Sutro Biopharma, Inc. (STRO) Earnings Call Transcript & Summary

Okay. Great. Thank you, everyone, for joining. We're thrilled to have you here as part of the Credit Suisse Healthcare Conference. Ryan [ Silva ] , Vice President on Credit Suisse's Equity Capital Markets team, I am here with Bill Newell from Sutro Biopharma will be presenting to you today. So with that, I'll turn it over to Bill, and we'll leave a handful of minutes at the end for any questions for the group. So with that, Bill, you can take it away.

Thanks, Ryan. It's a pleasure to be here. Let me share my screen on the slides that I'm going to be talking with you all about today. As is the case of every public company, what I will be sharing with you today will include information that qualifies as forward-looking statements. This is a bit of information that you should be aware of with respect to any statements that I may make that are forward-looking and gives you opportunities to better understand what we mean by forward-looking statements. So for those of you who are new to the Sutro Biopharma story, I'm Bill Newell. I've been the CEO here since 2009, and the company was founded in 2003. So over the last 18 years, we've been progressively building a unique and differentiated platform technology that allows us to make next-generation cancer therapeutics, things like antibody drug conjugates, bispecific antibodies, cytokine derivatives and more are all within our reach. We are the only company in the world to have a cell-free protein synthesis technology that is scalable into GMP manufacturing and that has drugs in the clinic that have been produced using that technology. It was really important in the early days for us to continue to build the cell-free platform, and we've continued to invest in that platform continuously since the company's foundation. Along the way, we established some key strategic partnerships with leading companies, Merck, Bristol-Myers Squibb and EMD Serono to name a few. And they've entrusted us to work with them on some of their most compelling new product opportunities, and I'll be talking about those a little bit later in this presentation. Right now, we're known as an ADC company for a lot of reasons, primarily the fact that we have 4 antibody drug conjugates in the clinic today, but we're much more than that. And as you'll see, we touch a lot of different modalities, and that creates a lot of value and diversifies the portfolio that Sutro has in a way that we think is unique amongst other biotech companies that are about the same size. Of course, we can't do everything. And so we look to achieve value for our investors through opportunities to create spinouts like our spinout, Vaxcyte, another publicly-traded company that is using our technology for a 24-valent pneumococcal conjugate vaccine. We're very excited about that company and their prospects and understand that it will be creating value for our investors as they continue to move forward both with that vaccine candidate and others that are in their pipeline. I'm going to have a very simplified statement about our cell-free protein synthesis technology. Traditionally, ADCs and other large biologics are produced in E. Coli cells to try to manipulate the antibody at the end to create an antibody drug conjugate or manipulate it in order to form a bispecific antibody. You can do the same thing with cytokines as well. We do something completely different. We take the cellular machinery that is inside the cell, and we remove it from the cells so that we don't have to deal with a living organism. That is then called an extract. With that extract, we can synthesize any protein of interest that we want that we get DNA that codes for that protein of interest. And in the course of as little as 18 to 24 hours, we have a fully formed antibody that can be then used for conjugating with a proprietary nonnatural immuno acid to get a linker and warhead that is attached to click chemistry, and that gives us a homogeneous product. This is high science. We've been investing in it for over 18 years. It is industrialized in the sense that we have a roboticized research environment that allows us to parallel process many different product candidates at the same time. It is scalable, as you can see on this slide, all the way up through GMP production. We have our own CGMP facility in San Carlos, California, which has a bioreactor that is 1,000 liter size for production of clinical trial material, and it's scalable, we believe, to commercial scale as we ultimately get there. So this integrated system from discovery to manufacturing really represents a differentiated approach to creating novel next-generation antibody drug conjugates and other molecules. What are the features that we look for when we're designing a molecule? Well, first and foremost, we want homogeneity. Heterogeneity creates issues in terms of manufacturability. It creates issues in terms of optimizing the therapeutic window. It creates potential for off-target toxicity. It's really a suboptimal approach. And so we believe that the best molecules are homogeneous and not heterogeneous. And we can help understand what the best ones are by making many of them and empirically selecting them through in vitro and in vivo tests to identify the best one that we think has the highest probability of commercial and clinical success. Hallmark of our technology is the ability to conjugate at precise positions, not randomly, but at controlled positions where we can compete, binding of position A versus binding of position B versus binding of position C in order to understand what the optimal therapeutic candidate looks like. We do this because we're looking to create a wider therapeutic window with the best single species, giving us the opportunity to give patient benefit in terms of disease modification, but also try and help them maintain a better quality of life from a less toxic molecule. And our approach, we believe, is bearing fruit in the clinic, and I'll share some of that data with you in a moment. I said we were known as an antibody drug conjugate company. And in fact, most people would characterize us that way. But the fact of the matter is we've been working for over 10 years on bispecific antibodies, both those that are dual blockers as well as T-cell engagers. Our antibody drug conjugates, which come in various species, a traditional ADC. We have an immunomodulatory ADC that we've been working on for the last several years and have released some preclinical data on. And we have a bispecific targeting antibody drug conjugate that's in the clinic. We've also been working on cytokine derivatives. Frankly, any 1 of these modalities would be enough to [ found ] a company on, but we've been able to pioneer new and differentiated molecules across all 3 different modalities. And we think that we have synergies by employing our technology across these different modalities as well as de-risk the overall platform because we're not reliant on a single approach to discovery of the next-generation cancer therapeutics. This is our pipeline. It is deep and it is robust. As I indicated, we have 4 programs in clinical development today. Our lead program is STRO-002 for which we have Fast Track designation for our trials in ovarian cancer. We also have trials in endometrial cancer that have opened up, and we are looking forward to trials in non-small cell lung cancer. We have STRO-001. It's a CD74 antibody drug conjugate that we are studying in dose escalation for lymphomas and multiple myeloma where we have orphan drug designation. We have 2 partnered programs, the first of which is the next program down, CC-99712 on, This is partnered with Bristol-Myers Squibb. It is a very important myeloma target BCMA and they have orphan drug designation for this molecule. It's in clinical development, and it started dose escalation in 2019. They've also started a very interesting combo trial with their own gamma secretase inhibitor as well that just got underway earlier this year. Of course, we have other programs in discovery that are ADCs, ROR1 and Tissue Factor among them. They are some of the more advanced ADCs that we have in research. We have a bispecific antibody drug conjugate. I alluded to before, this is a very important franchise molecule for our partner, EMD Serono, because it goes after and expands on their EGFR franchise. So this is a MUC1-EGFR antibody drug conjugate. We're targeting -- they are targeting because they are in control of clinical non-small cell lung cancer and esophageal cancer. That entered the clinic earlier this year. We have another preclinical asset in a T-cell engager 5T4-CD3. We have cytokine derivatives in our collaboration with Merck. We have not disclosed the cytokine targets, but we've made very good progress in our first program for which we've recently unveiled the fact that we have 2 product candidates that are moving forward in preclinical development. And we received a $15 million milestone earlier this year as one of those molecules is moving forward into IND-enabling studies. We also have our own discovery work ongoing for interferon alpha and IL-2 in our research group. And lastly, as I mentioned, there's VAX-24 the Vaxcyte 24-valent pneumococcal conjugate vaccine. So we're not a one-trick pony. We have multiple modalities. Each one has been designed to be best-in-class, and we're really excited as our clinical development data has been revealed this year and is going to be revealed again in 2022 to a greater extent. Let's talk a little bit about our lead program, our folate receptor alpha targeting antibody drug conjugate. This is a homogeneous antibody drug conjugate. Other molecules that are in clinical development for ovarian cancer are certainly much more heterogeneous, and that brings with them certain liabilities that we think limit their therapeutic utility to patients. This has a drug antibody ratio of 4. This is not an average drug antibody ratio. It is a precise antibody drug ratio. We know that a folate receptor alpha is overexpressed in ovarian cancer and endometrial cancer. Those are the reasons we started our initial studies on this molecule in clinical development. But as I indicated earlier, we are also priming for a non-small cell lung cancer study, which we hope can get initiated in the next 12 months. As I said, we design molecules precisely. And so we have specifically chosen the points of attachment out of an array of different points of attachment based on the screening data that we were able to establish preclinically to establish that these sites were the best sites for this type of molecule. We wanted a stable linker so that the molecule did not disassociate from the warhead before it was engaged in the tumor microenvironment. And we have a warhead that is unique. It's a hemiasterlin derivative, which we believe has a dual mechanism of action. It has the usual tubulin inhibitor cytotoxic properties, but it also, we believe, induces immunogenic cell death and so it provides a one-two punch to deal with cancer. When we look at our trial design, it is relatively traditional. We started with a dose escalation phase, overall, in the dose escalation phase, we had 39 patients. When we look at doses that we determined to be clinically active, we saw that 34 patients were treated at the 2.9 mg per kg dose or higher. And of those 34, 31 patients were evaluable for response using RECIST criteria. This is a very advanced patient population. They have been heavily pretreated. They have a median prior lines of therapy of 6. They have had a lot of different platinum regimens, taxanes. They've had -- 82% were treated with Avastin and almost 60% were treated with PARP inhibitors. It is fair to say that, but for our trial, these patients would have had no other available therapies to them and would likely have not had a very long life expectancy given that they had run through all the other potential treatments, including 1/3 of them have been through some experimental therapies. As I mentioned, the dose escalation proceeded in due course, and these are the numbers of patients studied at the respective dose levels. What we came to understand that this was -- that this molecule is very well tolerated. 86% of the treatment-emergent adverse events were grade 1 and 2. We have not seen, unlike other ADCs, particularly those targeting ovarian cancer, any ocular toxicity. We have not seen any pneumonitis or interstitial lung disease, again, differentiating this molecule from a safety perspective. What we do see are the type of adverse events that are expected for tubulin inhibitors. More precisely, we see neutropenia, and we see some neuropathy. Now additional patients who are enrolled in this study could have a preexisting neuropathy up to grade 2. And so it's not surprising that several of them had a grade 3 neuropathy given that they were close to borderline to grade 3 when they entered the study. We do know that the neutropenia was generally short-lived and was manageable either through a dose delay or a dose reduction without affecting, we believe, the efficacy of the molecule. We also know that at higher doses, the adverse event profile was worse. And as we have moved forward into our dose expansion phase, you'll see that we're studying 4.3 and 5.2 mg per kg as the likely go-forward doses in future clinical development. What you see here is the tumor reduction was observed in the majority of the patients that we had on study who were evaluable for RECIST. This is a really nice graphic because it showcases several things. First of all, one, we had 1 patient for whom a complete response was achieved. That is very rare to see in a patient population like this for ovarian cancer, given the nature of the lesions that you end up following in the prior surgeries and treatments that they've had. We had a total of 9 partial responses. So there were 10 responders that was their best observable response. 4 of those 9 were confirmed. 5 were unconfirmed. We feel that is very good for this patient population because they are so advanced in their disease state. And overall, we think that sets us up for an improved response rate as we move forward into patients who are less heavily pretreated. We also saw a deepening of response in those patients who are treated with our drug, and that's important because what we're trying to do is make sure that we attain control over the tumor and have control over the tumor for an extended period of time. You'll see the hash lines at the 26- and 52-week marks. Those show the number of patients who are benefiting from our treatment, whether they had a response or stable disease and their ability to have their disease controlled while they were on treatment for extended periods of time. Another way to showcase some of this data is with this swimmers plot here. And what you see is that we had fully 55% of our subjects on treatment for over 24 weeks. That's a disease control rate of 55%, 17 of 31. We had 5 patients for whom their disease was controlled for over a year and 3 for over 1.5 years. We're very pleased with the outcomes that we see here. And when you think about the patients who received a confirmed response, we saw a durability that was 5.8 months. Now chemo standard of care would be about 4.4 months for the same patient population. It's a small number, but it's an encouraging signal to us in a very heavily pretreated patient population. Another encouraging signal is when you look at all 39 patients on study, and we calculate a PFS score, that's at 7.2 months. Again, that is a significant advantage over standard of care and was very encouraging to us as we looked at the data. Now one of the things that we've come to understand with other modalities, other agents that are going after late-line ovarian cancer patients is that oftentimes, their therapies have to be dosed to a selected patient population that is much larger than the overall patient population. In many instances, companies are selecting out the high expressers of the target antigen and limiting their treatment to those patients. And the reason that they would do so is that they get their better efficacy when they are dosing patients who have more of the target antigen being expressed, and that's understandable. And that as a strategy, if you're trying to maximize the response rate in your patient population. Well, we had 18 patients in the dose escalation study for whom we were able to get tissue samples, we did not have the entire 39 set. We had 18. And we stratified these patients using immunohistochemistry and assay by Ventana that is being used by others in the industry. And we stratified them in a couple of different ways. There is a storing algorithm that is called the PS2+ storing system, where you look at the frequency of staining and the intensity of staining. And so frequency is 75% or higher and intensity is 2 or 3, then you're in the PS2+ category. And that's somewhere in the 30%, perhaps as much as 40% of the patient population. When you look at medium and low, that's everybody below that PS2+ scoring algorithm. You could also look at an H-score, which really gives you a sense of a different measure that is a little more flexible. And with the 18 patients admittedly a limited data set, who were dosed at greater than 2.9 mgs per kg and evaluable for RECIST, what you see is that if we had limited our initial study population to the high expressers only, we would not have seen the benefit in the moderate and weak expressers that this chart indicates. So we thought that was an interesting signal, and that suggests to us that our drug should be considered to be dosed for patients who are not just the highest of the high but a broader subset of patients, and that's a point that we are looking at expressly as we move into our dose expansion cohort. So this really summarizes the initiatives that we've undertaken over the last 12 months and that we'll be undertaking on a going-forward basis to really lean in on our STRO-002 franchise. The data on dose escalation is in the top box on the left. We have now announced that we have achieved our 40-patient enrollment rate in the U.S. and Spain in our dose expansion cohort. This trial was open for enrollment in January. And so we're really thrilled to achieve those enrollment numbers by this time late in the year. These patients were unselected for expression levels. We did, however, require that they provide us tissue for analysis so that we can really look for each and every one of the patients to understand what their expression level is and how it may correlate with the response rates and the durability of response that we're seeing in our patients. So this will be a retrospectively done analysis but one that gives us a chance to best understand where we might want to set an enrichment strategy break point at. These are less heavily pretreated patients, only having 1 to 3 prior lines of therapy, and we're on the cusp of being able to share data with you, interim data, a more mature data set won't be available until around the middle of next year. But right now, we're excited to really look at those initial patients who got on our study and see whether the signals that we saw in the dose escalation cohort are replicated in the dose expansion cohort. Because we think this is an important drug with good therapeutic benefit for patients with other cancers, we've also started an endometrial cancer cohort. We are preselecting for a certain level of folate receptor alpha expression and starting the initial enrollment for 15 patients. That cohort is open and enrolling patients, and we can enlarge it as time goes on if it makes sense for us to do that. Finally, we have got approval to start a combination trial with bevacizumab. That protocol has been cleared, and we're in the process of trying to enroll our first patient hopefully by the end of this year. But understanding how our drug combines with one of the mainstays of care for these ovarian cancer patients is going to be an important understanding for us as we think about both single-agent activity, which can lead to a registration that is in our foreseeable future, we hope, and that can also then allow the therapy to move up into earlier lines. We've also been working to understand the applicability of our molecule to treat patients with non-small cell lung cancer. We've got some late-stage preclinical work that's ongoing, and we look forward to talking more about our thinking as to whether or not we can open a basket trial for non-gynecological cancers, including non-small cell lung cancer sometime next year. With the information that we've gathered from our dose expansion cohort, and that we will be gathering as that data set matures, we expect to have a meeting with FDA and also one with EMA that will allow us to talk with them about the opportunity perhaps next year to start a single-agent registration-directed trial in advanced ovarian cancer. That's certainly been precedented with a couple of other companies who are studying ovarian cancer, and we think there's every reason to believe that we should have the same opportunity to proceed with a registration-directed trial and then add a confirmatory trial with a standard of care as another element that goes in that trial. That's to be discussed with FDA and EMA, so stay tuned for more details, but there will have to be a comparator trial that goes alongside the single-agent trial. Let me switch briefly to CD74 for B-cell malignancies. This is a different molecule, but the design principles that are behind [ 002 ] and all the other ADCs we design are applicable here. We have a homogeneous molecule with a drug antibody ratio of 2. We have precisely positioned the nonnatural immuno acids where we want. It is stable in circulation. And we've designed the derivatives, the maytansinoid derivative that is the active catabolite, not only to be effective at killing cells but also to minimize bystander effects. We've done a very traditional dose escalation design in both, myeloma is 1 cohort and non-Hodgkin's lymphoma is the other. We've now gotten to a dose level of 5.0 mgs per kg in the myeloma cohort and 4.2 mgs per kg in the non-Hodgkin's lymphoma cohort. We are continuing to escalate in both cohorts, and we're looking forward to establishing a recommended Phase II dose. We have recently partnered this program in Greater China with a company called BioNova, and I'll talk more about that in a few minutes. Again, this is a heavily pretreated patient population. This is data that we released at ASH in 2020 for the non-Hodgkin's lymphoma subtype. You see that the median prior -- number of prior therapies is 5 and a number of patients that had stem cell transplants or CAR-T therapy. The safety profile is a very good one. Most of the [indiscernible] are grade 1 or grade 2, really the lion's share of them are without a doubt. We have no ocular toxicity with this molecule to date as well. We've seen some encouraging initial treatment responses. We saw 1 CR in DLBCL patients, 2 PRs in DLBCL patients and then some stable disease in marginal zone and follicular lymphoma. While this is still early data, we are encouraged to see that we could achieve a complete response in a heavily pretreated patient at the 0.075 mg per kg. And then the 2 partial responses are in patients who had already had CAR-T therapy and an intervening therapy and yet they were still able to achieve a response on our therapy despite having failed those prior therapies. Where are we from a financial perspective? Well, we just released our numbers. We have $254 million in cash, cash equivalents and marketable securities as of the end of the third quarter. That gives us runway into the second half of 2023. I mentioned our spinout, Vaxcyte. We still own 1.6 million shares of that company, and those shares are not accounted for in our cash, cash equivalents and [ marketed ] securities number. And most importantly, this hasn't been funded on the back of investors alone. Our partners Bristol-Myers Squibb, Merck, EMD Serono have contributed funding over $400 million, and that's allowed us to build both the platform and the deep and rich pipeline we have today at Sutro and that we're looking forward to continuing to develop into 2022 and beyond. So where are we going? I said earlier, we are leaning in on STRO-002, our folate receptor alpha antibody drug conjugate. We have completed dose expansion enrollment. We are looking to present our initial dose expansion data soon and looking for an FDA meeting next year. We are also -- have initiated our endometrial study and are looking forward to initiating the combo study with bevacizumab. This is a significant investment in this molecule, and we think the data generated to date justifies us leaning in on further development of this molecule, including expanding into non gynecological tumor types like non-small cell lung cancer. STRO-001 is moving to continued dose escalation to achieve a recommended Phase II dose. Our partnership with BioNova really allows us to explore this drug in a different patient population than the one we're seeing in the United States. We look forward to supporting them as they pursue it in less heavily pretreated patients in multiple myeloma and non-Hodgkin's lymphoma and perhaps even AML. They have opportunities not only to go and access less heavily pretreated patients, but also potentially to do combination work that wouldn't be available for us for a while. So we're thrilled to be working with BioNova. We think their clinical development will provide us with a robust set of data that we can point to and form our own development plans for the rest of world outside Greater China. For 003, you're just going to have to wait a little bit longer. I have talked about the 5 programs all of which are competing to be the next molecule that we put into the clinic. So I ask you to stay tuned, but we're very excited, as each one of those programs has the potential, we believe, to be in the clinic sometime within the next 2 years. So please stay tuned for that. In the meantime, we're looking forward to hearing more of what our partner, Bristol-Myers Squibb, has seen with their clinical experience on CC-99712; our partner, EMD Serono, as they started their clinical development of our MUC1-EGFR; and then our partner, Merck, we look forward to the first program that we have partnered with them moving into the clinic, and we'll be delighted to see how that progresses as well. It's a unique, diversified balanced portfolio with a substantial amount of proprietary assets that we own 100% of at this point in time as well as strong partnerships that continue to fund and validate the platform and more to come. So with that, I want to acknowledge my team. This is a team that is deeply experienced in research, development, CMC, strategy, commercial, finance, as well as the core asset of our company, and that's our team, our people. And so I'm thrilled that we've been able to achieve this growth of our company since I started as CEO in 2009, and I look forward to what the future will bring. And with that, I think I will end and Ryan, give you a chance to come back in.

Thanks so much, Bill. Appreciate your comments. We've now opened up the queue for people listening to questions. So I think we can dive into a few of those with the remaining minutes that we have left. The first was, could you please highlight once more the benefits or the key highlights of -- just a moment. Can you please highlight once more just the key benefits of the cell-free protein synthesis platform and speak to what you view as its primary applications?

Yes. So I think some of the key benefits are the ability to rapidly create homogeneous molecules that can then be filtered through a variety of in vitro and in vivo tests to identify the best-performing molecule to take into clinical development. Really, a lot of companies end up getting something that is good enough and then having to live with liabilities and trying to come up with strategies to address those liabilities either through dosing regimens or pre-selecting patient populations that really mitigate against the liability. For us, we start with so many different molecules that we really are ruthless in our competition to identify the one that has the best characteristics across the board. And I'm pleased that the molecules that we've put in the clinic have not crashed and burned in the first 6 months as can happen with cancer molecules. So there's something unique about our design. Now we are well known for our antibody drug conjugate approach. I think it be well known as time goes on, for our cytokine derivative approach, but that's a story that's still developing. And certainly, the bispecific antibody approach is something where we offer a differentiated way to think about these molecules in the sense that we're able to make many different variants to deal with different affinities of the different arms of the bispecific antibody to really tune in what we think are the objective features and qualities preclinically that we want. But it's really that precise engineering, the ability to rationally select the best candidate and then to scale it up, having manufacturing controlled and in-house is a huge advantage for us over other modalities where they have to really rely on CDMOs for the entirety of their manufacturing process.

Great. Moving to our next question from the group. How does 002 differ from the other folate receptor ADCs out there? And how do you see it sort of fitting into the ever-evolving ADC landscape?

I think the differentiation is coming from the fact that -- and we'll have to evolve more data here, but at least on the data that we have today, we're seeing the ability to impact a larger patient segment than the other people who are developing antibody drug conjugates for ovarian cancer. They're all limiting themselves to some subsets. Now we may have to do a limitation of some sort, but I think what the data that I shared with you demonstrates is that we can have effect not only in high expressers, but in medium and those who have low expression patterns as well. So I think by being able to have a larger patient opportunity to benefit from our molecule is one thing. I think the second thing is the way we make our molecules, we think allows them to be more tolerable. As I indicated, we're looking to design molecules that have a wider therapeutic window, meaning that we do not have to dose at the absolute maximum dose in order to get therapeutic benefit for the patient. In fact, we got to be able to dose down from that maximum tolerated dose to find a dose that keeps the patient on therapy every 3 or 4 weeks. If you have to have a break from therapy because of a toxicity, you're giving the tumor opportunities to escape the threat that the ADC is imposing on it with its cytotoxicity. So we think we're going to get patients who are better able to tolerate our therapy, and we're going to be able to do it on a more regular basis. So when you look at other ADCs that have been exploring similar patient populations and dose expansion, what you'll see is their durability is very limited. Oftentimes 16 weeks or 20 weeks is what you see in the best phases of patients who are not heavily pretreated and not advanced in their disease. As I indicated, fully, 55% of our patients in the dose escalation at 2.9 mgs per kg or higher were able to stay on treatment for over 6 months. And given the late stage of their disease, that's significant. So when you look about response rates and you look at durability, we think we've demonstrated or are in the process of demonstrating that we may have the first, the best-in-class approach to treating ovarian cancer.

Great. And look, we have time for one final question here in our queue. Could you please just put some of the -- here we are, sorry. With the announcement of sort of the dose expansion data expected later this year, do you anticipate that being a substantial enough data set to significantly advance conversations with the FDA?

We're -- obviously, the data is fully enrolled, which is a great thing. And the patients who've come on most recently, we needed to have experience with them but not to have the full trial completed before we have dialogue with FDA. So we're starting, we'll be looking at the data and wanting to make certain that we have a good enough signal to answer critical questions that we need to discuss with FDA. What's our dose going to be in a pivotal registration study. We're studying 5.2 and 4.3. Important for us to be able to tell them what that dose is. Do we think there's an enrichment opportunity that's relevant here? And if so, what would that enrichment opportunity look like? We need to have confidence in that. How does the adverse event profile look at the various doses that we want to go forward with? And really what sort of response rate are we seeing in terms of an early signal. Some patients do respond relatively quickly to treatment. Other patients, they may not have a response, but they may have a tumor reduction. And over time, that tumor reduction may build to where it gets to be a response. So we're going to be looking at the totality of the data and deciding when we think we know enough about what we want to propose to the FDA to engage with them and EMA about the opportunity for a registration-directed single-arm study.

Wonderful. Well, thanks so much for that, Bill. I appreciate the time, and thank you all for joining. That's the conclusion of the presentation. So feel free to come back with any questions. Thanks all.

Thanks, Ryan. Thanks for having us.