urothelial cancer as well. How do you think about potentially coexisting with 8009?
Yeah. I mean, I would say that we cited in second-line bladder. And I think that market, as I said before, is a little fragmented. So I think a lot of it's riddled with toxicity. That's why it's so fragmented. Our market research shows that even in Padcev, it probably has about 18%-19% of the market. The Gilead product probably has like 16%-17%. We'll have to see what happens there over time. So I think there's still room. And I think the challenge is that most of these ADCs, they all have toxicities, albeit a little different. But they still are challenging when you get the patients who are moving second-, third-line beyond who already are probably the average bladder cancer is a little bit more elderly and sometimes can be frail. So it's shot and already probably has seen a medicine.
All these medicines at the end of the day are tough. I mean, you're fighting something that's very hard. So it has to have a hard hit. So I think that's we think there's still a big potential room there. But we have to be thoughtful about where everybody, prescribers, people see where this would be used, right? And so that we're doing some of that work now to have conversations to understand it better.
Okay. And then another hot topic in the space right now is radiopharm where you kind of outlined the capabilities that you have. Again, what's the differentiation? There's a lot of work going on in the space. You have your collaborations with Bayer and Novartis. But what differentiates the Bicycle platform now?
Well, I think it's like a long story, but let's try to go to the short. Currently, a lot of the approaches are focused on two kind of tumor antigen targets, whether it be the somatostatin and the PSMA. And I think that we've seen, obviously, commercial assets come from there, from Novartis and Bayer. But we think our approach may be more tumor antigen agnostic. That's why we're going after MT1-MMP. And I think if we're able to show in imaging, which that's still at a micro-dose equivalent, but important because really all you're doing to go to a therapeutic is not all you're doing in the trivialize it. But you're adding a very you're putting the potent isotope on of choice.
So I think if we're able to show that we're going after a different tumor target and can hit and have a similar uptake as we saw preclinically, as we showed at the R&D Day, I think that's really encouraging. I think also our approach, which I guess now gets more attention because I try to stay relevant. So I do actually look at what's going on in the world of biotech. People have been talking a lot about the isotopes. And we are isotope agnostic. I think we have flexibility to do whichever one works best for the modality or for the disease and kind of the population that we're going after. So we'd have to think about that. That gives us some flexibility, I think, as well.
I mean, those are kind of the two major core tenets of how the BRC differs from some of the other delivery approaches. And maybe my last thing I'd say is I think if you thought delivering a toxin conjugate, precision, specificity, affinity all really mattered, I can promise you it matters a lot more in radiopharm, right? Because you're delivering a radioactive isotope, slightly stating the obvious. So that's important. And if Kevin were here and is honorary CEO, I mean, he feels like the Bicycles have always been exquisitely positioned for something like this. And we've actually been in the field for about 8 years or so plus kind of looking at this. But when you're thinking about running a company, you have to kind of also think about where you want where things are and where the world's at.
So the world was not with radiopharm 8 years ago. But ironic how things come full circle because it is and because we always kept a relatively small operation going. We signed 2 deals with Novartis and Bayer last year before I heard anyone say the word radiopharm in a major way besides major players. And they were deals that would help us learn from what's going on from the leaders in the space. But we also kept that opportunity to ourselves. So we have a collaboration with DKFZ, which is effectively the partner side on any other target besides the targets that were in that deal. And so that could be really interesting, especially if we're able to show that we can broaden out the landscape as it is. And I think certainly radiopharms are here as a delivery tool.
But there's all like with all new modalities or reimagined modalities, there's a lot to imagine, figure out as it relates to supply and delivery and different things. And those things will get figured out. But having the flexibility and breadth to do so are truly, I think, a real competitive advantage here.
Okay. That's helpful. I'm conscious we're in the last 5 minutes or so. I just wanted to actually talk about financing. Relatively recently, you announced a $500 million or so PIPE. First question on that is what was the rationale for the timing? Why was now or 2 weeks ago the right time?
Well, I mean, I wish I could get down to a precise time. But I will give you some tenets in the $555 million, to be exact. We're in a world where I think when you think about data readouts, I mean, you guys know it better than me. It's hard to base your company's financing strategy around if the market's going to like your data or not anymore. Because I've seen some fine data come out and the stock sell off. And I've seen some good data and markets sell off, right? It's hard. And so if you're timing and waiting for that moment, I think that creates a lot of capital challenges. So I think we're moving into an era as a small mid-cap era where there has to be some opportunistic behavior because we're running a company.
The seconds that it takes to do these financings and stuff is disruptive to moving things about in a continuous and efficient way. So we obviously, I think we've been talking since the R&D Day about, "Hey guys, this is more than just 8009 and bladder versus Padcev." We tried to show that to everyone at R&D Day and tell the entire Bicycle story, how the Bicycle Advantage plays out in a lot of different ways. We spent a lot of the first half of the year doing that. I think the opportunity presented itself. Also, as you know, Rajan, last year in July 2023, we did an opportunistic financing around Duravelo-2 and said that we had the money to run the phase II,III study without interruption.
Lo and behold, if you play that out, actually the stock didn't perform well when we showed people what the regulatory design was. But we were able to operationalize and keep everything going as we are now. I think as people saw more and more data as we worked through, they were like, "Wait, that's actually pretty interesting." Well, what if we'd had to actually stop and press pause? That's very disruptive in a world that is competitive. I mean, all the spaces we're in are competitive. Biopharma in general is just very competitive. So I think you want the opportunity and runway that you can. So I think we're in a world where you're going to see less. You're going to see people kind of think about their business over three years, three, five years, and try to figure out the capital that's needed.
Also, the good thing is we have a lot of catalysts in the second half of the year. So there's no longer a financing overhang for this company at all because we probably pro forma have about $1 billion in cash today. So hopefully that will let the milestones be whatever they are for people. If they see them, if they think they're interesting, then hopefully the stock behaves in kind.
Okay. And again, probably not a question that you're going to like, but I just wanted to give you the opportunity to answer in terms of the timing and the size of the PIPE. It was nothing to do with Duravelo-2 and the need to do a head-to-head or any concerns around that?
Make sure you put this in the quotes. No period.
Good. Okay. Then in terms of the balance sheet now, you talked about $1 billion in liquidity. Where does that take you?
We set cash runway into the second half of 2027. We also don't include business development work or anything in our future runway. So I basically extended the runway and added on us to be able to invest in some projects of focus and interest as people will learn about as we kind of let the world know. So I think it's given us a lot more opportunity to kind of continue to build and diversify this company over the next three to five years plus a longer runway. I think when I worked on both sides of the business for a while, and you just never know when you come out of these markets. You have to have the runway and the cash to do what you need to do.
I think we're very fortunate to our shareholders that participate and current shareholders that they afford us the opportunity to do so so that we can go back to the focus of getting this platform, getting these medicines to patients as efficiently as we possibly can.
Okay. And then just thinking kind of more broadly about the strategy and you kind of outlined the BTC space in particular, kind of how you're confident in that. So what is the strategy from here as you think about new opportunities? Do you essentially use ADCs as your proof of concept, right? So anything that an ADC can target you feel you can go after with a BTC?
I mean, well, if you said, "I think that's one piece, but it's not all because we just are doing 5528," where an ADC has never done that. I think if you take a step back, which we don't really care about modalities of sorts. We care about ARMA about modality and what the company's building. Over the next 3-5 years, we want to be a leading solid tumor company in oncology. And I think somewhere over that period of time, we'd like to start being able to even think about outside of oncology. Right now, we think about outside of oncology and do a lot of BD deals that help us bring in capital. But as we continue to build out resources, I think that's the case. We would hope to be building a company that's going to be commercial staged.
I think I don't know what targets lead to what. Obviously, we're very focused on bladder, but we think there are opportunities outside. That's why I said leading solid tumor company. That's not bladder. That's others as well. So we have a lot of tools, a.k.a. medicines that are kind of helping us be able to think about where we can go. We have the capital to now do that and really operationalize that. So I think we're in a really good position over the next 3-5 years to really make some major steps in building out this platform and this company for patients.
Okay. Then just on that commercialization piece, how are you thinking about that right now? Obviously, this can evolve over time. You're not at the point of a launch at this point. Right now, are you thinking that Bicycle can commercialize 8009 alone?
Well, I mean, around the world, I think that's tough. But certainly in major areas, we would hope that we'd be able to kind of make major inroads. But at any given time, we just have to think about what's best for shareholders, right? So we have to see where this goes. And we raised the capital last year so that we had the ability to do this ourselves and really pushed as far as in a phase 2/3 study. And that still remains to be the case. But we'll have to see how it looks. But I think a lot of companies, every now and then, when you get really far along, may have to think about if you were trying to go into Asia or something, do you want to put those resources to work? I mean, that's formidable.
When you think about U.S., major parts of the ex-US, it certainly seems achievable.
Okay. Last 20 seconds, we didn't talk about IO. Could you just run us through next 12 months, what we should be looking for there?
Yeah. I think we've shown we're in an escalation study, a phase I dose escalation study. So it's all-comers. So we'll have to see what we get there. Safety is kind of key. And I think the IO part of the story is one where it could afford us interesting combinations. So we have to see there. So I think the key next step is to know what we're going to say about what's next for its development. But the profile that was at R&D Day, I think we were in cohort nine at that point, is encouraging. And so it will give us a lot of opportunities. And I mean, the thing about the plan, and it looks very safe, very consistent with what we've seen with the other Bicycles.
I think that's what's cool about our platform is we're able to possibly even think about combinations there within our own platform and whatever else is out there in the space that people care about.
Okay. Perfect. I think we're right at time. So thank you, Alethia.
All right. Thanks, Rajan.