Good day, and thank you for standing by. Welcome to the Q2 2023 REGENXBIO Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker’s presentation, there will be question-and-answer session. [Operator Instructions] Please be advised today’s conference is being recorded.

I would now like to turn the conference over to your speaker today, Patrick Christmas, Chief Legal Officer. You may begin..

Good afternoon and thank you for joining us today. Earlier this afternoon, REGENXBIO released financial and operating results for the second quarter ended June 30, 2023. 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, 2022 in comparable risk factors sections in 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, August 2, 2023 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 like to now turn the call over to Ken Mills, CEO of REGENXBIO.

Ken?.

retinal, neuromuscular and neurodegenerative diseases. In 2023, our team is executing on two pivotal phase programs that include over 1,000 subjects to support the goal we have to file our first BLA in 2024 and 2025. We're observing that, on average, one new patient is being dosed in REGENXBIO clinical trials daily.

Our work in retinal disease primarily centers around the strategic partnership we entered into with AbbVie at the end of 2021 to develop and commercialize ABBV-RGX-314 or 314 an investigational gene therapy. AbbVie is a strong and complementary partner for REGENXBIO.

We expect to leverage AbbVie's global development and commercial infrastructure within eye care with our expertise in AAV gene therapy clinical development and deep in-house knowledge of manufacturing.

Together, we're developing 314 to be the first onetime therapeutic option in major retinal vascular diseases to address significant unmet need for patients. Overall, our pipeline of AAV therapeutic candidates is addressing high unmet need for millions of patients in diseases that represent current market opportunities of over $20 billion.

Just a few weeks ago at our Investor Day in July, we introduced some new clinical trial data from our retinal programs using suprachoroidal delivery and our Duchenne microdystrophin candidate and we provided specific guidance about additional upcoming interim trial updates.

From our AAVIATE and ALTITUDE trials, we reported that mild-to-moderate intraocular inflammation previously observed with suprachoroidal delivery is mitigated with short-course topical steroid eye drop.

And we reported safety updates from the initial dosing in cohort 1 of the AFFINITY DUCHENNE study to support a well-tolerated profile of our candidate RGX-202 today. Now, I'll turn the call over to Steve, so that he can review in detail a bit more about the clinical progress and pipeline updates..

Thanks, Ken. I'll begin with 314, which is being developed in collaboration with AbbVie to treat wet AMD and diabetic retinopathy via subretinal and suprachoroidal route of administration. 314 utilizes our NAV AAV8 vector to deliver a gene encoding a therapeutic antibody fragment to inhibit VEGF.

The anti-VEGF market opportunity is poised to grow significantly as the population ages. 314 for the treatment of wet AMD via subretinal delivery is being evaluated in two ongoing pivotal trials ATMOSPHERE and ASCENT.

We recently announced the expansion of these studies to enroll a total of 1,200 patients in the US, Europe, Japan and Israel to support global development of the program. We also recently initiated a Fellow Eye treatment study as part of the pivotal program using subretinal delivery.

This study is evaluating the safety, efficacy and immunogenicity of subretinal 314 administration in the fellow eye of patients with bilateral disease from ATMOSPHERE and ASCENT, who previously received a subretinal injection of 314.

Overall, we plan to complete all these trials in time to support global regulatory submissions in late 2025 through the first half of 2026. Additionally, earlier this week, we presented new interim results from our Phase 2 pharmacodynamic study designed to evaluate the same dose levels being used in the 2 pivotal trials.

The updated interim data demonstrated that RGX-314 manufactured using our NAV Express platform process was well tolerated and in both the low-dose and high-dose cohorts through six months patients achieved expected protein levels along with stable to improved BCVA and CRT as well as meaningful reductions in anti-VEGF burden, with most subjects remaining injection free.

This study is now fully enrolled. We also have two ongoing Phase 2 trials that fall under our collaboration with AbbVie, assessing in-office suprachoroidal delivery of RGX-314 in for treatment of wet AMD in the AVA trial and treatment of diabetic retinopathy in the ALTITUDE study.

AVA is an active control dose escalation trial evaluating RGX-314 for the treatment of wet AMD. We recently presented safety data at our Investor Day from Cohort 6, evaluating dose level 1x12 GC pre eye that included short course prophylactic ocular steroids following administration of RGX-314.

The initial data presented and continues to support the safety profile of RGX-314 and highlighted the inclusion of short course prophylactic steroid eye drops, which resulted in 0 cases of intraocular inflammation. or IOI in all patients.

We plan to present full six-month results from Cohorts 5 and 6 at the Hawaiian Eye meeting in the beginning of 2024. ALTITUDE is the active controlled dose escalation study of RGX-314 suprachoroidal delivery for treatment of DR.

We're very excited about the opportunity in DR given the size of the market, which exceeds that of wet AMD and because we believe this patient population can benefit the most from a potential onetime gene therapy.

During our Investor Day, we presented initial interim data from Cohorts 4 and 5 at dose level 3, and with short course prophylactic steroid eye drops following RGX-314 administration. The data demonstrated that RGX-314 was well tolerated with no drug-related serious adverse events in 29 patients from these cohorts.

And just as observed in wet AMD, the inclusion of short course prophylactic steroid eye drops resulted in zero cases of IOI in all patients. We look forward to presenting full 12-month results from cohorts 1 to 3 at the American Academy of Ophthalmology Meeting later this year. Moving to Duchenne.

As Ken mentioned in his remarks, at our Investor Day, we were pleased to announce our new exon skipping program to complement RGX-202. Duchenne patients face high unmet need, and we are committed to bringing multiple treatment options for these boys.

Our first program, RGX-202 is a potential onetime gene therapy for the treatment of Duchenne being developed as a highly differentiated product designed to deliver a transgene for a novel microdystrophin that includes the functional elements of the CP domain found naturally in occurring dystrophin.

RGX-202 is designed to support the delivery and targeted gene expression throughout skeletal and heart muscle using our NAV AAV8 vector and a well-characterized muscle-specific promoter. During our Investor Day, we reported safety data from the Phase 1/2 affinity Duchenne trial.

The data we presented on the two patients, ages 4 and 10 showed that RGX-202 was well-tolerated in both patients with no drug-related serious adverse events. Time of post administration follow-up was 45 days and more than three months.

We continue to actively recruit patients in this trial, and we look forward to presenting additional data at the World Muscle Society Congress later this year, that will include longer-term safety data and initial microdystrophin protein expression levels in muscle at three months.

We also continue to enroll patients in affinity beyond an observational screening study that is evaluating the prevalence of AAV8 antibodies in patients with Duchenne. Moving to our other rare disease programs. We are developing two programs for Mucopolysaccharidosis, MPS II and MPS I.

RGX-121 is an investigational onetime AAV therapeutic for the treatment of MPS II, also known as Hunter syndrome, being evaluated in the ongoing Phase 1/2/3 CAMPSIITE trial. In May, we announced that we received regenerative medicine advanced therapy or RMAT designation from the FDA.

Recognizing the preliminary data we have presented to date indicates its potential to address the unmet medical need for patients with Hunter syndrome. We completed enrollment of 10 patients for our CAMPSIITE trial in the first half of 2023 and remain on track to support a BLA filing in 2024 using the accelerated approval pathway.

Now on to RGX-111, an investigation of onetime AAV therapeutic for the treatment of severe MPS I. We have completed enrollment of the Phase 1/2 trial and we remain on track to share additional updates on plans for this program later this year.

In addition to these two programs, we also are developing RGX-181 to treat the neurodegenerative manifestation and RGX-381 to treat the ocular manifestations of CLN2 or Batten disease.

Physician investigators in Brazil continue with follow-up for the first child with CLN2 disease dosed with RGX-181 under a single patient investigator-initiated study, and we expect investigators to report initial interim data from the single patient including six-month results at the Society for the Study of inborn errors of metabolism Annual Symposium later this year.

We are also happy to report the recent dosing of our first patient with RGX-381. To conclude, we have made significant progress with data updates and trial advancements across all our programs as we continue toward our goal of 5x25.

Lastly, I'd like to thank the patients, families, clinicians and patient advocacy representatives who are involved in and support all these trials. And with that, I turn the call over to Vit to review our financial guidance..

Thank you, Steve. REGENXBIO ended the quarter on June 30, 2023 with cash, cash equivalents and marketable securities totaling $415 million compared to $565 million as of December 31, 2022. The decrease was primarily driven by cash used to fund operating activities during the first half of 2023.

R&D expenses were $60 million for the second quarter of 2023 compared to $61 million for the second quarter of 2022. The decrease was primarily attributable to an increase in developmental cost reimbursement from AbbVie under our Eye Care collaboration.

We expect the balance in cash, cash equivalents and marketable securities of $415 million, as of June 30, 2023, to fund our operations into 2025.

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 developments or commercial milestones under our 314 collaboration. With that, I will turn the call back to Ken to provide final thoughts..

Thanks, Steve and Vit for those important updates about our clinical progress and our financial performance. REGENXBIO continues to perform at a high level, as we execute on our mission of improving lives for the curative potential of gene therapy.

In addition to our platform and pipeline, our end-to-end capabilities also set us apart as a leader, with our manufacturing innovation center here in Rockville running scalable commercial-ready batches of AAV Therapeutics. And our research and early development team continues to advance what's possible in gene therapy.

We provided clear examples of these capabilities at our Investor Day, when we presented data from the manufacturing innovation center performance, including on product quality and yield. And when we introduced plans for a new IND for a candidate with exon-skipping science to expand our commitment to Duchenne.

Looking ahead for the remainder of the year and early into next year, we anticipate a number of important clinical pipeline milestones. Let me summarize.

Next month, as Steve mentioned, investigators at the society for the study of Inborn Errors Of Metabolism will report the first initial data six-month follow-up from the first patient dosed with RGX-181 for the treatment of CLN2 form of Batten disease.

This is a five-year-old child and this is part of the data from our third neurodegenerative program. In October, at World Muscle Society, we expect to share additional interim data for patients in cohort 1 of affinity, Duchenne, including longer-term safety and the first Microdystrophin Expression protein levels in Muscle at three months.

In November, we plan to report additional interim data from the ALTITUDE trial of 314 suprachoroidal delivery for the treatment of diabetic retinopathy at the American Academy of Ophthalmology meeting being held. This will include full 12-month results from cohorts 1 and 2 and 3.

And finally, in January of next year, investigators will report on additional interim data from the Phase II/III trial of RGX-314 suprachoroidal delivery for the treatment of wet AMD including full six months results from Cohort 5 and 6, and this will be at the Hawaiian Eye and Retina meeting.

So we have a lot of important value-driving catalysts ahead of us this year.

And with the balance sheet in place to continue to fund our mission and operations into 2025, as Vit described, we have the focus and high-performing team, strong collaborators and the trust of the clinical and patient community partners, it's a clear and definable path for us to achieve our '5x'25 vision and continue to lead what's possible with AAV Therapeutics.

We want to thank all of you for listening today, we look forward to providing you additional updates, as we continue on this path for the remainder of this year and into next year. And with that, operator, we'll turn the call over for questions..

Thank you. [Operator Instructions] Our first question comes from Dane Leone with RJF. Your line is open..

Hi. Congratulations on all the progress, thanks for taking some questions for us. Two questions kind of have been percolating with investors recently. One, it seems like you've given us more detail around what efficacy data we could expect from both AAV and ALTITUDE.

Just one question regarding AAVIATE should we expect 12-month data from Cohorts 1-4 alkaline eye or will it be just a full look across all Cohorts two months fix? And then secondly, can your team elucidate what Axle assays around protein expression of microdystrophin we could see at world? And whether you would expect some method of comparability to your peers that have ongoing the DMD programs as well? Thank you..

Thanks, Dane, for the good question.

Steve, do you want to take the alkaline eye piece?.

Sure. So hi Dan and thanks for the questions. So for the AAVIATE Wet AMD update, we have discussed the latest results that we have for a six-month follow-up.

We haven't said more as far as longer-term follow-up in part because of the later Cohorts and the dynamic nature in these interim updates of ongoing studies as well as really seeing when we might be able to do a data cut, and we always have the overhang of also reaching alignment with AbbVie as we get closer to this type of meeting.

So that's the type of thing that we can update as we get a little closer..

And on the microdystrophin protein expression Dane, we are working with methods that we think will be able to be used for comparison to methods that have been used by others in clinical investigation of the microdystrophin class of products.

So I think that as we come into world muscle, I think we all know that forms of Western Blot Assays as well as Liquid chromatography-mass spec have been used in assessments of other patients.

And we think that we will have methods to support interpretation of that and some forms of comparison keeping in mind that there are always nuances in assays, but I think things that the community will be familiar with from us..

Excellent. I look forward to seeing the data. Thank you..

Okay. I appreciate it..

One for next question. Our next question comes from Gena Wang with Barclays. Your line is open..

Hi. It's Tony on for Gena. I have two questions.

I guess, first, briefly, can you remind us of the IP and Royalty status for some of your partner programs, including with the Rocket for Danon Disease and Ultragenyx or GSD1a as well as any IP rights to Rh74 And then another one on DMD with updates expected from Sarepta Advisory later this year, what kind of bar would you be looking for in terms of efficacy for protein expression and Nsa?.

Sure, Tony. Thanks a lot for the question.

Yeah, with respect to programs, that are part of our NAV Technology licensee universe, certainly Rocket and in program in the Ultragenyx GSD1a programs are under license for two different vectors, Rockets using AAV9, NAV AAV9and Ultragenyx using NAV AAV8 in the case of GSD1a licenses we entered into several years ago.

We tend to have royalties that are in the range or similar to the type of compensation that we're receiving, for example, on the Zulgensma royalty. So starting in the high-single-digits the and going up on a tiered basis up into double digit ranges.

With respect to IP as it relates to your second question, we currently have two lawsuits that are involving patents relating to the manufacturing of Sarepta's product as well as patents that involve the composition of Sarepta's product, both of which use AAV-Rh74that they refer to.

And so we updated recently on the second lawsuit, the first lawsuit that involves the patents relating to manufacturing of the product is actually scheduled for trial in the beginning of 2024.

With respect to your second question, I think this builds off of Dane's question about microdystrophin data and expression and where the program for RGX-202 is going, which we're very encouraged about some of the initial safety data we provided just a few weeks ago.

When it comes to microdystrophin expression, we think that, RGX-314 is within the class of, you know, treatments, candidates that have been explored clinically so far, including both Sarepta and Pfizer and some others, like Solid.

We're at a 1e14 dose currently in our trial, and I think that is, again, adjusting for understanding that there can be sometimes differences in assays and quantitation of different AAV products similar to where Pfizer is in its pivotal program.

And my understanding of Sarepta's accelerated approved product is that they're slightly above that 1.3e14 in terms of dose level. So we'd be coming into observations of some of the first clinical data that we'd see at 90 days looking to achieve similar protein expression with respect to RGX-202 to what others are achieving.

Now, the key there is that we believe that once we express microdystrophin in the muscle of children, that our microdystrophin has the potential to be more potent or more efficacious because we're the first clinical candidate to design into the AAV microdystrophin that's being expressed a substantial component of the C-terminus, as Steve alluded to, the C-terminal domain, which we've established pre-clinically, both in AAV experiments and in other work, to be meaningful in terms of improving the strength and the biological function of a microdystrophin.

And so, it's actually something that's more akin to what I would consider to be attenuated forms of Duchenne, like Becker muscular dystrophy that was sort of alluded to in the recent FDA adcom and discussions about microdystrophin and the possibility of microdystrophin being similar to things that occur in nature.

Ours is the first product that includes something that is most similar to things that occur in nature. And so, we think that will have an amplification of potential efficacy outcomes.

Now, the measurement of the efficacy outcomes will not be something that we'll be able to assess at the 90-day point on those considerations, of course, will be at later time points, maybe nearer to nine or 12 months. But that's when we would begin to get the type of responses like you were referring to in SFA, et cetera.

But for the update in the World Muscle Society, this will be longer-term safety data our first expression of microdystrophin in Cohort 1 at the 1E14 dose..

Our next question comes from [indiscernible] with Morgan Stanley. Your line is open..

This is [Indiscernible] on for Vikram Pure head.

So our question is what is your current view on where GX2fit for some competing DMD therapies in the rear setting?.

Yes, Gus, it's a great question. The design of RGX-202 in the target product profile is multi-threaded for us. First is, we believe strongly that there continues to be an unmet need in AAV gene therapy for boys when just a single product would be available or even two products.

And that's because, as you all know of pre-existing immunology that can exist in boys that may not allow them to access AAVs because of zero prevalence for pre-existing neutralizing antibodies.

So we estimate that's a potential market for an AAV-based capsid, which is what RGX-202 is based on, on an incident basis and on a prevalence basis, could include 15 or maybe up to 30% of the population that might not be able to access other capsids that are currently in development. That's the first point.

Second point is -- but I was just alluding to in my answer to Tony, which is we're the first -- RGX-202 is the first reagent to be brought forward scientifically and clinically that includes a domain of full-length microdystrophin that doesn't exist in other microdystrophin products, the C terminus which, again, evidence support preclinically that there's an improved effect of biological activity and strength of muscle when that terminal domain is present in truncated forms of dystrophin.

So that, we think, sets us up potentially for a form of best-in-class. When later in development, we can assess more clinical data, we'll be more clear on that. But I think the preclinical data points in that direction today and the evidence of the determinants is something that we strongly emphasized that our focus in development.

And then the last piece is, I think, on quality and yields when it comes to manufacturing. This is something that we just highlighted at our Investor Day a few weeks ago.

We think that the purity and the quality of the AAV products that are being manufactured here at the Rockville Manufacturing Innovation Center as well as the yields we're achieving with our NAV Xpress process will allow us to be competitive in a market when it comes to everything from showing improvement in things like potential safety profiles and as well as potentially on cost..

All right. Thanks very much..

Our next question comes from Alec Stranahan with Bank of America. Your line is open..

Hey, guys. Thanks for taking our questions. Just a couple from us.

First, actually on MPS II, just curious, your interactions with the FDA around the RMAT designation if you could give a sense of what it would take to show clinically for accelerated approval and if you intend to update the markets with the top line prior to filing? And then secondly is just around the AbbVie milestone.

I appreciate this is not in the runway guidance, but any additional color around this growth and timing around any additional milestone figures over the next year or two would be great. Thank you..

Hey, Alec, thanks for those questions. On MPS II, yes, we just announced today that we've completed the goal of enrollment of 10 patients with respect to the CAMPSIITE study to support our plans for accelerated approval.

And it was great timing with respect to the RMAT designation from FDA as well to support our continued execution here on the regulatory front.

I think that -- look, our RMAT is something that's a designation that only comes from FDA's acknowledgment of clinical data, right? There are other types of designations that sometimes can rely exclusively on preclinical data for support.

But in this case, RMAT is something where the FDA has already assessed clinical data that's been generated from our trials and provided input it believes that there's a potential status here for moving quickly.

And that's been consistent with our dialogue with FDA in the last several years with respect to how we've been thinking about transitioning from some of the first patients we've reported findings on all the way through to getting to that third dose level and our dose escalation and starting this phase of pivotal enrollment in the last year.

So I think that you absolutely can expect on a going-forward basis from us additional data before the time of the filing of the BLA that would include top line data that would go to support the BLA filing.

But at this phase, sitting here today, we've just completed enrollment in the second quarter of the 10 patients and we're going to compile the time line for not only completing the work to support the BLA, but also for those data updates. So look out for us on those updates going forward. When it comes to AbbVie, you're bringing me back.

I think when we first reported on this partnership in eye care with AbbVie.

We highlighted in our filings that -- in addition to the total number of milestones that may be earned out by REGENXBIO for development, regulatory and commercial, a big portion of that, I think, is over $750 million is actually associated with the development and regulatory milestones.

And I guess what we can say today is that the guidance that we can provide is that a substantial portion of that $780 million is associated with the execution and advancement of suprachoroidal development.

And so as Steve is alluding to as we come into updates later this year with respect to ALTITUDE and AAVIATE as we progress from 2023 into 2024, we're certainly learning a lot more about the potential for the advancement and the regulatory advancement and the development advancement of the suprachoroidal programs for both wet AMD and diabetic retinopathy and that starts to bring those development and regulatory milestones as potential earn outs for us into focus..

Thanks, Ken. Appreciate the color..

One moment for our next question. Next question comes from Ellie Merle with UBS. Your line is open. .

Hi guys. Thanks so much for taking my question. For DMD, I guess, can you maybe provide more color on when you expect to move to the second dose level. And I know you said we get data on the first to level at World Muscle.

But I mean, what are the time lines for seeing data from the second higher dose and then just your expectations around expansion level differences between the second dose and the first dose level. Thanks.

Thanks, Ellie. A few layers there. We haven't given any guidance or any sort of specific kind of plan around dose escalation or -- and this trial is also designed for the potential of dose expansion at the first dose level as well.

So that will be something that will be happening in phase where we have the opportunity to sort of complete and evaluate the first cohort level and take into account the different types of variables, including the initial measures of microdystrophin at dose level one.

With respect to dose level two, though, I mean, preclinically, we certainly have seen and it's designed into the study because we've seen evidence of higher microdystrophin expression. We've seen evidence of improvement in outcomes with respect to functional assessments in the animal models.

But of course, we want to understand how this could be recapitulated in human. And frankly, we've also seen really strong expression and functional outcomes at the 1e14 dose level as well. So there's definitely still an opportunity here for us to decide that expansion of 1e14 is the direction that we want to go.

And it's sort of a hand or function perhaps whether dose escalation to 2e14 occurs, I think we'll begin to talk about microdystrophin expression in more detail at World Muscle society when we have some of the data to be able to present.

And as I alluded to, I think in Dan's question, Ellie, there's variability, of course, in different assay methods that people are using to assess microdystrophin.

But we believe that we have really well characterized, validated methods for specifically quantifying microdystrophin that's coming from RGX-202 and we expect to bring that forward and put it into context for all the stakeholders, of course, investors, but also physicians and families when it comes to things that they've seen before from other programs.

And I think our team has done an excellent job at working on methods that we understand and view are reliable that regulators are going to view are reliable as well and are going to allow everyone to contextualize.

As I said, we're at the same dose as where Pfizer is, and where Pfizer REGENXBIO from a sort of stated dosing perspective or slightly below where Sarepta is I think the preclinical data and the clinical data all says that all of these are in sort of relative similar ranges.

So we're expecting our initial microdystrophin data to be within the range of what sort of microdystrophin dose levels are from other programs at similar dose levels.

I can't emphasize enough that important benefit of the same molecule that we express versus what someone expresses without a C-Terminal domain, it's going to have a different effect functionally to C-Terminal is something that enhances the potency, enhances the functionality of a microdystrophin expressed in gene therapy.

So, while we may achieve similar protein levels of microdystrophin and others, we think that our microdystrophin is going to be something on a molecule-by-molecule basis that is more effective. .

Great. Thanks so much for all the color..

Our next question comes from Luca Issi with RBC. Your line is open..

Hello guys. Thanks for taking our questions. This is Lisa on for Luca. Just a couple of questions on D&D. I just want to ask a more specific question on the microdystrophin expression levels and what the expectations are. So, Sarepta has a 40% to 50% change in microdystrophin expression from baseline on the label.

Is that what we should expect to see as a bar for success when you get more data in October. And also on D&D, despite starting a favorable regulatory precedent on the biomarker and gaining accelerated approval, Pfizer yesterday mentioned that their interim look for efficacy later this year will be on function and not on surrogate biomarkers.

I know it's still early days, but just wondering what's your strategy for gaining approval? And wondering if you are in the biomarker camp as functional camp? Thanks for taking questions..

Sure. Thanks, Lisa. Digging into it a bit, I think -- I mean, referencing the product approval label for Sarepta, I would say we can look at means -- we should also look at medians and distributions of patients. And we'll have small numbers and in certain cases, when they had fall numbers, there was quite a distribution of microdystrophin expression.

So, I think for us, we definitely view that we're going to be in the territory of things that have been reported by both Sarepta and Pfizer with respect to microdystrophin expression.

And I think that that does for me, I mean, I wouldn't go as far as to say something like the median of the first patients that were enrolled on the basis of Sarepta, which I think was anything from like nearly zero up to like over 100% because that would be ridiculous.

But I think what we've seen when it comes to media and means of things reported by Sarepta and Pfizer is that there's sort of a range of like 20% to 40%, and that would be something that for us would be adjusted for heterogeneity of the disease, the different types of methods and sort of the assessments that have been done something that I think would feel comfortable for us in terms of similarity.

With respect to the regulatory approach here, I think my observation -- well, I mean, let me just say that I think REGENXBIO both through our neurodegenerative franchise as well as since we've entered the development of products for Duchenne muscular dystrophy have been very much focused on discussions with regulators and stakeholders about the use of the accelerated approval pathway.

And I think that -- we continue to sort of approach our development and sort of regulatory execution on that basis, and we think that the validation of the first AAV therapeutic to be approved on the basis of accelerated approval is a great milestone to continue to support that confirmatory data and other people taking approaches of trying to establish different avenues to show more longer-term functional data, I think, are also valid and different.

And I think that -- we'll continue to sort of process all of the information that comes in from both our own trials and our own development experience, that of sort of stakeholders and patients as well as the FDA.

But from where we sit right now, there's an urgent need and especially with the approval on an accelerated basis of this first product, I think, we all know that there's a limited labeling that's supported the accelerated approval.

Average REGENXBIO, we're developing based on a clinical trial that's enrolling in voice from forward all the way up to age 11. There's still significant unmet need here, and there's a significant urgency here.

And so that's where I think we anchor ourselves to the patient needs and the regulatory understanding that accelerated approval is something that all the stakeholders are supportive of and that we think that we want to contribute to as well. .

Thanks for taking my questions..

One moment for our next question. Our next question comes from Brian Skorney with Baird. Your line is open. .

Hi. Thanks for taking our questions. This is Charlie on for Brian. We wanted to ask, it seems like suprachoroidal delivery for what AMD, what is going to take -- what it's going to take to progress in the Phase 3 is going to be fairly straightforward for AMD.

But for diabetic retinopathy, we wanted to get a little more color on how you're thinking about the interim results you'll be presenting later and what the kind of bar is in terms of efficacy.

And we also just kind of like a reminder on what kind of conversations you've had with the FDA so far regarding the NAV Express manufacturing platform? Thank you..

Do you want to take ER question?.

Sure. Thanks, Charlie. So as you mentioned, we have the opportunity to look at readouts for both wet AMD and DR. On DR, it's interesting.

There's the precedent of looking at two-step improvement on diabetic retinopathy severity, that's largely a technical consideration and a powering consideration for what's been done with prior repeat injection anti-VEGF agents. But what patients and their doctors really care about is preventing progression.

So really having a proportion of patients that can have improvement of a certain level is a proxy for, okay, then you're more likely to not have patients progress to vision-threatening or blinding complications, which is the ultimate goal. So the reason I give that context is both of those are clinically meaningful.

If you can have patients improving and if you could have a lower proportion of patients that worsen. And what we've seen to-date with six months results from our earlier cohorts is we really see both the overall trajectory of these patients is going in a better, not a worse direction.

And that's in contrary distinction to what we know happens in patient's natural history and also in our negative control arm with observation.

And what we also know is the bar that one thinks for repeat injections indefinitely is something totally irrelevant for us with a onetime in-office treatment because we know that with repeated injections, you can actually stave off vision-threatening complications, but the treatment burden for these asymptomatic patients is just too much and patients aren't signing up for this as I think it's fair to say many predicted initially.

But if you could have a one-time in-office treatment, that is a much lower bar for a benefit risk consideration. So when we talk to clinicians, experts and investigators really any clear reduction in clinically meaningful worsening is a very viable clinically and commercially target to shoot for.

So on top of looking for a proof-of-concept, that's really the way we're thinking about a target product profile. So we and AbbVie definitely look forward to seeing results that come later. The other thing I'd say is durability. So we've seen very good results at six months.

It's going to be great to have an opportunity to assess durability out to a year later this year..

On the NAV Express side of it, I think that we have started the process in 2023 of creating process qualification lots around the planning of BLAs for both RGX-121 and RGX-314. And so we've had the opportunity to have a lot of dialogue with FDA.

Again, we're running over 12 clinical trials, but for two late-stage studies, 121 and 314 with the subretinal approach, we've had more advanced discussions with FDA.

We've also had the opportunity conveniently being here in Rockville to have had people visit the facility and we feel like we have one of the strongest capabilities when it comes to high-quality, high-yield commercial-ready cGMP facilities that exists..

Great. Thank you..

One moment for our next question. Our next question comes from Andreas Argyrides with Wedbush Securities. Your line is open..

Yeah. Thanks for taking our questions here. Just two from us.

For RGX-121 and MPS II, can you elaborate on your interactions with the FDA and how they came to support the shorter time frame for accelerated approval versus the competitors? And then what additional data do you or AbbVie -- probably the second part of the question, so it need to collect to feel comfortable advancing 314 into pivotal trial for wet AMD and DR, and whose decision is it at end of the day? Thank you..

Hey, Andres, I can take the second one first.

So, I guess, the generic answer is, we obviously take into account all data updates that we give and look at traditional aspects like dose response, safety and tolerability always come first, if we're going to consider a potential dose, and I think the good news is in both indications, we have very clear noninvasive ways to assess for response and also potential dose response.

And there's not one line in the sand, I'd say that you can give in these cases because it really is looking at the overall results other than the suggestion I gave in terms of at least efficacy on diabetic retinopathy.

And to your related question of who makes the decision, we work very closely and collaboratively with AbbVie and we have the traditional joint committees like joint development and joint commercial committees that work together and cross-functionally evaluate all the data and really compare that against our target product profile to make such decisions..

Yeah. And with respect to the first question about 121, there really is not a close competitor to the target product profile of RGX-121, which is a one-time therapy to address strictly the CNS components of Hunter Syndrome.

So, you know, we think we sort of stand in a unique class here, both with the one-time nature and, standing on top of the unmet need for CNS features of MPS II because of the existing standard of care treatments in the US like Elaprase, not being able to address those features.

And I think that the FDA designation of the RMAT is supportive of the fact that they're encouraged by the clinical data that has been reported so far, such that they want it designated as, you know, a program that has the type of status that is meant to be accelerated. So I think that we feel really good about our data.

We feel good about the unique one-time profile of a treatment that addresses CNS manifestations of Hunter and we feel good about the data that we've reported and the support that we're seeing from stakeholders and regulators..

Great. Thanks for the color there and congrats on all the progress. We can follow-up on new one coming up meeting [ph]..

One moment for our next question. Our next question comes from Mani Foroohar with Leerink. Your line is open..

Hi. Good afternoon. This is Lorena Song [ph] on for Mani.

I know earlier you had touched a little bit on the infringement lawsuit and I was wondering if you could provide or if there were any updates that were available in terms of the timing for the second lawsuit as well as kind of the potential level of damages that is thought of and the potential division between the company and the University of Pennsylvania?.

So we don't have any update on the timing of the second lawsuit. As I alluded to, the first case is scheduled to go to trial in early 2024. And that's the otherwise the exact timing of the second lawsuit is not yet built..

Thank you.

And in terms -- so for the Duchenne program, so what do you expect to the certain recent approval, would you think that impact would be on potential recruitment or enrollment in your study as well as the potential impact from the – that study results that are expected later this year?.

Yes, again, I think an important feature that everyone understand in AAV gene therapy is that -- there continue to be voice, kids in some of our trials and in other trials that aren't able to access therapy for a variety of reasons, even sometimes commercial therapies because of the preexisting immunology, they can maybe achieve treatment from a certain type of vector because of serology, but not another.

And Duchenne a rare disease, but it's a larger incidence and prevalence than other areas that we operate in, in clinical development. So we have not seen nor do we really expect to see any impingement on our ability to enroll with respect to the RGX-202 program, a clinical stage right now.

And as we go forward, I think additional data for microdystrophin class of products on the basis of the fact that our product is of that class when we have the opportunity to show our microdystrophin data, emphasizing that our microdystrophin is a potentially better form of and more similar to full length dystrophin or more naturally biologically active forms of truncated dystrophin, I think should be really exciting because it could show that there's evidence of incremental improvement with existing technology.

But really, I think we should be thinking about RGX-202 as an improvement to the first generation of microdystrophin both on the basis of inclusion of the C-Terminal domain as well as the potential to bring some of the benefits of the manufacturing innovation center into focus.

And all of that's in addition to, look, there's just going to be boys that aren't going to be able to access the other treatments..

Thank you.

And actually speaking of the potential differentiation in terms of potency, should we expect to see impacts on muscle function or muscle strength maybe earlier than other programs, say at the six-month readout?.

I think that it's hard to assess that from the animal models because they're very different in certain forms than the human aspects of the disease, as you get later in the progression, the animal models can be fragile in different types of ways. And so you can always collect that same longitudinal data.

I think on the basis of our understanding, I think we would expect to see more clear separation at something like the one-year time point. And I think it could be possible for certain types of measures to distinguish themselves between the six and 12-month time points as well.

We certainly wouldn't expect it would be something that would accompany the microdystrophin measures from the biopsies at three months..

Thank you so much for your clarification..

Thanks..

[Operator Instructions] One moment for our next question. Our next question comes from Caroline Palomeque with Berenberg Capital Markets. Your line is open..

Hi, thanks for taking the question. So on RGX-314 for subretinal wet AMD, are there any updates on enrollment from AbbVie on the pivotal trial to set atmosphere, especially since they increased the number of patients as well as the trial sites in the study? Thanks..

Hi, Caroline, so we don't have any change in our guidance. So everything is going very well post the expansion, the global expansion of the pivotal program. And we continue on track to complete these studies so that we can achieve BLA and European regulatory submissions in late 2025 through the first half of 2026. And yes, we're trucking along..

Great, thanks..

And I'm not showing any further questions at this time. And this does conclude today's presentation. You may now disconnect, and have a wonderful day..