REGENXBIO Inc. Q1 FY2024 Earnings Call

Good day, and thank you for standing by. Welcome to REGENXBIO First Quarter 2024 Earnings Conference Call. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Patrick Christmas, Chief Legal Officer. Please go ahead.

Good afternoon, and thank you for joining us today. Earlier this afternoon, REGENXBIO released financial and operating results for the first quarter ended March 31, 2024. The press release is available on our website. Today's conference call will include forward-looking statements regarding our financial outlook in addition to regulatory and product development plans. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted and can be identified by words such as expect, plan, will, may, anticipate, believe, should, intend and other words of similar meaning. Any such forward-looking statements are not guarantees of future performance and involve certain risks and uncertainties. These risks are described in the Risk Factors and the Management's Discussion and Analysis sections of REGENXBIO's annual report on Form 10-K for the full year ended December 31, 2023, and comparable Risk Factors sections of REGENXBIO's quarterly reports on Form 10-Q, which are on file with the Securities and Exchange Commission and available on the SEC's website. Any information we provide on this conference call is provided only as of the date of this call, May 8, 2024, and we undertake no obligation to update any forward-looking statements we may make on this call on account of new information, future events or otherwise. Please be advised that today's call is being recorded and webcast. In addition, any unaudited or pro forma financial information that may be provided is preliminary and does not report to project financial positions or operating results of the company. Actual results may differ materially. I would now like to turn the call over to Ken Mills, CEO of REGENXBIO. Ken?

Thank you, Patrick. Good afternoon, everyone. Thanks for joining us. I'm pleased to begin today's call with a recap of the recent business highlights as well as an update on our corporate goals. Today, Curran Simpson, our Chief Operating Officer, will be speaking for Steve Pakola, Chief Medical Officer, who's unable to join us today. Curran will provide an update on our clinical programs. Then Vit, our Chief Financial Officer, will provide an overview of the financial results for the quarter ended March 31, 2024. At the end of the call, we'll open up the line for questions. We have some exciting updates today, and I want to get right into these topics. We started off the year making significant progress across our pipeline as we advance each of our programs toward pivotal stage clinical trials and commercialization. In 2024, we focused on large commercial opportunities where our product candidates are differentiated, can be expedited, and support meaningful value generation soon and for the long term. Our priority programs are RGX-202 for the treatment of Duchenne, AbbVie RGX-314 for the treatment of wet AMD and diabetic retinopathy, being developed in collaboration with AbbVie, and RGX-121 for the treatment of MPS II or Hunter syndrome. All of our programs remain on track to meet our goals for this year. Program milestones over the past couple of months further demonstrate how our new plan is supporting the acceleration of the development of our Gene therapies and the expansion of value for shareholders. Today, we're especially pleased to share new positive data and important updates about acceleration in our programs for Duchenne and diabetic retinopathy using in-office delivery. We are providing some new updated guidance on near-term milestones for these programs. We're thrilled to see RGX-202 demonstrating strong microdystrophin expression across a wide range of patients, including older boys, like those ages 8 to under 12. Importantly, we are seeing positive safety signals. No serious adverse events have been reported in patients who've received RGX-202, which is a highly notable differentiator in Duchenne Gene Therapy trials. Today, we announced that we have selected our pivotal dose. We have already begun a new expansion phase of our clinical development with the pivotal dose. This includes the enrollment of third and fourth boys already. Expansion using the pivotal dose will continue into the third quarter and can enroll a total of seven boys ages ranging from 4 to under 12. By early Q3, we expect to hold an end-of-Phase II meeting with the FDA, which will support a final pivotal design, and pivotal trial initiation is anticipated in late Q3 to early Q4 of this year. RGX-202 is a differentiated product candidate in the landscape for Duchenne, representing the closest thing to natural healthy dystrophin, and we believe has the potential to make a meaningful difference for a broad range of patients. Given these unique characteristics of RGX-202, a significant ongoing unmet need in the Duchenne community and conversations with the FDA, we're confident in our plans to file a BLA using the accelerated approval pathway. Separately, we believe there's a multi-billion dollar potential opportunity for AbbVie RGX-314 as a single injection treatment to become a first-in-class gene therapy for wet AMD and the standard of care to treat and prevent progression for diabetic retinopathy. Enrollment remains on track for our subretinal delivery program for wet AMD currently in pivotal trials. Today, we announced that based on positive interim results to date from the Phase II Altitude trial in diabetic retinopathy, the design and evaluation of two pivotal trials are ongoing, which would be the first pivotal trials for our in-office suprachoroidal delivery. These positive results and activities are in a planned discussion with the FDA at an end-of-Phase II meeting anticipated in Q1 2025 that can enable the rapid acceleration toward pivotal development. We expect to initiate the first two pivotal trials for suprachoroidal delivery of diabetic retinopathy in the first half of 2025. As a one-time treatment, we believe that 314 is well positioned to become the standard of care to treat and prevent progression of diabetic retinopathy, which is expected to impact over 20 million people globally in the next 5 years. Overall, we're thrilled about the current status and the way that 2024 can achieve meaningful value generation based on what we've seen in these first few months. With that, I'm going to turn the call over to Chief Operating Officer, Curran Simpson, who will take us through a bit more of a detailed update on the Duchenne data and our plans for accelerating the pivotal trial initiation for Duchenne in the second half of this year and diabetic retinopathy in the first half of next year. Curran?

Thank you, Ken. I'll start with RGX-202, a potential one-time gene therapy for the treatment of Duchenne. RGX-202 represents an alternative for boys who may not be eligible for other AAV-mediated microdystrophin therapies due to age or the presence of preexisting neutralizing antibodies. Today, we reported that new microdystrophin expression from the second patient aged 8.1 years, who received RGX-202 at dose level 2, was measured at 20.9% compared to control at 3 months. A reduction in baseline serum creatine kinase (CK) levels of approximately 90% was observed at 10 weeks. We're excited about this data and the robust response seen in this trial, particularly at dose level 2 and in older boys. As we shared previously, we used two methods of measuring microdystrophin protein: western blot and LC-MS. Notably, in this case, the microdystrophin measured using LC-MS for this patient was approximately 44% higher than the western blot result. Today's data adds to the totality of evidence demonstrating that all patients who completed 3-month trial assessments indicate consistent, encouraging increases in expression of RGX-202 microdystrophin and the reduction from baseline in serum CK levels, supporting early evidence of clinical benefit. In addition, early evidence of strength and motor function improvement were observed via trial clinic assessments and home videos shared with trial investigators by caregivers. As of May 3, 2024, RGX-202 continues to be well tolerated in all treated patients with no serious adverse events. Given the robust data and positive safety signals, we plan to move forward with dose level 2 at 314 per kilogram as our pivotal trial dose. We have initiated an accelerated dose level 2 expansion cohort and have already dosed two patients. We expect to treat up to a total of seven patients at the pivotal dose. Looking ahead, we remain on track to share strength and functional data for both dose levels and initiate dosing in the pivotal trial in late Q3 to early Q4 this year. Moving to 314, which is being developed in collaboration with AbbVie to treat wet AMD and diabetic retinopathy via subretinal and suprachoroidal routes of administration. We are evaluating 314 for the treatment of wet AMD via subretinal delivery in two ongoing pivotal trials, ATMOSPHERE and ASCENT in the U.S., Europe, and Japan. We anticipate global regulatory submissions in the first half of 2026. We are also evaluating 314 in the Phase II Altitude trial, which is the dose escalation study of 314 using suprachoroidal delivery. We're very excited about the opportunity in diabetic retinopathy given the size of the market, which exceeds that of wet AMD. One-year data from dose levels 1 and 2 showed 314 to be well tolerated, with patients demonstrating clinically meaningful improvements in disease severity with reductions in vision-threatening events. Based on these and other positive interim results from ALTITUDE, today, we are pleased to share more details about our past pivotal stage in diabetic retinopathy. We are evaluating the design for two pivotal trials in support of an end-of-Phase II meeting with the FDA anticipated in the first quarter of 2025. We expect to start the first pivotal trial in diabetic retinopathy in the first half of 2025. We've aligned with our partner AbbVie on this timing and believe there may be opportunities to further accelerate. To conclude, we continue to make significant progress with data updates and trial progression across all programs in our pipeline. Lastly, I'd like to thank the patients, families, clinicians, and patient advocacy representatives who have been involved and supported all these trials. And with that, I turn the call over to Vit to review our financial guidance. Vit?

Thank you, Curran. We ended the quarter on March 31, 2024, with cash, cash equivalents, and marketable securities totaling $381 million compared to $314 million as of December 31, 2023. The increase was primarily attributable to the $131 million in net proceeds received from an upsized public offering of common stock and prefunded warrants completed in March 2024, partially offset by cash used to fund operating activities in the first quarter of 2024. R&D expenses were $55 million for the first quarter of 2024 compared to $59 million for the first quarter of 2023. The decrease was primarily attributable to reduced manufacturing and clinical supply costs for our lead product candidates and personnel-related costs as a result of reduced headcount. It was partially offset by an increase in clinical trial expenses across our lead product candidates. We expect the balance in cash, cash equivalents, and marketable securities of $381 million as of March 31, 2024, to fund our operations into 2026. This cash runway guidance is based on the company's current operational plans and excludes the impact of any payments that may be received from AbbVie upon the achievement of development or commercial milestones under our 314 collaborations, including a potential milestone payment of $200 million receivable upon achieving the dosing of the first patient in the pivotal trial for suprachoroidal delivery for the treatment of diabetic retinopathy. Additionally, this cash flow guidance excludes any potential monetization of a priority review voucher that may be received for REGENX 21. With that, I will turn the call back to Kenneth Mills to provide final thoughts.

Thanks, Vit. To wrap things up, so far in 2024, our plans are on track and intended to generate significant value for shareholders as we're ensuring that resources are allocated to the most valuable assets and to accelerate the development of those assets. As outlined here today and supported by the press release announcements, we are motivated by expanding that value by addressing important unmet needs in patients and focusing on large commercial opportunities where we think our product candidates are differentiated and have a clear regulatory pathway forward. The recent efficacy and safety data has allowed us to determine the planned pivotal dose for RGX-202, which is enabling us to further accelerate this program. So far, this drug candidate is exceeding our expectations in the clinic. We've already begun a clinical trial expansion phase to add boys onto our pivotal dose, a step that we believe will contribute meaningfully to our accelerated approval plan. Duchenne is a market where there is a large unmet need for new therapies and that is capable of supporting multiple gene therapies, and we believe RGX-202 has unique differentiating features that support its potential to be a best-in-class product. Regardless of today's landscape of Duchenne treatments, communication from the FDA continues to support the need for alternative gene therapies for rare diseases, including Duchenne. Backed by strong data, we're acting with urgency and in concert with the FDA, taking steps to initiate the pivotal trial for RGX-202 as soon as possible this year and focusing on serving these in a broad range of patients. We're also continuing to grow value with our eye care partnership with AbbVie, using our one-time treatments that provide sustained vision health long term and overcome the clinical challenges of managing retinal diseases. The updates today highlight key alignment on important partnership goals in 2024 that are directed at completing trial designs and plans for initiating first pivotal trials for 314 using in-office suprachoroidal delivery for diabetic retinopathy and completing enrollment of our pivotal trials for 314 using subretinal delivery to support filing of global regulatory submissions. And as Curran mentioned, we believe there are opportunities to further accelerate these programs. RGX-121 is meaningfully changing the course of disease in patients with MPS II by restoring a missing gene. We're on track to file our first BLA as a company in 2024 using the accelerated approval pathway for RGX-121. Our pivotal trial achieved its primary endpoint of reduction of natural substrate in the CSF. Patients treated with RGX-121 have shown continued improvement in neurodevelopmental skill acquisition up to 4 years and have discontinued intravenous enzyme replacement therapy. Our pivotal trial was designed to enroll boys under the age of 5. A strong proportion of those enrolled in our program are below the age of 2. These are key features that are important in assessing neuronopathic Hunter syndrome. We're locking our clinical trial databases and our team is busy collecting final pivotal trial data and completing steps for the entire BLA filing process. By the end of 2024, our pipeline should be filled with programs that are initiating pivotal stage, fully enrolled at pivotal stage, or are under a filed BLA. And as Vit mentioned, in the fourth quarter, we announced a successful public offering. This range strengthens our balance sheet. It extends our operating runway into 2026 to support the acceleration of our candidates through multiple value-generating milestones today, but it's worth noting and restating that achievement of certain of these milestones would also trigger hundreds of millions of dollars of additional funds. As a result of these recent updates and the upcoming milestones announced today, we believe REGENXBIO is well positioned for success. Thanks, everyone, for your time today. That concludes our discussion part of the call. And now, we're going to move over to Q&A.

Our first question comes from the line of Vikram Purohit from Morgan Stanley.

This is Gospel on for Vikram. We have one question on the DMD program. So, what do you think are the trial enrollment and regulatory implications, if any, from Pfizer's update yesterday for 202?

Hi, Gospel, thanks for the question. I think that as we reflect on what was obviously a sad event reported by Pfizer yesterday, we continue to feel very strongly about the importance of safety with gene therapy and in rare diseases in general, especially in pediatric populations. This is why we continue to feel very strongly and enthusiastic about the safety profile of RGX-202 to date, being really a wind at our back for how we're thinking about being able to progress on a more accelerated basis into the pivotal phase. The same way that we had a reflection when we made those decisions about RGX-121 and advancing it into pivotal phase. I do think that from a regulatory perspective, this also has to, at a high level, be something that agencies like the FDA take into consideration for existing approved products as well as products in development. This is something that I think people should be cautious about generating data in certain populations. I personally feel that generating data in certain ages or progressed areas of disease is a must. When you consider the ability to gain understanding in certain areas, like the age or progression of disease. I also think that people should be cautious about where those lines and differences are, especially after seeing a younger boy enrolled in a trial, go through an event like that. I think it's something that we've been emphasizing for a while that it's important to generate the data, including in older boys where we have been doing so as we continue to think about how to progress into later stages of development to support that clinical understanding and the potential for commercialization.

Our next question comes from the line of Gena Wang from Barclays.

So, just want to confirm, did I hear you correctly that the fifth patient, the mass spec protein level was 44% higher, i.e., 65% level per mass spec? And also, will you pick one methodology for protein level for pivotal study? Would that be western blot or mass spec? Related question, sorry. Have you already scheduled the date for the end of the Phase II meeting in Q3? And also, regarding understanding you will still need to finalize the trial with FDA, but can you submit a BLA once 3 months of protein data is available?

Hi, Gena, we'll unpack that. Thanks for the good questions. On the first point about the microdystrophin results, Curran mentioned that we had approximately 44% higher LC-MS result compared to the western blot results. Typically for us, we've gotten comparable results in previous assessments between boys in this case. LC-MS was higher, but that 44% applied to the results we reported in the press release and gets to about 30% for the LC-MS result. With respect to the plans, what can I say? We're in constant communication with the FDA on all of our programs, but in particular, Duchenne, there's a lot going on in the space. I think Gospel's question can't be ignored as well. We continue to keep a close eye on these developments. We do have plans for an early Q3 meeting with the FDA to discuss end-of-Phase II pivotal planning and initiation. We've shared with them ideas about variables and features that are important to us or that we're hearing are important to them in order to design what we and they think is the most efficient and appropriate trial. We've focused on wanting to emphasize gaps in understanding for the community. We've talked a lot about the data generated and the focus on older boys, continuing to show positive microdystrophin results in this patient group. The last two patients we enrolled were 5 years and 6 years old. We feel like the data and the conversations that we have will set up for a very constructive discussion with the FDA in early Q3. We've also been open about the fact that we want to have that discussion on what could be on the other side of the potential action date with respect to the existing accelerated approved product. So, we feel like everything is really on track, and being able to declare the pivotal dose today to bring that into the conversation and discussion is something that is also important.

Our next question comes from the line of Alec Stranahan from Bank of America.

This is John on for Alec. So just a quick question from us. In terms of the second half data update for the DMD program, the 202. In terms of functional assessment data, what kind of data should we be expecting? If you were to give us a comparison to something, what would that be if you could touch on that?

Yes, John, sure. I think we're collecting the normal strength and functional assessment, including the full North Star domain on all the boys in the Duchenne trial. We showed some of the activities going on by sharing some home videos that were brought forward at the MDA conference a few months ago. So, we'll have the opportunity with boys that have achieved time points, with some reaching out to 12 months and maybe some a little bit earlier. NSAA scores as well as subdomains of North Star, including metrics that have been the focus of recent Duchenne approvals or discussions around confirmatory evidence presented by existing approved product sponsors, like time to stand and various metrics associated with the ability around movement. These are the types of things that you can expect from us in the second half of the year based on patients that have been enrolled to date.

Our next question comes from the line of Annabel Samimy from Stifel.

I guess on the DMD program, I want to sort of understand your view on this. You're saying that the microdystrophin levels are consistent, but it doesn't seem like it's specifically linear with age. And so, I was just wondering if you had any more insight into what's happening there? Is this maybe going to change what the clinical relevance is of microdystrophin specifically? Or are there other factors that they're considering here? And then the second question I have is obviously Sarepta has an FDA decision depending on final approval and label expansion. We're getting a lot of questions about what the various scenarios might be and sitting from your perspective, can you opine on how that might impact you and your opportunity going forward? And how you sort of view the different scenarios that are possibly emerging from that?

Yes, absolutely, Annabel. The partial answer to the first question, just to clarify, we're talking about different methods of measuring microdystrophin today that we generally have viewed as comparable. We've been using western blot and LC-MS. I think we're the only company to use both. We've presented western blot, which is more of an automated method, because people are more familiar with it, with respect to existing approved product labels. In terms of what we measured in this 8-year-old today, and what we've previously measured in the 12-year-old, we're talking about results that are positive measures of microdystrophin protein in age ranges that generally have not been reported with other products. Between the end of June when we enrolled at dose level 2, we're seeing an average of 50% microdystrophin level expression based on that western blot method. We're encouraged about this based on our preclinical data, what we see as the safety profile, and what we've started to see emerge from strength and functional assessments even at dose level 1. So, the safety profile, in particular, made the dose decision for the pivotal dose a straightforward one for us. We think we're continuing to see high levels of microdystrophin expression, especially in older boys. This is something that's representative of a strong, stable, and durable product candidate. Regarding the upcoming decision on the confirmatory evaluation evidence of Elevidys and the supplement, we’ve been cautious about that outcome. We also consider the opportunity for RGX-202. If some scenarios changed recently, we see the unmet need for Duchenne boys where gene therapy candidates are in development. We expect RGX-202 to hold a unique potential position in the market as boys may be excluded from access to other treatments due to preexisting immunology. As we've discussed, we estimate approximately 15% of the market could be addressed uniquely by RGX-202. If RGX-202 is second to market, that number could increase to 20% to 30%. Our focus on the go-forward plan for accelerating RGX-202 is about the strength of our differentiation, safety and efficacy data, and addressing unmet needs with first-generation microdystrophin products. Regardless of the competitive landscape, our data is showing strong potential, and we intend to showcase that through as fast and expansive an acceleration phase as possible while working with the FDA.

Our next question comes from the line of Eli Merrill from UBS.

This is Jasmine on for Ellie. So, we have another one on the strength in functional measures we'll be getting in the DMD update in the second half. So, what do you think would be meaningful to see at the time point that you'll share later this year, but 12 months follow-up or earlier relative to what you think would be meaningful in the longer term, so in another year or two?

Sure. Thanks, Jasmine. We believe that RGX-202 with the C-terminal domain has biological function and structure that translates into improvements in muscle function, as we've seen in its design in animal modeling. Early evidence of strength and motor function improvement was observed and reported with the investigator at the MDA conference in March. We are eager to accumulate the available strength and function metrics we can collect on the North Star measure and demonstrate this, supporting our differentiation in the second half of the year. This doesn’t affect our conversations with the FDA about the accelerated approval pathway and our regulatory plan. Instead, it enhances it because any evidence of early strength in motor function improvement is contributing to the totality of data and evidence we are collecting. Our discussions with the FDA center around gaps in understanding in the Duchenne population, even with current and known standard of care for boys who cannot access treatment due to preexisting immunology or boys who cannot engage in treatment in specific age ranges because they're seeking more data, or due to gaps in data. Our focus is to design something that's efficient for regulatory approval, addressing the needs of the FDA as well. The FDA has shown strong support for microdystrophin as a surrogate biomarker predictive of clinical benefit, and we are achieving levels of microdystrophin that we believe meet the regulatory expectations.

Our next question comes from the line of Brian Skorney from Baird.

First, a quick one. You've previously given the weight set dosing of the other. Just wondering if you can provide the weight of subject number five here. And not jumping out to me based on the data provided so far that there is differentiation between dose level 1 and 2 in western or CK level changes. So, I'm just wondering what's kind of informing that decision on those levels.

Yes, Brian. I don’t have that off the top of my head. I’ll follow up with you on that.

Our next question comes from the line of Danielle Brill from Raymond James.

This is Alex on for Danielle. A couple on RGX-314. Given the updates today, do you still plan to publicly close data updates from Altitude later this year? And just curious why the large gap between now and the guided end-of-Phase II meeting with FDA in Q1 '25? And then looking at wet AMD, to us, we think that wet AMD data set is a little bit more mature. So, we would have guessed that would have been advanced to pivotal as well. So, what kind of data or time points do you and AbbVie need to see to convince you to advance the suprachoroidal AMD forward to pivotal development?

Yes, thanks, Alex. You've hit on an important point. We're working in partnership with AbbVie here to ensure a successful program, including significant commercial and clinical value is achieved. We're well aligned with them on this guidance. We've been focused on bringing a robust package to the FDA for pivotal design—the first such pivotal package for suprachoroidal delivery for gene therapy and diabetic retinopathy. While we don’t rule out things being done on an accelerated basis, we felt confident in guiding toward Q1 2025. We also expect initiation of the pivotal in the first half of 2025, which emphasizes the time, energy, and effort needed for an end-of-Phase II discussion. Selecting one indication to advance first in pivotal is a consideration overall. We strongly believe the unique nature of the data we're seeing in diabetic retinopathy is very attractive for bringing that forward as the potential first application of the suprachoroidal delivery approach. We will provide guidance for the Q3 update for wet AMD as well.

Our next question comes from the line of Mani Foroohar from Leerink.

This is Lili on for Mani. So, maybe just a quick follow-up in terms of the suprachoroidal on RGX-314. So, in terms of the data updates, can you provide a little more granularity on the timing and potential data points that would influence your decision?

Sure. I don't think we have any more specific guidance right now on what the next data updates will include. Our process in partnership with AbbVie is focused on program execution and acceleration based on positive interim results. We expect our next program update and data for wet AMD suprachoroidal to be in Q3, but we're especially excited that the diabetic retinopathy program now has guidance for the first suprachoroidal program to move into pivotal phase.

Our next question comes from the line of Luca Issi from RBC Capital.

Maybe a quick one on Duchenne. Circling back on preexisting immunology. You're trying to differentiate in DMD in multiple ways, including the C-Terminal domain as well as targeting a broader patient population. But what percentage of patients will still be eligible for your therapy due to neutralizing antibodies against both Sarepta and Pfizer? Just trying to get a numerical percentage here. And maybe on the competitive landscape for ocular gene therapy, we recently saw some data for the long-acting TKI that was somewhat mixed for diabetic retinopathy despite good data for wet AMD. What are your thoughts on what drives that dichotomy between the two? And more broadly, what are your thoughts on the long-acting TKI as a potential competitive threat for your program?

Yes, thanks, Luca. We've generally offered that RGX-202 may be a solution on its own, especially with two competitive products, Sarepta and Pfizer. You’d be looking at cross-reactivity of the different AAVs and hunting for what remains uniquely for REGENX. My estimation would put that uniquely at around 15%. This can be drawn from known data sources. It's generally accepted that 30% to 40% of subjects have neutralizing antibodies against any AAV capsid. We feel RGX-202 with an Rh74, AAV9, or AAV8 capsid will yield 15% potentially available candidates. If we are second to market, that number might reach 20% to 30%. Regarding TKIs, there’s a distinction between the clinically established profile of a one-time treatment like RGX-314 that expresses an anti-VEGF molecule and broad-spectrum chemotherapeutic agents like TK inhibitors that are still being developed for retinal diseases. Our analysis shows no comparison between the outcomes of onetime treatment RGX-314 and TKIs. Our view is that TKIs haven’t worked out well in retinal diseases and lack the predictability of the continuous effects we're able to offer. We believe RGX-314 offers a clear clinical and commercial lead.

Our next question comes from the line of Daniil Gataulin from Chardan.

I have a follow-up on diabetic retinopathy. As we prepare for the end of Phase II discussions, what is your current thinking on the primary endpoint of greater than a three-step improvement on the DRSS versus the greater than or equal to three-step worsening that other companies are planning or considering to use?

Yes, good question, Daniil. The most important emphasis for the clinical and commercial opportunity in diabetic retinopathy is what Curran mentioned about vision-threatening events and complications. We have shown evidence of risk reduction up to almost 90% in vision-threatening complications among diabetic retinopathy patients. That's what's affecting their vision long term. To be able to address that longitudinally is a priority, and we will continue to collect data for this as part of our trials. When it comes to the DRSS scoring and how we will power the studies, we believe we have good options. We’ve shown data indicating a high proportion of patients have achieved improvement in DRSS relative to observational control, with 0% worsening in our population relative to a high number of patients experiencing worsening in observational control. Therefore, for us, we believe the regulatory endpoint will bear in mind our strong clinical focus on the reduction of vision-threatening complications.

At this time, I'm showing no further questions. This concludes today's conference call. Thank you for participating. You may now disconnect.