Summit Therapeutics Inc. (SMMT) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by. My name is Christa, and I will be your conference operator today. At this time, I would like to welcome everyone to Summit Therapeutics WCLC Update Conference Call. [Operator Instructions] I will now turn the conference over to Dave Gancarz, Chief Business and Strategy Officer. You may begin.

Good morning, and thank you for joining us. We issued a press release this morning -- yesterday morning relating to ivonescimab's Phase III HARMONi-2 data presented as a part of the Presidential Symposium at the International Association for the Study of Lung Cancer 2024 World Conference on Lung Cancer, otherwise known as World Lung. The press release is available via Summit's latest news button on our homepage of our website and our Form 8-K was also reported this morning and is available on our website and via the SEC's website. Today's call is being simultaneously webcast and an archived replay will also be made available later today on our website www.smmttx.com. Joining me today on the call is Bob Duggan, our Chairman and Chief Executive Officer; Dr. Maky Zanganeh, our Chief Executive Officer and President; Manmeet Soni, our Chief Operating Officer and Chief Financial Officer; Dr. Allen Yang, our Chief Medical Officer; and Dr. Howard Jack West, our Vice President of Clinical Development. Before we get started with the rest of the call, I would like to note that some statements made by our management team and some responses to questions that we make today may be considered forward-looking statements based on our current expectations. Summit cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Please refer to our SEC filings for information about these risks and uncertainties. Summit undertakes no obligation to update these forward-looking statements, except as required by law. Following comments from our team, we will take questions. And with that, I would like to hand the call over to Jack to speak to our HARMONi-2 trial that was presented at World Lung yesterday.

Thank you, Dave. A new checkpoint inhibitor-based treatment against PD-1 or PD-L1, either alone or combined with chemotherapy has become a current standard of care for patients with advanced non-small cell lung cancer that does not harbor a driver mutation. For a portion of these patients, an immune checkpoint inhibitor monotherapy is the current standard of care, particularly those patients with a PD-L1 TPS score of 50% or greater. Monotherapy PD-1 therapy is approved in most places for these patients with non-small cell lung cancer whose tumor has positive PD-L1 expression or a TPS score equal to or greater than 1%, although it's used as monotherapy is limited in patients with PD-L1 expression in the low or 1% to 49% range. On Slide 3, we have the schema for the HARMONi-2 trial. HARMONi-2 is a randomized double-blind clinical trial evaluating frontline monotherapy ivonescimab as compared to monotherapy pembrolizumab in patients with locally advanced or metastatic non-small cell lung cancer that has demonstrated positive PD-L1 expression, specifically a PD-L1 CPS score of 1% or greater. This is a single region multicenter Phase III clinical trial conducted and sponsored by Akeso and conducted in China. Our partners at Akeso generated and analyzed the data that we will walk through here. A total of 398 patients were randomized 1:1 and stratified by clinical stage, squamous versus non-squamous histology and PD-L1 expression of low versus high with a 50% cutoff. Patients received either ivonescimab at 20 milligrams per kilogram or pembrolizumab at 200 milligrams IV every 3 weeks. Treatment was to be continued for -- was to be discontinued for intolerability, no clinical benefit or initiation of new anti-tumor therapy and given for up to 24 months. The primary endpoint was progression free survival by Independent Radiologic Review Committee with secondary and exploratory endpoints as shown here. The patient characteristics demonstrate a median age of approximately 65, the population was predominantly male, just under 20% never smokers, more than 90% with Stage 4 disease, a split of about 45% of patients with squamous histology and 55% with non-squamous histology and approximately 42% of patients with high PD-L1 expression of 50% or greater. Approximately 13% of patients had liver metastases, 18% with asymptomatic brain metastases at baseline. Importantly, patients with central tumors, cavitation or necrosis as well as tumors encasing large blood vessels were eligible, including those patients with squamous non-small cell lung cancer histology. And all of these baseline characteristics were numerically higher in the patients randomized ivonescimab. Here is the primary endpoint of progression-free survival by Independent Radiologic Review Committee for the entire study at the time of the first planned interim analysis with a median follow-up of 8.67 months, demonstrating a significant improvement for ivonescimab with a hazard ratio of 0.51, corresponding to a 49% improvement over the control arm. The median PFS was 11.1 months versus 5.8 months in the ivonescimab and pembrolizumab arms, respectively. Of note, the curves begin to separate at the first point of radiographic assessment about 6 weeks and maintain separation over the entire duration of follow-up thus far. The 4 slot of PFS subgroups reveals that the PFS benefit with ivonescimab was observed across nearly all subgroups and is a comparable magnitude for the most clinically relevant variables. Specifically, the benefit is quite comparable across the spectrum of PD-L1 expression with a hazard ratio of 0.54 for patients with PD-L1 low expressions and 0.46 for patients with high PD-L1 expression of 50% or greater. As previously discussed and is particularly true in the United States and Europe, monotherapy checkpoint inhibitor usage is a standard of care for patients with high PD-L1 expression or those with a PD-L1 CPS of 50% or greater. With regard to non-small cell lung cancer histology, the benefit was also similar for patients with squamous non-small cell lung cancer, who showed a hazard ratio of 0.48 favoring ivonescimab and those patients with non-squamous histology with a hazard ratio of 0.54 favoring ivonescimab. This slide is a strong indicator that the benefit was seen across clinical subgroups and underscores that the success of the trial overall was not driven by an especially strong performance of a subgroup. Turning to response rates. You can see that the response rate is 50% and that approximately 90% of patients achieved disease control with ivonescimab compared with a response rate of 38.5% and disease control rates of 70.5% with pembrolizumab. With regard to safety, we see that there was a numerically higher rate of serious treatment-emergent adverse events with ivonescimab 20.8% compared to 15.6%, though this did not translate to greater treatment discontinuation or treatment-related adverse events leading to death, both of which were numerically higher in the pembrolizumab arm. This pattern held true in patients with squamous non-small cell lung cancer as well, where there were comparable rates of serious treatment-related adverse events, discontinuations and death in the ivonescimab arm compared with the pembrolizumab arm representing the first randomized Phase III clinical trial, evaluating the safety profile of ivonescimab in the squamous population and specifically confirming its tolerability in this group. In more detail, we see that nearly all of the higher -- of the treatment-related adverse events were lab-related abnormalities, hypertension and proteinuria, but generally did not lead to discontinuation of dosing. Finally, looking at the immune-related and possibly VEGF-related adverse events in the table to the left, we see comparable IRAEs with ivonescimab compared to pembrolizumab. On the right, we see that as expected, given that ivonescimab is a PD-1 VEGF bispecific antibody compared to pembrolizumab, which is a PD-1 monoclonal antibody, ivonescimab was associated with more possibly VEGF-related AEs both of all grades and Grade 3 or higher. Importantly, however, all Grade 3 AEs were classified as Grade 3. There were no Grade 4 or Grade 5 AEs that were possibly VEGF-related in either arm of the study. The table in the bottom right shows that most of the possible VEGF-related adverse events represented proteinuria and hypertension. There is no evidence of life-threatening or failed leading complications including among patients with advanced squamous non-small cell lung cancer and in patients with central tumors, cavitary lesions and/or tumor encasing large blood vessels. And with that, I'll turn it over to Allen.

Thanks, Jack, for a great review of the data that was presented at World Lung yesterday. We are excited about the results of Phase II and the great potential for ivonescimab to bring benefit to patients moving forward. Not to be lost in the data announced yesterday, we also have multiple Phase II data releases from studies conducted in China by our partners at Akeso, which further provide evidence of the antitumor activity and safety of ivonescimab in settings beyond metastatic non-small cell lung cancer. The trial designs for these 4 studies are contained in the appendix to this presentation. A few highlights on this slide include the early-stage non-small cell lung cancer data that was shared yesterday at the World Congress for Lung Cancer. In the perioperative trial, there was a promising pathological complete response and major pathological response noted in the cohort of ivonescimab in chemotherapy administered in the neoadjuvant setting for patients treated prior to surgery. Immunotherapy plus chemotherapy represents the standard of care for these patients. No treatment-related adverse events led to delayed or canceled surgery or postoperative wound healing complications in this Phase II study that consisted of both squamous and non-squamous patients. Abstracts from the European Society of Medical Oncology were released around midnight Central European time or in the evening in the U.S. A peek at that data from the first-line advanced triple-negative breast cancer, first-line metastatic microsatellite stable colorectal cancer and first-line recurrent or metastatic head and neck cancer abstracts were released. There will be oral presentations at ESMO next weekend for the breast cancer and colorectal cancer data, the head and neck cancer data will be presented in poster form at ESMO. Each showed promising new clinical data. For frontline microsatellite stable colorectal cancer, which is not a place where PD-1 therapy has been historically very successful, the data demonstrate the potential impact of the VEGF component of ivonescimab. Response rates for ivonescimab plus chemotherapy exceeded 80%, and there was a 100% disease control rate in this population. Of the 39 patients administered ivonescimab plus chemotherapy with or without AK 117 and the Akeso engineered anti-CD47 antibody, only 1 patient discontinued therapy due to treatment-related adverse events. In frontline, advanced triple-negative breast cancer, we also demonstrated a 100% disease control rate when ivonescimab was combined with chemotherapy irrespective of the PD-L1 status. Most patients enrolled had CPS scores less than 10%. No patient discontinued treatment due to treatment-related adverse events. And finally, for patients with frontline recurrent metastatic head and neck squamous cell carcinoma, we saw encouraging antitumor activity and manageable safety, again, without any treatment-related adverse events that led to discontinuation. We continue to be excited about the opportunity to make a meaningful difference in the lives of patients as well as our ability to continue to advance the clinical development plan that we believe a compound like ivonescimab deserves. As you saw yesterday morning in our press release, based on the HARMONi-2 data, we have announced our intention to launch our third Phase III clinical trial, which will be known as HARMONi-7, which is designed to be a global double-blind head-to-head study of ivonescimab versus pembrolizumab in PD-L1 high expressing tumors those with a PD-L1 TPS score of 50% or greater in advanced non-small cell lung cancer. We intend to start the study in early 2025. Given the importance of the HARMONi-2 trial in validating ivonescimab compared to PD-1 monoclonal antibodies, we are excited to expand our clinical development plan and look forward to providing additional details surrounding the study in the coming months. With that, I'll hand it back over to Dave.

Thank you, Jack and Allen. We're tremendously excited about the future and potential of ivonescimab, and we're particularly proud to be working with our partner at Akeso recently announced these Phase III trials -- recently announced 3 more Phase III trials to be conducted in China, including biliary tract cancer, head and neck cancer and pancreatic cancer. We worked hard at team Summit to collapse time in order to appropriately advance the development of ivonescimab as efficiently and effectively as possible, and we're thrilled to be working with the group that has the same mindset and collaborative nature that the Phase II data continues to be generated as well to lay the groundwork for the development of ivonescimab moving forward globally. As we are excited about the additional Phase II data to be presented, including the 2 oral presentations that Allen spoke to at ESMO next week. And of course, Akeso also provided an update on biliary tract cancer at ASCO a couple of months ago. Combined with the data presented yesterday at World Lung highlighted by HARMONi-2, there continues to be a lot of forward momentum with respect to ivonescimab. We'll now see if there are any questions that our team can help answer. And if you can open the line, Christa, that would be great.

[Operator Instructions] Your first question comes from Brad Canino with Stifel.

Can you hear me all right?

Loud and clear, yeah.

Great. Well, congratulations again to you and your partner. A couple of questions for me. First, given ivonescimab is still really being unveiled to a lot of the medical community, can you overview the physician and [indiscernible] response to the data at World Lung? And how this can be leveraged as you expand your development portfolio?

Yes. This is Jack. I have spent essentially every minute of yesterday after the presidential session speaking to my colleagues and I would say it's not surprising to me, it shouldn't be surprising to anybody that there was really enthusiastic support and excitement about this among my colleagues in the lung cancer community, really because and this I think a tone set by the person who provided expert commentary on our presentation at the presidential session that we have been at what's seeing kind of like an impasse in what we could achieve a plateau with the results pretty much since the presentation of the original data that led to monotherapy in -- with immunotherapy back in 2016, and that ushered in a new era, but what we've had since then has been largely achieving an elevated level of outcomes, but couldn't we pass that until what we saw yesterday. And this was importantly, I think people recognize that this wasn't a narrow win where you could just squint and see the differences between the 2 curves. But this was really an encouraging fee change in what we can hope to expect for patients. And everyone is really hoping that this is going to usher in a new era of better outcomes, a meaningful improvement for patients and ideally also a broader range of patients who are beneficiaries of immunotherapy because I think that's really one of the biggest issues is that while we recognize it's been a great improvement over the last 8 years or so to have the tools we've had. They work for a subset of patients, but even when you give monotherapy like pembrolizumab, the response rate in the KEYNOTE-024 trial is 45%, which means more than half are not having a response. And so if you can meaningfully raise that bar and particularly have more patients with the disease control and not have as many patients progressing, then that's really great. And the implication is also that this is just the beginning of all that we hope to do and plan to do is really the excitement that this is just one setting compared to all the others where we can hope to translate the benefits we've seen with ivonescimab into bigger benefits for patients, not just with non-small cell lung cancer, advanced non-small cell, but broadly across a whole range of oncology indications.

Okay. And as you would appreciate, there are a lot of investor inbounds asking about the potential first update for overall survival from HARMONi-2. Are you able to provide any rough guidance as to timing or talk about what your partner Akeso has suggested to their investors as to how that disclosure could unfold?

Yes. I think -- I appreciate the question, Brad. This is Dave. I think at this point, it's simply just too early. And so what we've always been very forthright about is that we will follow the data. And at this point, the data simply is not yet mature enough to speak to. And so at this point, we don't have a specific time where there will be an update. And so I think at this point, we're -- we've presented the data that was presented yesterday, and we will be very forthright in informing the investors in the greater community when that data becomes available, but we will follow that data and let you know as soon as we have that.

Okay. And last for me, kind of an extension to some of your comments, Jack. But as you look at the portfolio, ESMO data that you presented, how are you thinking about the additional development expansion even beyond areas where PD-1s work today because you've already started that with the second-line EGFR mutant non-small cell lung cancer trial and the success there. How much additional room is there for opportunities that fit into that bucket?

Yes, Brad, thanks for the question. To put it simply, there's a lot of room. I think, obviously, you would go where PD-1 has been successful and other checkpoint inhibitors, where VEGF or Avastin has been successful. And then we're starting to see maybe this hint of activity that we could be successful where neither of those drugs were successful. I think the EGFR data sort of represents that. In addition, this colorectal data is fascinating. You think of PD-1 being active in microsatellite in stable or unstable colorectal cancer and Avastin being really used in microsatellite stable. And then the question was, was ivonescimab sort of bridging those 2 populations and the data -- early data to start suggesting things like that.

Your next question comes from Yigal NojoModitz with Citigroup.

Congrats everyone on the very striking data. So I had a question, obviously, with the strength of the data across the subgroups in HARMONi-2 for both high and low PD-L1. I'm just curious about the potential to explore ivonescimab chemo-free regimen in PD-L1 low in both squam and non-squam because that would seem to fill in the missing piece in terms of exploring PD-L1 low non-squamous, which I don't believe is currently covered by HARMONi-3 and HARMONi-7.

Yes, Yigal, that's a great question, and we sort of discussed that internally that would really be a novel sort of study of putting ivonescimab against pembrolizumab chemotherapy in this TPS 1 or excuse me, TPS low population. However, probably the best thing is to keep it simple. We have HARMONi-7 now that will cover monotherapy, HARMONi-3 that covers squamous and expect a strategy to cover the non-squamous.

Yes. This is Jack. And I would just say that talking with a lot of my colleagues, certainly, it's encouraging. We recognize there is a significant subset of patients who are not ideal candidates for chemotherapy or particularly are averse to it. And this -- the data would suggest that ivonescimab is a viable alternative. As a higher priority, obviously, we have chemo and pembrolizumab as a clear standard. That's our comparator for the HARMONi-3 study and that will be moving forward. We've got the HARMONi-3 strategy for the squamous population, and that's from expression level of 0 all the way up to 100%, and we will be working on how to also study the same question in patients with non-squamous given the strong comparability, excellent results of ivonescimab in the non-squamous population. So we'll add that. But I think that my colleagues will prioritize that question. And then once we hopefully see that there is a clear evidence of benefit for chemo and ivonescimab across the board, across the entire spectrum of PD-L1 expression, they'll just selectively use or not use chemotherapy depending on the patient.

Okay. I think you basically answered my second question around how that would work with HARMONi-3 and HARMONi-7 regimens. Returning to some of the regulatory discussions. I'm just curious, I mean, obviously, everyone recognizes that HARMONi-2 is not likely to support any U.S. approval. But when you put the plans down for HARMONi-7, did you meet with the FDA in getting that study organized? And did you share the HARMONi-2 data with them in the context of that conversation, if there was a conversation with the FDA the plan HARMONi-7?

Yigal, this is Dave. So I very much appreciate the question. So one thing we've said from the time in which we entered into the deal with Akeso for ivonescimab is that we would always intend to go to the agency prior to announcing clinical trials and/or prior to executing clinical trials in order to align so we would provide our plans to the agency. We would very much engage with them in terms of feedback. We would implement comments, and then we would move forward with our clinical trials. Out of perspective to the agency, we're not going to get into individual levels of those conversations, but we certainly have engaged with the FDA. Very much appreciate the comments and time they put into discussing the trial plans with us, and we'll move forward accordingly from there. And so I think that more and less covers your question, but out of perspective to the agency, we won't get into the individual details that we're discussing.

Okay. And then I also get this question a lot from people interested in Europe, obviously, we saw what happened with BeiGene, with PD-1 getting approved there on the China trial, which opens up the question as to what progress you may make speaking with the EU regulators with HARMONi-2 in terms of getting a registration there. Is that a discussion that you intend to have?

Yes. I think at this point, Yigal, we haven't gone into details at our global regulatory approach long term here. But I think what we have said is that HARMONi-7 is intended to be a global trial. And so that's -- that will include regions, including in -- both in and outside of the United States and North America. And that's really our primary focus at this point.

But I will say, Yigal, we are exploring every option to make ivonescimab available globally. That includes U.S., North America, Europe and Japan.

As well as Latin America, Middle East.

And then just turning to some of the data, obviously, not seeing the bleeding risk that's typically associated with the anti-VEGF class is very promising. I mean I'm assuming it's -- this is driven -- the lack of bleeding is driven by the strong avidity of the bispecific and you don't get a lot of non-specific VEGF finding. Is that the explanation? Or is there more to it that supports this unexpectedly positive safety profile given you do use VEGF?

Well, I would say -- this is Jack. Thank you for the question. And it's a common issue. Of course, anybody would have some trepidation about giving anti-angiogenic therapy to patients with advanced squamous lung cancer. But I'd note that it's not unprecedented and that ramucirumab was studied in patients who got -- with squamous lung cancer and has been approved and used in clinical practice in patients with squamous as well as non-squamous for a decade without bleeding issues. So it's not really necessarily some inevitable class effect. I would say that, in my mind, the leading explanation is the shorter half-life of 6 to 7 days with ivonescimab and that it's 20, 21 days with bevacizumab, that's a big difference in terms of photonic inhibition of VEGF versus having kind of reintroduced into the extracellular matrix to potentially markedly decrease the risk of wound healing or bleeding issues. And again, that ramucirumab is in between those half-life. So I think that is the leading issue. Of course, we watch closely. We continue to do so. But at the end of the day, it's just an empiric issue that this has been tried and tested carefully in hundreds of patients now, and we just haven't seen anything like the issues that played bevacizumab and led to its being discontinued in further study or use in squamous lung cancer population.

Yes, Yigal, and this is Allen Yang. I'd add, there is a possibility that the cooperative binding will contribute to that and lead to sort of localization of ivonescimab in the tumor microenvironment. But with that said, I just want to remind everybody, after you get past the efficacy, which is very exciting, the next thing you notice is the safety profile, which is very, very important for this drug moving forward. And now this is the second Phase III study that's double-blind, confirming the safety profile of ivonesemab.

And then even though the bigger concern has been around the lack of bleeding with ivonescimab in squamous, we should take a moment to step back and appreciate that this is in terms of immune-related adverse events. There's no extra pause to that. It's certainly not higher end looking at the 2 results head-to-head of ivonescimab versus pembro, numerically a bit less. So you're not needing to pay some cost in terms of that toxicity for the increased efficacy.

Okay. And then just quickly, last question in terms of the broader development plan. Are you going to kind of go through the paces and explore all the different avenues in lung cancer obviously, HARMONi-7, you may consider something in the PD-L1 low, like KEYNOTE-189. Other earlier-stage disease, for example, all PACIFIC trial. Would you do all those things first in lung cancer and Phase III before start invoking late-stage registrational trials that could be supported by the Phase II data in some of these other tumor types you've highlighted at ESMO?

Yes. Paul, just to be clear, you pointed out the opportunity in neoadjuvant, adjuvant perioperative versus, I guess, tumors outside of non-small cell lung cancer. Our plan is to move both in parallel in lung cancer and outside of lung cancer aggressively.

Your next question comes from Mitchell Kapoor with H.C. Wainwright.

This is Dan on for Mitchell. Congratulations on the data. This is super exciting. We were mainly curious because it needs to work in so many of the different demographical types of patients and similar to Enhertu, where it's worse even in patients that seem to be incredibly low expressing for HER2 or even negative. Do you think that there is a floor for PD-1 expression that the efficacy of ivonescimab might floor out -- like what -- at what point -- what biomarkers do you start looking at if it keeps working and even those negative renewal or lower expressing individuals, how you stratify the population and design the trials for the future if it keeps working.

Yes. It's a great question. So without giving away details of our clinical development plan, we're exactly looking at those things, right? So do you take the opportunity since ivonescimab seems to be so broadly active even in those patients that have low PD-L1 expression, do you go after larger populations or do you go after sort of more limited low expressing unmet needs in a faster study and so those are a lot of the common questions we're asking internally.

Awesome. And if I could just add on, and I know that there's been a lot of discussion about the safety, but could you just give perhaps what is the patient experience that the safety margin on pembrolizumab are considered the Gold standard in here's ivonescimab, especially considering discontinuation rate is even lower and -- so what is -- what do you think that means for patients, I guess, if there's any anecdotal evidence on that experience on the safety?

I think the numbers are too low to say too much. I would really say that both the safety data and the limited quality of life data that were presented in the full presentation yesterday, and we didn't touch on here show that they are at least comparable with ivonescimab, arguably better, but we wouldn't want to overstate the case right now. I think it's more important to say that the clear feature is that with this dramatic significant improvement in efficacy, there isn't a counterbalancing toxicity cost or quality of life cost that these are at least equal, if not better as well.

Your next question comes from Dana Graybosch with Leerink Partners.

Congratulations on the data guys. I have one on your development strategy, another one, you've been answering many of them. And that is, as we look forward to frontline non-small cell lung cancer and early-stage non-small cell lung cancer. Some of the current leaders in the space like Merck and Astra are combining their PD-1 or PD-L1 checkpoints with ADCs, the 2 ADCs or exploring other novel combinations with CTLA-4 bispecifics or TIGIT biospecifics or KRAS. And I wonder as you think mid to long term, how you're thinking about combining ivonescimab with any other emerging combinations to sort of get the double novelty versus comparing to the historical standard of care as you're currently doing in your Phase III program? And take that example on lung cancer and also how are you thinking about it for indications outside of lung cancer?

Yes. So Dana great question. So yes, of course, we're thinking about combinations without giving any specific details, we're very interested -- the safety profile of ivonescimab is such that it seems to be combinable with other products. And then, again, Akeso partners have done a wonderful job of developing it, combining it with multiple chemo regimens in their internal pipeline of novel bispecific and monoclonal antibodies, and it seems to be combinable with all of those agents. So we expect that to be part of our development plan as well.

And maybe a guiding principal follow-up then. Given -- and you said it before, the wealth of options that you have, should we expect that you'll follow your partner Akeso given they have some of these early person concept studies? Or should we expect you partnering or doing things differently than what Akeso done that are relevant for the global market?

Thanks for the question, Dana. This is Dave. I think it will be individual tumor type by tumor type in terms of those decisions right? I think as you know, certain tumor types may be more prevalent in Eastern countries as opposed to Western countries. And I think it's not necessarily that every trial will be the same trial run or the same tumor type explored by both partners, we've been incredibly in lockstep in terms of the way in which we believe is best to further explore different tumor types and develop ivonescimab, but I wouldn't say it's necessarily always going to be a 1-for-1. And I think that's perfectly natural and fair based on the data. We'll certainly be following the data and looking to see to help as many patients as possible in this case.

That concludes our question-and-answer session. I will now turn the conference over to Dave for closing comments.

Thank you very much. I want to thank everybody for the time and joining us this morning. We're very excited about our opportunity in moving forward, and we're very excited to continue to provide updates as we move forward in this process. Again, the last thing I would emphasize is we're very happy in terms of what the potential is in terms of making a significant meaningful difference to patients based on the data that we've seen, and we look forward to continuing to work very hard in terms of accomplishing that mission. So thank you very much. I hope everyone has a wonderful day.

And this concludes today's conference call. Thank you for your participation, and you may now disconnect.