Earnings call transcript: Regenxbio Q2 2025 misses forecasts, stock dips

Regenxbio Inc. (RGNX) reported its second-quarter 2025 earnings, missing analyst expectations with an earnings per share (EPS) of -$1.38 compared to the forecasted -$0.94. The revenue also fell short, coming in at $21.36 million against the projected $38.7 million. Following the announcement, the company’s stock dropped 4.51% in pre-market trading, reflecting investor disappointment over the earnings miss and revenue shortfall. According to InvestingPro analysis, RGNX is currently undervalued, with a "FAIR" overall financial health score of 2.38 out of 5.

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Key Takeaways

• Regenxbio’s Q2 2025 EPS and revenue both fell short of expectations.
• The company’s cash position improved significantly due to strategic deals.
• Stock price declined by 4.51% in pre-market trading following the earnings release.
• Ongoing trials for gene therapy products show promise for future growth.
• Revenue and EPS guidance for the coming quarters reveal mixed expectations.

Company Performance

Regenxbio’s performance in Q2 2025 was marked by a significant shortfall in both earnings and revenue compared to analyst forecasts. Despite this, the company has made strategic advancements in its gene therapy pipeline, which could drive future growth. The industry continues to see strong interest in gene therapies, with Regenxbio positioning itself as a leader in this space through innovative approaches and strong partnerships.

Financial Highlights

• Revenue: $21.36 million, missing forecasts by 44.81%
• Earnings per share: -$1.38, missing forecasts by 46.81%
• Cash, cash equivalents, and marketable securities: $364 million as of June 30, 2025

Earnings vs. Forecast

Regenxbio’s actual EPS of -$1.38 was significantly below the forecasted -$0.94, resulting in a 46.81% negative surprise. Revenue also missed expectations by a wide margin, coming in at $21.36 million compared to the anticipated $38.7 million. This marks a notable deviation from the company’s historical performance, where it has often met or exceeded analyst expectations.

Market Reaction

Following the earnings announcement, Regenxbio’s stock fell 4.51% in pre-market trading, settling at $8. This decline reflects investor concerns over the company’s ability to meet financial targets. The stock’s movement is notable given its 52-week range, which has seen a high of $13.48 and a low of $5.04. The broader market has shown resilience, indicating that the decline is specific to Regenxbio’s performance.

Outlook & Guidance

Looking ahead, Regenxbio has provided mixed guidance for future quarters. The company expects to complete enrollment in its pivotal study for RGX-202 by October 2025, with potential market entry in 2027. Revenue forecasts for future quarters show a varied outlook, with expectations of $45.84 million in Q3 2025 and a decline in subsequent quarters.

Executive Commentary

Curran Simpson, CEO of Regenxbio, stated, "We now expect to complete enrollment in the ongoing pivotal study this October," highlighting the company’s progress in its RGX-202 program. Steve Picola, CMO, remarked on the efficacy of their treatment for diabetic retinopathy, saying, "A single in-office injection of Cirovec was well tolerated and demonstrated durable long-term efficacy." CFO Mitch Chan emphasized the company’s strong cash position, noting, "We expect the June 30 cash balance reported today to fund our operation into early twenty twenty seven."

Risks and Challenges

• Continued revenue shortfalls could impact investor confidence and stock performance.
• Regulatory hurdles remain a potential risk for the approval of new therapies.
• Competitive pressures in the gene therapy market could affect market share.
• Macroeconomic factors, such as inflation and interest rates, could influence operational costs.
• Execution risks in ongoing and upcoming clinical trials may delay product launches.

Q&A

During the earnings call, analysts inquired about the differentiation of Regenxbio’s gene therapies from competitors, with management highlighting their unique manufacturing and immune suppression strategies. Questions also focused on the company’s flexibility in clinical trial designs and potential interactions with the FDA, reflecting investor interest in the regulatory pathway and market dynamics.

Full transcript - Regenxbio Inc (RGNX) Q2 2025:

Conference Operator: Welcome everyone to the Second Quarter twenty twenty five BGENXBIO Earnings Conference Call. Please note, slide referenced during this call are available in the webcast and at the events page of Regenexx Bio’s website. At this time, I’d like to turn the conference over to Patrick Christmas, Chief Legal Officer of Regenexx Bio. Please go ahead.

Patrick Christmas, Chief Legal Officer, REGENXBIO: Good morning and thank you for joining us today. Earlier this morning, REGENXBIO released financial and operating results for the second quarter ended 06/30/2025. 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 in the Management’s Discussion and Analysis section of REGENXBIO’s Annual Report on Form 10 ks for the full year ended 12/31/2024, 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, 08/07/2025, 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 form a 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’ll now turn the call to Curran Simpson, President and CEO of REGENXBIO. Curran?

Curran Simpson, President and CEO, REGENXBIO: Thank you, Patrick, and thank you everyone for joining us. I hope that you’re having a great summer. Today, I’m pleased to be joined by Doctor. Steve Picola, our Chief Medical Officer and Mitch Chan, our Chief Financial Officer, to review the exceptional progress being made by the REGENXBIO team as we prepare for our first commercial approval this year and multiple potential near term product launches. Before we begin, I’d like to acknowledge the Duchenne community and the recent events they have faced.

We understand these have been incredibly challenging and uncertain times and express our deepest sympathies to the families experiencing loss. These recent events have only reinforced our strong commitment to deliver RGX-two zero two as a potential best in class gene therapy for Duchenne. We believe that RGX-two zero two has the potential to safely provide strong functional benefit and durability, offering hope for better lives. With positive and growing interest from the patient community and physicians, I am very pleased to share that we are accelerating our guidance for RGX-two zero two. We now expect to complete enrollment in the ongoing pivotal study this October.

Our ability to move this timeline up from end of year further solidifies RGX-two zero two’s position as the potential next gene therapy to market for Duchenne. The community is clearly in need of additional options. We continue to actively enroll and open new sites in the AFFINITY Duchenne pivotal trial with plans to roll directly into a confirmatory study to support our accelerated approval. Additionally, we are in the unique position of having drug supply in hand for our pivotal and confirmatory trials. We remain on track to report top line data in early twenty twenty six, submit a BLA in mid-twenty twenty six, and potentially be on the market by 2027, when the vast majority of the DMD population is expected to remain untreated.

From the beginning of this program, we implemented a differentiated therapeutic approach. We pioneered a proactive immune suppression regimen to drive improved safety outcomes and reduce the potential risk of known liver issues found in other programs. Our Phase onetwo data to date supports that our approach is effective. RGX-two zero two also has consistent industry leading purity levels in Duchenne with over 80% full capsid content in our product. This is important because higher purity leads to less total vector load delivered to patients and they contribute to the positive safety profile we’ve seen to date.

We believe our in house manufacturing capabilities are a highly strategic asset and gives us a unique ability to serve the large Duchenne market available at launch. We are pleased to announce we are initiating commercial manufacturing this fall at our Manufacturing Innovation Center here in Rockville, Maryland. This GMP facility can produce up to 2,500 doses of RGX-two zero two per year. With our strong momentum and is the only investigational gene therapy enrolling in a Phase three study in North America, RGX-two zero two is well positioned to be next to market and a potential best in class gene therapy for Duchenne. Let’s turn our focus to our retinal disease franchise.

In partnership with AbbVie, we continue to advance ADBV RGX-three fourteen, also known as serab gene Lumparvovec or Suravec, as the potential one time gene therapy for chronic retinal conditions. I’m very pleased that earlier this morning, we announced an update to our agreement with AbbVie to advance Suruvec into pivotal phase for diabetic retinopathy. Based on positive two year data from the Phase two ALTITE trial, we will initiate a Phase 2bthree trial. The cost of the study will be covered by the accompanying milestones, including the $100,000,000 we receive upon the first patient dosed in the Phase 2b portion of the trial. Steven Mitch will share more about the data and financials shortly, but let me reiterate our excitement about this program, which gives us another pivotal program in chronic eye care with our partner AbbVie.

Both wet AMD and Doctor represent large multibillion dollar commercial opportunities and we believe Suravec has the potential to preserve vision, prevent disease progression, and serve as a meaningful alternative to today’s standard of care. Last but not least, the FDA accepted our BLA for RGX-one hundred twenty one, now known as clomidzogine lemparvovec, for the treatment of MPS II or Hunter syndrome. This BLA was accepted under the accelerated approval pathway with a target PDUFA date of November 9. Pre BLA activities are progressing well. We have completed the mid cycle review meeting and our first PLI and BMO inspections with the FDA successfully with no observations.

These are exciting achievements and a testament to the exceptional quality of our people, process, and science. If approved, RGX-one hundred twenty one will be REGENXBIO’s first approved gene therapy. Commercial preparations with our partner Nippon Shinyaku are progressing well. Products intended for launch has already been produced and we are committed with our partner to bringing this potentially transformative treatment to patients in early twenty twenty six. These accomplishments demonstrate our seamless and focused execution against our strategy to bring potentially transformative gene therapies to patients.

We remain excited for and well positioned to deliver on opportunities ahead of us. With that, I would like to now turn the call over to Steve for an update on our clinical programs. Steve?

Steve Picola, Chief Medical Officer, REGENXBIO: Thank you, Keren. Today, we’re excited to share updates across our multiple pivotal programs. I’ll start with our retina franchise, Surovac, which is being developed in collaboration with AbbVie to treat wet AMD and diabetic retinopathy or Doctor. First, I’ll address CEROVEC for Doctor being evaluated in the Phase II ALPITUDE trial using in office suprachoroidal delivery. I’m pleased to highlight the data supporting our advancement to pivotal stage.

The data slides are available in the webcast and on the events page of our website, and you can follow along as I discuss. As outlined on slide three, Doctor impacts more than twenty million people globally and these patients are at increased risk of developing vision threatening complications. Moving to slide four, a one time in office injection of Suravec has the potential to provide long lasting improvement to disease severity and reduce the risk of vision threatening events or VTEs. Using one time in office suprachoroidal delivery is convenient for the working age population impacted by Doctor. Also, this route of administration allows targeted delivery into a compartmentalized space to limit exposure to the vitreous and anterior segment.

Slides five and six show the ALTI2 trial design and baseline characteristics of participants with non proliferative diabetic retinopathy or NPDR. Moving to safety data on slide seven, Cirovac was well tolerated at all dose levels. Further illustrated on slide eight, we are very pleased to share that at two years in dose level three with short course prophylactic topical steroids, there were zero cases of intraocular inflammation. Moving to efficacy on slide nine, starting with the one year results. As expected, in the untreated control group, patients generally get worse with forty one percent experiencing at least two step worsening in their diabetic retinopathy severity score or DRSS.

In stark contrast, NPDR patients treated with dose levels two and three are generally improving. And now on slide 10, for the first time, we share two year results. Suruvac demonstrated a dose dependent increased rate of meaningful DRSS improvement with fifty percent of dose level three patients achieving at least a two step improvement without need for any supplemental treatment, a rate six times that of historical control. Slide 11 further illustrates the durable efficacy seen over time at dose level three out to two years. Importantly, these imaging results are translating into benefit in terms of decreased risk of vision threatening events.

On slide 12, THERAVEC treated NPDR patients had a dose dependent reduction in VTEs with dose level three achieving at least a 70% reduction in VTEs compared to historical control. In summary, on slide 13, a single in office injection of Cirovec was well tolerated and demonstrated durable long term efficacy, including meaningful DRSS improvement and significant reduction in the risk of vision threatening events. Based on these compelling results and in agreement with AbbVie, we are initiating a global pivotal program. The initial pivotal trial will be a two part Phase 2bthree double masked placebo controlled superiority trial, including two dose arms of Cervak. The primary endpoint will be proportion of patients with at least a two step improvement on DRSS at one year.

This pivotal trial will have two sequential parts. The first part will be the dose selection phase that includes dose level three and dose level four arms from ALTITE to allow interim evaluation of safety and efficacy to then select the dose or doses to carry forward into enrollment of Part two of the pivotal protocol. Site selection is already in progress, and we look forward to sharing more on this program as we progress. In wet AMD, we are evaluating Surabac via two different delivery forms, subretinal and suprachoroidal. Within subretinal, we have two ongoing pivotal trials, Atmosphere and Ascent in The US, Europe and Japan.

These trials continue to progress well with enrollment nearing completion. Overall, we remain encouraged by the ongoing progress with Surabec, especially the safety profile observed in our suprachoroidal programs. This is particularly notable in the setting of short course prophylactic steroid eye drops, a significantly shorter regimen than those used in other gene therapy trials. Moving to RGX-two zero two, a potential best in class one time gene therapy for the treatment of Duchenne. RGX-two zero two is the only microdystrophin construct to include the C terminal domain, making it the closest to naturally occurring dystrophin.

The CT domain has been shown to prolong microdystrophin activity and preserve muscle health by protecting it against contraction induced damage. This preclinical research was recently published in ASGCT’s peer review journal. This construct combined with the highest purity levels in the field and a proactive immune suppression regimen are translating into the clinic with better functional outcomes and favorable safety profile, including in older boys. In June, we presented new positive Phase onetwo interim data for two zero two at the pivotal dose showing meaningful functional improvements compared to expected disease trajectory. Notably at twelve months, all patients demonstrated improvement on time function tests compared to baseline with time to stand, 10 meter walkrun, and time decline results exceeding the minimally important difference.

The majority of patients were eight years and older at dosing, an age when functional decline would typically be expected. Two zero two also continued to be well tolerated with no SAEs or adverse events of special interest. Even at our higher dose level, we have seen no thrombocytopenia and no evidence or signs of liver injury in any patient, including as assessed by liver function testing. To build on what Kern shared earlier, the differentiated therapeutic approach for two zero two includes a proactive short course immune suppression regimen that was developed from the outset of this program in collaboration with the patient community and leading Duchenne physicians. We pioneered this approach for improved safety outcomes.

We’re very pleased with how this patient focused approach, along with our differentiated product, is translating into a favorable safety profile observed to date. We expect to complete enrollment of the 30 patients in the Affinity Duchenne pivotal trial to support accelerated approval by October. And we will continue to enroll after that for a confirmatory trial. Now on to RGX-one21. It’s such an incredibly exciting time for REGENXBIO and the Hunter syndrome community with the ongoing progress for RGX-one hundred twenty one BLA.

01/2021 represents a potentially transformative one time treatment for patients with Hunter syndrome. We look forward to an anticipated FDA decision in November. Overall, we’re making significant progress across all our late stage programs. I’d like to express my sincere gratitude to all the patients, families, clinicians, site staff and patient advocacy representatives who have supported these trials. With that, I’ll turn the call over to Mitch to review our financial guidance.

Mitch.

Mitch Chan, Chief Financial Officer, REGENXBIO: Thank you, Steve, and good morning, everyone. REGENXBIO ended the quarter on 06/30/2025, with cash, cash equivalent, and marketable securities of $364,000,000 compared to $245,000,000 as of 12/31/2024. The increase was primarily driven by the $110,000,000 upfront payment from Dipan Shinyaku in the 2025 and the $145,000,000 in net proceeds received from the royalty monetization with healthcare royalty partners in the 2025 and was partially offset by cash used to fund operating activities in the 2025. R and D expenses were $60,000,000 for the quarter ended 06/30/2025, compared to $49,000,000 for the quarter ended 06/30/2024. The increase was primarily attributed to manufacturing related expenses and other clinical supply costs and clinical trial expenses for Cirovec and RGX-two zero two pivotal trials.

Turning to the specifics around Cirovec announcement today, Steve went through the very encouraging data we continue to generate in Doctor in a new Phase twothree study that both AbbVie and REGENXBIO believe will be designed to strengthen the body of evidence for CiroVec in Doctor and maximize the probability of success in a planned global Phase III program. Under the terms of the amended agreement, we are effectively being paid in advance half of the $200,000,000 milestone that would have been earned upon dosing of the pivotal trial. We will now be paid $100,000,000 upon first patient dose in the Phase IIbIII trial and receive the next $100,000,000 upon dosing of the first patient in the second Phase III trial. This brings in $100,000,000 upon first subject dose and more than covered the cost of the Phase IIb trial. Additionally, the amendment reflects AbbVie’s continued investment in the Cervak program and their independent pursuit of the Phase III ACHIEVE trial to further support the global commercial opportunity.

We expect the June 30 cash balance reported today to fund our operation into early twenty twenty seven and enables us to accelerate towards multiple product launches. Please note this cash runway guidance does not include multiple non dilutive financing opportunities that could further extend our cash runway significantly beyond 2027. These include development or sales milestone RGX-one21, the sale of our anticipated priority review voucher for RGX-one21, development milestones associated with AbbVie’s collaboration, including those in diabetic retinopathy program, as well as the potential additional funds from the May 2025 health care royalty agreement. With that, I will turn the call back to Curran to provide final thoughts.

Curran Simpson, President and CEO, REGENXBIO: Thank you, Mitch. Today’s exciting updates make clear that we are executing at a high level across all aspects of our business, bringing us one step closer to becoming a commercial company. Our strategy is clear and focused. With our leading in house end to end capabilities, we are rapidly advancing multiple late stage programs. These potential first or best in class gene therapies represent the opportunity to address significant unmet need for patients with rare and retinal diseases.

We have our first potential FDA approval on the horizon this year. Most importantly, we maintain a strong financial position and have multiple avenues for non dilutive financing to support the continued development and potential commercialization of our products. I want to thank our REGENXBIO team for their dedication, our physician partners for their collaboration and the patients and families who participate in our trials. Your contributions are essential to our mission of improving lives through the curative potential of gene therapy. With that, thanks for your time today.

I’ll turn the call over for questions. Operator?

Conference Operator: Thank you. We will now begin a question and answer session. Our Our first question comes from Judah Frommer from Morgan Stanley. Please go ahead.

Judah Frommer, Analyst, Morgan Stanley: Yeah. Hi, guys. Thanks for taking the questions and congrats on all the progress updates here. Maybe one on DMD and then another on Doctor. I guess with DMD, anything you can share regarding reaction from the DMD community, maybe more specifically about the conditioning or prophylaxis regimen that you have in 02/2002?

It seems like the community is probably a little more attuned to sirolimus specifically after that patient death in Brazil. So anything you can share about how the community is feeling about that regimen. And then switching to Doctor, I guess, any thoughts on what’s happening in dose level three between year one and year two to see that improvement in DRSS? And more generally, can you share with us kind of how the discussions with AbbVie went in changing the plan for, the pivotal design here to go through the 2b and then the three, any change in level of excitement from them or is it more just kind of proving out the dose level? Thank you.

Curran Simpson, President and CEO, REGENXBIO: Sure, thanks for the questions. I think on two zero two, I would characterize the interest at the patient community as kind of at an all time high for our type of program. I think certainly the proactive immune suppression regimen that we’ve been talking about since the beginning has even greater appeal in this way that people think about safety and high dose AAV treatments. And I think we are seeing that in our interest in the study itself and we’re doing things like conducting webinars with Cure Duchenne to maybe more broadly get the word out about the program and obviously as related to enrollment, we’re expanding sites pretty dramatically this year. I think at a base level, the interest in gene therapy is still very strong in the patient community and I think the interest in our program in particular has risen dramatically.

The one thing I would say is that I think the patients initially the immune suppression regimen was portrayed as onerous and potentially not commercially viable. We’re finding that the patients actually love the level of monitoring and surveillance that we’re doing as it related to the study because I think it brings them comfort that hopefully none of these events that are controllable will occur. I think I’ll ask Steve to characterize the Doctor data, if that’s okay.

Steve Picola, Chief Medical Officer, REGENXBIO: Sure, thanks for the questions Judah. So, as you pointed to the improved efficacy that we’ve seen over time, how do we look at that data? I think the overarching aspect is you certainly want durability to really confirm that you have the sustained anti VEGF activity. And I think if you’re having disease modification, then you even have that opportunity to see continuing improvement even after a single administration. And I think that’s the part that is so compelling, particularly for this indication that you can have a single injection that has durable benefit both in terms of DRSS imaging improvement, but also very key preventing those vision threatening complications.

So, I really think that we would have been excited with stability across the two dose levels. But to actually see this improvement at dose level three at two years has really given both us and AbbVie the excitement to pivot in a positive way to really make sure we don’t leave any efficacy on the table. You know, it’s worth noting this data came in first half of this year. So, we were rolling along, planning to move ahead, given that we’d already met the target product profile. But now we’ve got this amazing opportunity, and it’s not only the efficacy side, but it’s key that we’re seeing excellent safety without intraocular inflammation with a relatively short topical steroid regimen.

So, we have the flexibility to potentially not leave efficacy on the table because of our safety that we’ve seen with our compartmentalized delivery. So, that’s really how both we and AbbVie are looking at this as a tremendous opportunity.

Conference Operator: Thanks. Our next question comes from Gina Wang from Barclays. Please go ahead.

Gina Wang, Analyst, Barclays: Thank you. Maybe I just follow, Steve, your comments. Is that the reason you wanted to adding dose level four for the pivotal study phase 2b to evaluate, you know, the potential further improvement with a higher dose and giving a good safety? And, also, for the pivotal study, are you thinking about one year, or would that be two year study? Related question is, what is the reason to amend agreement?

And then if, Mitch, you can share with us how much cost will be for the running the phase 2b study? And then quickly on BMD, just wondering if you have any recent interaction with the FDA since Nicole Verdun departure, so as well, Prasad departure, any concerns regarding the pivotal path that was agreed on by the prior administration?

Curran Simpson, President and CEO, REGENXBIO: Thanks Gina, I’ll start and maybe work my way backwards to the questions. I think on FDA, we’re certainly having a lot of interaction with FDA as it relates to the hunter program now. I don’t think there’s a new facility inspection, the PLI that we mentioned that has come in with no observations, we’re super proud of that and I think that that not only plays well for our chances of approval on 01/2021 but our future chances of approval on the Duchenne program and of course 03/14. So we’re really pleased with the FDA interactions that we’re having and we haven’t seen any shift more broadly on say clinical trial design, to date on any other programs. So I would say right now it’s still what we’ve been saying, which is consistent interactions with FDA as expected in the late stage reviews that we’re encountering.

Steve, I’ll ask you to maybe comment on the question on, actually before I do, I think Mitchell characterized the milestone amendment change, but there’s actually a mechanical aspect to that, that in the original contract, a Phase 2B wasn’t really ever contemplated. So we were actually pleased to see AbbVie basically update that amendment to recognize the 2B and initiate part of that full milestone as part of that, that was something that I felt helped us in terms of cash runway being able to be paid at the initiation of the 2B rather than how it was originally written as first patient in a pivotal, even though we see the 2B as being intimately combined as a pivotal. Steve, did you want to comment on this question regarding Doctor for DL4?

Steve Picola, Chief Medical Officer, REGENXBIO: Yeah, hi. Hi Gina. So the first part of your Doctor question, why DL4? Certainly, it’s both efficacy and safety, the fact that we saw the improvement in DL3 and that data coming in at two years in the first half of this year. The other piece of the equation is safety.

And as you know, we have our altitude DME arm with DL4, as well as our AV8 wet AMD dose level four arm. So, in the first half of this year, we got to take advantage of interim follow-up on these patients, including those earlier months after dosing, which really gives you the read on the key time period as far as safety and tolerability. So, in short, we’re seeing what we want to see in terms of efficacy in the Doctor study, as well as what we see across dose level three and four. So, we’re going up because we can. And I think it makes sense that you really don’t want to leave efficacy on the table.

And it’s worth evaluating in a dose selection phase. When you think of how massive this Doctor opportunity is, particularly for a one time in office treatment, we in AbbVie felt this was a great opportunity where we can look at two separate doses to really risk mitigate leaving anything on the table. And as you know as well, it’s not uncommon in retina pivotal trials where relatively speaking, they’re not too large that you can often take two doses into pivotal. So, we’re really trying to keep open our options given the results that we’ve seen.

Curran Simpson, President and CEO, REGENXBIO: I think, I’m Michelle, have you found I missed that, Steve, on the one or two year Yeah, endpoint,

Steve Picola, Chief Medical Officer, REGENXBIO: yeah, and we also have the benefit of a lot of regulatory history with the FDA, including our prior end of phase two meeting, where we know that this DRSS endpoint is accepted for adequate and well controlled trials. And we know accepted at the one year time point. So, makes sense for us to take advantage of that opportunity. So, the primary endpoint is at one year.

Curran Simpson, President and CEO, REGENXBIO: Sorry for interrupting Steve. Mitch, did you want to comment again on the milestone structure?

Mitch Chan, Chief Financial Officer, REGENXBIO: Yeah, absolutely. And it’s a great question. I would say the $200,000,000 remains intact. I think as Keren mentioned, the amendment was made because the Phase IIb was not contemplated earlier. So in total, the 200,000,000 is basically split into 2, dollars 100,000,000 and 100 And the first $100,000,000 will more than cover this clinical trial for the Phase 2b.

We don’t want to go into specifics in terms of the costs, but I will reiterate that the $100,000,000 will more than cover the study costs. Thanks for your question.

Gina Wang, Analyst, Barclays: Thank you.

Conference Operator: Our next question comes from Mani Faroohar from Leerink Partners. Please go ahead.

Ryan, Analyst, Leerink Partners: Hey guys, you have Ryan on for Mani. Thanks for taking our question and congrats on the update. So I know it’s early days, still enrolling the pivotal, but as you guys look to a DMD launch playing out, I’m kind of just curious how you see the dynamics of the broader prevalent patient population versus those ineligible for existing therapies right now. Like do you see the first part of launch really being tailored to one more than the other or is this just going to be a pretty broad launch across the board? And then maybe just one on wet AMD.

Can you just talk about whether the subretinal launch is a means to the suprachoroidal or whether you see a durable albeit smaller market for this type of approach? Thanks.

Curran Simpson, President and CEO, REGENXBIO: I can start with the second question. I think we see it in subretinal as an entity on its own. Now, if down the road, a suprachoroidal wet AMD approach for Surovec has the same product profile in the clinic as what we’re seeing in sub retinal, you could argue that the in office procedure would be preferable but I think there will always be as well certain geographies that are very amenable to the sub retinal administration. We’re seeing really robust recruitment for example in Europe on our sub retinal study. So I think that both are very viable and I think the sub retinal product profile and clinical data we’re seeing can sustain itself, time will tell.

I think on the approach to the commercial market for Duchenne, if you look at our study design, we’re recruiting one and older. So we see the opportunity here for a broad label and we see the opportunity with a differentiated product that we’re seeing strong functional benefit and also a very favorable safety profile. We see opportunity to take a dominant position in the market based on our initial data. Right now we’re not exploring the non ambulatory aspect of Duchenne and that’s something we’re still contemplating, although you could make the thesis that our immune suppression regimen would be incredibly favorable for that patient population. Our focus is 100% on the ambulatory study that we’re running now and a broad label as the outcome.

Ryan, Analyst, Leerink Partners: Awesome, thanks guys.

Conference Operator: Our next question comes from Elle Mary from UBS. Please go ahead.

Elle Mary, Analyst, UBS: Hey, guys. Thanks for taking my question. Just a follow-up on the last question. Just curious how you’re thinking about a potential strategy in non ambulatory patients given your preconditioning regimen, and curious if you’ve had any discussions with the FDA on that in the past, and any color you can share in terms of how they might be thinking about non ambulatory safety. And then just second, as we think about the subretinal Phase III, which will be a major catalyst when that comes up, can you elaborate a little bit on what you think would be sort of competitive or clinically meaningful, particularly as we look towards some of those secondary endpoints?

Thanks.

Curran Simpson, President and CEO, REGENXBIO: Sure, I think on the question around non ambulatory, we have not one aspect I would point out for our ambulatory ongoing pivotal study, we pointed to completion in October, we do have a broader set of mutations allowed in the inclusion criteria than other studies, so we are taking, as I said, a broad approach to the labels, not just age but also mutation status. I think in non ambulatory, there’s still a lot to learn from some of the recent events that we’ve all heard about, and I think we’re taking a cautious approach to that right now. We have not had detailed discussions with the FDA around a non ambulatory study design, but that is something we plan to. But I think that’s going to be related with expansion of our safety database in our existing program. We want that to be a prerequisite to exploring non ambulatory that we establish early on a good safety profile in the ambulatory population.

I’ll ask Steve to comment on the subretinal question for secondaries.

Steve Picola, Chief Medical Officer, REGENXBIO: Sure, hi Ali. Yeah, I think as you mentioned, it’s a very significant milestone coming up, the completion of our two pivotal trials for subretinal treatment of wet AMD. You know, as far as what we’re looking for and what we think will fill a significant unmet need in the space, the two aspects are of course the primary endpoint where safety has to be maintained and we need to show non inferiority on VA both from a regulatory standpoint, but also from a commercial standpoint. You raise an important point on the secondary endpoints, particularly the injection burden. Because with a one time injection that’s certainly one of the key value propositions here where we know that patients are not getting the injections in the real world and are continuing to lose vision.

So, how do you quantify that? Well, it roughly hasn’t changed over time where what we hear from clinicians in a lot of discussions that we’ve had over the years, it’s been pretty stable that we’d like to see at least a fifty percent reduction in injection burden. And to be able to achieve that with a one time injection, while maintaining vision in a controlled study where the control arm is getting very prescribed on label treatment, We believe that not only will lead to lower injection burden and treatment burden for patients in the real world, but because they have that sustained anti VEGF activity, it also will be a benefit provision maintenance, which really makes the total package of the value proposition quite compelling.

Gina Wang, Analyst, Barclays: Great. Thanks.

Conference Operator: Our next question comes from Luca Ici from RBC. Please go ahead.

Elle Mary, Analyst, UBS: Oh, great. Good morning. Thanks for taking our questions. This is Lisa on for Luca. Maybe just on diabetic retinopathy.

Just wondering if you can walk us through the potential path to approval here. Can the phase 2bthree be used as a registrational study alone, or will an additional two phase three studies be required for approval? And maybe just on the efficacy here for Doctor, it looks like fifty percent of patients did not require further treatment, but just wondering if you can comment on the fifty percent that did. Did they go back to a regular cadence of anti VEGF injections, or did they need only periodic supplemental injections? And just last one on subretinal for wet AMD on the pivotal study, can you comment on the state of enrollment, has this trial been fully enrolled, and if so, when did enrollment close?

And that’s all for me, thanks so much.

Curran Simpson, President and CEO, REGENXBIO: Thanks for the questions. I can start with the last one around subretinal enrollment. We’re seeing really robust enrollment and I think we’re in a situation where completion of enrollment is essentially imminent, but we will certainly update when those studies are both fully enrolled looking forward to that. But we feel really good about enrollment and as I mentioned earlier, maybe unexpectedly, really strong trend in enrollment in Europe, which AbbVie is conducting those sites. So stay tuned, and that’s why we continue to guide to top line data in 2026 based on optimism around completing enrollment for those studies.

I’ll ask Steve to comment on the Doctor data.

Steve Picola, Chief Medical Officer, REGENXBIO: Yeah, so the first part of your question, Lisa, on the potential path to regulatory approval. So, we believe there is the requirement traditionally needed of course, of two adequate and well controlled studies. So, that’s our plan. Notably, the phase 2b3 study that will be starting would be intended to be one of those two studies. So, I think that’s encouraging.

That’s why we say we’re starting our pivotal program. In terms of the data from the two year results that we showed on DL3, fifty percent of the patients had at least two step improvement without needing supplemental injections. That doesn’t mean that the other fifty percent of patients needed supplemental injections. It actually was a minority of patients who wound up getting any intravitreal injections. And we felt it was important to really lay out how each of these DL3 patients did over one year and two years, so you can see that evolution.

And I refer you to slide 11, so you can see those details. But again, it was only a minority of patients that wound up getting any injections. And those fifty percent where we saw at least two step improvement without any injection is really the key take home message.

Conference Operator: Our next question comes from Alec Stratham from Bank of America. Please go ahead.

Alec Stratham, Analyst, Bank of America: Hey, guys. Thanks for taking our questions. Just a couple from us. First on 02/2002, I guess given everything that’s happened the past few months with Sarepta, what is your current view on the market dynamic at launch? And any updated sort of percent breakdown of the prevalent pool at that point would be helpful.

And then, I appreciate the differences between two zero two and Elevitus as well as the emerging safety profile for two zero two. But do you expect a class effect for liver injury could be applied to label given they are both AAV gene therapies? And then lastly on 03/14, I guess how should we view the two pivotal studies versus the Phase three ACHIEVE study that AbbVie is planning to launch? You think data from the first two subretinal studies will be sufficient to file with ACHIEVE more for being leveraged for commercialization with the physicians? Any color there would be helpful.

Thank you.

Curran Simpson, President and CEO, REGENXBIO: Sure, thanks for the question, Alex. The last one is fairly straightforward, the sub retinal pivotal studies, ATMOSEER and ASCENT will be sufficient for filing an approval. And the study that we mentioned today is really a post marketing approach to judge the efficacy of the product against real world outcomes. So they’re very separate and the two pivotals that we’re running, which are highly powered as a result of some sample size increases we made, we feel will be very adequate for filing. And I think in terms of the market dynamic at launch for, back to your question on 02/2002, we certainly see a really significant level of the prevalent population still being available to us based on some of the interruptions in launch, maybe greater than 90% of what we initially estimated of the prevalent population.

So that will lead us to potentially at launch itself, ensuring that we have adequate quantities of drug available for launch, which is readily possible given that we have in house manufacturing, we have really highly productive process and we can stockpile at launch a significant number of doses. So our intention is to be able to be in a position to take on a significant portion of the market at launch and I think where we’re positioned in terms of timeline and our differentiated product profile really makes this a potential blockbuster opportunity. The question around

Steve Picola, Chief Medical Officer, REGENXBIO: labeling On the

Mitch Chan, Chief Financial Officer, REGENXBIO: liver injury

Curran Simpson, President and CEO, REGENXBIO: Yes, Steve, I was gonna defer that to you. Question, yep.

Steve Picola, Chief Medical Officer, REGENXBIO: Okay, great. So Alec, yeah, you refer to the existing therapy and the liver injury components and liver failure components in the label. How that could potentially lead to any kind of class effect considerations. Think each program has to be looked at in its own right. And I think that’s why the points Karen has made about the clear differentiation that we have in terms of product purity with a much higher full to empty capsid ratio that’s industry leading.

And of course, our proactive immune modulation approach. And the existing therapy has per label up to forty percent rate of liver injury. And I think we’re seeing our differentiated approach translate in the clinic to a clear differentiation in terms of risk of liver injury, where we in our phase onetwo study, zero of thirteen patients with any signs or symptoms of liver injury, including on LFT assessment, so. This gives us a lot of confidence in terms of how we can show differentiation on safety overall. But also, in terms of potential risks to deliver.

Conference Operator: Our next question comes from Jack Padavanaugh from Stifel. Please go ahead.

Patrick Christmas, Chief Legal Officer, REGENXBIO0: Hi team, this is Jack on for Annabel. Thanks for taking our questions. So on the rationale for the Phase 2b with three fourteen, I know you mentioned that you don’t want to leave efficacy on the table, which makes sense. So the two step improvement for dose level two seemed equivalent to dose level one at year one or sorry, I think I may have gotten that mixed up for dose level three equivalent to dose level two at year one. And the real differentiation only emerges at year two.

Was the decision to include dose level four here partially driven because you feel like you need to improve efficacy even further to sufficiently convince FDA with just the year one data? Kind of essentially asking if that twenty one percent, efficacy is sufficient for approval already and you just think you can do even better?

Curran Simpson, President and CEO, REGENXBIO: I think it’s the latter. I think we feel dose level four has the opportunity to do better, but on its own, the dose level three results we feel are sort of the anchor dose that met our product profile and would be I think received well in a review. Steve, do you want to comment a little bit on just power of the signal that we’re seeing?

Steve Picola, Chief Medical Officer, REGENXBIO: Sure, so Jack, you point to the equivalence in terms of two step improvement at one year. The key consideration is the effect size we’re seeing there meets our target product profile. And the reason it meets that is we know that that’s an acceptable endpoint and acceptable effect size from a benefit risk standpoint when you take into account this being a single injection and the ability to decrease treatment burden when you look at that overall benefit risk consideration. The other key aspect is what the clinicians care most about is the effect on imaging translating into actual benefits for patients in terms of not only decreased injection burden, but actually preventing patients from developing the blinding complications. So, that’s why we feel comfortable with the one year results where we’ve seen that translate into a meaningful reduction in those important events.

And we see that held up to a very significant clinically meaningful level at the two year time point. So, that’s why we in AbbVie feel very comfortable with the one year endpoint. And we know we’re going to continue to get two year data and long term data to give even more confidence to the clinical community.

Patrick Christmas, Chief Legal Officer, REGENXBIO0: Great, thanks.

Conference Operator: Our next question comes from Brian Scorney from Baird. Please go ahead.

Patrick Christmas, Chief Legal Officer, REGENXBIO1: Hey, good morning, everyone. Thank you for taking my question. I also want to just push to get a little more granularity on the Doctor 2b your 2b3 versus three study design. On the 2b3, is this a 2b portion where you get some interim data from a small sample size and then roll into a Phase III portion? Or is sort of the whole thing running blinded before full readout?

I’m trying to get a feel for the cadence where this is going to be one readout and then you would start the second pivotal Phase III? Or there’s an earlier IIb portion readout that leads to a start of the Phase III portion of the 2bthree and then at some time later at the start of the second Phase III portion. And in terms of the control arm, is it going to be sham or open label? And have you potentially thought about an active control in any of these studies? Just looking at the event rates you have in DEL3, it wouldn’t be out of the question to even potentially show benefit over EYLEA particularly if events are compliance driven though.

Curran Simpson, President and CEO, REGENXBIO: Thanks for the question, Brian. I think at a high level I can comment, the way the 2B is designed is to as efficiently as possible move through different phases. So it’s structured that the 2B has an interim readout in which it rolls into a phase three and the concept and the plan with AbbVie is that would also trigger immediately starting the second pivotal so that we could go as quickly as possible. I’ll let Steve comment on the other details you asked about.

Steve Picola, Chief Medical Officer, REGENXBIO: Yes, I think the key is really that the phase 2b three study, we are going to roll over into the part two of that study and it’s all under one protocol. So, yes, the part one informs that. Now, we do plan to take advantage of interim looks at that data to really help inform by assessing ongoing safety and efficacy of the ability to then advance into part two. On your second question, both pivotal including part one of the first study will be double masked. So, we really want to get the highest quality from these studies.

So, we are going to use a sham injection to get the greatest validity in terms of looking at actual treatment effect. The interesting question about active control for diabetic retinopathy before vision threatening events has occurred is that while other drugs like Eylea have treatment of Doctor on label, the reality is this is clearly not standard of care precisely because of the unsustainable treatment burden of repeated injections indefinitely. Because when you stop those repeated injections, patients rebird and you wind up going back to the risk of vision threatening events. So, even if we wanted to run a active comparator, it would frankly bank enrollment almost impossible because patients don’t want to go through that repeated injection. So, it basically validates why we feel a one time injection has so much potential for this massive unmet need.

Curran Simpson, President and CEO, REGENXBIO: And the inclusion, Steve of the sham control was something we covered in all of the regulatory sessions we had last year, is that correct?

Steve Picola, Chief Medical Officer, REGENXBIO: Yeah, that’s right, that’s always been our plan and we’ve always had alignment with the FDA on that.

Patrick Christmas, Chief Legal Officer, REGENXBIO0: Thank you.

Conference Operator: Our next question comes from Bill Morgan from Clear Street. Please go ahead.

Patrick Christmas, Chief Legal Officer, REGENXBIO2: Hi, good morning and thanks. So you’ve mentioned a few different aspects of two zero two that make it differentiated from Alevitas, those being, for example, the full capture ratio, your manufacturing process and your immune modulation condition regimen. So I just wanted to ask around the immune modulation and whether or not you think that that is the majority of the differentiation? And if so, if you simply added immune modulation to Alevitus, is there a chance that this could become more similar than different in terms of safety? Thank you.

Curran Simpson, President and CEO, REGENXBIO: Thanks for the question. I think in general, it’s hard to pull those apart from each other. We wouldn’t have preclinical data where we look at each effect in isolation but maybe I’ll let Steve comment. I do believe from what we’re seeing that they all play into effect because our goal is to deliver the maximum dose that’s in line with our preclinical data to deliver a functional benefit and that’s what drove us really to initially go to the highest purity we could, which is above eighty percent. But the immune suppression was a separate thought from our clinical development group as Steve mentioned, put together I think that both of them have power in establishing the safety profile that we’ve seen so far.

But I can’t comment on whether or not that immune suppression regimen would perform the same with the Lavitas. Steve, do you have thoughts on that?

Steve Picola, Chief Medical Officer, REGENXBIO: Yeah, agree that we think all of these components play a part. It’s really not possible to give any percentage breakdown on that. And they probably all interact as well. I think one of the key considerations is, because we built this in upfront, because we cared about safety in the overall sense of benefit risk for our product and realize that that was a key differentiator. We’re the only program that actually has safety and efficacy data where we can begin to answer that question in terms of with this constellation of differentiation, are we seeing a favorable safety profile?

So, as Karen mentioned, we don’t know what would happen with other programs if they added any of our proactive immune modulation. So, that would remain to be seen.

Patrick Christmas, Chief Legal Officer, REGENXBIO2: Thank you.

Conference Operator: Our next question comes from Sean McConchan from Raymond James. Please go ahead.

Patrick Christmas, Chief Legal Officer, REGENXBIO3: Hey guys, thanks for squeezing me in. One on two zero two. So moving the full enrollment of that pivotal cohort up to October, can you speak to the flexibility this may allow you to potentially over enroll or to get a head start on the enrollment of the confirmatory study to position yourselves well amid some of the shifting, let’s call them perspectives and uncertainty at the FDA? Thanks.

Curran Simpson, President and CEO, REGENXBIO: Thanks, that’s a great question. I think we’ve pointed out in the release and other venues that we do intend to continue to enroll once we fully enroll the pivotal program. Our protocol was originally written to enroll approximately 30 patients in the pivotal arm and then an additional 30 patients in the confirmatory study as well. So we have plenty of room to continue to add patients throughout the year and we can make amendments along the way. But I think I would express our main goal is to continue enrollment and expand our safety database.

We have all of the drug supply we need and we’re making more as we pointed out, because we think that that will be important and it will address any risk in sample size discussions for example, and that’s one of the rationales as well as why we’re expanding sites dramatically from where we were only a year ago.

Conference Operator: Our next question comes from Please go ahead.

Patrick Christmas, Chief Legal Officer, REGENXBIO4: Hey, good morning. Thank you for taking my questions. I have a couple. First on 02/2002, given the uncertainty in the DMD gene therapy space, are you considering requesting another meeting with the FDA before your pre BLA meeting to ensure that you’re thinking has not changed too dramatically? Maybe if you can mention if you can if you’re considering a special protocol assessment for TLT2.

And second, for 03/14, with your suprachoroidal space microinjector partner going through a significant restructuring, what is the strategy to ensure that you have access to microinjectors going forward? And are you considering switching to a different microinjector partner? Thank you.

Curran Simpson, President and CEO, REGENXBIO: Sure, I can address the, excuse me, the last question first. I think we feel confident with continued supply of microinjector regardless of business situation with Clearside. We have significant inventories in hand and also provisions for continuing supply that were part of the original contract that we’ve signed. So we feel very confident in our ability to continue to access the devices and are in close contact with Clearside as well to just ensure no issues with continuity. In terms of the, just trying to pull back to the first question, an FDA meeting sooner than planned, that’s something I think we’re thinking about.

I don’t think there’s any urgency to do that because right now, our primary goal is enrollment and not just the pivotal but the confirmatory study. And as we get further along, I would expect we’ll look for a check-in with FDA. But I don’t think right now we’re getting any signals from FDA that make that urgent because we’re in constant contact with the review teams both for 01/2021 and for 02/2002. We’re not detecting any significant shifts in what they’re looking for in the study or study design. And I think in particular, Makary’s statements about rare disease development, I think the situation in Duchenne over the last couple of months has only underscored the need for additional therapies to be available and for that to be done urgently.

And I feel like our data package, if what we did in Phase onetwo replicates in our pivotal program will be very compelling for FDA.

Conference Operator: Our next question comes from Paul Choi from Goldman Sachs. Please go ahead.

Patrick Christmas, Chief Legal Officer, REGENXBIO5: Hi, good morning and congratulations on all the progress. Thanks for taking our questions. I want to maybe continue the questions just on the FDA landscape here and I guess what your confidence for the DMD program is in the absence of a permanent head of CBER just given the sort of focus on that particular disease state and indication? Then my second question is, I guess, as you think about the Medicare changes to the and recent RIA changes for reimbursement of injectable VEGFs, How are you potentially thinking about pricing for your product there over the longer term given what seems to be continual downward pressure from the Medicare reimbursement side? Thank you very much for taking our questions.

Curran Simpson, President and CEO, REGENXBIO: Sure, I think on this last question, it’s pretty early days. We haven’t really had substantive discussions with AbbVie regarding pricing strategy. But I think as we conclude enrollment of the sub retinal studies and we look forward to top line data next year, those discussions will increase and we’ll be able to talk a bit more about at least how we’re thinking about that. But I think early days right now and not something I would want to comment on in absence of discussion with AbbVie. But I think in terms of FDA and leadership change, if you think about it, we are enrolling our pivotal study, we’ve said that we will conclude that in October and then we will continue enrollment for the confirmatory study.

We will probably still be enrolling the confirmatory study at the time of our pre BLA meeting. And so if there’s anything that surfaces along the way, we have the opportunity to adjust and either increase enrollment if that’s the ask or stand on our data, which we think will be extremely strong. And so I don’t think there’s any near term need to contact leadership at FDA, we have good contact at the review division level and avenues for information requests and going back and forth or meetings, Type C meetings if we choose these are other elements of it. But I do wanna reiterate, our pivotal protocol was reviewed by the review team that was very similar to the team that reviewed Alevitus and in detail. And that review team from what we can tell is largely intact today, even though there have been many changes in leadership at FDA and I think that’s comforting to us and again, the urgency for additional therapies in Duchenne couldn’t be at a higher level in my view based on what we’ve seen happen over the last couple of months.

Conference Operator: Our next question comes from Yi Chen from H. C. Wainwright. Please go ahead. Thank you for taking my question.

Could you please comment on whether the dosing level of Sirovac for the subretinal delivery for wet AMD is much lower than the suprachoroidal delivery for wet AMD, ER and DME, and whether the dosing difference is associated with the route of delivery to achieve similar efficacy. Thank you.

Curran Simpson, President and CEO, REGENXBIO: Thanks. Steve, I’ll have you comment on that.

Steve Picola, Chief Medical Officer, REGENXBIO: Thanks for the question Yi. So the doses that we’re looking at in subretinal pivotal studies are lower. These are two separate routes of administration. We’ve been leaders in the exploration in suprachoroidal, looking across two different indications. So, we knew from the start that different route of administration and also in the case of diabetic retinopathy, different indication with different VEGF drive that we had to really look for dose response anew in that new route of administration.

And so, we thoroughly looked at that and also looked at safety with this new route of administration where going higher on dose we knew we had that flexibility from our preclinical data. So, here as well we were able to go higher and show importantly not only the clear meeting of target product profile with suprachoroidal, But also, we wanted to replicate the good parts of subretinal, but not needing a surgical procedure. So, to be able to do that in office. And Early on, we chose suprachoroidal because it preserved the targeted local delivery into the a compartmentalized space, the suprachoroidal space. And that really increases the belief in safety both within the eye or any systemic effect.

So, we also have bilateral dosing with good safety and efficacy results that we’ve seen in a bilateral study. So, all these, this constellation of aspects had us confident to be able to go higher on dose with this new route of administration.

Conference Operator: There are no further questions at this time. And this concludes today’s conference call. Thank you for joining. You may now disconnect.

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