Welcome everyone to the Q2 2024 REGENXBIO's Earnings Conference Call. All lines have been placed on mute to prevent background noise. After the speakers' remarks, there will be a question-and-answer session. [Operator Instructions] 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 second quarter ended June 30th, 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 31st, 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, August 1st, 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 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 Curran Simpson, President and CEO of REGENXBIO.

Thank you, Patrick. Good afternoon everyone and thank you for joining us. I'm pleased to be leading today's call. My first one is REGENXBIO's Chief Executive Officer. Today, we'll be sharing a number of exciting positive updates and discuss the momentum happening across our pipeline of differentiated AAV therapeutics. I'll begin with a recap of our business highlights as well as an update of our corporate goals and key milestones that we have achieved. Dr. Steve Pakola, our Chief Medical Officer, will provide an update on our clinical programs; and then Vit Vasista, our Chief Financial Officer, will provide an overview of financial results for the second quarter ended June 30th, 2024. At the end of the call, we'll open up the line for questions. It's been a productive first half of the year for REGENXBIO as we make significant progress advancing each of our programs toward pivotal stage clinical trials and future commercialization. Our priority programs are RGX-202 for the treatment of Duchenne; AbbVie RGX-314 program for the treatment of wet AMD and diabetic retinopathy or DR, being developed in collaboration with AbbVie; and RGX-121 for the treatment of MPS II or Hunter syndrome. Our lead programs, specifically 202 and 314 represent large commercial opportunities where our product candidates are differentiated from current standard-of-care, can be expedited via accelerated approval due to significant unmet need and support meaningful value generation soon and for the long-term. Let me begin with RGX-202 which represents the next generation of microdystrophin gene therapies and is poised to potentially be the second AAV-based product to reach the market. There are a number of exciting developments for RGX-202. Steve will share more details about the positive data reported today, demonstrating consistent, robust microdystrophin expression across treated patients reflecting a broad range of ages, but I…

Thank you, Curran. I'll start with RGX-202, a potential one-time gene therapy for the treatment of Duchenne. Today, we reported new microdystrophin expression data from the two new patients, aged 5.8 and 8.5 years, who received RGX-202 at dose level 2, the dose we are advancing to pivotal phase. Microdystrophin expression was measured to be 77.2% and 46.5%, respectively, compared to control at three months. As of July 8, 2024, RGX-202 continues to be well tolerated with no serious adverse events. In all patients who reach three-month trial assessments indicate meaningful increases in expression of RGX-202 microdystrophin, and reduction from baseline in serum creatinine kinase levels, supporting evidence of clinical improvement. We are very excited as today's data adds to the totality of evidence, demonstrating consistent high microdystrophin expression across all treated patients. In addition, early evidence of strength in motor function improvement were observed via trial clinic assessment and home videos shared by caregivers. On the continued strength of our data, in June, we announced the expansion of the AFFINITY DUCHENNE trial to include a new cohort of patients aged one to three years. This is a cohort of boys where there remains no approved gene therapy products and a cohort that represents a significant portion of the untreatable prevalent population of Duchenne boys. As we ultimately seek a broad label for RGX-202, we will continue to produce data where limited or no data exists to further establish a differentiated product profile that can enhance RGX-202 commercial potential. Moving to 314, which is being developed in collaboration with AbbVie to treat wet AMD, DR, and DME via subretinal and suprachoroidal route of administration. I'll start with 314 for DR, being evaluated in the Phase 2 altitude trial using in-office suprachoroidal delivery. As Curran mentioned, with our partner, AbbVie, we…

Thank you, Steve. REGENXBIO ended the quarter on June 30th, 2020 with cash, cash equivalents, and marketable securities of $327 million compared to $314 million as of December 31st, 2023. The increase was primarily attributable to $131 million in net proceeds received from an upsized public offering of common stock and prefunded wanted completed in March 2024, partially offset by cash used to fund operating activities in the first half of 2024. R&D expenses were $49 million for the second quarter of 2024 compared to $60 million for the second quarter of 2023. The decrease was largely driven by reduced manufacturing and clinical supply costs for AbbVie RGX-314 and RGX-202 and personnel-related costs as a result of reduced headcount. The decrease was partially offset by increases in clinical trial expenses for AbbVie RGX-314 and RGX-202. REGENXBIO expects its balance in cash, cash equivalents, and marketable securities of $327 million as of June 30th, 2024 to fund its operations into 2026. This cash rollway guidance is based on the company's current operational plans and excludes the impact of any payments that may be received from AbbVie upon the achievement of development or commercial milestones under AbbVie RGX-314 collaboration, including a potential $200 million milestone for achievement of the first patient dose in the pivotal trial for suprachoroidal delivery for treatment of DR. Additionally, our runway guidance excludes the potential monetization of our priority review voucher that may be received for RGX-121. With that, I will turn the call back to Curran to provide his first set of final thoughts.

Thanks Vit. Today was another exciting day for our 202 program with additional positive data and as we look ahead to the rest of the year, we are encouraged by our discussions with the FDA and are finalizing pivotal plans that will enable us to utilize the accelerated approval pathway to rapidly advance 202 as a potential best-in-class treatment for Duchenne. Additionally, we are pleased to be accelerating the end-of-Phase 2 meeting for DR in partnership with AbbVie to enable a pivotal start next year. As we close today and reflect on the first half of the year, I'll emphasize that our plans are on track, and we continue to expand value as we make excellent progress in advancing therapies that address significant unmet needs. Thanks, everyone, for your time today. I'll turn the call over for questions. Operator?

Thank you. We will now begin the question-and-answer session. [Operator Instructions] Your first question comes from the line of Gena Wang of Barclays. Please go ahead.

Thank you. Congrats on the new data regarding the 202 in DMD. So I have two questions, one is a 202. I know you will meet with the FDA, finalized the pivotal study. But do you have a goal of the protein level you wanted to achieve? And do you expect FDA will set some threshold in order for accelerated approval? And another question is regarding the 314, suprachoroidal indication in DR and wet AMD, what's the reason for dose level 4? And will you also inculcation with existing neutralizing antibody?

Thank you for the question, Gena. In terms of -- can I clarify the first question, a goal for--

Protein level.

Microdystrophin level. We've proposed a threshold with FDA, and that's one of the things that we'll be waiting for the minutes [ph] and sort of final agreement in addition to the back and forth that will occur with the pivotal plan that will be submitted. We feel that just in general, thinking about the field and what we've been able to glean from our investigators that a level above 10% is likely to result in functional benefit. I think that will be a discussion that we have going forward. But that's -- if you think about our data, to-date, every patient that we've published data on is above that threshold. I'll field the second question to Steve, if that's okay?

Hi Gene, thanks for the questions. So, 314 and going to dose level 4 in our Phase 2 studies, why do that? We've certainly met our target product profile in diabetic retinopathy. And that's why we're so excited with the advancement towards pivotal that Curran and I have summarized. We've also seen, as I have highlighted, excellent safety. So, I think the key consideration is we're going higher in part because we can. We really have the flexibility given the excellent safety that we believe is due to the compartmentalized route into the suprachoroidal space as opposed to less compartmentalized spaces like the intravitreal space and particularly with our product, RGX-314. So, in collaboration with AbbVie, we're doing this. And I think it also fits just general basic drug development, where if you have good safety to really fully characterize a product, it makes sense to continue looking at higher doses, if you can.

Thank you.

Your next question comes from the line of Vikram Purohit of Morgan Stanley. Please go ahead.

Great. Thanks for taking our questions. We had two, first, on 202. Could you just speak a bit more about the functional assessment data we're going to be getting later this year? What your guidance is to best interpret that to get a sense of differentiation, real-world differentiation and how that data set might play into discussions with regulators on next steps? And then secondly, on 314, for suprachoroidal and wet AMD. Could you talk a bit about how you see that program moving towards a pivotal program? And how that pivotal program potentially for 314 and wet AMD could overlap with efforts with the subretinal approach? Thanks.

Okay. I can take the first question or Steve, do you want to start with the second one or?

Could you -- I missed the second one. Could you repeat the second one?

Sure. Yes. It was about 314 suprachoroidal and wet AMD. Just wondering what the path is to a pivotal program there? And how you see a potentially pivotal effort 314 and wet AMD overlapping with your efforts with the subretinal program you currently have underway?

Sure. So, with all the experience we have with wet AMD, we have a pretty good sense of assessing both safety and efficacy, both from our subretinal experience and also the prior cohorts we've done with suprachoroidal. So, I think it's the usual endpoints that we think of. We get to take advantage of the totality of evidence on top of, of course, having good safety. So biomarkers like retinal thickness, where we get a very good objective measure, BCBA, and of course, a reduction in treatment burden. So, we'll really look at all of those to see what type of response we get at six months and longer and really compare that to what's been seen, for example, even in our subretinal program, where we want to see good durability and really maintain anatomic control as measured by retinal thickness and BCVA control, while dramatically reducing injection burden. And we've often talked about at least 50% of patients not needing any injections and over 50% reduction in injection burden.

And this is Curran. To the first question, in terms of functional data in the fall, just to baseline, we measure microdystrophin at a three-month time point. And then on the functional assays, we measure generally every three months, a month, a number of functional assessments that you've seen historically with other programs. And in the fall, I would expect to see a significant amount of functional data out to 12 months for the dose level 1 patients. And for some of the early dose level 2 patients, you'll see six and probably nine-month data for them, things like time to rise and SAA as an example. We haven't finalized exactly what data will come out because it's still emerging, but that's the plan for the fall.

Vikram, you also had the question of how do we see this in the context of our ongoing pivotal subretinal program for wet AMD when thinking about suprachoroidal. I think it's fair to say that both we and AbbVie really see opportunities in both, and that's why we both are together advancing further evaluation of SCS at DL4 for this while we continue with the pivotal program with subretinal. Certainly, the opportunity that we see with subretinal given the gold standard in safety and efficacy that we've shown an excellent durability has us very excited about that. There's, of course, the opportunity to expand the optionality by having an in-office procedure. And we look forward to gathering more data in the additional cohort to keep evaluating that option.

That’s helpful. Thank you.

Your next question comes from the line of Paul Choi of Goldman Sachs. Please go ahead.

Hi, good afternoon and thanks for taking our questions. My first is, I was wondering if you can maybe just elaborate on interest levels in the patient community and clinical community for 202, a potential pivotal trial later this year or early next year in the wake of the recent elevates label expansion and approval there? And then my second question on 314 is with regard to dose cohort 4 here. I know you specified that there would be prophylactic steroid use here, but could you maybe comment on a view whether there would be potentially reduced need for rescue VEGF use, a competitor recently provided some updated data for their program. And then I think this came as a bit of a surprise. So, just any thoughts there as to whether dose cohort 4 could potentially either increase the injection-free frequency or reduce the rescue usage as you prosecute that cohort? Thank you.

I can take the first one, and then I'll have Steve address the second question. I think on patient recruitment 202, we've been able to check in with sites and investigators at meetings like PPMD, and we've seen nothing but really strong interest in the program. Many of these centers have up to 100 patients. And just having discussions with the investigators around are people still interested in our study, given that there's a product on the market. The resounding answer is yes. There are many patients that are looking at our program and seeing the differentiation that it offers, seeing the safety that's been demonstrated to-date. And I would say that there's strong interest. And therefore, on our end, strong confidence in our ability to recruit the study. So, early days, I feel very confident in our ability to recruit the pivotal program. And I'll turn it over to Steve to address the 314 question.

Sure. So, regarding DL4 assessment in these indications, we certainly think there's the opportunity that we could decrease rescue use further than what we've seen while maintaining visual acuity benefit instability and also anatomic control. As I mentioned to one of the earlier questions, we have the flexibility to do that. You referred to some other data that's come out earlier this year. And I think one always has to look at that issue of can you go up higher on dose and if there's either a concern about additional safety issues, including immune response and inflammation. And also, if you start to run into the issue of how long a duration of prophylactic steroids can really be tolerated. So, that's why we're very excited about our safety profile where we don't need extended prophylactic steroids. So, I think the totality of that does give us the chance to go up higher and see if we can reduce injection burden further.

And just one follow-on, Paul, to the question on recruitment. I mean one of the purposes of the data release we did today was really to show people the differentiated level of microdystrophin in some of the older patients that have been treated. So, that's just another piece of information that a patient can use when they're deciding what therapy to have their child treated with. So, that was one of the purposes of that release is to help people understand our product a bit more.

Great. Thanks for taking our questions.

Your next question comes from the line of Alec Stranahan from Bank of America. Please go ahead.

This is Mary [Indiscernible] on for Alec today. Thanks for taking our questions. Just one on DMD. Given questions around safety for other in field, what kind of safety database do you expect you'll be required to collect for approval in terms of size and duration of follow-up? Thank you.

Yes, that's, I think, something that we're still working on and probably will tie out completely in the pivotal plan that will submit to FDA. So, we're really not able to comment in terms of various specifics there. I think in general, our proposal on sample size is in the 30 to 40 patient region, but that's really a discussion that's ongoing with FDA. But I think the reasons that we feel that's a valid number is, number one, we have a commercial-ready process that we won't make changes to during the -- in terms of product profile during the pivotal studies and so that should reduce the sample size. And second, the initial safety record that we've already demonstrated in the trial to date should be a positive in terms of how FDA might view the program and how they assess what the sample size should be. So, we feel like we're in a good position there. And I think that gives us a good feeling that the recruitment will be accelerated into next year.

Understood. Thank you.

Your next question comes from the line of Annabel Samimy of Stifel. Please go ahead.

Hi, thanks for taking my question. We also have two. First, on DMD. Just bringing back the question of functional data and what you might be looking for, given the broad age group that you're looking at and maybe the different levels of ambulation, are you giving any consideration to stratifying those patients based on age group and measuring them on different metrics depending on their age and then matching against the natural history for that specific age group. So, how much granularity might we see already and maybe what are you possibly baking into Phase 3? And then on 314, I guess I'm trying to understand how you're thinking about this dose level 4 in light of other competitors in the space. Do you feel that the benchmark for you is your subretinal? Is it the benchmark for you, other competitors in the space? And given, I guess, maybe a little bit of a race in the gene therapy space, is there less urgency to be the first one out there or the one to get it right because the population is large and maybe they're a little bit less desperate than, say, in the genetic rare disease area, are people looking at this competitive landscape the wrong way? So, a little broader question. Thanks.

I can start with 202. And I think we think about functional data in sort of two dimensions. As it relates to accelerated approval, our primary driver will be measuring microdystrophin at three months as our primary endpoint. But along with that, of course, we're measuring functional data along the way. And initially, what I would expect in the fall is likely a reference of functional data to baseline levels for the specific patient. Now, if we think about a confirmatory study, you're absolutely correct that studying natural history and matching patients either by age or by disease progression, would be part of that strategy that we're having discussions on. So, it's actually -- I would expect to see both sort of views as it relates to functional data. I'll turn it over to Steve for the 314 question.

Thanks Annabel. So, as far as benchmarking, as I mentioned, we got a lot of experience, many of us from prior programs as well, but certainly in-house with our subretinal program. Really, the target is pretty similar in terms of what you have to show when we think of suprachoroidal, perhaps slightly a little broader, given the nonsurgical in-office opportunity of suprachoroidal. I think an important context when thinking of different programs is really assessing how much durability has really been shown. So, really being able to look out to six months and beyond relative to when the last loading dose may have been given, for example, in indications like wet AMD. And I think with certain agents that require repeat injection, even though they have greater durability, there's the reality that at some point, you're going to need the reinjection. And if you're looking at a time point, that's too early to see that are you going to start seeing the need for rescue creep up. And that's why we're excited about a gene therapy approach where you have stable, consistent anti-VEGF activity that can allow for really the ultimate goal of having in a sizable proportion of patients not needing any injections. So, we feel good about this approach, and we know how to look at the safety and efficacy to really know when we're in a position to move forward.

Thank you.

Your next question comes from the line of Mani Foroohar of Leerink Partners. Please go ahead.

Hi, good afternoon. This is C.J. Yeh on for Mani. Thanks for taking our question. Could you please comment on your strategy in DMD. Are you targeting younger patients than structs current label since you've announced you've expanded age range to one to three, while youngest age is four? Thanks.

This is Curran. I think it's safe to say we want to build an adequate safety database at a minimum for the patients in ages one to three, but we'll be enrolling across a wide variety of ages in the studies.

And we had made the decision to expand and look at this broad age range, including one to three before any [Indiscernible] label expansion. So, we've seen this opportunity. And now with the results safety that we've seen in the microdystrophin expression we've seen across a wide age range on the upper end. It's a great opportunity to look at one to three-year old.

Perfect. Thanks for commentary.

The question comes from the line of Eliana Merle of UBS. Please go ahead.

Hi, this is Eric [Indiscernible] calling in for Eliana. Thanks so much for question. My first one is 202. Do you have any in-house data on patients already dosed with 202 beyond the three months to help us better understand ability and what the effects might be over time? And what do you expect to see over time? Do you expect label to be stable for three months or more? Or do they deepen over time? And I have a follow-up.

I'm sorry, are you referring to microdystrophin levels beyond three months or other functional data, for example?

Microdystrophin?

Okay. No, we're taking a biopsy prior to treatment and then at three months. We don't have biopsies beyond that time point per -- basically per direction with FDA. However, we'll obviously be measuring durability in terms of functional outcomes in the out periods. Yes, we don't have data beyond three months. But I think our preclinical data would suggest really excellent durability. And the construct that includes the C terminus has a longer half-life than microdystrophin that's devoid of that. So, I would expect both higher levels of microdystrophin and perhaps sustained levels relative to what you've seen in other literature.

Got it. And just one quick follow-up. Is there anything that you've been able to identify in terms of patient characteristics that's correlated so far with a higher microdystrophin expression or higher functional assessment?

So, the usual caveat that there aren't enough patients that really have confidence in terms of predictors. I'd say the biggest learning so far is actually that age is not predicting a lower microdystrophin as you go up on age, which has been a concern that the community has had, whether that might be the case in some data from other programs suggest that that may be an issue, but we've not seen that at all. So, I think the striking thing from our data is even in eight and older, we're seeing very robust microdystrophin levels. Beyond that, we're seeing microdystrophin levels across the patients. So no clear differentiator or predictor in this sample to-date.

Got it. Thank you.

Your next question comes from the line of Luca Issi of RBC. Please go ahead.

Great. Thanks so much for taking my question and congrats on the progress. Maybe, Curran, can you just expand a bit more on your recent end-of-Phase 2 meeting with the FDA? I appreciate it, you're still waiting for the minutes, but can you confirm that your read is that you can get accelerated approval and expression across all patients with DMD and not only patients that are excluded from the Sarepta label today, either because of age or existing immunity. I think it's an important distinctive -- so any color, much appreciated. And then maybe still in DMD, how you're thinking about a confirmatory trial? Will we still use North Star as the primary endpoint? Or do you think there are other endpoints that can be more sensitive here? Any color, much appreciate it. Thanks so much.

I can work a bit in reverse. We'll use North Star, but we're obviously measuring a number of additional functional indicators. -- that you've seen, as I mentioned earlier, time to rise and some of the timed walks that are associated. So, I would characterize it as we're measuring everything because there are -- it's still a field where I think the functional assays are evolving and each product is different. And I think we want to be able to capture as much functional data as we can across as many indices as we can. Related to accelerated approval, our strategy is to approach this for a broad approval, not a narrow approval for only patients that are ineligible for current therapy. And the basis for that is simply the differentiation of the product. That's, I think, one of the basic tenets of the accelerated approval is unmet need. And we feel we have a really strong evolving case that addresses unmet need, and our ambition will be to obtain as broad a label as possible.

Got it. Thanks so much.

Your next question comes from the line of Brian Skorney of Baird. Please go ahead.

Hey thanks for taking the question. On the Phase 3 plans for diabetic retinopathy, just trying to engage sort of your level of confidence in AbbVie's level of confidence in the first half initiation next year. What are sort of the primary questions that the company is we to get answered by the FDA or the FDA hopes do you think the FDA will need to answer so at the end-of-Phase 2 meeting to sort of ensure that this Phase 3 gets kicked off? And maybe just some color on the DME cohort. And is the consideration -- is there a consideration to pursue these more progressed patients? Or is the thought you're really just to supplement with some data in patients who have progressed on to DME?

I'll give a brief comment and then turn it over to Steve. I certainly think we and AbbVie have a really high level of confidence in DR progressing into pivotal next year. And I think that's shown in the acceleration of the end-of-Phase 2 meeting into this year. We're eager to get this study up and going. And I think I'll let Steve comment on the details of the pivotal approach, but we feel like there's a very standard approach to developing in diabetic retinopathy established endpoints and precedent. But I'll let Steve comment on the details of what we're thinking and how that study should go.

Yes. Fortunately, as Curran mentioned, there's a road map for diabetic retinopathy that's been laid by repeat injection anti-VEGF that has really allowed us to know what do you expect from a negative control arm if you're not receiving an active agent. And that, of course, really helps us to power studies in combination with the actual proof-of-concept data that we have. We also know a lot about the endpoints that are accepted. So, we feel very confident that this has really derisked quite a lot from a regulatory standpoint. So, it's really assessing some things around the edges and some definitions and the like, frankly, when it comes to the pivotal design. So, I think that's one of the aspects that given the positive results that we've seen why we have been able to accelerate and bring this end-of-Phase 2 meeting into Q4 instead of Q1 next year. And then your--

I was just going to ask about the DME cohort?

Yes. So, we are looking at center involved DME. Of course, that's the traditional indication. So, we don't see a need to go outside the box in terms of the type of patient population that we'd be looking at so that we can really have the context of what others have looked at and what others have seen. So, yes, it's just a great opportunity. We do know diseases like DME or the complication of DME and wet AMD that there's a little higher VEGF drive than exists with, say, non-proliferative diabetic retinopathy without DME. So, we think we're right around the dose response range where this is going to be very interesting to look at DL4 in this patient population.

Great. Thank you.

Your next question comes from the line of Daniil Gataulin of Chardan Capital Markets. Please go ahead.

Hey guys. Thank you for taking the question and congrats on your role. I have a quick question on wet AMD program, this retina delivery. When do you anticipate sharing data from the Fellow Eye study. And as a follow-up to that, how it translates to suprachoroidal injections given those are more likely interact with the immune system? What is your long-term strategy for treating Fellow Eye using suprachoroidal to a degree [ph]? Thank you.

I'll turn that one to Steve.

Hi Daniil. So, as far as when we would have Fellow Eye results, we have the update today that we completed enrollment of the Fellow Eye study. So, if you add on up to six months or so from that would give you kind of a rough range of when we traditionally have been comfortable releasing data in this type of indication to really show a stable effect at least. We were excited to have this study not just from a regulatory standpoint to have that label expansion to allow bilateral disease. But as you referred, the immune response, whether you would have a greater immune response that could affect safety and/or efficacy when you dose the second eye. Subretinal, I think, is the most straightforward to feel confident that you won't have an issue dosing the fellow because of the immune privileged status of the subretinal space. Suprachoroidal we've seen much less inflammation and no safety issues in terms of inflammation compared to, say, intravitreal administration. So, that gives us confidence that suprachoroidal would have that opportunity as well. So, we decided to take it one step at a time, first look at subretinal Fellow Eye, but over time, certainly, it would make sense to assess Fellow Eye with suprachoroidal as well.

Got it. Thank you very much for taking the question.

Ladies and gentlemen, there are no questions. That concludes today's call. Thank you all for joining. You may now disconnect.