REGENXBIO Q2 2023 Earnings Call Transcript

Quartr
Provided by Quartr
August 2, 2023

There are 14 speakers on the call.

Operator

Good day and

Speaker 1

thank you for standing by. Welcome to the Q2 2023 REGENXBIO Earnings Conference Call. After the speakers' presentation, there will be a question and answer session. Please be advised today's conference is being recorded.

Operator

I would now like to

Speaker 1

turn the conference over to your speaker today, Patrick Christmas, Chief Legal Officer, you may

Speaker 2

begin. Good afternoon, and thank

Speaker 3

you for joining us today. Earlier This afternoon, REGENXBIO released financial and operating results for the Q2 ended June 30, 2023. The press release is available on our website at atwww.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.

Speaker 3

These risks are described in the Risk Factors and the Management's Discussion and Analysis section of REGENIC Bio's Annual Report on Form 10 ks for the full year ended December 31, 2022, and Comparable Risk Factors section 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 this call, August 2, 2023, 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.

Operator

I would now like to

Speaker 3

turn the call over to Ken Mills, CEO of REGENXBIO. Ken?

Speaker 4

Thank you, Good afternoon, everyone. Thanks for joining us. I'm pleased to begin today's call with a recap of some recent business highlights as well as an update on our corporate goals. Doctor. Steve Piccola, our Chief Medical Officer, will then provide an update on our clinical programs and Vikt Vasista, our Chief Financial Officer, will provide an overview of financial results For the Q2 ended June 30, 2023.

Speaker 4

At the end of the call, we will open up the line for questions. At REGENXBIO, our mission is to improve lives through the curative potential of gene therapy and we're focused on developing therapies For diseases that have significant unmet needs. We continue to be a leader in gene therapy with thousands of patients who have been dosed with AAV therapeutics derived from our Recently, it's been a significant time of growth for the AAV gene therapy industry and at REGENXBIO. We're developing a deeper understanding of gene therapy market access models and digesting regulatory approvals, including the FDA's support of biomarkers as surrogate endpoints to support accelerated approvals. There are now 5 FDA approved AAV therapeutics.

Speaker 4

And I'm pleased how REGENXBIO remains a leader in the gene therapy space as our 5x25 strategy is on track for advancing 5 AAV therapeutics from our internal pipeline and licensed programs into pivotal stage or commercial products by 2025. What distinguishes REGENXBIO as a leader in AAV therapeutics is our platform, pipeline and products. There are thousands of patients who have been dosed with AAV therapeutics derived from our NAV technology platform and 100 more receiving treatment every quarter. We estimate approximately 2 children per day are receiving ZOLGENSMA, which uses our NAV AAV9 vector. We believe that we have a strong pipeline of AAV therapeutics ourselves with the potential to deliver one time treatments to address unmet need for patients living with common and rare diseases.

Speaker 4

At REGENXBIO, we are conducting over 12 active clinical trials using 6 different forms of delivery devices in 3 therapeutic areas, retinal, neuromuscular and neurodegenerative diseases. In 2023, our team is executing on 2 pivotal phase programs that include over 1,000 subjects to support a goal we have to file our first BLA in 2024 2025. We're observing that on average one new patient is being dosed in REGENXBIO clinical trials daily. Our work in retinal disease primarily centers around the strategic partnership we entered into with AbbVie at the end of 2021 To develop and commercialize ADDV RGX-three fourteen or 314, an investigational gene therapy. AbbVie is a strong and complementary partner for REGENXBIO.

Speaker 4

We expect to leverage AbbVie's global development and commercial infrastructure within eye care with our expertise in AAV gene therapy clinical development and deep in house knowledge of manufacturing. Together, we're developing 314 to be the first One time therapeutic option in major retinal vascular diseases to address significant unmet need for patients. Overall, our pipeline of AAV therapeutic candidates is addressing high unmet need for millions of patients in diseases that represent Current market opportunities of over $20,000,000,000 Just a few weeks ago at our Investor Day in July, we introduced a new clinical Trial data from our retina programs using suprachoroidal delivery and our Duchenne microdystrophin candidate and we provided specific guidance about additional upcoming interim trial updates. From our AVIATE and ALTITUDE trials, we reported that mild to moderate Intraocular inflammation previously observed with suprachoroidal delivery is mitigated with short course topical steroid eye drops. And we reported safety updates from the initial dosing in Cohort 1 of the APHINITY Duchenne study to support a well tolerated profile of our candidate RGX-two zero two to date.

Speaker 4

Now I'll turn the call over to Steve, so that he can review in detail a bit more about

Speaker 5

Thanks, Ken. I'll begin with 314, which is being developed in collaboration with AbbVie to treat wet AMD and diabetic retinopathy via subretinal and suprachoroidal routes of administration. 314 utilizes our NAV AAV8 vector to deliver a gene encoding, a therapeutic antibody fragment The anti VEGF market opportunity is poised to grow significantly as the population ages. 314 for the treatment of wet AMD via subretinal delivery is being evaluated in 2 ongoing pivotal trials, Atmosphere and Ascent. We recently announced the expansion of these studies to enroll a total of 1200 patients In the U.

Speaker 5

S, Europe, Japan and Israel to support global development of the program. We also recently initiated a FLOI treatment study as part of the pivotal program using subbreT ALK delivery. This study is evaluating the safety, efficacy and immunogenicity of subretinal 314 administration In the follow eye of patients with bilateral disease from AtmosFear and Ascent, who previously received a subretinal injection of 314. Overall, we plan to complete all these trials in time to support global regulatory submissions in late 2025 through the first half of twenty twenty six. Additionally, earlier this week, we presented new interim results from our Phase 2 pharmacodynamics study designed to evaluate the Same dose levels being used in the 2 pivotal trials.

Speaker 5

The updated interim data demonstrated that 314 manufactured using our Navix REST platform process was well tolerated and in both the low dose and high dose cohorts through 6 months, Patients achieved expected protein levels along with stable to improve BCVA and CRT as well as meaningful reductions in anti VEGF burden with most subjects remaining injection free. This study is now fully enrolled. We also have 2 ongoing Phase II trials that fall under our collaboration with AbbVie assessing in office suprachoroidal delivery of 314 for treatment of wet AMD in the AVA trial And treatment of diabetic retinopathy in the ALTITUDE study. AVIATE is an active control dose escalation trial evaluating 314 We recently presented safety data at our Investor Day from Cohort 6 evaluating dose level 3, 1e12 gcperi that included short course prophylactic ocular steroids following administration of 314. The initial data presented continues to support the safety profile of 314 and highlighted the inclusion of short course prophylactic steroid eye drops, which resulted in 0 cases of intraocular inflammation or IOI in all patients.

Speaker 5

We plan to present full 6 month results from Cohorts 56 at the Hawaiian Eye Meeting in the beginning of 2024. ALTITUDE is the active controlled dose escalation study of 314 suprachoroidal delivery For treatment of Doctor, we're very excited about the opportunity in Doctor given the size of the market, which exceeds that of wet AMD and because we believe this patient population can benefit the most from a potential one time gene therapy. During our Investor Day, we presented initial interim data from Cohorts 45 at dose level 3 with short course prophylactic steroid eye drops Following 314 administration, the data demonstrated that 314 was well tolerated with no Drug related serious adverse events in 29 patients from these cohorts and just as observed in wet AMD, The inclusion of short course prophylactic steroid eye drops resulted in 0 cases of I OI in all patients. We look forward to presenting full 12 month results from cohorts 1 to 3 at the American Academy of Ophthalmology meeting later this year. Moving to Duchenne.

Speaker 5

As Ken mentioned in his remarks at our Investor Day, we were pleased to announce our new Exxon skipping program To complement RGX-two zero two, Duchenne patients face high unmet need and we are committed to bringing multiple treatment options for these boys. Our first program, RGX-two zero two is a potential one time gene therapy For the treatment of Duchenne, being developed as a highly differentiated product designed to deliver a transgene for a novel microdystrophin That includes the functional elements of the CP domain found naturally in occurring dystrophin. Our GX-two zero two is designed to support the delivery and targeted gene expression throughout skeletal and heart muscle Today, we reported safety data from the Phase onetwo AFFINITY Duchenne trial. The data we presented on the 2 patients, ages 410, Showed that RGX-two zero two was well tolerated in both patients with no drug related serious adverse events. Time of post administration follow-up was 45 days and more than 3 months.

Speaker 5

We continue to actively recruit patients in this trial, and we look forward to presenting additional data at the World Muscle Society Congress later this year that will include longer term safety data And initial microdystrophin protein expression levels in muscle at 3 months. We also continue to enroll patients in AFFINITY beyond An observational screening study that is evaluating the prevalence of AAV8 antibodies in patients with Duchenne. Moving to our other rare disease programs, we are developing 2 programs for buccopolysaccharide ocs, RGX-one hundred and twenty one is an investigational one time AAV therapeutic For the treatment of MPS II, also known as Hunter Syndrome, being evaluated in the ongoing Phase 1, 2, 3 campsite trial. In May, we announced that we received regenerative medicine advanced therapy or RMAT designation from the FDA. Recognizing the preliminary data we have presented to date indicates its potential to address the unmet medical need for patients with Hunter syndrome.

Speaker 5

We completed enrollment of 10 patients for our CAMSIGHT trial in the first half of twenty twenty three and remain on track to support a BLA filing in 2024 using the accelerated approval pathway. Now on to RGX-one hundred and eleven, an investigation of one time AAV therapeutic for the treatment of severe MPS I. We have completed enrollment of the Phase onetwo trial and we remain on track to share additional updates on plans for this program later this year. In addition to these two programs, we also are developing RGX-one hundred and eighty one to treat the neurodegenerative manifestation and RGX-three eighty one to treat the ocular manifestations of CLN2 or Batten disease. Physician investigators in Brazil continue with follow-up for the first child with CLN2 disease dosed with RGX-one hundred and eighty one under a single patient investigator initiated study, and we expect investigators to report initial interim data from this single patient, including 6 month results at the Society For the Study of Inborn Errors of Metabolism Annual Symposium later this year.

Speaker 5

We are also happy to report the recent dosing of our first patient with RGX-three eighty one. To conclude, we have made significant progress with data updates and trial advancements across all our programs as we continue toward our goal of 5x25. Lastly, I'd like to thank the patients, And with that, I'll turn the call over to Vit to review our financial guidance.

Speaker 6

Thank you, Steve. REGENXBIO ended the quarter on June 30, 2023 with cash, cash equivalents And marketable securities totaling $415,000,000 compared to $565,000,000 as of December 31, 2022. The decrease was primarily driven by cash used to fund operating activities during the first half of 2023. R and D expenses were $60,000,000 for the Q2 of 2023 compared to $61,000,000 for the Q2 of 2022. The decrease was primarily attributable to an increase in developmental cost reimbursement from AbbVie under our eye care collaboration.

Speaker 6

We expect the balance in cash, Cash equivalents and marketable securities of $415,000,000 as of June 30, 2023 To fund our operations into 2025, 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. With that, I will turn the call back to Ken to provide final thoughts.

Speaker 4

Thanks, Steve and Vit for those important updates about our clinical progress and our financial performance. REGENXBIO continues to Perform at a high level as we execute on our mission of improving lives for the curative potential of gene therapy. In addition to our platform and pipeline, Our end to end capabilities also set us apart as a leader with our manufacturing innovation center here in Rockville running scalable commercial ready batches of AAV therapeutics and our research and early development team continues to advance what's possible in gene therapy. We provided clear examples of these capabilities at our Investor Day when we presented data from the Manufacturing Innovation Center performance, including our product quality and yields. And when we introduced plans for a new IND for a candidate with exon skipping science to expand our commitment to Duchenne.

Speaker 4

Looking ahead for the remainder of the year and early into next year, we anticipate a number of important Clinical pipeline milestones. Let me summarize. Next month, as Steve mentioned, investigators of the Society For the study of inborn errors of metabolism, we'll report the first initial data 6 month follow-up from the first patient dosed With RGX-one hundred and eighty one for the treatment of CLN2 form of Batten disease, this is a 5 year old child and this This is part of the data from our 3rd neurodegenerative program. In October at World Muscle Society, we We expect to share additional interim data from patients in Cohort 1 of APHINITY Duchenne, including longer term safety and the 1st micro dystrophin expression protein In November, we plan to report additional interim data from the Phase 2 ALTITUDE trial of 314 suprachoroidal delivery for the treatment of diabetic retinopathy at the American Academy of Ophthalmology mode. This will include full 12 month results from Cohorts 1 and through 2 and 3.

Speaker 4

And finally, in January of next year, investigators will report on additional interim data from the Phase 2 AVA trial of RGX-three fourteen suprachoroidal delivery For the treatment of wet AMD, including full 6 month results from Cohorts 56, and this will be at the Hawaiian Eye and ResMed Meeting. So we have a lot of important value driving catalysts ahead of us this year and with the balance sheet In place to continue to fund our mission and operations into 2025 as Vit described, we have the focus and high performing team, Strong collaborators and the trust of the clinical and patient community partners, it's a clear and definable path for us to achieve our 5x25 vision And continue to lead what's possible with AAV Therapeutics. We want to thank all of you for Listening today, we look forward to providing you additional updates as we continue on this path for the remainder of this year and into next year. And with that, operator, we'll turn the call over for questions.

Operator

Thank

Speaker 1

Our first question comes from Dayton Leon with RJS. Your line is open.

Speaker 7

Hi, congratulations on all the progress and thanks for taking some questions for us. Two questions kind of have been percolating with investors recently. One, it seems like you've given us more detail Around what efficacy data we could expect from both AVA and ALTITUDE. Just one question regarding AVA, Should we expect 12 months data from cohorts 1 through 4 at Hawaiian Eye? Or will it be just a full look across all cohorts up to month 6?

Speaker 7

And then secondly, can your team elucidate what actual assays Around protein expression of micro dystrophin, we could see at worlds and whether You would expect some method of comparability to your peers that have ongoing DMD programs as well. Thank you.

Speaker 4

Thanks, Dane, for the good questions. Steve, do you want to take the Hawaiian IP?

Speaker 5

Sure. So Hi, Dane. Thanks for the questions. So for the ABA wet AMD update, we have discussed The latest results that we have for 6 month follow-up, we haven't said more as far as longer term follow-up in part because of the later cohorts And the dynamic nature in these interim updates of ongoing studies, as well as Really seeing when we might be able to do a data cut and we always have the overhang of also reaching alignment with Appy as we get Closer to these type of meetings, so that's the type of thing that we can update as we get a little closer.

Speaker 4

And on the microdystrophin protein expression, Dane, we are working with methods that we think will So I think that as we come into world muscle, I think we all know that Forms of western blot assays as well as liquid chromatography mass spec have been used In assessments of other patients, we think that we will have methods to support interpretation of that And some forms of comparison, keeping in mind that there are always nuances in assays, but I think things that the community will be familiar with from us.

Speaker 7

Excellent. I look forward to seeing the data. Thank you.

Speaker 4

Thanks a lot. Appreciate it.

Speaker 1

One moment for our next question. Our next question comes from Gena Wang with Barclays. Your line is open.

Speaker 8

Hi, it's Tony on for Gina. I have two questions. I guess first briefly, can you remind us of the IP and royalty status for some of your partner programs, including with Rocket for Dantenzies and Ultragenyx for GSD1a, as well as any IP rights And then another one on DMD, with updates expected from Sarepta and Pfizer later this year, What kind of bar would you be looking for in terms of efficacy for protein expression and NSAA?

Speaker 4

Sure, Tony. Thanks a lot for the questions. Yes, with respect to programs that are part of our NAV Technology licensee universe, Certainly, ROCCAT's stand in program and the Ultragenyx GSD1a programs are under license for 2 different vectors, ROCCAT using AAV9, NAV AAV9 and Ultragenyx using NAV AAV8 in the case of GSD1a. We these are licenses that we entered into several years ago. We tend to have Royalties that are in the range or similar to the type of compensation that we're receiving, for example, on the Zolgensma royalty, so starting in the high single digits and going up on a tiered basis up into double digit ranges.

Speaker 4

With respect to IP as it relates to your second question, We currently have 2 lawsuits that are involving Patents relating to the manufacturing of Sarepta's product as well as patents that involve of Sarepta's product, both of which use AAVrh74 that they refer to. And so We updated recently on the second lawsuit. The first lawsuit that involves the patents relating to Manufacturing of the product is actually scheduled for trial in the beginning of 2024. With respect to your second question, I think this builds off of Dane's question about microdystrophin data and expression and where the Program for RGX-two zero two is going, which we're very encouraged about some of the initial safety data that we provided just a few weeks ago. When it comes to microdystrophin expression, we think that RGX-three fourteen is within the class of Treatment candidates that have been explored clinically so far, including both Sarepta and Pfizer and some others like SOLID, We're at a 1e14 dose currently in our trial, and I think that is, again adjusting for understanding there can be sometimes differences In assays and quantitation of different AAV products, it's similar to where Pfizer is in its pivotal program.

Speaker 4

And My understanding of Sarepta's accelerated approved product is that they're slightly above that 1.3e14 in terms of dose level. So We'd be coming into observations of some of the first clinical data that we'd see at 90 days looking to achieve Similar protein expression with respect to RGX-two zero two to what others are achieving. Now the key there is that We believe that once we express microdystrophin in the muscle of children that our microdystrophin Has the potential to be more potent or more efficacious because we're the 1st clinical candidate to design into The AAV microdystrophin that's being expressed, a substantial component of the C terminus, as Steve alluded to, the C terminal domain, which We've established pre clinically, both in AAV experiments and in other, work To be meaningful in terms of improving the strength and the biological function of a microdystrophin. And so it's actually something that's more akin to What I would consider to be attenuated forms of Duchenne like Becker muscular dystrophy that was sort of alluded to in The recent FDA adcom and discussions about microdystrophin and the possibility of microdystrophin being similar to things That occur in nature. Ours is the first product that includes something that is most similar to things that occur in nature.

Speaker 4

And so we think that will have amplification of potential efficacy outcomes. Now the measurement of the efficacy outcomes will not be something that we'll be able to Assess at the 90 day point, those considerations, of course, will be at later time points, maybe nearer to 9 or 12 months. But that's when we would begin to get This will be longer term safety data and our first expression of micro dystrophin in cohort 1 at the 1e14 dose.

Speaker 1

One moment for our next question. Our next question comes from Gaspar Alsangay with Morgan Stanley. Your line is open.

Speaker 8

Hi, everyone. This is Gaspar on for Vikram Purehead. So our question is, what is your current view on where RGX-two zero two could fit for some competing DMD therapies in the real world and we're well set.

Speaker 4

Yes, Ghastal, it's a great question. The design of RGX 2 0 2 in the target product profile is multi threaded for us. First is, We believe strongly that there continues to be an unmet need in AAV gene therapy For boys when just a single product would be available or even 2 products. And that's because, as you all know, of Preexisting immunology that can exist in boys that may not allow them to access AAVs because of 0 prevalence for pre existing neutralizing antibody. So we estimate that the potential market for an AAV8 based capsid, which is what RGX-two zero two is based on an incidence basis and on a prevalence basis could include 15% or maybe up to 30% of the population that might not be able to access other capsids that are currently in development.

Speaker 4

That's the first point. 2nd point is What I was just alluding to in my answer to Tony, which is, we're the 1st RGX-two zero two is the 1st reagent To be brought forward scientifically and clinically that includes a domain of full length microdystrophin that doesn't exist in other microdystrophin products, the C terminus, Which again, evidence to support preclinically that there is an improved effect of biological activity and strength of muscle When that C terminal domain is present in truncated forms of dystrophin. So that we think sets us up potentially for a A form of best in class. When later in development, we can assess more clinical data, we'll be more clear on that. But I think the preclinical data points in that direction today and the evidence of the C Data points in that direction today and evidence of the C terminus is something that we strongly emphasize as our focus in development.

Speaker 4

And then the last piece is, I think, on quality and yields when it comes to manufacturing. This is something that we just Highlighted at our Investor Day a few weeks ago, we think that the purity and the quality of the AAV Our products that are being manufactured here at the Rockville Manufacturing Innovation Center as well as the yields we're achieving with our NAV Express process We'll allow us to be competitive in a market when it comes to everything from showing improvement in Things like potential safety profiles and as well as potentially on cost. All right.

Speaker 8

Thanks very much.

Speaker 9

Thanks.

Speaker 1

One moment for our next question. Our next question comes from Alex Cernahan with Bank of America. Your line is open.

Speaker 2

Hey guys, thanks for taking our questions. Just a couple from us. First, actually on MPS II, just curious Your interactions with the FDA around the RMAT designation, if you could give a sense of what it would take to show clinically for accelerated approval and if you intend to update the markets with the top line data Prior to filing. And secondly, it's just around the AbbVie milestone. I appreciate this is not in The runway guidance, but any additional color around the scope and timing around any additional milestone triggers over the next year or 2 would be great.

Speaker 2

Thank you.

Speaker 4

Hey, Alec. Thanks for those questions. On MPS II, yes, we just announced today that we've completed The goal of enrollment of 10 patients with respect to the campsite study to support our plans for accelerated approval And it was great timing with respect to the RMAT designation from FDA as well to support our continued Execution here on the regulatory front, I think that, look, RMAT is something that's a designation that only comes from FDA's acknowledgment Of clinical data, right? There are other types of designations that sometimes can rely exclusively on preclinical data for support. But in this case, RMAD is something where the FDA has already assessed clinical data that's been generated from our trials and provided input that it believes that there's a potential status here for moving quickly.

Speaker 4

And that's been consistent with our dialogue with FDA In the last several years, with respect to how we've been thinking about transitioning from some of the first patients we've reported Findings on all the way through to getting to that 3rd dose level in our dose escalation and starting this phase of pivotal enrollment in the last year. So I think that you absolutely can expect on a going forward basis from us additional data before the time of the filing of the BLA That would include top line data that would go to support the BLA filing. But at this stage, sitting here today, we've just Completed enrollment in the Q2 of the 10 patients and we're going to compile the timeline for not only completing the work to support the BLA, but Also for those data updates, so look out for us on those updates going forward. When it comes to AbbVie, You're bringing me back. I think when we first reported on this partnership in eye care with AbbVie, we Highlighted in our filings that in addition to the total number of milestones that may be earned out by REGENXBIO For Development, Regulatory and Commercial, a big portion of that, I think, is over $750,000,000 It's actually associated with the development and regulatory milestones.

Speaker 4

And I guess what we can say today is that The guidance that we can provide is that a substantial portion of that $780,000,000 is associated with The execution and advancement of suprachoroidal development. And so as Steve is alluding to, as we come into updates Later this year with respect to altitude and aviate as we progress from 2023 into 2024, We're certainly learning a lot more about the potential for the advancement and the regulatory advancement and the development advancement Of the suprachoroidal programs for both wet AMD and diabetic retinopathy and that starts to bring those development and regulatory milestones as potential earn out for us into focus.

Speaker 2

Thanks, Ken. Appreciate the color. One moment for our next question. Our

Speaker 1

Our next question comes from Ellie Merle with UBS. Your line is open.

Speaker 10

Hey, guys. Thanks so much for taking the question. For DMD, I guess, Can you maybe provide more color on when you expect to move to the 2nd dose level? And I know you said we'll get data on the 1st dose level at World Muscle, but maybe what are the timelines for us seeing data from the second higher dose? And then just your expectations around

Speaker 4

Thanks, Ellie. A few layers there. We haven't given any guidance or any sort of specific Kind of plan around dose escalation or and this trial is also designed for the potential of dose Expansion at the first dose level as well. So that will be something that will be happening in the Phase where we have the opportunity to sort of complete and evaluate the first cohort level, and take into account The different types of variables, including the initial measures of microdystrophin at dose level 1. With respect to dose level 2 though, I mean pre clinically we certainly

Speaker 9

expression levels and what the expectations are. So Sarepta has a 40% to 50% new change in micro dystrophin expression from baseline on the label. Is that what we should expect to see, as the bar for success, when we get more data in October? And also on DMD, despite Strepus setting a favorable regulatory precedent on the biomarker and gaining accelerated approval, Pfizer yesterday mentioned that their interim look for efficacy later this year will be on function and not on surrogate biomarker. I know it's still early days, but just wondering what's your strategy for gaining approval and wondering if you are in the biomarker camp or the functional camp?

Speaker 9

Thanks for taking

Speaker 4

questions. Sure. Thanks, Lisa. Digging into it a bit, I think, I mean, referencing The product approval label for Sarepta, I would say, we can look at means, we should also look at medians And distributions of patients and we'll have small numbers and in certain cases when they have small numbers, there was quite a distribution of microdystrophin expression. So, I think for us, we definitely view that we're going to be in the territory of things that have been reported by both Sarepta and Pfizer with respect to microdystrophin expression.

Speaker 4

And I think that does for me, I mean, I wouldn't go as far as to say something like the median of the first patients that were enrolled on the basis of Sarepta, which I think was anything from like Nearly 0 up to like over 100%, because that would be ridiculous. But I think what we've seen when it comes to median and means of things reported By Sarepta and Pfizer is that there's sort of a range of like 20% to 40%, and that would be something that for us would be Adjusted for heterogeneity of the disease, the different types of methods and sort of the assessments that have been done, something that I think would I feel comfortable for us in terms of similarity. With respect to the regulatory approach here, I mean, I think my observations well, I mean, let me just say that I think REGENXBIO, Both through our neurodegenerative franchise as well as since we've entered the development of products For Duchenne muscular dystrophy, we have been very much focused on discussions with regulators and stakeholders about the use of the accelerated approval pathway. And I think that mode. We continue to sort of approach our development and sort of regulatory execution on that basis, and we think that the validation of The first AAV therapeutic to be approved on the basis of accelerated approval is a great Milestone to continue to support that.

Speaker 4

Confirmatory data and other people taking approaches of trying to establish Different avenues to show more longer term functional data, I think are also valid and different. And I think that We'll continue to sort of process all of the information that comes in from both our own trials and our own development experience That of sort of stakeholders and patients as well as the FDA, but from where we sit right now, there is an urgent need and especially with the approval On an accelerated basis of this first product, I think we all know that there is a limited labeling that Support of the accelerated approval, at REGENXBIO, we're developing based on a clinical trial that's enrolling in boys from 4 all the way up to age 11. There's still significant unmet need here and there's a significant urgency here. And so that's where I think we anchor ourselves to the patient need and the regulatory understanding that accelerated approval is something that all the stakeholders are supportive of And that we think that we want to contribute to as well.

Speaker 9

Thanks for taking our questions.

Speaker 1

One moment for our next question. Our Our next question comes from Brian Skorney with Baird. Your line is open.

Operator

Hi. Thanks for taking our questions. This is Charlie on for Brian. We wanted to ask, it seems like suprachoroidal delivery for wet AMD, what is going to take What it's going to take to progress into Phase 3 is going to be fairly straightforward for wet AMD. But for diabetic retinopathy, we wanted to get a little more color on How you're thinking about the interim results you'll be presenting later and what the kind of bar is in terms of efficacy.

Operator

And we'd also just kind of like a reminder on what kind of conversations you've had with the FDA so far regarding the NaVXPress Manufacturing platform. Thank you.

Speaker 4

You want to take the DRO question?

Speaker 5

Sure. Thanks, Charlie. So As you mentioned, we have the opportunity to look at readouts for both wet AMD and Doctor. On Doctor, it's interesting there's the precedent of looking at 2 step improvement On diabetic retinopathy severity, that's largely a technical consideration and a powering Consideration for what's been done with prior repeat injection anti VEGF agents. But what Patients and their doctors really care about is preventing progression.

Speaker 5

So really having a proportion of patients that can have improvement of a certain level is a proxy for, okay, then you're more likely to not have patients progress 2 vision threatening or blinding complications, which is the ultimate goal. So the reason I give that context is Both of those are clinically meaningful if you can have patients improving and if you can have a lower proportion of patients that worsen. And what we've seen to date with 6 months results from our earlier cohorts is we really see both. The overall Trajectory of these patients is going in a better, not a worse direction, and that's in contradistinction to what we know happens In patients' natural history and also in our negative control arm with observation. And What we also know is the bar that one thinks of for repeat injections indefinitely is something Totally irrelevant for us with a one time in office treatment because we know that With repeated injections, you can actually stave off vision threatening complications, but the treatment burden for these Asymptomatic patients is just too much and patients aren't signing up for this, as I think it's fair to say many predicted So when we talk to clinicians, experts and investigators, really any Clear reduction in clinically meaningful worsening is a Very viable clinically and commercially target to shoot for.

Speaker 5

So on top of looking for proof of concept, That's really the way we're thinking about a target product profile. So we and AbbVie definitely look forward to seeing results The other thing I'd say is durability. So we've seen very good results at 6 months. It's going to be great to have an opportunity to Assess durability out to a year later this year.

Speaker 4

On the NAV Express I think that we have started the process in 2023 of Creating process qualification lots around the planning of BLAs for both RGX-one hundred and twenty one and RGX-three fourteen. And so we've had the opportunity to have a lot of dialogue With FDA, again, we're running over 12 clinical trials. But for 2 late stage studies, 121 and 314 with the Our retinal approach, we've had more advanced discussions with FDA. We've also had the opportunity Conveniently being here in Rockville to have had people visit the facility and we feel like we have one of the strongest

Operator

Great. Thank you. Great.

Speaker 1

One moment for our next question. Our next question comes from Andreas Agariz with Wedbush Securities. Your line is open.

Speaker 11

Yes. Thanks for taking our questions here. Just 2 from us. For RGX-one hundred and twenty one and PS2, Can you elaborate on your interactions with the FDA and how they came to support the shorter timeframe for accelerated approval versus the competitors? And What additional data do you or AbbVie, sorry, this is probably second part of the question to it, need to collect if you're comfortable Advancing 314 into

Speaker 1

pivotal trials

Speaker 11

for wet AMD and Doctor and whose decision is it at the end of the day? Thanks. So

Speaker 5

I hey, Andres, I can take the second one first. So I guess the generic answer is we obviously take into account all data updates That we give and look at traditional aspects like dose response, safety and tolerability always come first If we're going to consider a potential dose and I think the good news is in both indications, we have very clear noninvasive ways to assess Forward response and also potential dose response. And there's not one Line in the sand, I'd say, that you can give in these cases because it really is looking at the overall results Other than the suggestion I gave in terms of at least efficacy on diabetic retinopathy. And to your related question of who makes the decision, we work very closely and collaboratively with AbbVie and we have the traditional joint committees like joint development and joint commercial committees that work together and cross functionally evaluate All the data and really compare that against our target product profile to make such decisions.

Speaker 4

Yes. And with respect to the first question about 121, there really is not a Close competitor to the target product profile of RGX-one hundred and twenty one, which is a one time therapy to address Strictly the CNS components of Hunter syndrome. So we think we sort of stand in a unique class here, Both with the one time nature and standing on top of the unmet need for CNS features of MPS II because of the existing standard of care treatments in the U. S. Like eliprise, not being able to address those features.

Speaker 4

And I think that the FDA designation of the RMAT is supportive of the fact that They're encouraged by the clinical data that has been reported so far, such that they want to designate it as A program that has the type of status that is meant to be accelerated. So I think that we feel really good about our data. We feel good Unique one time profile of a treatment that addresses CNS manifestations of Hunter and we feel Good about the data that we've reported and the support that we're seeing from stakeholders and regulators.

Speaker 11

Great. Thanks for sharing the color there and congrats on all the progress we can forward talking to you guys.

Speaker 1

One moment for our next question. Our next question comes from Mandy Freuhar with Leerink. Your line is open.

Speaker 12

Hi, good afternoon. This is Lelina Songo on for Manny. I know earlier you touched a little bit on the infringement lawsuit And I was wondering if you could provide or if there were any updates that were available in terms of the timing for the second lawsuit, as well as kind of the potential level

Speaker 4

So we don't have any update on the timing of the second lawsuit. As I alluded To the first cases scheduled to go to trial in early 2024 and that's the Otherwise, the exact timing of the second lawsuit is not yet known.

Speaker 12

Thank you. And in terms so for the Duchenne program, so what do you expect to the Serta's Elvida's recent approval, would you expect that impact to be on potential recruitment or enrollment in your study As well as the potential impact from the AMBARFE study results that are expected later this year.

Speaker 4

Again, I think an important feature that everyone understands in AAV gene therapy is that There continue to be boys, kids in some of our trials and in other trials that aren't able to access therapy For a variety of reasons, even sometimes commercial therapies because of the pre existing immunology, they can maybe achieve treatment from a certain type of Vector because of serology, but not another. And Duchenne is a rare disease, but it is a Larger incidence and prevalence than other areas that we operate in clinical development. So we have not seen nor do we really expect to see any impingement on our ability to enroll with respect to the RGX-two zero two program At clinical stage right now and as we go forward, I think additional data for Microdystrophin class of products on the basis of the fact that our product is of that class, When we have the opportunity to show our microdystrophin data, emphasizing that our microdystrophin is Potentially better form of and more similar to full length dystrophin or more naturally biologically If forms of truncated dystrophin, I think should be really exciting because it could show that there's evidence of Incremental improvements with existing technology, but really I think we should be thinking about RGX-two zero two as an improvement to the 1st generation of microdystrophin, And both on the basis of inclusion of the C terminal domain as well as the potential to bring Some of the benefits of the Manufacturing Innovation Center into focus, and all of that in addition to look, there's just going to be boys that aren't going to be able to access the other treatment.

Speaker 12

Thank you. And actually speaking of the potential differentiation in terms of potency, Should we expect to see impacts on muscle function or muscle strength maybe earlier than other program, Say you know what, the 6 months readouts?

Speaker 4

I think that It's hard to assess that from the animal models because they're very different in certain forms than the human aspects of the disease As you get later in the progression, the animal models can be Fragile in different types of ways, and so you can't always collect that same longitudinal data. I think on the basis of Our understanding, I think we would expect to see more clear separation at something like the 1 year time point. I think it could be possible for certain types of measures to distinguish themselves between the 6 12 month time points as well. We certainly wouldn't expect it would be something that would accompany the micro dystrophin measures from the biopsies at 3 months.

Speaker 12

Thank you so much for your clarifications.

Speaker 4

Thanks.

Speaker 1

One moment for our next question. Our Our next question comes from Caroline Palomeque with Berenberg Capital Markets. Your line is open.

Speaker 9

Hi. Thanks for taking the question.

Speaker 13

So on RGX-three fourteen for subretinal Y A and B, are there any updates in enrollment from AbbVie on the pivotal trial of ASCENT ATOMASPHERE, especially They increase the number of patients as well as the trial sites in the study? Thanks.

Speaker 5

Hi, Carolyn. We don't have any change in our guidance. So everything is going very well post the expansion, the global expansion of the pivotal program. And we continue on track to complete these studies so that we can achieve BLA And European regulatory submissions in late 2025 through the first half of twenty twenty six. And yes, we're trucking along.

Speaker 9

Great. Thanks.

Speaker 1

And I'm not showing any further questions at this time. And this does conclude today's presentation. You may now disconnect and have a wonderful

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Earnings Conference Call
REGENXBIO Q2 2023
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