REGENXBIO Q2 2024 Earnings Call Transcript

Quartr
Provided by Quartr
August 1, 2024

There are 13 speakers on the call.

Operator

Welcome everyone to the Q2 2024 Regan X Bio Earnings Conference Call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. At this time, I'd like to turn the conference over to Patrick Christmas, Chief Legal Officer of REGENXBIO. Please go ahead.

Speaker 1

Good afternoon and thank you for joining us today. Earlier this afternoon, REGENXBIO released financial and operating results for the Q2 ended June 30, 2024. The press release is available on our website at www.regenxbio.com. Today's conference call will include forward looking statements regarding our financial outlook in addition to regulatory and product development plans. These forward looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted and can be identified by words such as expect, plan, will, may, anticipate, believe, should, intend and other words of similar meaning.

Speaker 1

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 December 31, 2023, and comparable Risk Factors sections of REGENXBIO's quarterly reports on Form 10 Q, which are on file with the Securities and Exchange Commission and available on the SEC's website. Any information we provide on this conference call is provided only as of the date of this call, August 1, 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 form a financial information that may be provided is preliminary and does not purport to project financial positions or operating results of the company.

Speaker 1

Actual results may differ materially. I will now turn the call over to Curran Simpson, President and CEO of REGENXBIO.

Speaker 2

Thank you, Patrick. Good afternoon, everyone and thank you for joining us. I'm pleased to be leading today's call, my first one as 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.

Speaker 2

Doctor. Steve Pakola, our Chief Medical Officer will provide an update on our clinical programs and then Vikt Vasista, our Chief Financial Officer will provide an overview of financial results for the Q2 ended June 30, 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-two zero two for

Speaker 3

the treatment of

Speaker 2

Duchenne, AbbVie RGX-three fourteen program for the treatment of wet AMD and diabetic retinopathy or Doctor being developed in collaboration with AbbVie and RGX-one hundred and twenty one 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-two zero two, which represents the next generation of microdystrophin gene therapies and is poised to potentially be the 2nd AAV based product to reach the market. There are a number of exciting developments for RGX-two zero two. 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.

Speaker 2

But I first want to highlight the differentiating factors that we believe will make RGX-two zero two a best in class product and the excellent progress we are making to both expedite its development and maximize its commercial potential. RGX-two zero two is a differentiated product candidate utilizing an advanced micro dystrophin construct with potential for improved functional benefit as shown in our preclinical data. It is the only microdystrophin product that includes the C terminal domain, a key region of the naturally occurring dystrophin gene, which has been shown in preclinical studies to protect the muscle from contraction induced stress and improve the ability of the muscle to repair itself. As I mentioned, RGX-two zero two is demonstrating consistently high levels of microdystrophin expression across patients of all ages. But I want to note that it is in older ambulatory boys where we're seeing the highest levels of microdystrophin expression reported in older ambulatory patients, especially compared to other published data.

Speaker 2

And RGX-two zero two has been well tolerated and no SAEs have been reported, which is a significant element of the overall risk benefit analysis for patients, caregivers and regulatory agencies and a meaningful differentiator versus other Duchenne gene therapy trials. As I mentioned, our goal is to be the next approved gene therapy in Duchenne and we are taking all of the necessary steps towards this goal. We recently completed a successful end of Phase 2 meeting with the U. S. FDA and walked away from this meeting confident in our plans to file a BLA using microdystrophin as the primary endpoint for accelerated approval.

Speaker 2

The meeting also involved discussion of our industry leading NAV Express suspension based commercial ready manufacturing process used in this trial. At our in house manufacturing facility, we have the capacity and yields to produce 2,500 doses of RGX-two zero two per year. Given the differentiating characteristics of RGX-two zero two and the significant ongoing unmet need in the Duchenne community plus our manufacturing expertise, we are well positioned to advance this program towards commercialization. Turning to AbbVie RGX-three fourteen, our gene therapy being developed in chronic retinal diseases with our partner AbbVie, we have made several advancements across suprachoroidal trials in diabetic retinopathy and wet AMD. First, with regard to the ALTITUDE trial of 314 for the treatment of Doctor using suprachoroidal delivery, we are accelerating plans for our end of Phase 2 meeting with the FDA.

Speaker 2

This meeting is now expected to take place in the Q4 of this year versus our initial guidance of Q1 2025. The new timeline supports the rapid acceleration towards pivotal trials with initiation expected in the first half of twenty twenty five. Importantly, REGENXBIO will be entitled to a $200,000,000 milestone payment upon successful dosing of the first patient with AbbVie RGX-three fourteen in Doctor, which again is anticipated in 2025. We are also excited to announce that working with our partners at AbbVie, we will be expanding the broad multi indication global potential of 314 by initiating a new cohort in the ALTITUDE trial for patients with diabetic macular edema, DME, 314 is well positioned to become the standard of care to treat and progression of diabetic retinopathy. Broadening the ALTILTILDE trial to include patients with DME further expands the global potential of 314.

Speaker 2

We have also made important progress on our 314 programs for wet AMD as well as in our RGX-one hundred and twenty one program for MPS II as we approach potential approval and becoming the first gene therapy for Hunter syndrome. We remain on schedule to initiate a rolling BLA filing in the Q3 of 2024. Approval of the planned BLA could result in receipt of a priority review voucher in 2025. Overall, we are making excellent progress and have provided positive updates across all programs with a number of additional catalysts on track to be shared later this year. We remain excited by our progress as we continue on the strategic plan.

Speaker 2

We are accelerating the development of our pipeline and expanding their value for shareholders, while bringing potentially life changing therapies to patients facing great unmet need. With that update, I'd like to now turn the call over to Steve for an update on our clinical programs. Steve?

Speaker 1

Thank you, Curran. I'll start with RGX-two zero two, a potential one time gene therapy for the treatment of Duchenne. Today, we reported new microdystrophin expression data from the 2 patients aged 5.88.5 years who received RGX-two zero two at dose level 2, the dose we are advancing to pivotal phase. Microdystrophin expression was measured to be 77.2 and 46.5 percent respectively compared to control at 3 months. As of July 8, 2024, RGX-two zero two continues to be well tolerated with no serious adverse events and all patients who reach 3 month trial assessments indicate meaningful increases in expression of RGX-two zero two microdystrophin and reduction from baseline in serum creatinine kinase levels, supporting evidence of clinical improvement.

Speaker 1

We are very excited as today's data adds to the totality of evidence demonstrating consistent high micro dystrophin expression across all treated patients. In addition, early evidence of strength and motor function improvement were observed via trial clinic assessments and home videos shared by caregivers. On the continued strength of our data, in June, we announced the expansion of the AFFINITY to Duchenne trial to include a new cohort of patients aged 1 to 3 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-two zero two, we will continue to produce data where limited or no data exists to further establish a differentiated product profile that can enhance RGX-two zero two's commercial potential.

Speaker 1

Moving to 314, which is being developed in collaboration with AbbVie to treat wet AMD, Doctor and DME via subretinal and suprachoroidal routes of administration. I'll start with 314 for Doctor being evaluated in the Phase 2 ALTITUDE trial using in office suprachoroidal delivery. As current mentioned with our partner AbbVie, we have accelerated our end of Phase 2 meeting with the FDA and believe this puts us in an excellent position to initiate our first pivotal trial in Doctor. Today, we announced that we are now enrolling a new cohort of the ALTITU trial to evaluate 314 in patients with center involved diabetic globally. We are also evaluating 314 for the treatment of wet AMD via subretinal delivery in 2 ongoing pivotal trials ATMOSPHERE and Ascent in the U.

Speaker 1

S, Europe and Japan. These trials continue to progress well. Our long term follow-up data from the Phase onetwo subretinal trial out to 4 years have set the gold standard in clinical development for wet AMD gene therapy. We have also fully enrolled the open label fellow eye study evaluating 314 in patients previously treated with 314 in the other eye. This study is expected to support a label inclusive of bilateral use, representing a meaningful option for the significant number of patients with wet AMD in both eyes.

Speaker 1

Also in wet AMD, today we announced 314 was well tolerated at dose level 3 in the AVEA trial for wet AMD using in office suprachoroidal delivery. In patients who received short course prophylactic steroid eye drops, there were no drug related SAEs and no cases of intraocular inflammation, endophthalmitis, vasculitis, retinal artery occlusion, choroidal effusion or hypotony. We are encouraged by the positive safety profile seen to date and we plan to enroll a new cohort at dose level 4 as we evaluate dose levels on a path toward pivotal stage. We continue to be encouraged by the progress on our 314 programs and I'd like to particularly highlight the safety profile observed, including in our suprachoroidal programs. We are confident on our plan to advance into new disease states and dose levels because of this safety profile, particularly in the setting of short course 7 week prophylactic steroid eye drops.

Speaker 1

In more than 130 patients treated in office, we're seeing a differentiated safety profile for ocular gene therapies, representing a meaningful potential treatment option for patients and physicians globally. Finally, on RGX-one hundred and twenty one being developed for the treatment of MPS II or Hunter syndrome. In February at the World Symposium, we announced that the campsite pivotal trial met its primary endpoint with high statistical significance. Patients treated with RGX-one hundred and twenty one achieved decreased cerebrospinal fluid, CSF, levels of heparan sulfate D2S6, a key biomarker of brain disease activity to below maximum attenuated disease levels. We plan to share new data from the CAMSIGHT trial in the second half of this year.

Speaker 1

We believe RGX-one hundred and twenty one is well positioned to be the first gene therapy and one time treatment for Hunter syndrome. We've completed a successful pre BLA meeting with the FDA that finalized details of our planned rolling BLA submission. The key takeaways from the meeting included alignment on the use of CSF D2S6 as a key biomarker and surrogate endpoint reasonably likely to predict clinical benefit to support accelerated approval. We also reached alignment on CMC manufacturing requirements and on the confirmatory trial design. To conclude, we continue to make significant progress with data updates in trial progression across all programs in our pipeline.

Speaker 1

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

Speaker 3

Thank you, Steve. REGENXBIO ended the quarter on June 30, 2024 with cash, cash equivalents and marketable securities of $327,000,000 compared to $314,000,000 as of December 31, 2023. The increase was primarily attributable to $131,000,000 in net proceeds received from an upsized public offering of common and pre funded warranties completed in March 2024, partially offset by cash used to fund operating activities in the first half of twenty twenty four. R and D expenses were $49,000,000 for the Q2 of 2024 compared to $60,000,000 for the Q2 of 2023. The decrease was largely driven by reduced manufacturing and clinical supply costs for AbbVie RGX-three fourteen and RGX-two zero two and personnel related costs as a result of reduced headcount.

Speaker 3

The decrease was partially offset by increases in clinical trial expenses for AbbVie RGX-three fourteen and RGX-two zero two. REGENXBIO expects its balance and cash, cash equivalents and marketable securities of $327,000,000 as of June 30, 2024 to fund its operations into 2026. This cash runway guidance is based on the company's current operational plans and excludes the impact of any payments that may be received from AbbVie upon the achievement of developments or commercial milestones under AbbVie RGX-three fourteen collaboration, including a potential $200,000,000 milestone for achievement of the 1st patient dose in the pivotal trial for suprachoroidal delivery for treatment of Doctor. Additionally, our one way guidance excludes the potential monetization of our priority review voucher that may be received for RGX-one hundred and twenty one. With that I will turn the call back to Curran to provide his first set of final thoughts.

Speaker 2

Thanks, Nick. Today was another exciting day for our 202 program with additional positive data. As we look ahead to the rest of the year, we are encouraged by our discussions with the FDA and are finalizing pivotal plans 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 Doctor 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.

Speaker 2

Thanks everyone for your time today. I'll turn the call over for questions. Operator?

Operator

Thank you. We will now begin the question and answer session. Your first question comes from the line of Gena Wong of Barclays. Please go ahead.

Speaker 4

Thank you. Congrats on the new data regarding the 202 in DMD. So I have two questions. One is the 202, I know you will meet with the FDA, finalize the pivotal study. Do you have a goal of a protein level you wanted to achieve?

Speaker 4

And do you expect FDA will set some threshold in order for accelerated approval? And another question is regarding the 314 of suprachoroidal indication in Doctor and wet AMD. What's the reason for dose level 4 and will you also include patient with existing neutralizing antibody?

Speaker 2

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

Speaker 4

protein level?

Speaker 2

Protein microdystrophin level. We've proposed a threshold with FDA and that's one of the things that we'll be waiting for the minutes and sort of final agreement in addition to the back and forth that will occur with the pivotal plan that we 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 percent 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.

Speaker 1

Hi, Gina. 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.

Speaker 1

So I think the key consideration is we're going higher in part because we can. We really have the flexibility given that 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-three fourteen. 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.

Speaker 4

Thank you.

Operator

Your next question comes from the line of bikrath Parikh of Morgan Stanley. Please go ahead.

Speaker 5

Great. Thanks for taking our questions. We had 2. 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?

Speaker 5

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.

Speaker 2

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

Speaker 1

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

Speaker 5

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 for 314 in wet AMD overlapping with your efforts with the subretinal program you currently have underway?

Speaker 1

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, reduction in treatment burden.

Speaker 1

So we'll really look at all of those to see what type of response we get at 6 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% of patient reduction in injection burden.

Speaker 2

And this is Curran. To the first question, in terms of functional data in the fall, just to baseline, we measure micro dystrophin at a 3 month time point. And then on the functional assays, we measure generally every 3 months a number 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 6 and probably 9 months data for them. Things like time to rise and NSAA as an example.

Speaker 2

We haven't finalized exactly what data will come out because it's still emerging, but that's the plan for the fall.

Speaker 1

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 in excellent durability has us very excited about that. There's, of course, the opportunity to expand the optionality by having an in office procedure.

Speaker 1

And we look forward to gathering more data in the additional cohort to keep evaluating that option.

Speaker 5

That's helpful. Thank you.

Operator

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

Speaker 5

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 Alevitus 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, veg use, a competitor recently provided some updated data for their program. And then I think this came out as a bit of a surprise.

Speaker 5

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.

Speaker 2

I can take the first one and then I'll have Steve address the second question. I think on patient recruitment for 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.

Speaker 2

And I'll turn it over to Steve to address the 314 question.

Speaker 1

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 and stability 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.

Speaker 1

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.

Speaker 2

And just one follow on, Paul, to the question on recruitment. I mean, one of the purpose 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.

Speaker 5

Great. Thanks for taking our questions.

Operator

Your next question comes from the line of Alex Treinen from Bank of America. Please go ahead.

Speaker 6

Hi, good afternoon. This is Mary Kate on for Alex today. Thanks for taking our question. Just one on DMD, given questions around safety for others in the 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.

Speaker 2

Yes, that's I think something that we're still working on and probably will tie out completely in the pivotal plan that we'll submit to FDA. So we're really not able to comment in terms of very 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 1, 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.

Speaker 2

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.

Speaker 4

Understood. Thank you.

Operator

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

Speaker 7

Hi, thanks for taking my question. We also have 2. 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?

Speaker 7

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?

Speaker 7

So a little broader question. Thanks.

Speaker 2

I can start with 202. And I think we think about functional data in sort of 2 dimensions. As it relates to accelerated approval, our primary driver will be measuring microdystrophin at 3 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.

Speaker 2

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

Speaker 1

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 non surgical 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.

Speaker 1

So really being able to look out to 6 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.

Speaker 4

Okay. Thank you.

Operator

Next question comes from the line of Mani Pohar of Leerink Partners. Please go ahead.

Speaker 8

Hi, good afternoon. This is CJ Yang on for Mani. Thanks for taking our question. Could you please comment on your strategy in DMD? Are you targeting younger patients than Sarepta's current label since you've announced you've expanded the age range to 1 to 3 while Sarepta's youngest age is 4?

Speaker 8

Thanks.

Speaker 2

Hi, this is Curran. Yeah, think it's safe to say we want to build an adequate safety database at a minimum for the patients in ages 1 to 3. But we'll be enrolling across a wide variety of ages in the studies.

Speaker 1

And we had made the decision to expand and look at this broad age range including 1 to 3 before any levetis label expansion. So we've seen this opportunity and now with the results safety that we've seen and the micro dystrophin expression we've seen across a wide age range on the upper end, it's great opportunity to look at 1 to 3 year olds.

Speaker 8

Perfect. Thanks for the commentary.

Operator

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

Speaker 9

Hi, this is Eric Musambam calling in for Eliana. Thanks so much for the question. My first one is on 2, do you have any in house data from patients already dosed with 2 zero two beyond the 3 months to help us better understand their ability and what the effects might be over time? And what are you expecting to see over time? Do you expect label to be stable for 3 months or more or could they deepen over time?

Speaker 1

And I have one follow-up.

Speaker 2

I'm sorry, are you referring to micro dystrophin levels beyond 3 months or other functional data, for example? Micro dystrophin, yes. Okay. No, we're taking a biopsy prior to treatment and then at 3 months. We don't have biopsies beyond that time point basically per direction with FDA.

Speaker 2

However, be measuring durability in terms of functional outcomes in the periods. Yes, we don't have data beyond 3 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.

Speaker 9

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 micro dystrophin expression or higher functional assessment?

Speaker 1

So the usual caveat that there aren't enough patients that really have confidence in terms of predictors. I'd say that the biggest learning so far is actually that age is not predicting a lower micro dystrophin as you go up on age, which has been a concern that the community has had, whether that might be the case and 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 8 and older, we're seeing very robust micro dystrophin levels. Beyond that, we're seeing micro dystrophin levels across the patients. So no clear differentiator or predictor in this sample to date.

Speaker 5

Got it. Thank you.

Operator

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

Speaker 10

Great. Thanks so much for taking my question. Congrats on the progress. Maybe, Karen, 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 the view read that you can get accelerated approval on 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?

Speaker 10

I think that's an important distinction. So any color much appreciated. And then maybe still on DMD, how you think you would have confirmatory trial? Will you still use NORSTAR as the primary endpoint or do you think there are other endpoints that can be more sensitive here? Any color, much appreciate it.

Speaker 10

Thanks so much.

Speaker 2

I can work a bit in reverse. We'll use NeuroStar, 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.

Speaker 2

And the basis for that is simply the differentiation of the product. That's I think one of the basic tenants 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 broader label as possible.

Speaker 10

Got it. Thanks so much.

Operator

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

Speaker 11

Hey, thanks for taking the question. On the Phase III 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 supposed to get answered by the FDA or the FDA hopes you think the FDA will need answers to 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 here really just to supplement with some data in patients who have progressed on to DME?

Speaker 2

I'll give a brief comment and then turn over to Steve. I certainly think we and AbbVie have a really high level of confidence in Doctor 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.

Speaker 2

But I'll let Steve comment on the details of what we're thinking and how that study should go.

Speaker 1

Fortunately, as current mentioned, there's a roadmap 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 is 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 designs.

Speaker 1

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 into Phase 2 meeting into Q4 instead of Q1 next year. And then your

Speaker 9

Yes. No, I was just going to

Speaker 11

ask about the DME cohort.

Speaker 9

Yes.

Speaker 1

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.

Speaker 1

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.

Speaker 11

Great. Thank you.

Operator

Your next question comes from the line of Daniel Gautaulin of Chardan Capital Markets. Please go ahead.

Speaker 12

Hey, guys. Thank you for taking the question and congrats on your new role. I have a quick question on wet AMD program, the spread on 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 to interact with the immune system, what is your long term strategy for treating fellow eyes using suprachoroidal delivery?

Speaker 12

Thank you.

Speaker 2

I'll turn that

Operator

one to Steve.

Speaker 1

Hi, Danilo. 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 6 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. Sub retinal, I think is the most straightforward to feel confident that you won't have an issue dosing the fellow eye because of the immune privileged status of the subretinal space.

Speaker 1

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 Y, but over time certainly it would make sense to assess fellow Y with suprachoroidal as well.

Speaker 12

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

Remove Ads
Powered by Quartr
Earnings Conference Call
REGENXBIO Q2 2024
00:00 / 00:00
Remove Ads