REGENXBIO Q1 2024 Earnings Call Transcript

Quartr
Provided by Quartr
May 8, 2024

There are 11 speakers on the call.

Operator

Good day, and thank you for standing by. Welcome to Regenxbio First Quarter 2024 Earnings Conference Call. At this time, all participants are in a listen only mode. After the speakers' presentation, there will be a question and answer session. Please be advised that today's conference is being recorded.

Operator

I would now like to hand the conference over to your speaker today, Patrick Christmas, Chief Legal Officer. Please go ahead.

Speaker 1

Good afternoon and thank you for joining us today. Earlier this afternoon, REGENXBILE released financial and operating results for the Q1 ended March 31, 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 and the Management's Discussion and Analysis sections 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, May 8, 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 would now like to turn the call over to Ken Mills, CEO of REGENXBIO. Ken?

Speaker 2

Thank you, Patrick. Good afternoon, everyone. Thanks for joining us. I'm pleased to begin today's call with a recap of the recent business highlights as well as an update on our corporate goals. Today, Curran Simpson, our Chief Operating Officer, will be speaking for Steve Pakola, Chief Medical Officer, who is unable to join us today.

Speaker 2

Curran will provide an update on our clinical programs. Then, Asista, our Chief Financial Officer, will provide an overview of the financial results for the quarter ended March 31, 2024. At the end of the call, we'll open up the line for progress across our pipeline as we advance each of our programs toward pivotal stage clinical trials and commercialization. In 2024, we've put a focus on large commercial opportunities where our product candidates are differentiated, can be expedited and support meaningful value generation soon and for the long term. Our priority programs are RGX-two zero two for the treatment of Duchenne, ABVD RGX-three fourteen or 314 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.

Speaker 2

All of our programs remain on track to meet our goals for this year. Program milestones over the past couple of months further demonstrate how our new plan is supporting the acceleration of the development of our gene therapies and the expansion of value for shareholders. Today, we're especially pleased to share new positive data and important updates about acceleration in our programs for Duchenne NDR using in office delivery. We are providing some new updated guidance on near term milestones for these programs. So let me explain.

Speaker 2

We're thrilled to see RGX-two zero two is demonstrating strong microdystrophin expression across a wide range of patients, including in older boys, like those ages 8 to under 12 and importantly we are seeing positive safety signals. No SAEs have been reported in patients who've received RGX-two zero two, which is highly notable differentiator in Duchenne gene therapy trials. Today, we announced that we have selected our pivotal dose. Also, we have already begun a new expansion phase of our clinical development with the pivotal dose. This includes the enrollment of 3rd and 4th boys already.

Speaker 2

Expansion using the pivotal dose will continue into the 3rd quarter and can enroll up to a total of 7 boys in the ages ranging from 4 to under 12. By early Q3, we expect to hold an end of Phase 2 meeting with the FDA, which will support a final pivotal design and pivotal trial initiation is anticipated in late Q3 to early Q4 of this year. RGX-two zero two is a differentiated product candidate in the landscape for Duchenne, representing the closest thing to natural healthy dystrophin and we believe has the potential to make a meaningful difference for a broad range of patients. Given these unique characteristics of RGX-two zero two, a significant ongoing unmet need in the Duchenne community and conversations with the FDA, we're confident in our plans to file a BLA using the opportunity for ABVD RGX-three fourteen as a single injection treatment to become a 1st in class gene therapy for wet AMD and the standard of care to treat and prevent progression for diabetic retinopathy. Enrollment remains on track for subretinal delivery program for wet AMD currently in pivotal trials.

Speaker 2

And today we announced that based on positive interim results to date from the Phase 2 ALPTED trial in Doctor, the design and evaluation of 2 pivotal trials is ongoing, which would be the first pivotal trials for our in office suprachoroidal delivery. These positive results and activities are in support of a planned discussion with the FDA at an end of Phase 2 meeting anticipated in Q1 2025 that can enable the rapid acceleration toward pivotal development. We would expect to initiate the first two pivotal trials for suprachoroidal delivery of diabetic retinopathy in the first half of twenty twenty five. As a one time treatment, we believe that 314 is well positioned to become the standard of care to treat and prevent progressive progression of diabetic retinopathy, which is expected to impact over 20,000,000 people globally in the next 5 years. Overall, we're thrilled about the current status and the way that 2024 can achieve meaningful value generation based on what we've seen in these first few months.

Speaker 2

With that, I'm going to turn the call over to Chief Operating Officer, Curran Simpson, who will take us through a bit more of a detailed update on the Duchenne data and our plans for accelerating the pivotal trial initiation for Duchenne in the second half of this year and diabetic retinopathy in the first half of next year. Curran?

Speaker 3

Thank you, Ken. I'll start with RGX-two zero two, a potential one time gene therapy for the treatment of Duchenne. RGX-two zero two represents an alternative pre existing neutralizing antibodies. Today, we reported that new microdystrophin expression from the second patient aged 8.1 years who received RDX-two zero two at dose level 2 was measured at 20.9% compared to control at 3 months. A reduction in baseline in serum creatinine kinase CK levels of approximately 90% was observed at 10 weeks.

Speaker 3

We're excited about this data and the robust response seen in this trial, particularly in dose level 2 and in older boys. As we shared previously, we use 2 methods of measuring microdystrophin protein, western blot via JAS and LCMS. Notably, in this case, the microdystrophin measured using LCMS for this patient was approximately 44% higher than the Western blot result. Today's data adds the totality of evidence demonstrating that all patients who completed 3 month trial assessments indicate consistent, encouraging increases in expression of RGX-two zero two microdystrophin and the reduction from baseline in serum CK levels, supporting early evidence of clinical benefit. In addition, early evidence of strength and motor function improvement were observed via trial clinic assessments and home videos shared with trial investigators by caregivers.

Speaker 3

As of May 3, 2024, RGX-two zero two continues to be well tolerated in all treated patients with no serious adverse events. Given the robust data and positive safety signals, we plan to move forward with dose level 2, 2e14 per kilogram as our pivotal trial dose. We have initiated an accelerated dose level 2 expansion cohort and have already dosed 2 patients. We expect to treat up to a total of 7 patients at the pivotal dose. Looking ahead, we remain on track to share strength and functional data for both dose levels and initiate dosing in the pivotal trial in late Q3 to early Q4 this year.

Speaker 3

Moving to 314, which being developed in collaboration with AbbVie to treat wet AMD and diabetic retinopathy via subretinal and suprachoroidal routes of administration. We are evaluating 314 for the treatment of wet AMD via subretinal delivery in 2 ongoing pivotal trials, ATMOSPHERE and Ascent in the U. S, Europe and Japan. We anticipate global regulatory submissions in the first half of twenty twenty six. We are also evaluating 314 in the Phase II ALTITUDE trial, which is the dose escalation study of 314 using suprachoroidal delivery.

Speaker 3

We're very excited about the opportunity in Doctor given the size of market, which exceeds that of wet AMD. 1 year data from dose levels 12 showed 314 to be well tolerated with patients demonstrating clinically meaningful improvements in disease severity with reductions in vision threatening events. Based on these and other positive interim results from ALTITUDE, today we are pleased to share more details about our path to pivotal stage in Doctor. We are evaluating the design for 2 pivotal trials in support of an end of Phase 2 meeting with the FDA anticipated in the Q1 of 2025. We expect to start the 1st pivotal trial in Doctor in the first half of twenty twenty five.

Speaker 3

We've aligned with our partner AbbVie on this timing and believe there may be opportunities to further accelerate. To conclude, we continue to make significant progress with data updates and trial progression across all programs in our pipeline. Lastly, I'd like to thank the patients, families, clinicians and patient advocacy representatives who've been involved and supported all of these trials. And with that, I turn the call over to Vit to review our financial guidance. Vit?

Speaker 3

Thank you, Curry.

Speaker 4

REGENXBIO ended the quarter on March 31, 2024 with cash, cash equivalents and marketable securities totaling $381,000,000 compared to $314,000,000 as of December 31, 2023. The increase was primarily attributable to the $131,000,000 in net received from an upsized public offering of common stock and prefunded warrants completed in March 2024, partially offset by cash used to fund operating activities in the Q1 of 2024. R and D expenses were $55,000,000 for the Q1 of 2024 compared to $59,000,000 for the Q1 of 2023. The decrease was primarily attributable to reduced manufacturing and clinical supply costs

Speaker 2

for our

Speaker 4

lead product candidates and personnel related costs as a result of reduced headcount. It was partially offset by an increase in clinical trial expenses across our lead product candidates. We expect the balance in cash, cash equivalents and marketable securities of $381,000,000 as of March 31, 2024 to fund our 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 development or commercial milestones under our 314 collaboration, including a potential milestone payment of $200,000,000 receivable upon achieving the dosing of the first patient in the pivotal trial for suprachoroidal delivery for the treatment of Doctor. Additionally, this cash flow guidance excludes any potential monetization of a priority review voucher that may be received for REGENX-1 hundred and twenty one.

Speaker 4

With that, I will turn the call back to Ken Mosabi to provide final thoughts.

Speaker 2

Thanks, Vitt. So to wrap things up, so far in 2024, our plans are on track intended to generate significant value for shareholders as we're ensuring that resources are allocated to the most valuable assets and to accelerate the development of those assets. As outlined here today and supported by the press release announcements, we're motivated by expanding that value by addressing important unmet need in patients and focusing on large commercial opportunities where we think our product candidates are differentiated and have a clear regulatory pathway forward. The recent efficacy and safety data has allowed us to determine the planned pivotal dose for RGX-two zero two, which is enabling us to further accelerate this program. So far this drug candidate is exceeding our expectations in the clinic.

Speaker 2

We've already begun a clinical trial expansion phase to add boys onto our pivotal dose, a step that we believe will contribute meaningfully to our accelerated approval plan. Duchenne is a market where there is large unmet need for new therapies and that is capable of supporting multiple gene therapies. And we believe RGX-two zero two has unique differentiating features that support its potential to be a best in class product. Regardless of today's landscape of Duchenne treatments, communication from the FDA continues to support the need for alternative gene therapies for rare diseases including Duchenne. Backed by strong data, we're acting with urgency and in concert with the FDA taking steps to initiate the pivotal trial for RGX-two zero two as soon as possible this year and focused on serving needs in a broad range of value with our eye care partnership with AbbVie.

Speaker 2

It's using our one time treatments that provide sustaining vision health long term and overcome the clinical challenges of managing retinal diseases. The updates today highlight key alignment on important partnership goals in 2024 that are directed at completing trial designs and plans for initiating 1st pivotal trials for 314 using in office suprachoroidal delivery in diabetic retinopathy and completing enrollment of our pivotal trials for 314 using subretinal delivery to support filing of global regulatory submission. And as current mentioned, we believe there are opportunities to further accelerate these programs. RGX-one hundred and twenty one is meaningfully changing course of disease in boys with MPS II by restoring a missing gene. And we're on track to file our first BLA as a company in 2024 using the accelerated approval pathway for RGX-one hundred and twenty one.

Speaker 2

Our pivotal trial achieved its primary endpoint of reduction of natural substrate in the CSF. Patients treated with RGX-one hundred and twenty one have showed continued improvement in neurodevelopmental skill acquisition up to 4 years and have discontinued intravenous enzyme replacement therapy. Our pivotal trial was designed to enroll boys under the age of 5. A strong proportion of those enrolled in our program are below the age of 2. And these are key features that are important in assessing neuroneopathic Hunter syndrome.

Speaker 2

We're locking our clinical trial databases and our team is busy collecting final pivotal trial data and completing steps for the entire BLA filing process. By the end of 2024, our pipeline should be filled with programs that are initiating pivotal stage, fully enrolled at pivotal stage or under a filed BLA. And as Vit mentioned in the Q4, we announced a successful public offering. This rate strengthens our balance sheet. It extends our operating runway into 2026 to support the acceleration of our candidates through multiple value generating milestones today, but it's worth noting and restating that achievement of certain of these milestones would also trigger 100 of 1,000,000 of dollars of additional funds.

Speaker 2

As a result of these recent updates and the upcoming milestones announced today, we believe REGENXBIO is well positioned for success. Thanks everyone for your time today. That finishes our discussion part of the call. And now we're going to move over to Q and A.

Operator

Thank you. Our first question comes from the line of Vikram Purohit from Morgan Stanley.

Speaker 5

Hi, everyone. This is Gaspar on for Vikram. We have one question on the DMD program. So what do you think are the trial enrollment and regulatory implication, if any, from Pfizer's update yesterday for 202?

Speaker 2

Hi, Gospel. Thanks for the question. I think that, as we reflect on what was obviously a sad event reported by Pfizer yesterday, we continue to feel very strongly, as we always do about the importance of safety with gene therapy and in rare diseases in general, especially in pediatric populations, which is why we continue to feel very strongly and enthusiastic about the safety profile of RGX-two zero two to date being really the wind at the back for how partly how we're thinking about being able to progress on a more accelerated basis into pivotal phase. The same way that we had reflection when we made those decisions about RGX-1 hundred and twenty one and advancing it into pivotal phase. I do think that from a regulatory perspective, this also has to at a high level be something that agencies like the FDA take into consideration for existing approved products as well as products in development.

Speaker 2

I think it's going to this is something that I think people should be cautious about generating data in certain populations. I personally feel it is a must when you think about the ability to apply and understanding in certain areas, like in certain ages or certain progressed areas of disease. I think you also have to think about where those lines and differences are in seeing a younger boy enrolled in a trial, go through an event like that, I think is something that we've been emphasizing for a while that it's important to generate the data including in older boys where we have been doing so as you continue to think about how to progress into later stages of development to support that clinical understanding and the potential for commercialization there. So I imagine that many stakeholders are reflecting on that as well.

Speaker 3

Thank you.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Gena Wang from Barclays.

Speaker 6

Thank you for taking my questions. So just want to confirm, did I hear you correctly that the 5th patient, the mass spec protein level was 44% higher, I. E. 65% protein level per mass spec? And also will you pick one methodology for protein level for pivotal study?

Speaker 6

Would that be western blot or mass spec? Related question, sorry, have you already scheduled the date for end of a Phase 2 meeting in 3Q? And also regarding understanding you will still need to finalize the trial with FDA, but can you submit BLA once 3 months protein data available?

Speaker 2

Hi, Gina. We'll unpack that. Thanks for the good questions. On the first point about the micro dystrophin results, what Kern said is that we had approximately 44% higher LC MS result compared to the Western blot just result. Typically for us, we've gotten comparable results in previous assessments between boys in this case LC MS was higher, but that 44% applied to the result we reported in the press release gets to about 30% for the LC MS results.

Speaker 2

With respect to the plans, can I say, I mean, we're just in constant communication with the FDA on really all of our programs, but in particular Duchenne, there's a lot going on in the space? I think Ghospel's question can't be ignored as well. So we continue to see very close. We do have plans for an early Q3 meeting with the FDA on sort of end of Phase 2 pivotal planning and initiation. We have shared with them already during the course of the program, ideas about variables and features that are important to you, Oscar, that we're hearing are important to them in order to be able to design what we and they think is the most efficient and appropriate trial.

Speaker 2

We've really been focused on wanting to emphasize gaps in understanding for the community. We've talked a lot about the data that we've been able to generate and the focus that we've been able to put on older boys continuing to show positive micro dystrophin results, measurable micro dystrophin results in this case reported today in another 8 year old. We continue to enroll in that age range. The last two patients we enrolled were 5 year old and an 8 year old. So, we feel like the data and the conversations that we have are going to set up for a very constructive discussion with FDA in early Q3.

Speaker 2

And we've also been open about the fact that we want to have that discussion on what punitively would be the other side of the potential action date with respect to the existing accelerated approved product. So we feel like everything is really on track and being able to declare the pivotal dose today to bring that into the conversation discussion is something that is also important.

Speaker 6

Thank you. Thank you.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Alex Stranham from Bank of America.

Speaker 5

Hey, guys. This is John. I'm on for Alec. So just a quick question from us. In terms of second half data update for DMD program, the 2 zero two, in terms of functional assessment data, what kind of data should we be expecting?

Speaker 5

Like if you were to give us a comp, like something to look to as like a standard, what would that be, if you could shed some light on that? Thank you.

Speaker 2

Yes, John, sure. I mean, I think we're collecting the normal strength and functional assessment, including the full Northstar domain on all of the boys in Affinity Duchenne. We showed some of the activities that were going on in this trial by sharing some Doctor. Panda shared some video that he was able to bring forward at the NDA conference just a few months ago. So we're going to have the opportunity to with boys that have achieved time points, some of which will be by the second half of the year reaching out to 12 months and maybe some a little bit earlier.

Speaker 2

NSAA scores as well as sub domains of North Star including things that have been the focus of other recent Duchenne approvals or even discussions around the time to stand and sort of time to stand and sort of domains associated with the ability around movement. So these are the types of things that I think you can expect from us in the second half of the year based on patients that have been enrolled to date.

Speaker 5

Thank you.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Annabel Samimy from Stifel.

Speaker 7

Hi, thanks for taking my question. I guess on the DMD program, I want to sort of understand your view on this. You're saying that the micro dystrophin levels are consistent, but it doesn't seem like it's specifically linear with age. And so I was just wondering if you had any more insight into what's happening there? And is this maybe going to change what the clinical relevance of is of micro dystrophin specifically?

Speaker 7

Or are there other factors that they're considering here? And then the second question I have is obviously Sarepta has an FDA decision pending on final approval and label expansion. And we're getting a lot of questions about what the various scenarios might be. And sitting from your perspective, can you opine on how that might impact you and your opportunity going forward? And how you sort of view the different scenarios that are possibly emerging from that?

Speaker 7

Thanks.

Speaker 2

Yes, absolutely Annabel. Again, I think that, so partial answer to the first question, just to clarify, we're talking about different methods of measure for micro dystrophin today that we generally have viewed as comparable. We've been using Western blot and LCMS. I think we're the only company to use both. We've been presenting Western blot, which is more of an automated Western Blot data in general to the community, because people are more familiar with it with respect to what is in the existing approved product label.

Speaker 2

In terms of what we measured in this 8 year old today and what we previously measured in the 12 year old, let's remind everyone that we're talking about results that are positive measures of microdystrophin protein in age ranges that generally have not been reported with other products. And in this case, between the NF2 that we enrolled at dose level 2, we're seeing about an average of 50% microdystrophin level expression based on that Western blot method. So we're really encouraged about that based on what we've seen in our preclinical data, what we see of the safety profile and what we've seen that has started to emerge from some of the strength and functional assessment even at dose level 1, again referring back to what Doctor. Panda was able to share a bit on podium at MDA. So I think this the safety profile in particular made the dose decision about the pivotal dose a rather straightforward one for us.

Speaker 2

We think we're continuing to see high levels of micro dystrophin expression, especially in older boys. And we think that that in particular is something that's representative of a really strong, stable and durable product candidate. When it comes to the upcoming decision on the confirmatory evaluation evidence of a Levitus and the supplement, I think we've been reasonably cautious with all of you all along about what that outcome maybe. And also what we think the opportunity for RGX-two zero two is. Now, something's changed in the last couple of days and we've often talked about this unmet need for Duchenne boys with gene therapy is having at least 2 or 3 other candidates in development.

Speaker 2

And yesterday, obviously, there's been a bit of a change to the profile of one of them, which I think everyone is still trying to digest. We continue to view that RGX-two zero two with new biology, with the C terminal domain, with the type of micro dystrophin expression that we've been showing in older boys, but also in 4 to 7 year olds as being robust and significant and unique is a differentiated product profile and that's without even having reached the time points yet on strength and function where we can really exercise an understanding of the benefits of the C terminal domain. Those are things that are we think coming in front of us. So, we see a differentiated product profile here as being very important. It's important for the incident population of Duchenne boys always.

Speaker 2

I think it's important for the prevalent population of boys as they are considering what their options are or will be as families and as physicians. And we've talked often about the fact that in general RGX-two zero two also holds a unique potential position in the market as boys are certainly going to be excluded from access to other treatments due to pre existing immunology, just like they would be for our own. And in the case that we've talked about where there would be 2 products on the market that both were, let's say, ahead either on the market or in pivotal phase development ahead of 202. We've sort of labeled that as maybe 15% of the market prevalent market that would be able to be uniquely addressed by 202. If you change that to REGENX with RGX-two, could be second to market and that number could be higher.

Speaker 2

It could be something more like 20% to 30%. So I think for us, the work that we're doing to focus on the go forward plan for accelerating RGX-two zero two is about the strength of our differentiation, the strength of our data, safety data, the efficacy data and addressing what we still think is unmet need with 1st generation microdystrophin products. But the case of just being as good as other things is also something that an economic perspective is foundationally valuable. But we think that RGX-two zero two of course is much more than that and we think that the data is showing that and we intend to continue to show that through as fast an expansion and acceleration phase as possible working with the FDA.

Speaker 7

Thank you.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Ellie Merle from UBS.

Speaker 8

Hi, this is Jasmine on for Ellie. Thanks so much for taking our question. So we have another one on the strength and functional measures we'll be getting in the DMD update in the second half. So what do you think would be meaningful to see at the time point that you'll share later this year, so at 12 months, I'll offer earlier, relative to what you think would be meaningful in the longer term, so in another year or 2?

Speaker 2

Sure. Thanks, Jasmine. Look, I mean, I think we believe that RGX-two zero two with the C terminal domain has biological function and structure that translates into improvements in muscle function that we've seen in its design, in animal modeling and that even early evidence of strength in motor function improvement was observed that we reported back with the investigator at the MDA conference in March. So we continue to be eager to accumulate the domains of the North Star that we can collect on strength and function and be able to show that and show the support for that differentiation coming into the second half of the year. That is not impacting though our conversations with the FDA on the approach to the accelerated approval pathway and the regulatory plan that we have.

Speaker 2

If it is, it's only enhancing it because any evidence of early strength and motor function improvement that's being observed is becoming a contribution to the totality of evidence. But in the conversations with the FDA are about continued unmet need in the Duchenne population even with existing and known standard of care, boys who cannot get access to treatment because of pre existing immunology, boys who may not be able to access treatment in certain age ranges because they're looking for more data or there are gaps in data and that understanding boys who may have certain types of mutations that have not been able to be studied and explored either due to profiles of other products or simply because they haven't been done. And so that's been our focus is to design something that is both efficient, effective and accelerated in sort of pivotal design, but also something that's answering not just questions that FDA feels like it already has answers to. And I think FDA has evidence pretty strongly that it is supportive of microdystrophin as a surrogate biomarker predictive of clinical benefit. And we certainly with RGX-two zero two are achieving levels of microdystrophin at or really above what I think is expected in terms of the regulatory process.

Speaker 2

So where we're going next is moving quickly on microdystrophin accelerated approval and then focusing on strength and function data that we accumulate over time to further differentiate us in the commercial market and on more of a confirmatory basis.

Speaker 8

Great. Thank you.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Brian Skorney from Baird.

Speaker 9

Hey, good afternoon. Thank you for taking the question. First, quick one. You previously given the weights at dosing of the other patients, just wondering if you can provide the weight of patient number 5 here. And not jumping out to me, based on the data provided so far, that there is differentiation between dose level 12 in Western or CK level changes.

Speaker 9

So I'm just wondering what's kind of informing the decision to go at dose level 2? Thanks.

Speaker 2

Yes, Brian, again, I mean, I think we're looking at a data set in dose level 2 right now that is entirely based in 8 and above. And the dose level 1 data includes, 1 patient from that age range, but the 2 other patients that are in the 4 to 7 range, which I know to all of you and to most people is a more familiar territory because that's what the data is that has been shared most often and almost entirely with respect to existing labeling of the accelerated approved product as well as data from other datasets from other programs. For us, look, I think there's several things. We are seeing ranges of results here that are consistent with what we've observed in animal models, where we've seen differentiation of those doses in terms of functional outcomes in the animal. The other thing is that, we're looking at the range of the results overall and we're incredibly happy and proud of the fact that everything that we're seeing in reporting is already in double digit micro dystrophin ranges, not the case with other data sets as you look at them.

Speaker 2

So achieving that I think says something to us about the overall stability and the overall quality of RGX-two zero two as a candidate as designed. But secondarily, I think we do see RGX-two zero two at DL2, again having something that is just between those two results, close to 50% micro dystrophin expression. And these are in boys, 1 who is 12 and 1 who is 8. And for us, those are the types of boys that are more progressed disease with frankly that are more challenged to be able to get levels of micro dystrophin expression with gene therapy. And I think that's reflective of the evidence that other programs haven't even chosen to progress or share data in those types of age ranges.

Speaker 2

So this is what has got us incredibly enthused and excited is that dose level 1 showed us, yes, we can get great results in 4 to 7 year olds and we got a strong result also in an older boy, a 10 year old in that case. But in dose level 2, the first two kids that we enrolled were older boys and we got what we think are phenomenal results. That and the safety profile was an easy decision along with discussions we've been having with FDA to designate that as our pivotal dose.

Speaker 9

Great. And just how about the weight for patient number 5, you have Yes.

Speaker 2

Sorry, I didn't hear you. Did you say weight?

Speaker 9

Yes. Can you tell us the weight of patient number 5? I think that you provided the other weights.

Speaker 2

Yes. I don't have that off the top of my head. I'll have to follow-up with you on that.

Speaker 9

Okay. Thanks.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Danielle Brill from Raymond James.

Speaker 5

Hey, guys. This is Alex on for Danielle. Thanks for the question. A couple on 314. Given the updates today, do you still plan to publicly disclose data updates from ALTITUDE later this year?

Speaker 5

And just curious why the large gap between now and the guided end of Phase 2 meeting with FDA in 1Q 25? And then looking at wet AMD, to us, we think that wet AMD as a data set, it's a little bit more mature. So we would have guessed that that would have been advanced to Pivotal as well. So what kind of data or time points do you and AbbVie need to see to convince you to advance the suprachoroidal wet AMD forward to pivotal development? Thanks.

Speaker 2

Yes. Thanks, Alex. You've hit on an important point. We're working in partnership with AbbVie here to ensure successful program, including significant commercial and clinical value is achieved. We're well aligned with them on this guidance and we've been focused on the fact that when we bring a package forward to the FDA for pivotal design, which would be the 1st such pivotal package for suprachoroidal delivery for gene therapy in diabetic retinopathy that it's going to be as robust and sort of important as you could expect for that conversation.

Speaker 2

And we don't rule out that things could be done on an accelerated basis to beat that guidance. But right now, we sort of felt most confident in the Q1, twenty twenty five guidance, which is months away, right? And so for us, also the fact that we view initiation of the pivotal in the first half of twenty twenty five, I think can sort of emphasize that we think that the sort of time, energy and effort that would be put into an end of Phase 2 discussion will be something that we can accelerate off of in terms of pivotal initiation overall. With respect to suprachoroidal device overall and program plans between diabetic retinopathy and wet AMD. This is actually pretty consistent and predicted for us.

Speaker 2

We talked about back in the end of 2023 that's the diabetic retinopathy data that was presented was maturing and kind of coming into focus in terms of key measures of efficacy and safety that was a little bit ahead of where we saw things with respect to wet AMD suprachoroidal. We updated wet AMD suprachoroidal in the client eye meeting earlier in the year at 6 month data and said we were encouraged by that, but also viewed that it was the decision was potentially frame shifted from diabetic retinopathy by at least a few months. And so we continue to maintain and sort of guide that overall. What I would say is, eventually one of the indications has to be the first to go into pivotal phase and into that discussion with FDA. I think that the view that the first also would be the one that would be a 2 pivotal trial design approach is something that I think is consideration overall and that we feel strongly, I know at REGENXBIO in alignment with AbbVie about this that the unique nature of the data that we're seeing in diabetic retinopathy and the unique unmet need is also something that is very attractive for bringing that forward as the potential first application of the suprachoroidal delivery approach.

Speaker 2

But we have guidance for Q3 update on wet AMD as well and we'll be able to talk more about that program then.

Speaker 5

Great. Thanks so much.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Mani Foroohar from Leerink. Hi, this is Lily on for Mani. Thank you for taking my question.

Operator

So maybe just a quick follow-up in terms of the super corridor for 314. So in terms of the data update, can you maybe just give us a little bit more granularity in terms of so we've seen 6 months, the follow-up timing that we would be seeing and also the potential data point that would basically influence your decision? Thank you.

Speaker 2

Sure. I don't think we have any more specific guidance right now on what the next data updates are going to include again in our process here working in partnership with AbbVie is, right now we're focused on program execution and acceleration based on these positive interim results that we've decided for diabetic retinopathy led us to this updated guidance on initiation of the pivotal. But we generally have kept a reasonably steady cadence of updating the community at conferences and when we're able to bring additional data forward usually in settings of medical conferences we do. Right now, we expect the next program update in data for wet AMD suprachoroidal to be in Q3. But we're especially excited that diabetic retinopathy program now has guidance for the 1st suprachoroidal program to move into pivotal phase.

Operator

Thank you. Our next question comes from the line of Luca Izzi from RBC Capital.

Speaker 10

Great. Thanks so much for taking my question. Congrats on the progress. Maybe a quick one on DMD, Circling back on the pre existing immunology, you're obviously trying to differentiate in DMD in multiple ways, including C terminus domain as well as obviously going after broader patient population. But what percentage of patients will be eligible for your therapy simply because they have neutralizing antibody against both Sarepta and Pfizer.

Speaker 10

Just trying to get a numerical percentage here on that kind of lowest hanging fruit. And then maybe on the competitive landscape for the ocular gene therapy, we recently saw some data for the long acting TKI, data was somewhat mixed for Doctor, despite actually pretty good data for wet AMD. What are your thoughts on what drives that dichotomy between the 2? And maybe more broadly, what are your thoughts on long acting TKI as a potential competitive threat for your program? Thanks so much.

Speaker 2

Yes. Thanks, Luca. So I think you do a pretty solid job at modeling that concept of the cross reactivity of different serotypes. I think we generally have offered up that 202 maybe a solution on its own. Again that's with 2 other competitive products, let's say Sarepta and Pfizer competitive with a REGENX product in a hypothetical firm where you'd be looking at cross reactivity of the different AAVs and say what's left uniquely for REGENX, I think that's about 15%.

Speaker 2

I think you can draw on that from a number of sources of data. Again, it's generally accepted and known that the and known that the prevalence of neutralizing antibodies against any AAV capsid is going to be something on the order of 30%, maybe even 40% of subjects. I mean, even more for some of the earlier AAVs like AAV2 for instance. But in general where we are with an rh74, AAV9 or REGENX is AAV8. So I think in the case where there's 2 competing products, 15% in the case when we're second to market, which I think is a possibility we need to start considering here for RGX-two zero two in terms of where we are positioned to continue to execute the safety profile, the data that we're showing can be above that number.

Speaker 2

I could see 20% to 30% in a head to head comparison with another vector. On the comment about TKI, I mean good observation. I know there was a couple of data sets that have been presented in the last few months, both in NPDR. I mean, obviously, like AAV gene therapy, RGX-three fourteen, the body of evidence around the clinical data between subretinal and suprachoroidal and its ability in a continuous way with its PT profile to target anti VEGF or VEGF with basically a molecule that's a known approved therapeutic entity, I think is very different than the continuation that people have worked on to try to bring forward broad spectrum chemistry agents like Tyrosine Kinase inhibitors to affect VEGF in the eye. Our view is nothing compares to the profile of a one time treatment expressing an anti VEGF biologic that is part of the known standard of care for wet AMD and related conditions.

Speaker 2

Remember, treatments like EYLEA and LUCENTIS are actually labeled for Doctor and NPDR population. They're just not used at all. They're not adopted even arguably in the 1% cases. So what we are bringing forward to the market is importantly a profile of something that is already established clinically as showing benefit, but just hasn't had the commercial adoption. I think TKIs are coming from a different space.

Speaker 2

I don't think that necessarily the chemistry and the formulations have completely been worked out. I don't think that TKIs have been worked out entirely overall across retinal diseases. And I think that they're certainly not one time treatments, which is well I think is what a meaningful differentiation for 314 suprachoroidal is. So for us at this stage, we think we have a profile that is a clear commercial leadership profile and a clinical leadership profile.

Speaker 9

Thank you so much.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Dhanil Goetelin from Chardan.

Speaker 5

Hey, guys. Thank you for taking the question. I have a follow-up on the 314 in diabetic retinopathy. As you begin to prepare for the end of Phase 2 discussions, what is your current thinking on the primary endpoint of greater than or equal to 2 step DRS S improvement versus the greater than or equal to 3 step worsening that some other companies are planning or considering to use? Thank you.

Speaker 2

Yes. Good question, Danielle. I think that, look, I think the most important emphasis for us about the clinical and commercial opportunity in Doctor is actually what Curran mentioned about vision threatening events or vision threatening complications. We have shown evidence of risk reduction up to almost 90% in vision threatening complications in diabetic retinopathy patients. And this is the thing that in the long term is what is affecting their vision.

Speaker 2

And so to longitudinally be able to affect that is the priority and that will be something that we will continue to collect in trials. When it comes to the concepts of DRS scoring 2 step worsening or 2 step improvement, these are regulatory outcomes that I think have meaning in terms of how we're going to power studies and I think that we've shown evidence of data previously in our development where we've had really high propensity of patients who overall have achieved improvement in DRSS relative to observational control and we've had 0% of patients worsen relative to a high number of patients on a percentage basis who are worsening in these observational controls. So I think there's good options there for us in terms of the regulatory endpoint, but I want to really emphasize that we think that the focus clinically and commercially for bringing especially uniquely one time treatment forward would be the emphasis on the reduction of vision threatening events. And for there, I think again we can point to at least an 89% reduction in data we presented last year as some of the we think best data and supportive evidence for this type of treatment in diabetic retinopathy.

Speaker 5

Got it. Thank you.

Operator

Thank you. At this time, I'm showing no further questions. This concludes today's conference call. Thank you for participating. You may now disconnect.

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REGENXBIO Q1 2024
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