Welcome everyone to the Q3 2024 REGENXBIO Earnings Conference Call. [Operator Instructions] Please be advised that today’s conference is being recorded. At this time, I’d like to turn the conference over to Patrick Christmas, Chief Legal Officer of REGENXBIO. Please go ahead..

Good afternoon and thank you for joining us today. Earlier this afternoon, REGENXBIO released financial and operating results for the third quarter ended September 30, 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 section 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, November 6, 2024, and we undertake no obligation to update any forward-looking statements we may make on this call on account of new information, future events or otherwise. Please be advised that today’s call is being recorded and webcast.

In addition, any unaudited or pro forma financial information that may be provided is preliminary and does not report to project financial positions or operating results of the company. Actual results may differ materially. I will now turn the call over to Curran Simpson, President and CEO of REGENXBIO..

Thank you, Patrick, and thank you, everyone, for joining us today. On the call with me today are Mitchell Chan, our newly appointed Chief Financial Officer; and Dr. Steve Pakola, our Chief Medical Officer. I will begin by recapping our business highlights and key upcoming milestones.

Steve will then provide an update on our clinical programs before passing to Mitch, who will review our financial results for the quarter. I’ll then provide some closing remarks and open the call for Q&A.

This is a very exciting time for REGENXBIO as we continue to generate positive clinical data and prepare to commercialize multiple potential first and best-in-class gene therapies. We’ve had another productive quarter and have several important milestones expected before year-end.

These include the first functional data from our Duchenne program, which is expected in the coming weeks. We’re also very excited to have initiated the BLA filing in MPS 2, also known as Hunter syndrome and for the End-of-Phase 2 meeting coming up later this month for RGX-314 in diabetic retinopathy, which we’ll refer to as DR.

Recall that this meeting was accelerated from first quarter 2025 to fourth quarter 2024 by AbbVie, our partner for the retinal franchise. You’ll hear more from Steve about the great progress being made in RGX-314, including continued progress in DR and wet AMD.

Diving into our programs, I’ll start with RGX-202, our next-generation potential best-in-class gene therapy for Duchenne. We expect to initiate the pivotal phase of the ongoing AFFINITY DUCHENNE study imminently. Once that has begun, RGX-202 will be the only next-generation gene therapy in Phase 3 study for this devastating disease.

We’ve had productive discussions with the FDA as we have advanced RGX-202 to pivotal phase and have confirmed that the accelerated approval pathway remains open to us.

RGX-202 continues to demonstrate the potential to drive increased benefit to patients compared to available therapies, and our clinical data to date are checking all the boxes to demonstrate this differentiation. Thus far, we have seen a favorable safety profile, no SAEs and consistent robust microdystrophin expression.

The last box to check is functional outcomes, which, as I mentioned, we will begin sharing this month. Earlier this year, we shared encouraging early functional observations from clinic and caregiver videos.

We’re excited to share the first functional results, which will include data on some of these patients from dose level 1 and 2 at later, more meaningful time points very soon.

Another key element of differentiation, we believe, is the fact that we are commercial ready when it comes to manufacturing RGX-202 today, which can be a key driver of an effective commercial launch. Our manufacturing uses a modern suspension-based bioreactor process that is highly productive.

Needless to say, we are very excited about RGX-202 as a potential best-in-class gene therapy in Duchenne and continue to aggressively accelerate development to potentially be second to market. Let’s now pivot to RGX-121, the program furthest in development.

RGX-121 is on track to be the first gene therapy and one-time treatment for MPS 2 or Hunter syndrome. Today, as we announced, the first module of a rolling BLA for RGX-121 was submitted as planned in Q3 2024, and we expect to complete filing the BLA in the first quarter of 2025.

Like Duchenne, MPS 2 occurs in boys and is a progressive devastating disorder. Also like Duchenne, we are pursuing a BLA under the accelerated approval pathway and would receive a PRV upon regulatory approval.

The initiation of our BLA marks a major milestone for patients for whom there is currently no cure and no treatments to address the significant neurocognitive decline.

It also marks a major milestone for REGENXBIO as RGX-121 represents both our first potential commercial product and an opportunity to build commercial infrastructure that will benefit our other programs, those in line for commercialization.

Lastly, I will make a few comments on RGX-314, the late-stage retinal franchise we are developing with our partner, AbbVie. As you’ll hear from Steve, we continue making great strides across multiple indications.

The recent positive news from our fellow eye study offer an opportunity to expand the addressable patient population for RGX-314 in wet AMD, where the majority of patients eventually develop bilateral disease. And the data and progress we are making in DR, another large commercial opportunity is highly encouraging.

In DR, we expect to initiate a global pivotal trial in the first half of 2025. We are excited that we will soon have both programs, wet AMD and DR in Phase 3 studies. We look forward to continuing to work with AbbVie to tap the potential of RGX-314 to prevent vision loss for millions worldwide.

In summary, we are making excellent progress and look forward to sharing several important catalysts in the coming weeks and continue to see clinical results supporting the immense potential of these novel programs. With that, I would like now to turn the call over to Steve for an update on our clinical programs.

Steve?.

Thank you, Curran. I’ll start with RGX-202, a potential one-time gene therapy for the treatment of Duchenne. Today, we announced exciting progress in the Phase 1/2 AFFINITY DUCHENNE trial.

This is a multicenter dose escalation and dose expansion clinical study to evaluate the safety, tolerability and clinical efficacy of a one-time dose of RGX-202 in patients with Duchenne aged 1 to 11.

As we approach pivotal phase, I’m pleased to share that we have dosed the last patient in the expansion cohort of dose level 2, which is the pivotal dose level. On the continued strength of our data, we expanded the AFFINITY DUCHENNE trial to include a new cohort of patients aged 1 to 3 years.

And today, we announced that the first patient has been dosed in this cohort. The 1 to 3 age group represents a significant portion of the prevalent population, yet this group has no access to approved or investigational gene therapy. In the U.S., REGENXBIO is the only company recruiting patients under 4 years old.

We look forward to initiating the pivotal study and sharing the first functional data from this program in the coming weeks. Now on to updates from our retina franchise, RGX-314, which is being developed in collaboration with AbbVie to treat wet AMD and DR via subretinal and suprachoroidal routes of administration.

I’ll start with RGX-314 for DR being evaluated in the Phase 2 ALTITUDE trial using in-office suprachoroidal delivery. Like wet AMD, DR is a progressive disease that causes vision loss and ultimately, blindness if not treated appropriately. It is a leading cause of blindness in working age adults.

As we’ve shared with our partner, AbbVie, we have accelerated the End-of-Phase 2 meeting with the FDA to this quarter. We look forward to completing this meeting and sharing our proposed pivotal trial program soon.

As you may recall, we previously expanded the broad multi-indication global potential of RGX-314 by initiating a new cohort in the ALTITUDE trial for patients with diabetic macular edema or DME, a vision-threatening complication of diabetic eye disease that impacts more than 30 million patients worldwide.

RGX-314 is already well positioned to potentially become the standard of care to treat diabetic retinopathy. Broadening the ALTITUDE trial to include patients with DME further expands the global potential to benefit more patients. In wet AMD, we are evaluating RGX-314 via two different routes of delivery, subretinal and suprachoroidal.

Within subretinal, we have two ongoing pivotal trials, ATMOSPHERE and ASCENT in North America, Europe and Japan. These trials continue to progress well and global regulatory submissions remain planned for the first half of 2026.

We recently announced exciting news from our Phase 2 fellow eye study of subretinal RGX-314 in patients with bilateral wet AMD. This study is the first of its kind, evaluating a potential one-time gene therapy as a treatment for patients with bilateral disease.

The positive data demonstrated RGX-314 at the same dose being evaluated in the pivotal program was well tolerated with no cases of intraocular inflammation. We also see continued impressive efficacy, including a 97% reduction in treatment burden at 9 months. 100% of patients needed zero or one supplemental injections.

And 78% of patients were completely injection-free while demonstrating sustained vision stability and disease control. Notably, these positive results were seen in difficult-to-treat patients with high treatment burden prior to RGX-314.

The fellow eye study supports plans for a label inclusive of bilateral use, representing a meaningful option for the significant number of patients with wet AMD in both eyes. Overall, we continue to be encouraged by the progress on our retinal programs.

I’d like to particularly highlight the safety profile observed, including in our suprachoroidal programs. We are confident in advancing the pivotal phase because of this safety profile, particularly in the setting of short course 7-week prophylactic steroid eye drops, a significantly shorter regimen than those used in other gene therapy trials.

In more than 180 patients treated in office, we’re seeing a differentiated safety profile, representing a meaningful potential treatment option for patients and physicians. Finally, on RGX-121 being developed for the treatment of MPS 2.

Earlier this year, we announced that the CAMPSIITE pivotal trial met its primary endpoint with high statistical significance. Patients treated with RGX-121 achieved decreased CSF levels of heparan sulfate D2S6, a key biomarker of brain disease activity to below maximum attenuated disease levels.

Our BLA uses the accelerated approval pathway and is based on D2S6 as a surrogate endpoint reasonably likely to predict clinical benefit. We also previously reported that 80% of patients who received the pivotal dose discontinued enzyme replacement therapy or remained treatment naive.

This is a meaningful update for patients and families whose only option today is weekly enzyme replacement therapy that does not address the neurocognitive decline of this disease. RGX-121 is well positioned to be the first gene therapy and one-time treatment for Hunter syndrome that can directly address neurocognitive decline.

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 in and supported all of these trials.

And with that, I’ll turn the call over to Mitch to review our financial guidance.

Mitch?.

Thank you, Steve. REGENXBIO ended the quarter on September 30, 2024, with cash, cash equivalents and marketable securities of $279 million compared to $314 million as of December 31, 2023.

The decrease was primarily driven by cash used to fund operating activities during the 9 months ended September 30, 2024, partially offset by $131 million in net proceeds received from an upsized public offering of common stock and prefunded warrants completed in March 2024.

R&D expenses were $54 million for the third quarter of 2024 compared to $58 million for the third quarter of 2023. The decrease was primarily due to decreases in headcount and preclinical activities. REGENXBIO expects its cash balance, cash equivalents and marketable securities of $279 million as of September 30, 2024, to fund its operation into 2026.

This cash runway guidance is based on the company’s current operational plans and excludes the impact of any payment that may be received from AbbVie upon the achievement of development or commercial milestones under our RGX-314 collaboration.

Additionally, our runway guidance excludes the potential monetization of a Priority Review Voucher that may be received for RGX-121. With that, I will turn the call back to Curran..

Thanks, Mitch. As you heard, we are making significant progress advancing each of our late-stage programs in multiple large commercial opportunities and are heading into year-end with strong momentum and multiple derisking events.

To recap, in Q4 of this year, we plan on initiating a pivotal trial for RGX-202 under an accelerated approval pathway and look forward to sharing both the trial design and our first functional data. Also in Q4 of this year, we will complete our End-of-Phase 2 meeting with the FDA for RGX-314 in DR.

This will pave the way for initiation of the first global pivotal trial in the first half of 2025 and trigger milestones in our collaboration with AbbVie. Finally, we will continue the progress of the rolling BLA submission for RGX-121 and expect to complete the submission in Q1 2025.

If approved, this would become the first approved gene therapy for treatment of Hunter syndrome, a very meaningful development for the patients and families living with this devastating disorder and would receive a PRV upon regulatory approval. It has been a turning point year for us.

As we look toward the next 12 months and beyond, we see a company that is positioned to deliver on multiple late-stage opportunities. The groundbreaking science that underlies our programs is demonstrating differentiation against standard of care and available treatments.

Each of our programs represent one-time treatments with the potential to transform the trajectory and management of disease for patients in need of new and better options. And we look forward to continued momentum in achieving the important milestones in the last quarter of this year and beyond. With that, thanks to everyone for your time today.

I’ll turn the call over for questions.

Operator?.

Thank you. [Operator Instructions] Our first question comes from the line of Gena Wang with Barclays. Your line is now open..

Hi, it’s Tony on for Gena. Quick questions on DMD.

For the age 1-year-old to 3-year-old cohort, are there any concerns there on durability given the patients are still young and may be growing additional muscle tissue? And then if you all do receive biomarker approval – accelerated approval, would multiple time points be needed for a biopsy versus just one-time point at 3 months? And then also for the data at year-end, how should we think about the magnitude of functional change?.

Hi, Tony, Steve here. Thanks for the questions. So I’ll start with your question about the 1 and 3-year-olds. Yes, it is a topic that comes up in the field of how young can you go in terms of the issue of replicating cells.

We’re actually quite excited about the opportunity here when we think of AAV8, our vector because we have a proxy for considering the potential dilution effect of dividing cells and durability because we know AAV8 for liver-directed hemophilia treatment, we actually have durability now out beyond 12 years for a lot of these kids where we see very sustained activity.

And of course, liver cells divide. So that gives us a lot of confidence here as well. And certainly, there’s a major unmet need here because there are no gene therapies currently available for this age group..

Hi, Tony, to your other question around biomarker, we don’t have any requests for additional biomarker data beyond what’s included in the protocol. So I wouldn’t expect anything additional to be requested there.

And I think to answer your question about magnitude of effect, certainly, there are benchmarks for what people consider magnitude effect – of effect to be adequate for consideration for approval, including the benchmarks we can pull from even Peter Marks’ assessment of ELEVIDYS.

And so I think that sets a good precedent for our data that will be coming shortly and how we’re thinking about the program.

And I think just to reiterate, we’re super excited by the biomarker data that we’ve got in terms of the levels of microdystrophin we’re seeing, especially in the 8 and older patient population that upfront looks considerably higher than other programs. So thanks for your question..

Got it. Thanks so much..

Thank you. Our next question comes from the line of Vikram Purohit with Morgan Stanley. You line is now open..

Hi, everyone. This is Gospel on for Vikram. We have one question on RGX-202. Could you recap for us your latest view on how best to gauge the functional data we are expecting later this month? Thank you..

Hi, Gospel, thanks for the question. We’re very excited to soon be able to present our functional data. This is something we’ve been looking forward to. I think we come with the benefit of a lot of precedent and a lot of learnings in the space where we get to look at the totality of the data.

So a lot of the usual suspects that you’ll be aware of, certainly the timed function tests such as 10-meter walk/run or time to stand, which are measures that we know are valid, clinically meaningful. We’ll also look at NSAA, which historically has been looked at. And we have the opportunity as well to look at caregiver-reported outcomes.

So it’s really a unique chance for us to look at a lot of different ways to see how these boys are doing to really assess clinical benefit..

And Gospel, I would also point to our ability to look at external controls as we think about individual patient data. We can mine pretty substantial databases to look at what the natural history is and expect to include that as part of our analysis. But thanks for the question..

Thank you very much..

Thank you. Our next question comes from the line of Mani Foroohar with Leerink Partners. Your line is now open..

Thanks for taking my question. I guess a little more detailed question.

So when you think about the data we’re going to see from this initial group of patients, is it reasonable to expect that their experience and follow-up and data will be rolled into a larger pool of data collectively for a pivotal data set? Or will a future pivotal data set include being patients recruited in the future, not including these first handful of patients? And I have a quick follow-up..

Thanks for the question, Mani. Yes, we certainly do expect to use data that was – is being accumulated in our Phase 1/2 study, particularly for patients that were dosed at dose level 2. I’d say most of the functional assessments that we’re doing for those patients will be the same as what we’re doing in pivotal.

And I think one area I would point out that we’re really excited about in terms of transitioning from Phase 1/2 to pivotal is that the process and product quality will be the same through Phase 1/2 development and pivotal development.

And so if you think back to the AdCom for Sarepta, they made a major process change in the middle of their pivotal program. And you could see comparisons of process A and process B. We won’t have any of that.

And I think that will work well in terms of including those patients in our safety database because the product profile is the same throughout the study. So we do intend to leverage them as part of that, and that will obviously help us with recruitment, and we will talk further very near term about the details of the pivotal study.

I’ll turn it over to Steve to comment as well..

Yes. I just wanted to elaborate on one aspect that further supports the ability to use the patients already dosed in Phase 1/2 is the primary endpoint for accelerated approval is microdystrophin.

So it makes perfect sense that the data that we have, particularly with dose level 2, that it’s quite natural that we’d be able to use that data in addition to the patients we enroll in the future in the pivotal..

That’s helpful. I’m going to hop over to ophthalmology for a follow-up if that’s okay. You guys have disclosed some detail, including a fairly chunky one-time sizable milestone for achievement of first patient dosed in a pivotal suprachoroidal delivery treatment of DR.

Can you walk us through on what time line we might see milestones following your End-of-Phase 2 meeting and how those would be recognized, i.e., how they would flow through the financial statements, when they show up on the balance sheet versus income statement, etcetera, just to clear that up for our own modeling?.

Sure, Mani. I’ll turn that question over to Mitch..

Yes. So for modeling purposes, the potential milestone payment could actually show up in the balance sheet. That’s where you can actually account for that. And for the P&L, this will be recognized as a one-time non-recurring for obvious reasons, one-time payment there. Hopefully, that helps from that standpoint, Mani..

So the recognition will be all – will all be recognized in the same quarter as received? Or is this something that will be recognized ratably over time?.

No, it’s going to be upon receivable..

Okay, thanks, guys..

Thank you. Our next question comes from the line of Annabel Samimy with Stifel. Your line is now open..

Hi, this is Jack on for Annabel. Thanks for taking our question. So for RGX-202, I believe you’ve mentioned previously that you might – you were considering imposing a minimum threshold of microdystrophin expression on your cells in the pivotal trial, even though that might not be something that the agency would necessarily require.

I think the number was something maybe like 10% expression for approval.

Is that something that you still feel confident in doing? And have you ever discussed that with the FDA?.

As Curran highlighted, we’re going to be coming out with details of our pivotal design in the future – in the very near future. What I can say now is that concept of a 10% threshold is something that in the field has roughly been considered something to think about as what would relate potentially to a clinically meaningful amount.

Fortunately, we’re seeing microdystrophin levels that are much higher than that level. So that really gives us a lot of flexibility when we think of designing a study and powering a study. So we look forward to giving more details on that in the coming weeks..

Got it. And then if I may just ask one more. One of the biggest pushbacks that we hear from investors is not necessarily around RGX-202 microdystrophin expression or safety, but rather just that we have a pretty small sample size to work with at the moment.

So how meaningful do you think the functional data, the upcoming functional data will be in kind of defining that profile given it’s only from a couple of patients? Or in other words, how well might it translate into a more general population?.

I think, Jack, that’s a good question. And we do have a relatively limited data set. But I think what we’re looking for primarily in this data set is conviction that a pivotal trial is highly likely to succeed and that we have a demonstration of efficacy.

And I think that I would sort of reiterate that the fact that we have a differentiated product, we’re almost threefold higher in microdystrophin levels than other programs for patients at a similar age.

All of those factors I think will come together even with limited functional data to, I think, especially in the patient community, bring a really strong interest in the program and allow us to enroll quickly.

And so we’re really excited about where we are, and I think we’re eagerly anticipating being able to share our results just in a few weeks around the functional data..

Great. Looking forward to it. Thanks, guys..

Thank you. Our next question comes from the line of Alec Stranahan of Bank of America. Your line is now open..

Hi, Matthew on for Alec. Thanks for taking our questions. Two quick ones from us.

For DMD, are you concerned at all about the durability of impact, especially going into younger patients? And are you at all thinking about redosing? And then for wet AMD, can you provide some color on how you think about the Eylea biosimilars from Amgen and potential market impact?.

I’ll let Steve take that..

Thanks for the question. So the durability aspect in the younger patients was something we touched on earlier in the call that we have evidence, particularly with our serotype that there is not a dilution of effect over time and that you have good durability even in organs where you have dividing cells.

So that’s one of the aspects that made us excited to go after this unmet need age group of 1 to 3. So – also excited that we announced today the dosing of the first patient in that cohort. Redosing, that’s something that the field, I think, is going to be evaluating over time.

Right now, our focus is on first time treatment with one-time gene therapy for the very large patient population that’s out there that isn’t going to be able to get treatment for some time even with available treatment options. We expect to have good durability, as I just mentioned.

But certainly, there’s the opportunity for us to explore ways that we could go after redosing.

Lastly, on wet AMD, so we’re very excited in our pivotal programs with subretinal in collaboration with AbbVie and also in collaboration with AbbVie, the suprachoroidal advancement where, as just discussed, we have diabetic retinopathy that we look forward to finishing our End-of-Phase 2 meeting and being able to advance into pivotal development there.

What was the other – if I could ask what was the other aspect about the wet AMD program?.

Yes. Just how you’re thinking about Eylea biosimilars from....

Yes. So the biosimilar aspect has been something that’s been around over time, and we’re starting to see more biosimilars come in. We’re actually seeing no impact of biosimilars on, for example, some of the branded longer durability products.

So if you think of incremental benefits in terms of durability of high-dose Eylea or faricimab, we’re not seeing those impacted, which really shows the value proposition that clinicians and patients are seeing.

And so we would expect no impact for an even bigger paradigm shift of a one-time treatment that would not only decrease injection burden, but potentially even prevent the need for injection..

Thank you. Our next question comes from the line of Luca Issi with RBC Capital Markets. Your line is now open..

Great. Thanks so much for taking my question and congrats on the progress. Maybe, Steve, bigger picture, what was your reaction to the Phase 3 data presented by Pfizer a few weeks back at World? It looks to me that they show pretty impressive evidence of expression there, but still, there was no functional benefit whatsoever there.

So is there a scenario where the FDA here changes the kind of regulatory standard going forward in light of that data and maybe decide to put a little more emphasis on function versus expression here? Again, any thoughts there, much appreciated. And then maybe, Mitch, I believe this is your first time that you’re joining the earnings call.

Can you just maybe talk about why you decided to join the team as you were doing diligence on REGENX, what do you find particularly attractive about it? Thanks so much..

Thanks, Luca. I’ll take the first part before we hand it over to Mitch. So the Pfizer results. So as you mentioned, there’s microdystrophin expression, but not a clear signal of efficacy from their trial.

As far as we’re concerned, this actually is exactly why we right from the beginning of our program focused on designing the best construct that we could. And part of what that means is reconstituting as closely as we can the native dystrophin molecule in terms of the key functional elements.

So that’s a key reason why we and our team took the time to develop a second-generation construct that, for example, includes the important C-terminal domain elements and some other improvements. So really, the overarching aspect is not all constructs are created equal.

So the farther you are away from a native dystrophin, the less confidence that you can have that you’re going to translate expression into clinical benefit.

And the FDA acknowledged that as well in the AdCom for ELEVIDYS, for example, where they raised the importance of C-terminal domain elements and the fact that those being absent in some constructs takes away the confidence in terms of the reasonably likely to predict bar.

So for those reasons, we think the differentiation that we have with our product and how close we are in terms of the key elements preserves our reasonably likely to predict benefit aspect for our program. And certainly, we’ve seen no change in our discussions with the FDA as recently as our End-of-Phase 2 meeting.

So we’re aligned on how to proceed with the pivotal program..

And Luca, this is Curran. I guess I would add one thing to Steve’s comment that – I mean, if you look at the accelerated approval for ELEVIDYS, they utilized this functional data in that assessment. So it won’t surprise us at all that FDA would want to see maybe not as a primary endpoint, but supportive data on the functional side.

So we’re well prepared to address those questions at the time of filing for accelerated approval, and we’re planning for that eventuality. And obviously, I think for – we see good uptake now in the market.

I think in general, what we are looking for is that with functional data being demonstrated that a lot of patients are going to be interested in our program and certainly around the differentiation aspect given the levels of microdystrophin we are showing. I will turn it over to Mitch..

Yes. Thanks Luca, for the question as well, too. And I must say, I have been here for almost two months. And one of the major reasons why I joined is really the scientific excellence at the company. And during my brief time here, that has translated to be very much true.

And I think the other aspect is over the next, let’s call it, 18 months to 24 months, there are potentially several BLAs that could happen at our company. And entering this commercial phase is actually very exciting to say the least. And these aren’t just simple BLAs. These are great opportunities to deliver great medicines to patients.

So, these are potential best-in-class, if not even blockbuster opportunities for this company. So, with that, I would say the value proposition is too great to pass and hence, is why I am here, and I am surrounded by great teammates here, which could actually deliver and execute towards these pivotal moments at the company..

Got it. Thanks so much guys..

Thank you. Our next question comes from the line of Paul Choi of Goldman Sachs. Your line is now open..

Hi. Thanks. Good afternoon and thank you for taking our questions. I want to switch gears maybe to RGX-121. And I want to see what your latest thoughts are on a potential AdCom for – following the filing.

And then secondly, what are the latest, I guess a bit of feedback you are hearing relative to the Denali asset and maybe just how doctors and the physician community are thinking about potentially sequencing these drugs? Thank you very much..

Thanks Paul. Thanks for joining the call. I think on the first question, we are preparing as if there will be an AdCom. That’s something that normally you are not notified by FDA until the filing is accepted and they map out their plan for review.

But on our end, we are certainly planning that an AdCom could be required, but we have no information to say that it’s required at this point. I think to your second question, I think there is a huge difference between our approach and Denali’s.

I think our approach is extremely inviting for patients, meaning a one-time gene therapy that doesn’t require a patient to go in for a weekly IV would be incredibly valuable, and that’s how we are thinking about the program.

In addition, the data that we released early in the year that showed that the majority of patients that were on enzyme replacement therapy before they went on to study haven’t had to go back on to it. So, there is more benefit if you think of it that way than even the initial product profile that we had developed.

So, we feel like we are in a really strong position with the MPS community as we get closer and closer to a potential commercial approval and feel like we will be able to position our product as a first choice for patients based on the data that we have in hand..

Great. Thank you..

Thank you. Our next question comes from the line of Brian Skorney of Baird. Your line is now open..

Hi guys. Thanks for taking our questions. This is Charlie on for Brian. So, yes, I just wanted to revisit the youngest cohort of DMD patients.

Just knowing that in general, they are not diagnosed until they are about 4-years-old to 5-years-old, are you having any issues identifying these patients relative to the older cohorts? And do you think there are any efforts there you could make for the potential future market in terms of moving that average age of diagnosis up? Thanks..

Thanks. I will turn that over to Steve..

Thanks Charlie, for the questions. So, I think one aspect is although that’s traditionally been the time point of diagnosis, we are seeing newborn screening pick up. And I think we are going to progressively, over the next few years, see more and more states take on newborn screening. So, that’s going to move things earlier.

We announced today that we actually dosed our first patient in that age group. So, that gives you early anecdotal, albeit sense that these patients are there. And we feel confident we are going to be able to find these patients with the investigators that we have.

And we think once these patients are found and the families consider the options, just like in the other age groups, the opportunity to consider a second-generation potential best-in-class product that has the differentiating aspects that we have been describing is going to be really a compelling opportunity for a lot of these families.

And certainly, that’s one of the reasons we want to get functional data out there as well. Not only does it inform us and the community, but it actually plays an important part in the considerations of the actual families when they are seeing our investigators..

Great. Thank you so much..

Thank you. Our next question comes from the line of Daniil Gataulin with Chardan. Your line is now open..

Hey. Thank you for taking the question and congrats on the progress. I have a couple of questions. One on 202 program, I saw in your press release that you got an approval or authorization to start clinical trial in Canada, which you plan on doing in the first half.

Can you share some of the details of that trial and whether the data from that trial will be part of the pivotal data package? And then a question on RGX-314, given recent data from the bilateral study, what are your plans for the fellow eye study for suprachoroidal program, both for – both for Wet AMD MDR? Thank you..

Thanks Daniil. So, we are excited that we have expanded for inclusion with Canada in the program. So, we are going to be able to open up multiple sites there.

And we will give more details when we give the overall details on the design, but we had no issues getting approval in Canada, which I think supports the quality that we see with our product and the overall design of our plan and consistency with feedback that we have heard from the FDA.

So, similar to what we discussed before, any of the data that we see in the program from whatever region is going to be relevant both for the pivotal endpoint for accelerated approval, microdystrophin, but also the functional data that Curran mentioned would also be looked at, but not really be the primary focus for the initial approval.

314, the bilateral study, we started with the subretinal program as far as evaluating bilateral treatment since we had a lot more exposures, a lot more data. So, it made sense to have the first step be looking at bilateral dosing with that route of administration.

Since, we are advancing rapidly along with AbbVie, the DR into pivotal, it’s a great question you are raising that we will want to also evaluate bilateral treatment with suprachoroidal. So, we will be planning that. We haven’t announced any specific details yet, but certainly, it makes sense that that’s what we would want to do.

We are excited at that opportunity because we have seen excellent safety and certainly not the type of immune response that’s been seen with, for example, intravitreal or non-localized delivery of gene therapy, where if you have significant inflammation in a first eye, the immune response seen there, if there is any spillover to the systemic circulation, then you would wonder, will that affect the safety and efficacy in the fellow eye.

So, that’s why we are excited that subretinal with the compartmentalized delivery, we didn’t expect to see any issues in fellow eye and we haven’t.

And suprachoroidal also because it’s a compartmentalized delivery where we are not seeing significant immune-mediated responses in the first eye, that also gives us confidence that we will be able to dose in the fellow eye..

Thank you. Our next question comes from the line of Yi Chen with H.C. Wainwright & Company. Your line is now open..

Hi. Thank you for taking my question. With respect to the pivotal program in diabetic retinopathy, can you comment on the – whether you plan to enroll a lot of patients without symptoms? And if so, what would you measure as the primary efficacy endpoint? Thank you..

Sorry, it was a little bit difficult to hear you.

Could – was this referring to the RGX-202 pivotal plan?.

No, for 314 for the diabetic retinopathy pivotal program, do you expect to enroll a lot of patients without symptoms? And if so, what would you measure as the primary efficacy endpoint?.

Okay. So, I think this – correct me if I am wrong, but this would relate to the diabetic retinopathy indication in our pivotal program. It’s an excellent point in that. In diabetic retinopathy, these patients are often asymptomatic until they develop the blinding complications like diabetic macular edema and proliferative diabetic retinopathy.

But yet they are at significant risk of developing these conditions. So, what’s needed is a treatment that could prevent patients from ever developing these blinding complications. And the existing therapies, repeated injections are just not sustainable because patients are asymptomatic.

So, clinicians and patients are choosing to not be treated because the treatment burden is just too much. So, the whole reason or one of the significant reasons we and AbbVie see this as such a major opportunity is it’s a one-time in-office treatment.

So, that really does allow this to be a compelling case for the clinician and their patients that one-time in-office treatment can help prevent them from developing the symptoms and the need for repeated treatment. So, yes, we would include asymptomatic patients.

We would then monitor for actual measures of whether their severity of their diabetic retinopathy is getting worse. And also, we can look at those hard outcome measures of vision-threatening complications, where we saw already in our Phase 2 study close to a 90% reduction in vision-threatening complications of DME and PDR.

So, that’s what has us and the community so excited about being able to move forward with the end of Phase 2 meeting and then into pivotal development next year..

Thank you..

Thank you. I would now like to turn the call back over to Curran Simpson, President and CEO, for closing remarks..

Okay. I would like to thank everybody for joining us for the call. We have a lot of really important and exciting milestones to report through the rest of the year and really excited to reach out to you as each of those are realized, and have a great evening. Look forward to following-up with several of you. Thank you..

This concludes today’s conference call. Thank you for your participation. You may now disconnect..