Q1 2024 Regenxbio Inc Earnings Call

Participants

Patrick Christmas; Chief Legal Officer; Regenxbio Inc

Kenneth Mills; President, Chief Executive Officer, Director; Regenxbio Inc

Curran Simpson; Chief Operating Officer; Regenxbio Inc

Vit Vasista; Chief Financial Officer; Regenxbio Inc

Vikram Purohit; Analyst; Morgan Stanley

Gena Wang; Analyst; Barclays

Alec Stranahan; Analyst; BofA Global Research

Annabel Samimy; Analyst; Stifel

Ellie Merle; Analyst; UBS

Brian Skorney; Analyst; Robert W. Baird & Co., Inc.

Danielle Brill; Analyst; Raymond James

Mani Foroohar; Analyst; Leerink Partners

Luca Issi; Analyst; RBC Capital Markets

John Neal; Analyst; Charden

Presentation

Operator

(audio in progress) Regenxbio first-quarter 2024 earnings conference call. (Operator Instructions)
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.

Patrick Christmas

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 at www.regenxbio.com.
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 2020, 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 purport 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?

Kenneth Mills

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. Current Simpson, our Chief Operating Officer, will be speaking for Steve Fekola, Chief Medical Officer, who's unable to join us today. Carin will provide an update on our clinical programs. Then that assist our Chief Financial Officer, will provide an overview of the financial results for the quarter ended March 31st, 2024. At the end of the call will open up the line for questions.
We have, I think, are some exciting updates today. And so 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've put a focus 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. two for the treatment of dilution, ABBVRGX. three one four three one four for the treatment of wet AMD and diabetic retinopathy or DR being developed in collaboration with AbbVie and RGX. one to one for the treatment of MPS 200 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 dilution and ER using in-office delivery. We are providing some new updated guidance on near term milestones for these programs.
So let me explain. We're thrilled to see our GX. two is demonstrating strong microdystrophin expression across a wide range of patients, including in older boys like those ages eight to under 12. And importantly, we are seeing positive safety signals. No SAEs have been reported in patients who've received RGX. two, which is highly notable differentiator in use in gene therapy trials. Today, we announced that we have selected our pivotal dose. Also, 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 up to a total of seven boys in the ages ranging from four to under 12 by early Q. three. We expect to hold an end of Phase two 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. two is a differentiated product candidate in the landscape. Production 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. two the 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 multibillion dollar potential opportunity for AVVDRGX. three one four 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 range remains on track for a subretinal delivery program for wet AMD currently in pivotal trials. And today, we announced that based on positive interim results to date from the Phase two ALPHA2 trial in DR, the design and evaluation of two pivotal trials is ongoing, which would be the first pivotal trials for our in-office suprachoroidal delivery. These positive results and activities are in support of a planned discussion with the FDA at an end-of-Phase two meeting anticipated in Q1 2025 that can enable the rapid acceleration toward pivotal development, we would expect to initiate the first two pivotal trials for suprachoroidal delivery of diabetic retinopathy in the first half of 2025 as a onetime treatment. We believe that three one four is well positioned to become the standard of care to treat and prevent prevent progressive progression of diabetic retinopathy, which is expected to impact over 20 million people globally in the next five 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 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 dilution 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?

Curran Simpson

Thank you, Ken. I'll start with RGX. two, a potential onetime gene therapy for the treatment of Duchenne RGX. two represents an alternative for boys who may not be eligible for other AAV mediated microdystrophin therapies due to age or presence of preexisting neutralizing antibodies. Today, we reported that new microdystrophin expression from the second patient aged 8.1 years who received RDX. two oh two at dose level two was measured at 20.9% compared to control at three months a reduction in baseline in serum creatinine 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 in dose level two and in older boys being, as we shared previously, we used two methods of measuring microdystrophin protein, Western blot, PHS and LCMS. Notably, in this case, the micro-dystrophin measured using LC-MS for this patient was approximately 44% higher than the Western blot results. Today's data adds to the totality of evidence demonstrating that all patients who completed three month trial assessments indicate consistent encouraging increase in expression of RGX. two to microdystrophin and the reduction from baseline in serum CK levels supporting early evidence of clinical benefit in addition, early evidence of strength in motor function improvement were observed in the trial clinic assessments and home videos shared with trial investigators by caregivers as of May third, 2020 for RGX. two oh two continues to be well tolerated in all treated patients with no serious adverse events. Given robust data and positive safety signals, we plan to move forward with dose level two, Q3 14 per kilogram. As our pivotal trial dose, we have initiated an accelerated dose level two expansion cohort and have already dosed two patients. We expect to trade 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 or early Q4 of this year.
Moving to slide 14, which is being developed in collaboration with AbbVie to treat wet AMD and diabetic retinopathy via subretinal and suprachoroidal route of administration. We are evaluating three, 14 for the treatment of wet AMD via subretinal delivery in two ongoing pivotal trials, atmosphere and assent in the U.S. Europe and Japan. We anticipate global regulatory submissions in the first half of 2020. We are also evaluating three 14 in the Phase two altitude trial, which is the dose escalation study of three 14 using suprachoroidal delivery. We're very excited about the opportunity in DR. Given the size of market, which exceeds that of wet AMD one year data from dose levels one two showed three 14 to be well tolerated with patients demonstrating clinically meaningful improvements in disease 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 path to pivotal stage in DR. We are evaluating the design for two pivotal trials in support of an end-of-Phase two meeting with the FDA anticipated in the first quarter of 2025. We expect to start the first pivotal trial in DR 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 supportive of these trials.
And with that, I turn the call over to Vit to review our financial guidance. Vit?

Vit Vasista

Thank you, Curran. Bio ended the quarter on March 31st, 2024, with cash, cash equivalents and marketable securities totaling $381 million compared to $314 million as of December 31st, 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 31st, 2024, to fund our operations into 2020. 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 fund the achievement of development or commercial milestones under our three one four collaboration, 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 DME. Additionally, this cash flow guidance excludes any potential monetization of a priority review voucher that may be received for Retalix one to one.
With that, I will turn the call back to Ken.
Most Harvey to provide final thoughts.

Kenneth Mills

Thanks, Vit. So to wrap things up so far in 2024, 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 and outlined here today and supported by the press release, announcements are motivated motivated by expanding that value by addressing important unmet need in patients and focusing on large commercial opportunities where we think our product candidates are differentiated, have a clear regulatory pathway forward the recent efficacy and safety data has allowed us to determine the planned pivotal dose for RGX. two, 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 voice onto our pivotal dose, a step that we believe will contribute meaningfully to our accelerated approval plan. Fusion is a market where there's large unmet need for new therapies, and that is capable of supporting multiple gene therapies. And we believe RGX. two S. unique differentiating features that support its potential to be a best-in-class product regardless of today's landscape of Dushan treatments.
Communication from the FDA continues to support the need for alternative gene therapies for rare diseases, including U-Shin backed by strong data. And we're acting with urgency and in concert with the FDA, taking steps to initiate the pivotal trial for RGX. two as soon as possible this year and focused on serving needs in a broad range of voice. We're also continuing to grow value with our Eye Care partnership with AbbVie. It's using our onetime treatments that provide sustaining vision health long term in overcoming the clinical challenges of managing retinol 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 three look for using in-office suprachoroidal delivery in diabetic retinopathy and completing enrollment of our pivotal trials for three one four using subretinal delivery to support filing of global regulatory submissions. And as Karl mentioned, we believe there are opportunities to further accelerate these programs.
RGX. one T. one is meaningfully changing course of disease in boys with MPS two by restoring the missing gene. And we're on track to file our first BLA as a company in 2024 using the accelerated approval pathway for RGX. one to one. Our pivotal trial achieved its primary endpoint of reduction of natural substrate in the CSF patients treated with RGX. one to one and showed continued improvement in neuro developmental scale acquisition up to four years and as discontinued intravenous enzyme replacement therapy, our pivotal trial was designed to enroll boys under the age of five. A strong proportion of those enrolled in our program are below the age of two. And these are key features that are important in assessing neuropathic 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 were under a file BLA. And as we've mentioned in the fourth quarter, we announced a successful public offering. This raise strengthens our balance sheet and extend 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 Agennix bio is well positioned for success.
Thanks, everyone, for your time today that finishes our discussion part of the call. And now we're going to move over to Q&A.

Question and Answer Session

Operator

(Operator Instructions) Vikram Purohit from Morgan. Emily.

Vikram Purohit

Hi, everyone. This is Kasper on for Vikram.
We have one question on the DMD program. So what do you think the trial enrollment and regulatory implication, if any, from Pfizer's update yesterday for sure, Craig, I will thanks for the question.

Kenneth Mills

I think that as we reflect on what was obviously a sad event reported by Pfizer yesterday, we continue to feel very strongly as we always do about the importance of safety with gene therapy and in rare diseases in general, especially in pediatric populations, which is why we continue to feel very strongly and enthusiastic about the safety profile of RGX. two to date being really the wind at the back for how you know, partly how we're thinking about being able to progress on a more accelerated basis into pivotal phase the same way that we had a reflection when we made those decisions about RGX. one T. one and advancing it into pivotal phase. And 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. I think it's going to this is something that I think people should be cautious about generating data in certain populations. I personally feel it is a must when you think about the ability to apply an understanding in certain areas like in certain ages or certain progressed areas of disease, I think you also have to think about where those lines and differences are and seeing a younger boys 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 data, including in older boys where we have been doing. So as you continue to think about how to progress into later stages of development to support that clinical understanding and the potential for commercialization there. So I imagine that many stakeholders are reflecting on that as well.

Vikram Purohit

Thanks.

Operator

Gena Wang from Barclays.

Gena Wang

Thank you for taking my questions. So just wanted to confirm, did I hear you correctly the fifth patient at them protein level was 44% higher, i.e., 65% protein level, a level perm? And also, will you pick one methodology for protein level for pivotal study? Or would that be Western blot and related question, sorry, here. Have you already scheduled the date for another Phase two meeting in 3Q? And also regarding your understanding you still need to finalize the trial with FDA, can you submit BLA once three months protein data?

Kenneth Mills

Gena, will unpack that. Thanks for the good questions. On the first point about the micro-dystrophin result, what Kurt said is that we had approximately 44% higher LC-MS results compared to the Western blot test result. Typically for us, we've gotten comparable results in previous assessments between noise. In this case, LC/MS was higher, but that 44% applied to the result we reported in the press release, it gets to about 30% for the LCMS. result on with respect to the plans of what can I say, I mean, we're just in constant communication with the FDA on really all of our programs. But in particular addition, there's a lot going on in the space. I think hospitals question can't be ignored as well. So we continue to see very close. We do have plans for an early Q. three meeting with the FDA on sort of end of Phase two of Pivotal planning and initiation. We have shared with them already during the course of the program and ideas about variables and features that are important to us or that we're hearing are important to them in order to be able to design what we and they think is the most efficient and appropriate trial we've really been focused on wanting to emphasize gaps in understanding for the community. We've talked a lot about I mean, the data that we've been able to generate and the focus that we've been able to put on our older boys continuing to show positive microdystrophin results, measurable microdystrophin results in this case reported today and in another eight year old. We continue to enroll in that age range. The last few patients we enrolled were five year old and an eight year old. So we feel like the data and the conversations that we have are going to set up for a very constructive discussion with FDA in early Q3. And we've also been open about the fact that we want to have that discussion on what putative we would be 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 conversations. Discussion is something that is also important.
And Kim.

Operator

Alec Stranahan from Bank of America.

Alec Stranahan

Yes, guys, this is John among for Alec. So just a quick question from us in terms of the second half data update for DMD program, the tool, too, in terms of functional assessment data, kind of what kind of data should we be expecting and what like if you were to give us a call, but something to look, I look to as like a standard. What would that be if you could shed some light on that?

Kenneth Mills

Yes, John, sure. I mean, I think where we're collecting the normal strength in functional assessment, including the full North Star do mean on all of the boys in Affinity Dushan, we showed some of the activities that were going on in this trial by sharing some Dr. Panda shared some video that he was able to bring forward at the MDA conference just a few months ago. And so we're going to have the opportunity to with boys that have achieved time points, some of which will be by the second half of the year, reaching out to 12 months and maybe some a little bit earlier on NSA. scores as well as sub domains of NorthStar, including things that have been the focus of other recent approvals or even discussions around the recent sort of confirmatory evidence that was presented by the existing approved product sponsor. So things like time to stand and sort of still manage associated with the ability around movement. So on the fees, these are the types of things that I think you can expect from us in the second half of the year based on patients that have been enrolled to date.

Alec Stranahan

Yes.

Operator

Annabel Samimy, Stifel.

Annabel Samimy

Yes, hi. Thanks for taking my question. I guess on the DMD program. I wanted to sort of I your view on this. You're saying that the microdystrophin levels are consistent, but it doesn't seem like 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 of 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 pending on final approval and label expansion. And now we're getting a lot of questions about what the various scenarios might be 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.

Kenneth Mills

Yes. Yes, absolutely, Annabel, again, I think that I'm so partially answered to the first question. Just to clarify, we're talking about different methods this measure for microdystrophin today that we generally have viewed as comparable. We've been using Western blot and LCMS. I think we're the only company to use both. We've been presenting Western blot, which is more of an automated Western blot data in general to the community because people are more familiar with it with respect to what is in the U.S. existing approved product label on in terms of what we measured in this eight year old today, we previously measured in the 12 year old with let's remind everyone that we're talking about results that are positive measures of microdystrophin protein in age ranges that generally have not been reported with other products. And in this case, between the end of two that we enrolled at dose level two, we're seeing about an average of 50% microdystrophin level expression based on that Western blot method. So we're really encouraged about that based on what we've seen in our preclinical data, what we see of the safety profile and what we've seen that has started to emerge from some of the strength in functional assessments, even at dose level one again, referring back to what Dr. Panda was able to share a bit on podium and MDA. So I think this, you know, the safety profile in particular made the dose decision about the pivotal dose, a rather straightforward one for us. We think we're continuing to see high levels of microdystrophin expression, especially in older boys. And we think that in particular is something that's representative of our really strong, stable and durable product candidate.
When it comes to the upcoming decision on the confirmatory valuation, evidence of Alavert S. and the supplements, I think we've been reasonably cautious with all of you all along about what that outcome may be and also what we think the opportunity for RGX. two two is now if something's changed in the last couple of days. And we've often talked about this unmet need for Duchenne boys with gene therapy is having at least two or three other candidates in development. And yesterday, obviously, there's been a bit of a change to the profile of one of them, which I think everyone is still trying to digest. We continue to view that RGX. two with new biology with the C-terminal domain with the type of microdystrophin expression that we've been showing in older boys, but also in four to seven year olds has been robust and significant and unique. It is a differentiated product profile. And that's without even having reached that time point yet on strength and function where we can really exercise an understanding of the benefits of the C-terminal domain. Those are things that are we think, coming in front of us. So we see a differentiated product profile here as being very important, it's important for the incident population of Duchenne boys. Always, I think it's important for the prevalent population of boys as they are considering what their options are or will be as families and as physicians. And we've talked often about the fact that in general, our GX. two also holds a unique potential position in the market. As you know, boys are certainly going to be excluded from access to other treatments due to preexisting immunology just like they would be for our own. And in the case that we've talked about where there would be two products on the market that both were, let's say, ahead either on the market or in pivotal phase development ahead of two. We've sort of labeled that as maybe a 15% of the market prevalent market that would be able to be uniquely addressed by two. If you change that to offer Agennix with RGX. two Crew two could be second to market, then that number could be higher. It could be something more like 20% to 30%. So I think for us, the work that we're doing to focus on the go forward plan for accelerating our GX. two is about the strength of our differentiation and the strength of our data, the safety data and efficacy data and addressing what we still think is unmet need with first-generation micro-dystrophin products. But the case of just being as good as other things is also something that from an economic perspective, is foundationally valuable. But we think that RGX. two, of course, is much more than that. And we think that the data is showing that and we intend to continue to show that through as fast and expansion and acceleration fees as possible working with the FDA.

Annabel Samimy

Thank you.

Operator

Ellie Merle from UBS.

Ellie Merle

Gavin, on for Ali. Thanks so much for taking our question. Another one on the strength and functional measures, we'll be getting in the DMD update in the second half. It's meaningful to see at the time point that you'll share later this year.

Kenneth Mills

12-month follow-up earlier relative to what you think would be meaningful in the longer and so in another year or two certain things, Jasmine, look, I mean, I think we believe that RGX. two with the C-terminal domain has biological function and structure that translates into improvements in muscle function that we've seen in its design in animal modeling. And that even early evidence of strength in motor function improvement was observed that we reported back and with the investigator at the MDA conference in March. So we continue to be eager to accumulate the domains of the North Star that we can collect on strength and function and be able to show that and show the support for that differentiation coming into the second half of the year. And that is not impacting though our conversations with the FDA on the approach to the accelerated approval pathway and the regulatory plan that we have, if it is, it's only enhancing it because any evidence of early strength in motor function improvement that's being observed is becoming a contribution to the totality of evidence, but and the conversations with the FDA are about continued unmet need. In addition, population, even with existing and known standard of care of boys who cannot get access to treatment because of preexisting immunology, boys who may not be able to access treatment in certain age ranges because they're looking for more data are there gaps in data and that understanding of boys, you may have certain types of mutations that have not been able to be studied and explored either due to profiles of other products or simply because they haven't been done. And so that's been our focus is to design something that is both efficient, effective and accelerated in sort of pivotal design but also something that's answering not just questions that FDA feels like it already has answers to. And I think FDA has evidence pretty strongly that it is supportive of microdystrophin as a surrogate biomarker predictive of clinical benefit. And we certainly with RGX. two are achieving levels of microdystrophin at or really above what I think is expected in terms of the regulatory process. So where we're going next is moving quickly on micro-dystrophin accelerated approval and then focusing on strengthen functions, either that we accumulate over time to further differentiate us in the commercial market and on more of a confirmatory basis.

Ellie Merle

Great. Thank you.

Operator

Brian Skorney from Baird.

Brian Skorney

Yes. Good afternoon. Thank you for taking the questions.
First, a quick one, I think increasingly given the weights and dosing of the other big, just wondering if you can provide a way of bucket number five here, not jumping out to me based on the data provided so far from that there is differentiation between dose level one and two and Western or CK level changes. So I'm just wondering what's kind of warming with a certain degree.

Kenneth Mills

Yes. Brian, again, I mean, I think we're looking at a data set in dose level two, right now that is entirely based in eight and above. And the dose level one data includes one patient from that age range. But the two other patients that are in the four to seven range, which I know to all of you and to most people is a more familiar territory because that's that's what the data is that has been shared on most often and almost entirely with respect to existing labeling of the accelerated approved product as well as data from other datasets from other programs for us.
Look, I think there's several things we are seeing ranges of results here that are consistent with what we've observed in animal models, where we've seen differentiation of those doses up in terms of functional outcomes in the animals. The other thing is that we're looking at and the range of the results overall, and we're incredibly happy and proud of the fact that everything that we're seeing and reporting it already in double digit micro-dystrophin ranges, not the case with other datasets as you look at them. So achieving that, I think says something to us about the overall stability in the overall quality of RGX. two as a candidate as designed. But secondarily, I think we do see RGX. two at DL. two, again, having something that is just between those two results of close to 50% microdystrophin expression and these are in boys one who's 12 and one whose eight. And for us, those are the types of boys that are more progressed disease with a frankly that are more challenged to be able to get levels of microdystrophin expression with gene therapy. And I think that's reflective of the evidence that other programs haven't even chosen to progress or share data in those types of age ranges. So this is what has got us incredibly enthused and excited is that dose level one showed us, yes, we can get great results in four to seven year olds and we got a strong result also in I know I on an older boy, a 10 year old in that case. But in dose level two, the first two kids that we enrolled were older boys and we got what we think are phenomenal results that in the safety profile was an easy decision along with discussions we've been having with FDA. You designate that as our pivotal dose.

Patrick Christmas

Great and just have to wait for patient number about alpha.

Kenneth Mills

You're citing here, you see weak.

Patrick Christmas

Yes.
And can you tell us the latest number, but I think you provided the other.

Kenneth Mills

Yes, I don't have that off the top of my head have to fully follow up with you on that.

Operator

Danielle Brill from Raymond James.

Danielle Brill

Hey, guys, this is Alex on for Danielle. Thanks for the question. A couple on three one four. And given the update today, do you still plan to publicly disclose close data updates from altitude later this year. And just curious why the large gap between now and the guided end of Phase two meeting with FDA in 1Q 25 and then looking at Wet AMD to us. We think the wet AMD is datasets a little bit more mature. So we would have guessed that that would have been advanced to pivotal as well. So what kind of data or time points to you and have the need to see to convince you to advance the suprachoroidal wet AMD is forward the pivotal development?

Kenneth Mills

Yes, 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, and we're well aligned with them on on this guidance. And we've been focused on the fact that when we bring a package forward to the FDA for pivotal design, which would be the first such pivotal package for suprachoroidal delivery for gene therapy in diabetic retinopathy that it's going to be as robust and sort of important as you could expect for that conversation?
We don't rule out that things could be done on an accelerated basis to beat that guidance. But right now, we sort of felt most confident in the Q1 2025 guidance, which is still months away.
Right. And so for us also the fact that we view initiation of the pivotal in the first half of 25, I think can sort of emphasize that we think that the sort of time energy and effort that would be put into an end of Phase two discussion will be something that we can accelerate off of in terms of our pivotal initiation overall with respect to a suprachoroidal device overall and program plans between diabetic retinopathy and wet AMD, this is actually pretty consistent and predicted for us. We talked about back in the end of 2023 that the diabetic retinopathy data that was presented was maturing and kind of coming into focus in terms of our key measures of efficacy and safety. That was a little bit ahead of where we saw things with respect to wet AMD suprachoroidal, we updated wet AMD suprachoroidal in a play in a meeting earlier in the year at six month data and said, we were encouraged by that, but also viewed that it was the decision was potentially frame shifted from diabetic retinopathy by at least a few months. And so we continue to maintain and sort of guide that overall. And what I would say, as you know, eventually, one of the indications has to be the first to go into pivotal phase and into that discussion with FDA. I think that the view that the first also would be the one that would be a two pivotal trial design approach is something that I think is consideration overall and that we feel strongly, I know at Regeneron bio and in alignment with AbbVie about this, that the unique nature of the data that we're seeing in diabetic retinopathy and the unique unmet need. It's also something that is very attractive for bringing that forward as the potential first application of the suprachoroidal delivery approach but we have guidance for q three update on wet AMD as well and be able to talk more about that program.

Danielle Brill

Great. Thanks so much.

Operator

Mani Foroohar from Leerink.

Mani Foroohar

Hi, this is Lily on for Manny. Thanks for taking my question. So maybe just a quick follow-up in terms of the super corridor for 2014. And so in terms of the data update, can you maybe just give us a little bit more granularity in terms of the we've seen six months follow up timing that we would be seeing? And also on the potential data point that would that would basically influence your decision? Thank you.

Kenneth Mills

Sure. I don't think we have any more specific guidance right now on what the next data updates are going to include?
Again, our process here, working in partnership with AbbVie is right now. We're focused on program execution and acceleration based on these positive interim results that we decided for diabetic retinopathy lead us to this updated guidance on initiation of the pivotal, but we generally have kept a reasonably steady cadence of updating the community at conferences. And when we're able to bring additional data forward usually in settings of medical conferences, we do right now, we expect the next program update and data for wet AMD suprachoroidal to be in queue three, but we're especially excited that the diabetic retinopathy program now has guidance for the first suprachoroidal program. You move into pivotal phase.

Operator

(Operator Instructions) Luca Issi from RBC Capital.

Luca Issi

Okay, great. Thanks so much for taking my question and congrats on the progress. Maybe a quick one on DMD. Have circling back on the pre-existing immunology. You're obviously trying to differentiate in DMD in multiple ways, including C-terminal domain as well as obviously going after broader patient population percentage of patients will be eligible for your therapies simply because they have neutralizing antibody against both Sarepta and Pfizer.
Just trying to get a numerical percentage here on the kind of lowest thing is lowest hanging fruit.
And then maybe on the competitive landscape for the ocular gene therapy, we recently saw some data for the long acting TKIs. It was somewhat mixed for DR despite actually pretty good data for wet AMD. What are your thoughts on what that what drives that dichotomy between the two and maybe more broadly, what are your thoughts on long acting TKIs, a potential competitive threat for your program? Thanks so much.

Kenneth Mills

Yes. Thanks, Luca. So I think you do a pretty solid job of modeling the concept of the cross-reactivity of different serotypes. We look, I think we generally have offered up that to may be a solution on its own. Again, that's with two other competitive products. Let's say in a Sarepta and Pfizer competitive with a rigid flex product in a hypothetical firm where you'd be looking at cross reactivity of the different AAVs and say what's what's left uniquely for Agennix. I think that's about 15%. I think you can draw on that from a number of sources of data. Again, it's generally accepted and known as the prevalence of neutralizing antibodies against any the capsid is going to be something on the order of 30, maybe even 40% of subjects. I mean, even even more for some of the earlier, AAV like AAV two, for instance, but but in general, where we are with rh 74 AAV9 or Agennix is 88. So I think in the case where there's two competing products, 15%. In the case when we're second to market, which I think is a possibility we need to start considering here for RGX. two in terms of where we are positioned to continue to execute the safety profile. The data that we're showing can be above that number. I could see 20% to 30% in a head-to-head comparison with another another vector.
And on the comment about TKIs, I mean good observation. I know there was a couple of datasets that have been presented in the last few months on both in NPDR. on I mean, obviously like AAV gene therapy, RGX. three, one four, the body of evidence around the clinical data between subretinal and suprachoroidal and its ability in a continuous way with its PK profile to target anti-VEGF or VEGF with with basically a molecule that's a new approved therapeutic energy, I think is very different than the continuation that people have worked on to tried to bring forward broad-spectrum chemistry agents like tyrosine kinase inhibitors to affect VEGF in the eye on our view is and nothing compares to the profile of a onetime treatment expressing an anti-VEGF biologic that is part of the known standard of care for wet AMD and related conditions. Remember, treatments like Eylea and Lucentis are actually labeled for DR. and NPDR. populations. They're just not used at all. They're not adopted even arguably in the 1% cases. So what we are bringing forward to the market. Importantly, a profile is something that is already established clinically as showing benefit, but just hasn't had the commercial adoption. I think I think TKIs are coming from a different space. I don't think that necessarily the chemistry and the formulations have completely been worked out. I don't think that TKIs have been worked out entirely overall across immuno retinal diseases. And I think that they're certainly not onetime treatments, which as well, I think is what a meaningful differentiation for three one for suprachoroidal is. So for us at this stage, we think we have a profile that is and a clear commercial leadership profile and a clinical leadership profile.

Luca Issi

It's John.

Operator

[John Neal, Charden].

John Neal

Hey, guys. Thank you for taking the question. I have a follow up on that for you on for diabetic retinopathy.
As you begin to prepare for the end of Phase two discussions, what is your current thinking on the primary endpoint of greater than or equal to two step on DRSS. improvement versus the greater than or equal to the three step worsening that some other companies are planning or considering to use? Thank you.

Kenneth Mills

Yes, good. Good questions. And yes. I think that on I think the most important emphasis for us about the clinical and commercial opportunity in DR is actually what Karin mentioned about vision threatening events or vision threatening complications. We have shown evidence of risk reduction up to almost 90% in vision-threatening complications in diabetic retinopathy patients. And this is the thing that in the long term is what is affecting their vision. And so to longitudinally, be able to affect that is the priority. And that will be something that we will continue to collect in trial when it comes to the concept of DRSS. scoring, two-step worsening or two-step improvement, either regulatory outcomes that I think of meaning in terms of how we're going to power studies and I think that we've shown evidence of data previously in our development where we've had really high propensity of patients who overall have achieved improvement in GROSS relative to observational control than we've had 0% of patients worsened relative to a high number of patients on a percentage basis or worsening in these observational control. So I think there's good options there for us in terms of the regulatory endpoint. But I want to really emphasize that we think that the focus clinically and commercially for bringing especially uniquely a onetime treatment forward, would be the emphasis on the reduction of vision threatening events. And for there, I think, again, we can point to at least an 89% reduction in data we presented last year as some of the we think best data and supportive evidence for on this type of treatment in diabetic retinopathy.

John Neal

Got it. Thank you.

Operator

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