Good morning, and welcome to the Bicycle Therapeutics call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your touch-tone phone. To withdraw your question, please press star then two. Please note, this event is being recorded. You may listen to a webcast replay of this call by going to the investor section of Bicycle's website. I would now like to turn the conference over to 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 regulatory update for BT8009. I'm Stephanie Yao, and joining me in the room today are our CEO, Dr. Kevin Lee; our Chief Financial Officer, Alethia Young; our Chief Development Officer, Dr. Santiago Arroyo; our Chief Scientific Officer, Dr. Nick Keen; and our Head of Commercial, Jennifer Perry. Before we get to the presentation, I want to make you aware of our forward-looking statements. Now I'd like to turn the call over to Kevin Lee, our CEO. Kevin?
Thank you, Stephanie, and thank you to everyone for joining us this morning. We're excited to provide an update on the regulatory pathway for BT8009 in metastatic bladder cancer, following our discussions with the U.S. FDA. Here is the agenda for today's call. After I make some opening remarks, I'll hand over to Santiago to provide an overview of BT8009 and the regulatory update. Jennifer, our Head of Commercial, will give a brief primer of the metastatic bladder cancer landscape and how we believe BT8009 fits into this landscape. Finally, Alethia and Nick will join us for Q&A. Next slide, please. At Bicycle Therapeutics, we are using our novel platform to pioneer a new and differentiated class of medicines. Our initial focus is in oncology, where we have multiple therapeutics, including BT8009, that are in clinical testing.
We look forward to providing updates on these clinical programs later in the year. We have various partnerships in a diverse range of therapeutic areas like radiopharmaceuticals and neurology, demonstrating the broad utility of our platform. And with our last financing round, we are well-funded and well-positioned to execute on our plans for BT8009 and the rest of our pipeline, which is shown on the next slide. Our pipeline highlights the broad utility of Bicycles. We've experimented with our platform to test its capabilities, and we've been successful in most areas. Now we can decide how best to use it and to have the greatest impact for patients. Our call today focuses on BT8009, and I will now turn it over to Santiago, our Chief Development Officer, to provide an overview of this investigational therapy and our recent interactions with the FDA. Santiago.
Thank you, Kevin. I'm Dr. Santiago Arroyo, Chief Development Officer at Bicycle. I'll be walking you through the regulatory update for BT8009 that we have announced today. But first, a bit about BT8009 and the target. Next slide, please. Nectin-4 is a cell adhesion molecule, and it's overexpressed in a number of solid tumor cancers, including bladder or urothelial, lung, breast, and ovarian cancers. We designed BT8009 to target Nectin-4. It has a highly specific bicyclic peptide, or Bicycle, which binds to Nectin-4, and a RGD-MMA linker payload system that selectively delivers MMA to tumors expressing Nectin-4. Next slide, please. We have conducted extensive clinical testing of Bicycle conjugates, which have exhibited superior performance through their selectivity, their unique and advantageous PK profile, potent antitumor activity, and validated tumor penetration demonstrated independently in humans using imaging technology. Next slide, please.
BT8009 is currently being studied in a phase I/II clinical trial as a potential therapy for multiple Nectin-4-expressing tumor types, including metastatic bladder cancer. Later this year, we anticipate sharing dose escalation and dose expansion data for more than 100 patients enrolled in this trial. Next slide. Here is a summary of what we know about BT8009, based on data from the dose escalation studies. Objective response rates are in line with currently approved antibody-drug conjugates for ADCs. In clinical testing, we've seen no discontinuation of BT8009 due to adverse events. This is very differentiated from MMA-bearing class of ADCs, which have all shown severe skin reactions, peripheral neuropathy, and ocular toxicity. And BT8009 could potentially have longer duration of response versus ADCs.
Based on the totality of this data so far, we believe that BT8009 has a differentiated profile compared to other treatments for metastatic bladder cancer. Next slide. Since its discovery, we have been focused on expediting the development of BT8009 for metastatic bladder cancer. In January, we announced that the FDA awarded Fast Track designation to BT8009 in previously treated metastatic bladder cancer. Today, we are excited to share that we have reached alignment with the FDA on the regulatory path for BT8009 and the design of our phase II/III registration trial called DURAVELO-2. Importantly, we have aligned on clinical trial endpoints that could support potential accelerated approval in a broad metastatic bladder cancer population. In untreated metastatic bladder cancer, the first-line setting, BT8009 in combination with pembrolizumab will be evaluated against chemotherapy.
Potential accelerated approval will be determined by objective response rate, ORR, and progression-free survival, PFS, will be used to confirm the clinical benefit. In previously treated metastatic bladder cancer, the second-line plus setting, potential accelerated approval for BT8009 monotherapy and in combination with pembrolizumab will be determined by ORR, ORR compared to historical control data. Discussions with the FDA about the design of the confirmatory trial are ongoing. Obviously, we are very pleased with the outcome of our discussions. We sincerely appreciate the FDA collaboration and guidance. I will now go over the design of the DURAVELO-2 trial on the next slide. Here is an overview of the DURAVELO-2 trial, a global multicenter adaptive study designed to assess the safety and efficacy of BT8009 for metastatic bladder cancer. We are planning for more than 250 sites in 30 to 40 countries across the five continents.
Patients will be enrolled in two cohorts, those with untreated metastatic bladder cancer, cohort one, and those with previously treated metastatic bladder cancer, cohort two. In cohort one, two doses of BT8009 plus a standard pembrolizumab regimen will be initially assessed. Following selection of the optimal dose, BT8009 plus pembrolizumab will be evaluated against chemotherapy. Potential accelerated approval will be determined by objective response rate, ORR, and progression-free survival. PFS will be used to confirm clinical benefit. In cohort two, two doses of BT8009 as monotherapy will be initially studied. Following selection of the optimal dose, an additional arm of BT8009 plus a standard pembrolizumab regimen will be added. Potential accelerated approval for BT8009 monotherapy, and in combination with pembrolizumab, will be determined by ORR compared to historical control data.
As I previously stated, we continue to have discussions with the FDA to align on the confirmatory trial for this indication. With respect to dose selection, we plan to investigate two doses of BT809 in both settings. This is in line with current FDA guidance, and we will select one in each setting that provides the greatest clinical benefit for patients. Preparation for this outcome, we have put in place the clinical trial infrastructure, including manufacturing of all of our drug products, that will allow us to start the key presentation of the trial early next year. Next slide, please. In summary, we are extremely pleased with the update we are sharing with you today. We have designed a robust and innovative development plan for BT809 that could support potential accelerated approval in a broad metastatic bladder cancer population.
We plan to start the phase II/III DURAVELO-2 registration trial early next year, and we remain focused on our goal to get this much-needed therapy to patients as quickly as possible. I will now turn it over to Jennifer for an overview of the metastatic bladder cancer landscape. Jennifer?
Thanks, Santiago. Hi, I'm Jennifer Perry, Senior Vice President and Head of Commercial at Bicycle. I'll be giving a brief primer of the metastatic bladder cancer landscape. As you can see on this slide, bladder cancer is the 10th most common cancer in the world and 6th most common in the United States. More than 570,000 people worldwide and more than 85,000 people in the U.S. are diagnosed with bladder cancer each year. Many patients, nearly a quarter with bladder cancer, go on to develop metastatic disease. Current therapies for first-line treatment of metastatic bladder cancer have shown poor durability of response, highlighting the significant need for new, safe, and effective therapies in this area. Next slide, please. This slide shows just how complex the metastatic bladder cancer treatment journey can be.
Chemotherapy remains by far the treatment of choice in the first-line setting, despite the challenges that can be associated with its use. As we progress into later line, a wide variety of treatments are used, with none standing out as the treatment of choice. Notably, despite a number of targeted therapies approved in second line, Pembrolizumab is most commonly used. Additionally, Sacituzumab is used most often in third line. Based on our market research, it's interesting to note that Enfortumab still has relatively modest use in second line plus since its approval nearly four years ago. We believe this underlines the need for safe and effective new therapies. Next slide, please. So why is this the case?
If we consider Enfortumab, which also targets nectin-4 and has also demonstrated compelling initial response rates, we see that its tolerability profile, both in combination therapy and monotherapy, can result in significant dose interruptions, delays, and discontinuation, which presumably can limit its potential for longer durability. These concerns related to tolerability and maintaining patients on therapy have been well documented in the scientific literature, and the three abstracts from ASCO 2023 noted on this slide are just a sample. In view of this, we believe there's an opportunity for a therapy with a differentiated profile, such as BT8009, which could provide significant benefit, and in doing so, become the treatment of choice for patients with metastatic bladder cancer. Next slide, please.
We have had numerous interactions with key opinion leaders who specialize in the treatment of bladder cancer, and as you can see on this slide, their feedback supports this view. Next slide, please. Based on our understanding of how this disease progresses, the treatment landscape, and our current market research, we believe BT8009 has the potential to be a best-in-class treatment for metastatic bladder cancer, where there's still unmet need for additional therapies. Our vision for BT8009 is that it will become standard of care in first-line combination, standard of care in second-line plus as monotherapy and combination therapy, and to expand BT8009 to use beyond metastatic disease. Thank you very much. Kevin, back to you.
Thanks, Jennifer. In closing, we're extremely happy to share this positive regulatory update about BT8009 today. As a reminder, data for BT8009 show robust anti-tumor activity and a differentiated safety profile, potentially making it the partner of choice for PD-1, PD-L1s, and novel combinations in metastatic bladder cancer and other Nectin-4-expressing tumors. Earlier this year, BT8009 was awarded Fast Track designation in previously treated metastatic bladder cancer, supporting its potential as an important new drug for patients with this disease. We've aligned with the FDA on expedited clinical development plan and path to market in untreated first-line and previously treated second-line plus metastatic bladder cancer. An evaluation of BT8009 is advancing in other cancers, lung, ovarian, breast. We look forward to providing clinical updates for BT8009 and additional pipeline programs later this year. We'll now begin the Q&A portion of our call.
Our CFO, Alethia Young, and our CSO, Nick Keen, are here with us in the room to take your questions. Operator, first question, please.
Thank you. Ladies and gentlemen, as a reminder, if you'd like to ask a question, please press star then one. Our first question today comes from Jay Olsen with Oppenheimer. Please go ahead.
Well, hey, congrats on the progress, and thank you for taking the questions. In cohort one, can you talk about how long you think it will take to find the optimal dose, and then how long it might take to have sufficient ORR data to file for accelerated approval? And then in cohort two, can you elaborate on the use of historic data for control and what kind of historic data will be used? Thank you.
Hi, Jay. Thanks for the question. Yeah, we're very excited by this news. We think it's a really positive thing for patients. I think the best person to answer your question is Santiago. I'll hand it over to Santiago.
Yeah, I will talk about the number of patients that we will include for getting to those milestones. We are planning to enroll 30 patients per cohort for the dose selection phase, so basically 60 patients. For Cohort 1, in the comparison between pembrolizumab plus BT8009 with chemotherapy, we are planning to draw 296 patients. So that's for the first question. I believe that your second question was about the Cohort 2 sample size considerations and how we are considering what will be the historical control. We have two types of historical controls for the Cohort 2. One for monotherapy and historical control there is 25% response rate, which is the response rate that typically you see with previous ones.
For cohort 2, in combination therapy with Pembrolizumab, we have an historical control based on past test data, which is about 40%.
Great. Thank you very much. And if I could, maybe one follow-up on cohort 2. Can you just talk about if Padcev experienced patients will be included or excluded?
They will be excluded.
Okay, great. Congrats again, thanks for taking the questions.
Thanks, Jay.
Thank you.
Thank you, and our next question today comes from Li Watsek with Cantor Fitzgerald. Please go ahead.
Hey, good morning, and congrats on the update. Just a couple questions from us. The first is, can you give us a sense of, you know, what data has the FDA seen for the trial alignment? How much of the phase II data did they review?
Hi, Li. Yes, so we announced in, as you as I'm sure you recall, in November, that we were starting our expansion cohorts. And within those expansion cohorts, we're also doing a safety cohort of 8009 and Pembrolizumab, and we've been able to share some of the emerging data from those cohorts with the FDA.
Okay. And then, you know, given that EV and pembro will be fully approved in front line and become one of the standard care next year, just wondering, would that approval change FDA's view on a pathway for BT8009, or its pathways independent of Padcev regulatory status?
Yeah, I mean, we have no information to suggest things will change. We had a very good, collaborative, informative conversation with the FDA. And you know, we agreed and aligned on the path that we're sharing today. I think Jennifer gave a pretty good overview of the metastatic bladder cancer market. As you're aware, it's a devastating disease. No one therapy being used to the exclusion of others. There's a lot of therapies out there being used in a lot of different ways. No one standard of care, and it's entirely appropriate. It makes a lot of sense that chemotherapy, with its you know, history still very widely used, is you know, currently considered the standard of care.
So we see no reason to believe that that's gonna remain the case during to the foreseeable future. I don't know if you wanna add anything, Santiago?
Yeah, I'm not putting in our conversations with the agency. The issue of having a Padcev comparator was raised. Obviously, they know, and everybody knows that Padcev will be filing for confirmatory of final approval probably later this year. So that's not an issue. Again, as Kevin was saying, there is not a single standard of care, and actually, Padcev penetration in the late market has been very slow. And we have to see, I mean, the Padcev has obviously a good efficacy, but also has a fair amount of of adverse events. And the risk benefit is something that physicians and patients really look at when they want treatment.
That's why I think, you know, BT819 brings a differentiated opportunity for patients and for physicians with what we hope to be a good risk benefit for them.
I don't know if Jennifer has anything you wanted to add.
Yes. Hi, Li, Jennifer here. So a couple things just to give some, like, color around the numbers. When you look at our data, in first-line, like Kevin said, chemotherapy is still the dominant regimen, and, for example, in cisplatin-eligible, it's still over 80% used in terms of cisplatin gemcitabine. And obviously, even with chemo-free options, as we hear oncologists call it, are important, like the recent accelerated approval of EV plus pembro. They still are struggling with the fact that they still have high rates of discontinuation, around, 30% to 35%, high rates of dose interruption, around 70%, and then high rates of dose, reduction, around half patients have the dose reduced. So I think it's early days to see how that regimen gets utilized and how much uptake that they'll get longer term.
Okay, thank you.
Thank you. And our next question today comes from Kelly Shi with Jefferies. Please go ahead.
Congrats on the great progress. My first question is, just curious why the 6 milligrams was chosen, as one of the two doses in evaluation, for pivotal trial, given that previously 7.5 was one of the two RP2Ds? And I also have follow-up. Thanks.
Yeah, sure.
I'll run it to you, Santiago.
Okay.
Hi, Kelly.
Hi.
Yeah, I mean, we already mentioned the, you know, our initial results in the dose escalation and the doses and dosage schedules that we explored. We've done a lot of PK/PD analysis to try to come with the right dosing. We believe the 5 milligrams every week is an adequate dose in which the risk-benefit is, is appropriate for patients. And 6 milligrams two weeks on, one week off, is a dose that is not very far from 5 milligrams every week. It has some advantages in patient convenience, and so we wanted to explore that dose. Again, we believe that both of them will show efficacy, and we believe that both of them will be well tolerated, and the decision between one and the other will be done on the basis of the overall clinical benefit for the patient.
Thank you. Also for the data update of BT8009 this year, do you include other tumor types and also the cohort data that include a prior Padcev treatment?
Sure. Yeah, our intent is to give as full of an update as we can. So we will include the other tumor types that we mentioned in our November update, including the data that we have in the prior exposed EV patients. I think we've been fairly clear with that, that that's a difficult population to recruit to. The patients are very sick at the end of the treatment phase, so it's proven challenging, but we'll share what we have.
Thank you. Congrats again.
Thanks, Kelly.
Thank you. Our next question today comes from Jonathan Chang with Leerink Partners. Please go ahead.
Hi, guys. This is Jonathan. I just wanted to clarify in cohort two, does that also exclude patients with prior pembro exposure, or are you enrolling those patients as well? And then, second question is, could you tell us a little bit about how much data for PD-1 combo we'll get in the update later this year? Thank you.
Santiago, do you want to-
Yes, we'll be excluding any patients with MMAE for cohort 2. So, patients that have been exposed to Padcev before will be excluded. About the data for that will be shared at later this year, we'll share the data from the first cohort of patients in our therapy, which will be about seven patients.
I think Jonathan was asking about pembro usage in the second line. Will we exclude the patients who had pembro in second?
No, no, we will not exclude previously, previously treated pembro patients. We will not.
Thank you. And, and our next question today comes from Peter Lawson at Barclays. Please go ahead.
Thanks for the update. Appreciate taking my questions. So Cohort 1, you enrolling, is that, would that just be, cisplatin-eligible patients for Cohort 1?
Y ou kind of expect the ineligible kind of to go to Cohort 2. Just your thoughts around the kind of paradigm around eligible versus ineligible for cisplatin.
No, I mean, to be clear, in Cohort 1, we'll be taking all first-line patients, cisplatin-eligible or not. And I think that's one of the really exciting things about this trial is it really gives us the opportunity to make a huge difference to the lives of all patients suffering from metastatic urothelial cancer, regardless of cisplatin status.
Gotcha. Thank you. That's really interesting. And what would happen with the cisplatin-ineligible patients? What do they automatically kind of go onto Bicycle's arms, or just how does that- how are those patients triaged in the trial?
Then they will go to Carboplatin, or the Bicycle. So the randomization will be between Bicycle plus Pembrolizumab or Gemcitabine. If it is Cisplatin eligible, it will be Cisplatin. If it is Cisplatin-ineligible, it will be Carboplatin.
Gotcha. Okay, perfect. Thank you so much. And then just the degree of data we get by year-end, kind of how much should we think about in various different cohorts, and in particular, kind of will we get kind of longer-term follow-up around the pembro patients, or how much follow-up are we gonna get around the pembro plus BT8009?
Yeah. So the, that cohort, the pembro combination cohort, was finished and run relatively recently. We will provide all the information that we have with the follow-up that we have, which will be, probably limited in the sense that the data will not be extremely mature. But at least, I think that, we'll be able to give an idea of the safety and tolerability for sure of the compound in that limited, number of patients. We'll also be presenting the data that we have available in EV-exposed patients and data in other tumor types.
Perfect. Thank you so much. Sure, bye.
Thank you. Our next question comes from Amy Fadia with Needham. Please go ahead.
Hi, good morning. Thanks for taking my question. Can you talk about what your expectation is with regards to how long it will take to enroll the studies and get to the interim analysis, to identify the optimal dose, and then to full data readout? And then I've got another question.
Yeah, I mean, I'm sure that's a question that a lot of people are wondering. As you'll appreciate, we've been putting together all the operations to support the trial. We're not yet at the point of starting the trial, and once we're there, we'll give more clarity on expected timelines, et cetera.
Good. And maybe just thinking about the combination of the BT8009, the pembro versus BT8009 monotherapy, what is your sort of expectation with regards to the efficacy of the combination? Would it be sort of more in line with how we've seen Padcev plus pembro versus Padcev alone? Or do you anticipate maybe a greater synergistic benefit to patients? Thanks.
Yeah, we are anticipating, you know, better efficacy than with BT8009 in monotherapy. In second-line or in pre-treated population, we are anticipating that the efficacy of the combination will be in between what we will get with the pembro combination in Cohort 1 and the monotherapy in Cohort 2. So that's what we are aiming, and that's how we have powered that Cohort 2 line.
Thank you.
Thank you. Our next question today comes from Ren Benjamin with JMP Securities. Please go ahead.
Hey, good morning, guys. Congratulations on the update, and thanks for taking the questions. I guess just a clarification one. You talk about ORR as being the primary endpoint, and then progression-free survival will be used to confirm clinical benefit. Are these co-primary endpoints? And kind of, you know, how does that work? And one you know hit your stat sig, and then the other not, and it could still be approved. Any sort of clarity on that? And then this is a follow-up. You mentioned that this is in line with the FDA's Project Frontrunner, and I'm more familiar with Optimus. Can you talk a little bit about, you know, this Frontrunner project?
Maybe I'll start, and then Santiago can provide a bit more detail. The Project Frontrunner concept or the philosophy to try and, you know, move therapies as quickly as possible into frontline setting, avoiding the historical, you know, starting late line and then move slowly up. So it's really designed to get, you know, good active medicines into the hands of patients who, you know, have the potential for greatest benefit at the earliest possible stage. So we're really pleased that we were able to, I think, reach very good consensus with the FDA about how to do this, and, you know, the trial that we've come up with today.
I don't know if you wanna talk a little bit about the ORR and the PFS, Santiago?
I mean, something, you know, in a sense, the proof, or rather, crystallizes in the guidance from the FDA from last March. There was a guidance for accelerated approval that basically kind of delineates how they would like to see drugs to advance for the treatment and for the obtaining accelerated approval in the treatment of cancer. And we basically, what we've done is follow closely the guidance, and I think that that's why we've been successful. On the question of the endpoints, the accelerated approval for first line and for second line is based on ORR. And the prior analysis for potential clinical benefit for the cohort one, so previously untreated, is based on PFS, not on OS. So PFS will be the primary.
Got it. So, should I be thinking about that as co-primaries or not?
No, for accelerated approval, the primary will be ORR. For the final approval, the primary will be PFS. There is no co-primary.
Got it. Great. Thanks very much for the clarification, and congratulations.
Thank you.
Thank you. Our next question comes from Bill Maughan with Canaccord Genuity. Please go ahead.
Good morning, and thanks. So, now enrolling potentially in a trial with a chemo comparator versus in a landscape that has shifted in the past few years, do you expect any significant differences in the patient population and the performance of the chemo control arm in frontline? And then just eventually down the line, you know, assuming the profile holds up and, you know, and that the drug is better than Padcev, but with the lack of, you know, direct head-to-head data, what do you expect to need to be able to effectively market against Padcev in the frontline? Thank you.
First one, Santiago, and then maybe Jennifer, you take the second one.
Yeah, we don't expect, I mean, major changes. As Jennifer was saying, you know, still in first line, most patients are treated with chemotherapy. There is also a fair amount of patients treated with PD-L1. The efficacy in that setting is well known and well documented, and we are powering the study for that type of efficacy. So our chemotherapy arm versus our combination arm is well powered with the number of patients that you can see in the slide. Maybe for the second question, Jennifer?
Yeah, I'm happy to take that. So, there's an example that's really near and dear to my heart because I launched ibrutinib, and I always think of this when I think about the situation that we're in here with Bicycle coming behind, another agent, at the same target. So, obviously, we launched ibrutinib for full approval in July 2019, relapsed/refractory CLL. Very quickly, obviously, the medical community adopted it as what we were considering standard of care, as in it was becoming treatment of choice, and people were using it before some of the older therapies. About five years later, as you know, 2019, acalabrutinib received approval, but were not asked to do a head-to-head by the FDA for that approval. They started their study about a year after the initial ibrutinib approval.
Their message was really one of, more targeted, less off-target effects and a better safety profile, in particular, outperforming, on a tolerability standpoint, Acalabrutinib and the bleeding events with Ibrutinib. As you all know, the story as it goes, we were certainly surprised. For Ibrutinib, when Acalabrutinib, in their first nine months in 2020 on the market, they reached $340 million, and they were receiving already then 35% share of all new patient CLL starts. Obviously, last year, they did about $2 billion and were at 54% share of all new CLL starts. So what that shows us, just as an example, is that there is opportunity for a new targeted agent without having to do a head-to-head for the approval.
Now, of course, they did go on to do a head-to-head, showing non-inferiority efficacy and a superior safety, but that came about two years after their approval. So it's not necessary to actually get FDA and regulatory approval for their initial indication. So again, following that model, we're very hopeful that our profile of DURAVELO-2 into its promise, BT8009, will be a new differentiated potentially best-in-class Nectin-targeted agent versus Padcev.
Thank you very much.
Thank you. Our next question today comes from Jeff Hung with Morgan Stanley. Please go ahead.
Hi, good morning. This is Catherine on for Jeff Hung. Thank you so much for taking our question. For the cohort two confirmatory trial that's still undergoing discussion, could you provide more color on what aspects remain outstanding when it comes to alignment with the FDA?
Yes, Santiago.
Yeah. So when we embarked in this, in the design of this trial, one thing that we were, we wanted to discuss with the agency, if we would need one or two confirmatory studies. Obviously, we had a built-in confirmatory study for cohort one for previously untreated. We believed that it was not necessary to do a confirmation study in a similar population for cohort 2. The FDA, however, thinks differently. They believe that they are two different populations, so they ask us to do a confirmatory study for cohort two. That's the situation. So we need to put it together. We still don't have the design of the study.
We have plenty of time to do that because we don't have to. We don't need to have the study enrolling until we hopefully obtain accelerated approval for the cohort 2 population. So that will be something that we'll be working on with the FDA, determining what is the adequate control for that. Again, at no time during the conversation, the FDA mentioned that we will need to compare to EV. So but again, we haven't put together the plan. Something to mention, for the accelerated approval in cohort 2, I think it's we have two doses or two ways of dosing BT8009. One is in monotherapy, and the other is in combination therapy. We believe that each one has its merits in order to be able to achieve accelerated approval.
In both of the cases, the clinical benefit, we are hoping it will be better for patients because safety, durability, duration of response. In the case of BT8009 plus Pembrolizumab, in addition, we believe that we have a chance to show higher efficacy than perhaps in monotherapy in previously treated population. So, that's the situation for the accelerated approval, and again, the confirmatory study is something that we'll be working on.
Thank you so much.
Thank you. Our next question comes from Rajan Sharma with Goldman Sachs. Please go ahead.
Hi, thanks for taking my question, and yeah, congrats on the progress. A couple left from me. So first, just given that with the last subject for BT8009, we saw some elevated neutropenia rates. So just in the potentially registrational program, do you expect to allow for investigators to use GCSF if they think that's necessary? And then second, just on financing. So Alethia, maybe if you could just give us an update on how you're thinking about cash runway post the update, and if you're confident that there's sufficient liquidity to get through to a potential accelerated approval.
Thanks, Rajan. So first, the Neutropenia, Santiago.
Yeah, we, you know, even though we obviously have some Neutropenia, it has been pretty manageable, and we've had direct knowledge with investigators. Generally, when it reaches a level, it just needs some reduction. Actually, it has been very, very rare that the investigators need to use growth factors, and growth factors are not in the protocol to be used in every case. So I think that the neutropenia or, you know, the data that we have until now show, indicates that neutropenia is not going to be something difficult to manage, or that will need a special treatment.
And Alethia?
Rajan, your, your finance question. With the last raise we did in July, we have $600 million in pro forma funds, so we are well funded to get through the trial, obviously, on BT8009. And, you know, as we think about kind of future opportunities, because this, this opportunity today kind of unlocks a lot of opportunities, potentially, we'll be very thoughtful about how to continue with tumor, other type, tumor-type development and any other kind of work we want to do. But right now, we're sufficiently funded for what we need to do here.
Thank you very much.
Thank you. Our next question today comes from Arthur He with H.C. Wainwright. Please go ahead.
Hi, good morning, everyone. This is Arthur Ong for RK. Congrats on the progress. I have two quick ones. First is for the cohort 2 study design, especially for the endpoint for the committed study, when we could expect the update on that part?
I think Santiago's already stated that's something that we'll continue to have discussions with the FDA on. I don't think it's terribly pressing, to be honest. It's something that we'll work with them on and give an update as and when appropriate.
Okay, thanks for that. The second question is regarding the other tumor types. Can we expect the similar strategy or route for other tumor indication compared to the bladder cancer? Thanks.
Yeah, I mean, I think you have to let that data play out and see how the data looks. If it looks as strong and as exciting as it does for 8009 in bladder cancer, then it would, again, following the philosophy of Project Frontrunner, make a lot of sense to try and take the molecule, you know, into a more earlier setting. That's entirely in keeping with the FDA guidelines, and I think very exciting for patients and for Bicycle as well. So yeah, that's something that we'll consider as we get the data.
Thanks again, and I appreciate you taking my question.
Cool. Thank you.
Thank you. This concludes our Q&A session. I'd like to turn the conference back over to Stephanie Yao for any closing remarks.
All right. Thanks for joining us this morning. A replay of this call and a copy of the slides will be posted to our website. If you have any questions, please reach out to ir@bicycletx.com. Thank you.
Thank you. This concludes today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines and have a wonderful day.