Q2 2023 REGENXBIO Inc Earnings Call

Okay.

Good day, and thank you for standing by walking through the Q2 2023 region extra bio earnings conference call. At this time all participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session to ask a question during the special need to press Star one on your telephone you will then hear an automated message advising your hand is raised to withdraw your question. Please press star one.

Please be advised today's conference is being recorded I would now like to turn the call over to your speaker today, Patrick Christmas Chief Legal Officer, Chief Legal Officer, you may begin.

Good afternoon, and thank you for joining us today.

Earlier. This afternoon are getting released financial and operating results for the second quarter ended June 32023.

This release is available on our website at Www Dot <unk> Dot 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.

You May anticipate believes should intended and other words of similar meaning.

Any such forward looking statements are not guarantees of future performance and involve certain risks and uncertainties. These risks are described in the risk factors and the management's discussion and analysis sections.

<unk> annual report on Form 10-K for the full year ended December 31.

2022, and comparable risk factors section of <unk> quarterly reports on Form 10-Q, which are on file with the Securities and Exchange Commission and available on the SEC's website.

We provide on this conference call is provided only as of this call August <unk> 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 forma financial information that may be provided is preliminary and does not purport to project financial positions or operating results for the company.

Actual results may differ materially.

I would now like to turn the call over to Ken Mills CEO for <unk>.

Thank you Patrick 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 Dr. Steve <unk>, Our Chief Medical Officer will then provide an update on our clinical program.

Our Chief Financial Officer will provide an overview of financial results for the second quarter ended June 32023 at the end of the call. We will open up the line for questions.

Average earnings by our mission is to improve lives through securities potential of gene therapy.

We're focused on developing therapies for diseases, there are significant unmet needs.

We continue to be a leader in gene therapy.

Thousands of patients who have been dosed with <unk> therapeutics derived from our proprietary NAV technology platform.

Recently.

Significant time of growth for the Caribbean industry and average unit volume.

Developing a deeper understanding of gene therapy market access models, and digesting regulatory approvals, including the FTE support of Biomarkers as surrogate endpoints to support accelerated approval.

There are now five FDA approved AED therapeutics and I'm pleased however, <unk> remains a leader in the gene therapy space as our five by 'twenty five strategy is on track for advancing <unk>.

<unk> therapeutics for our internal pipeline and license program.

Pivotal stage, where commercial products by 2025.

What distinguishes Virginia expire with the leader in AAV Therapeutics.

Our platform pipeline and products.

There are thousands of patients who have been dosed with <unk> therapeutics derived from our NAV technology platform and hundreds more are receiving treatment every quarter.

We estimate approximately two children per day are receiving as old Gen.

Which uses our NAV <unk> vector.

We believe that we have a strong pipeline of <unk> therapeutics ourselves with the potential to deliver onetime treatment to address significant unmet need for patients living with common and rare diseases.

<unk> expire we're conducting over 12 active clinical trials using six different forms of delivery devices in three therapeutic areas retinal neuromuscular neuro degenerative diseases and.

In 2023, our team is executing on two pivotal phase programs that include over 1000 subjects to support nickel, we have to file our first BLA in 2024 and 2025.

We are observing that on average one new patient is being dosed <unk> bio 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 ABV Rdx 314, or three one for an investigational gene therapy.

Abbvie has a strong complementary partner for <unk> bio, we expect to leverage <unk> global development and commercial infrastructure within high gear with our expertise in AAV gene therapy clinical development and deep in house knowledge of manufacturing.

Together, we are developing 314 to be the first one time therapeutic option and major retinal vascular diseases to address significant unmet need for patients.

Overall, our pipeline to be therapeutic candidates that you're addressing high unmet need for millions of patients in diseases that represent current market opportunities of over $20 billion.

Just a few weeks ago at our Investor Day in July we introduced a new clinical trial data from our retina programs using super Cradle delivery and our Duchenne micro dystrophin Kennedy and we provided specific guidance about additional upcoming interim trial update.

From our <unk> at an altitude trials, we reported that mild to moderate intra ocular inflammation previously observed with Super Choroidal delivery is mitigated with short course topical steroid eye drop.

And we reported safety updates from the initial dosing in cohort one of the affinity Duchenne study to support a well tolerated profile of our candidate Rdx Q over Q to date.

Now I will turn the call over to Steve So that he can review in detail a bit more about the clinical progress and pipeline updates.

Thanks, Ken.

I'll begin with $3 14, which is being developed in collaboration with Abbvie to treat wet AMD and diabetic retinopathy.

Bret and Supercoil routes of administration.

314 utilizes our NAV <unk> vector to deliver a gene encoding a therapeutic antibody fragment to inhibit VEGF.

The anti VEGF market opportunity is poised to grow significantly as the population ages.

314 for the treatment of wet AMD via sub retinal delivery is being evaluated in two ongoing pivotal trials atmosphere in effect.

We recently announced the expansion of these studies to enroll a total of 200 patients in the U S Europe , Japan and Israel.

To support global development of the program.

We also recently initiated a fellow eye treatment study as part of the pivotal program using sub breath on delivery.

This study is evaluating the safety efficacy and Immunogenicity of sub retinal 314 administration and the fellow eye of patients with bilateral disease from atmosphere Anderson, who previously received a sub retinal injection of $3 14.

Overall, we plan to complete all of these trials in time to support global regulatory submissions in late 2025 through the first half of 2026.

Additionally earlier this week, we presented new interim results from our phase III Pharmacodynamic study designed to evaluate the same dose levels being used in the two pivotal trials the.

The updated interim data demonstrated that $3 14 manufactured using our <unk> platform process was well tolerated and in both the low dose and high dose cohort through six months patients achieved expected protein levels, along with stable to improved <unk> CVA 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 two ongoing phase II trials that fall under our collaboration with Abbvie assessing in office Supercoil delivery of $3 14.

For treatment of wet AMD, and the AVR trial and treatment of diabetic retinopathy and the altitude study.

Aviate as an active control dose escalation trial evaluating $3 14 for the treatment of wet AMD, we reached 3% of safety data at our Investor day from cohort six evaluating dose level three 112 GC per eye that included short course prophylactic ocular.

Right.

Following administration of <unk>.

The initial data presented continues to support the safety profile of $3 14, and highlighted the inclusion of short course, prophylactic steroid eyedrops, which resulted in zero cases of intraocular inflammation or IOR in all patients with.

We plan to present full six months' results from cohort five and six at the Hawaiian eye meeting in the beginning of 2024.

Altitude is the active controlled dose escalation study of $3 14, supercritical delivery for treatment of Dr.

We're very excited about the opportunity and Dr. 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 onetime gene therapy.

During our Investor day, we presented initial interim data from cohorts four and five at dose level three with short course prophylactic steroid eyedrops following 314 administration.

Data demonstrated that $3 14 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 eyedrops resulted in zero cases of IRI and all patients.

We look forward to presenting full 12 month results from cohorts one to three at the American Academy of Ophthalmology meeting later this year.

Moving to Duchenne as Ken mentioned in his remarks at our Investor Day, we were pleased to announce our new exon skipping program to complement rgs to O two.

Duchenne patient state high unmet need and we are committed to bringing multiple treatment options for these boys.

Our first program RG <unk> is a potential onetime gene therapy for the treatment of Duchenne being developed as a highly differentiated product designed to deliver a transgene for our novel Micro dystrophin that includes the functional elements of the <unk> domain.

Found naturally in occurring.

Okay.

Our Gx 202 is designed to support the delivery and targeted gene expression throughout skeletal and heart muscle using our NAV AAV vector and a well characterized muscle specific promoter.

During our Investor Day, we reported safety data from the phase one two affinity Duchenne trial. The data we presented on the two patients ages four and 10 showed that <unk> 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 three months.

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 micro dystrophin protein expression levels and muscle at three months.

We also continue to enroll patients and affinity beyond.

An observational screening study that is evaluating the prevalence of AAV eight antibodies in patients with Duchenne.

Okay.

Moving to our other rare disease programs, we are developing two programs for Mucopolysaccharide saccharide, Ocs NPS too and NPS one.

Archie ex 121 is an investigational onetime AAV therapeutic for the treatment of NPS to also known as Hunter syndrome.

Being evaluated in the ongoing phase 123 campsite trial.

In May we announced that we received regenerative medicine advanced therapy or <unk> designation from the FDA recognizing.

Recognizing the preliminary data we have presented to date indicates its potential to address the unmet medical need for patients with Hunter syndrome.

We completed enrollment of 10 patients for our campsite trial in the first half of 2023 and remain on track to support a BLA filing in 2020 for using the accelerated approval pathway.

Now onto <unk> hundred 11, and investigation of onetime AAV therapeutic for the treatment of severe Mpls Wan we.

We have completed enrollment of the phase one two 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 <unk> 181 to treat the neuro degenerative manifestation and rgs <unk> to treat the ocular manifestations of CRM, two or batten disease.

Because just physician investigators in Brazil continue with follow up to the first child with CRM to disease dosed with <unk> 181 under a single patient investigator initiated study and we expect investigators to report initial interim data from the single patient, including six month results at the society.

For the study of inborn errors of metabolism annual symposium.

Later this year.

We're also happy to report the recent dosing of our first patients with <unk> 381.

To conclude we have made significant progress with data updates and trial advancements across all of our programs as we continue toward our goal of five by 'twenty five.

Lastly, I'd like to thank the patients families clinicians and patient advocacy representatives, who are involved in and support all of these trials.

And with that I'll turn the call over to Beth to review our financial guidance.

Thank you Steve <unk> ended the quarter on June 32023, with cash cash equivalents and marketable securities totaling $415 million compared to $565 million as of December 30.

<unk> 2022.

The decrease was primarily driven by cash used to fund operating activities during the first half of 2023.

R&D expenses were $60 million for the second quarter of 2023 compared to $61 million for the second quarter of 2022.

The decrease was primarily attributable to an increase in developmental cost reimbursement from Abbvie under our eye care collaboration.

We expect to balancing cash cash equivalents and marketable securities of $415 million as of June 32023 to fund our operations into 2025.

This cash runway guidance is based on the company's current operational plans and exclude the impact of any payments that may be received from abbvie. Upon the achievement of development or commercial milestones under our three one for collaboration.

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

Thanks, Stephen for those important updates about our clinical progress and our financial performance.

<unk> continues to perform at a high level as we execute on our mission of improving lives for the curative potential of gene therapy and.

In addition to our platform and pipeline are 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 <unk> therapeutics.

And our research and early development team continues to advance with 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 on product quality and yield and.

And when we introduced plans for new IMD for Kennedy with exon skipping science to expand our commitment to duchenne.

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 at the society for the study of Inborn errors of metabolism will report first initial data six months follow up from the first patient dosed with <unk> one for the treatment of <unk> form of Batten disease. This is a five year old child and this is part of the data from.

Our third neuro degenerative program.

In October at World Muscle Society, we expect to share additional interim data from patients in cohort one of affinity duchenne, including longer term safety and the first micro dystrophin expression protein levels and muscle at three months.

In November we plan to report additional interim data from the phase <unk> trial of <unk> three one for supercritical delivery for the treatment of diabetic retinopathy at the American Academy of Ophthalmology.

Meeting being held.

This will include full 12 month results from cohorts, one and two and three.

And finally in January of next year investigators, who will report on additional interim data from the phase <unk> trial of Rdx, three reinforce supercritical delivery for the treatment of wet AMD, including full six months results from cohort five and six and this will be at the Hawaiian eye and retina 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 we've described we have the focus and high performing team strong collaborators and the trust of the clinical and patient community partners. It is a clear and definable path for us to achieve our five by 'twenty five vision and continue.

To lead what's possible with EEV therapeutics, we want to thank all of you for.

Mmm, what efficacy data, we can expect from both aviation altitude. Just one question regarding aviate should we expect 12 month data from cohorts one through four at Hawaiian eye or will it be just a full look across all cohorts two months six and then secondly can your team elucidate.

What actual assays around protein expression of micro disrepair, and we could see at worlds and whether you would expect some some method of compare ability to your peers that have ongoing D. M D programs as well thank you.

Thanks for the good question <unk> sure so.

<unk>.

Thanks for the questions. So for the aviate when a M. D update we we have discussed the the latest results that we'd have for six month follow up we we haven't said more as far as longer term follow up in part because of the later cohorts in the.

The dynamic nature and and these interim updates of ongoing studies.

As well as really seeing when we might be able to do a data cards and we always have the overhang of also reaching alignment with Abby as we get closer to these type of meetings. So that's the type of thing that we can update as we got a little closer.

And on the micro district and protein expression. Jean we are working with message that we think will be able to be used for comparison message that had been used by others in clinical investigation of the mic redistricting class of products.

So I think that as we come into world muscle.

I think we all know that you know forms of western blot assays as well as liquid chromatography mass back have been you know use in assessments of other patients. We think that we will have methods to support interpretation of that and some forms of compare.

<unk> keeping in mind that you know, they're always nuances in assays, but I think things that the community will be familiar with from us.

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

I appreciate it one moment for our next question.

[noise]. Our next question comes from Gina wagons Barclays. Your line is open.

I, it's Tony on Virgina I have two questions I guess first briefly can you remind us of.

V I P and royalty status for someone your partner programs, including with rocket for dances and ultra <unk>.

As well as any I P rights two alright, 74, and then another one on T. M. D. With you know updates expected from swept adviser later this year, what kind of bar would you be looking for in terms of efficacy for protein expression at N S. A.

Sure Tony Thanks, a lot of questions. Yeah with respect you programs that are part of our NASA technology licensee universe, certainly rocky standing program and the <unk> G. S. Do you want any programs are are under license for.

Two different vectors rocket using a V nine navvy B nine handles Virginia excusing at 88 in the case of G. S. T. One a we.

Can I get your 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 were receiving for example on the the magenta royalty so starting in the high single digits and going up on it.

<unk> up into a double digit ranges with respect to I P. As it relates to your second question.

Uhm, we currently have.

Two lawsuits that are involving patents relating to the manufacturing of syrup to this product as well as patents that involve the composition of <unk> products, both of which use E V. R age 74 that they refer to.

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 bills off Dean's question about micro dystrophin data and expression, where the program for our G X. Two two is going which we're very encouraged about some of the initial safety data that we provide in just a few weeks ago.

When it comes to micro dystrophin expression, we think that you know RG of 314 is within the class of you know treatments candidates that had been explored clinically so far including Pulitzer Raptor, and Pfizer and some others like solid.

Where at one E 14 dose currently in our trial and I think that is again adjusting for understanding there can be sometimes differences in and asses in quantitation of.

If any D products similar to wear <unk> and it's pivotal program and my understanding of <unk> accelerated approved product is that they're just slightly above that 1.3 E 14 in terms of dose levels. 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 <unk> to to to what others are achieving now <unk>.

The key there is that we believe that once we express micro dystrophin in the muscle of children that are micro dystrophin has the potential to be more potent are more efficacious because we are the first clinical candidate to design into the AAV micro dystrophin, that's being expressed.

A substantial component of the C terminus of Steve alluded to the C terminal domain, which we've established pre clinically both we and AED experiments and and other work to be meaningful in terms of improving the strength and the biological function of a micro dystrophin and so it's actually something that's more akin to.

To.

I would consider to be attenuated forms of <unk> like bucket Becker muscular dystrophy that would sort of alluded to in the recent F. D. A had calm and discussions about micro dystrophin in the <unk>.

Possibility of micro dystrophin 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 and so we think that will have an amplification of potential efficacy outcomes now the measurement of the efficacy outcomes will not be something that will be able to assess it.

The 98 point on those considerations of course will be at later time points, maybe near two nine or 12 months, but that's when we would begin to get the type of responses like you were referring to in in SSA et cetera, but for the update and world muscle Society this'll be longer term safety data.

And our first expression of micro dystrophin Incor won at the 1014 dose.

One moment for our next question.

Mmm.

Our next question comes from Costco, Austin day with mortgage failure lines open.

Hi, everyone. This is gospel I'll fall victim to your head. So Christmas. So what is your current view on where objects to it too cause fit fresh companion's DMT tap is indifferent and rewards 70.

Yeah, <unk>, that's a great question.

The design of Argy X, two two and the target product profile.

Is multi threaded for us first.

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 M or even two products and that's because as you all know a preexisting immunology that can exist in boys that may not allow them to access <unk> because of <unk>.

And through preexisting neutralizing antibody. So we estimate that the potential market for an AED Beast capsid, which is what our gx. Two two is based on an an incidence basis and on a prevalent spaces could include 15, or maybe up to 30% of the population that might not be able to access.

Other capsid that are currently in development. That's the first 0.2nd point is.

But it was just a leading to a my answer to Tony which is.

The first Rd. Two two is the first reagent to be brought forward scientifically and clinically that includes a domain of full length, Mike her dystrophin that doesn't exist in other microtus from our products. The C terminal, which again evidence to support Preclinically that there's an improved effect biological activity and strength and muscle.

When that C terminal domain is present in truncated forms of dystrophin. So that we think sets us up potentially for a form of best in class. When later in development. We can assess more clinical data will be more clear on that but I think the preclinical data points in that direction today and evidence of the C terminus is.

Something that we strongly emphasizes our focus in development and then the last pieces 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, and we think that the purity and the quality of the AAV products that are being manufactured.

Here at the Rockville manufacturing innovation center as well as the yields were cheating with our Nab Express process will 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.

Alright, Thank you very much.

Thanks, one moment for our next question.

Our next question comes from Alex Right ahead with Bank of America. Your line is open.

Hey, guys. Thanks for taking our questions just just a couple from US first action on M. P. S. Two.

Just curious your interactions with the F D. A around the on that designation if you could give a sense of you know what.

What it would take to so clinically for accelerated approval.

And if you intend to to update the markets with the top it off prior to file away and.

Secondly, assessed all around us that'd be modified appreciate this is not in the the runway guidance by any additional color around they spoke in Thailand.

Additional milestone fingers.

<unk>. Thank you.

Hey, thanks.

Thanks for those questions on M. P. S. Two yeah, 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 <unk> designation from SCA as well to support our continued execution here on the regulatory front.

I think that look or Matt is something that's a designation that only comes from Fda's acknowledgement of clinical data right. There are other types of designations that sometimes can rely.

Exclusively on preclinical data for support but in this case <unk> is something where the FDA is is already assess clinical data that's been generated from our trials and provided input that it believes that there is a potential status here for moving quickly and that's been consistent with our dialogue with FDA.

And the last several years with respect to how we been thinking about transitioning from some of the first patients. We've reported findings on all the way through to getting to that third dose level in our dose escalation in starting this fees are 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 phase.

Sitting here today, we have just completed enrollment in the second quarter 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 update so look out for us.

On those updates going forward.

When it comes to add the you're bringing me back I think when we first reported on this partnership and I care with Abby we.

Highlighted in our filing that.

In addition to that the total number of milestones that maybe earned out <unk> for.

For development regulatory and commercial a big portion of that I think is over $750 million is actually associated with the development and regulatory milestones and guess what we can say today is that.

The guidance that we can provide is that a substantial portion of that 780 is associated with the execution and advancement of Super Choroidal 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 23 into 2024, well, we're certainly learning a lot more about the potential for the advancement in the regulatory advancement in the development and advancement of the Super criminal programs for both wet AMD and diabetic retinopathy and that starts to bring those development and regulatory milestones.

As potential earn outs for us into focus.

Thanks, I appreciate the call us.

One moment for our next question.

And next question comes from early Tomorrow would you be extra large as often.

Hey, guys. Thanks, so much for taking my question for Dan D. I guess, maybe.

<unk> when you activate up to the second does that work.

And I know you said would that data of the first pet by law at at World muscle, but I mean, what are the timelines for Assam data.

From that that that Howard desk, and then just your expectations, especially level differences between the the second test in the first step.

Well thanks.

Thanks, Eliot a few layers there.

We haven't given any guidance or any sort of specific kind.

Kind of plan around dose escalation or in this trial is also designed for the potential of dose expansion at the first dose level as well so.

That'll 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.

And take into account the different types of variables, including the.

Initial measures of micro dystrophin had dose level one.

With respect to dose level too, though I mean preclinical we certainly have seen and it's designed into the study because we've seen evidence of higher micro dystrophin expression, we've seen evidence of improvement.

<unk>.

Outcomes with respect to functional assessments in the animal models.

But of course, we want to understand how this could be recapitulated in human and frankly, we've also seen really strong expression and functional outcomes at the <unk> 14 dose level as well so there's definitely still an opportunity here for us to decide that expansion of 114 is the direct.

<unk> that we want to go and it sort of and and or function, perhaps whether dose escalation to 214 occurs I think will begin to talk about micro dystrophin expression in more detail at world Muscle Society. When we have some of the data to be able to present and as I alluded to.

Think Indians question.

Ellie.

Variability of course in different assay methods that people are using to assess micro dystrophin, but.

We believe that we have really well characterized validated methods for specifically quantifying micro dystrophin, that's coming from our Gx two two and we <unk>.

Expect to bring that forward and put it into context for all the stakeholders.

Of course investors, but also physicians and families. When it comes to things that they've seen before from other programs and I think our team has done an excellent job.

Working on methods that we understand reviewer reliable that regulators are going to view, a reliable as well and are gonna allow everyone to contextualize as I said, where at the same dose as where Pfizer is and we're Pfizer Imogen expire from Ah sort of stated dosing perspective are slightly.

<unk> is I think the preclinical data in the clinical data all says it all.

All of these are in sort of relatives similar ranges. So we're expecting our initial micro dystrophin data to be within the range of what sort of micro dystrophin dose levels are from other programs that similar dose levels I can't emphasize enough that important.

Benefit of the same molecule that we express versus what someone expresses without the C terminal domain.

Have a different effect functionally the C terminus is something that.

Enhances the potency enhances the functionality of a micro dystrophin, that's being expressed in gene therapy. So while we made achieve similar protein levels of micro dystrophin as others. We think that our micra dystrophin is going to be something on a molecule by molecule basis that is more effective.

Mmk. Thank you so much for all that color.

One moment for our next question.

Okay.

Our next question comes from Lucchese with RBC. Your line is open.

Oh, okay. Thanks for taking our questions definitely sponsor Luka just a couple of questions on candy I I I just want to.

The more specific question on me <unk> assertion levels I hope your expectations at.

I'm, so sorry that that has a 40 to 50 per cent will change in my car just as an expression Sunday signed on the label is that which we should expect to see.

As the bar for success when you get more data on October and also on the Nd.

L at the space shuttle, sending a favorable regulatory president on the biomarker and can accelerate approval Uhm Pfizer yesterday mentioned that their insurance <unk>. Sir advocacy later this year will be function and not on the start by a Martha uhm.

No. It's still early days, but just wondering what's your strategy offered getting approval and wondering if you are in the yes, I would like to cancel at the wall functional camp. Thanks for taking questions.

Sure Thanks, Lisa digging into it a bit.

I think I mean, referencing the the product approval label for <unk> I would say.

We can look it means we should also look at mediums and distributions of patience and and we'll have small numbers and uncertain cases, when they had phone numbers there was quite a distribution of micro dystrophin expression. So I.

I think for US we definitely view that we're going to be in the territory of things that have been reported by both <unk> and Pfizer with respect to micro dystrophin expression and I think that 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 a sorretto, which I think was anything from like nearly zero 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 <unk> and Pfizer is that they're sort of a range of like 20% to 40% and that would be something that for us would be a.

Justin for the heterogeneity of the disease of different types of methods and sort of the assessments that had been done something that I think would feel comfortable for us in terms of similarity.

With respect to the regulatory approach here.

You know I mean.

I think my observations well I mean, let me just say that I think <unk>, both through our Neurodegenerative franchise as well as since we've entered the.

Development of products for Duchenne muscular dystrophy have been very much focused on discussions with regulators and stakeholders about the use of the accelerated approval pathway and I think that.

We continue to sort of approach our development and sort of regulatory execution on that basis, and we think that the validation of the.

The first AAV therapeutic.

To be approved on the basis of accelerated approval is agree milestone to continue to support that.

Confirmatory data and other people taking approaches of trying to establish a different avenues to show more longer term functional data I think are also valid and different and I think that will continue to sort of process. All of the information that comes in from both our own trials in our own development <unk>.

<unk> that are sort of stakeholders impatient as 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's a.

Limited labeling that's supported the accelerated approval. We're <unk>, we're developing based on a clinical trial, that's enrolling in boys from floor. All the way up to age 11, there are still significant unmet need here and there is a significant urgency here and so that's where I think we anchor ourself.

<unk> 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.

And you said I can <unk>.

One moment for our next question.

And next question comes from Brian Accordingly Bear to your line is open.

Hi, Thanks for taking our questions. This is Charlie on for Brian We wanted to ask it seems like Super Choroidal, a delivery for what AMD what is gonna take what it's gonna take to progressing at 830 is gonna be fairly straightforward for what AMD, but for diabetic retinopathy we.

I wanted to get a little more color on Ah you're thinking about the interim results will be presenting later and what the kind of bar is in terms of.

<unk> <unk>.

And we'd also just kind of like a reminder, on what kind of conversations you've had with the F. D. A so far regarding the Nab Express.

Manufacturing platform. Thank you.

<unk> sure. Thanks.

Thanks, Charlie so.

As you mentioned, we have the opportunity to look at Readouts for for both wet AMD and D. R.

On on D. R. It's interesting there's the precedent of <unk>.

Looking at two step improvement.

On diabetic retinopathy severity that's.

Largely a technical consideration.

Powering consideration for what's been done with prior repeat injection anti ipatieff agents, but what <unk>.

Patients and their doctors really care about is preventing progression so really having a proportionate patients that can have improvement of a certain level is is a proxy for okay. Then you're more likely to not have patients progress.

Two vision threatening are blinding complications, which is the ultimate goal. So the reason I give that context is.

Both of those are clinically meaningful if he could have patients improving and if you could have a lower proportion of patients that worsen and what we've seen to date with six months the results from our earlier cohorts as 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 an art negative control arm with observation.

And what we also know as the bar that one thank so for repeat injections indefinitely is something.

Totally irrelevant for 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 and patients are in signing up for this.

S. I think it's fair to say many predicted initially, but if you could have a one time in office treatment.

That is a much lower bar for a benefit risk considerations. So while we talked to clinicians experts and investigators really any.

Clear reduction in clinically meaningful worsening.

Is a very viable clinically and commercially tar.

Target to shoot for so on top of looking for proof of concept.

That that's really the way, we're thinking about target product profile. So we.

<unk> definitely look forward to seeing results that come later.

Other thing I'd say is durability. So we've seen very good results at six months, it's going to be great to have an opportunity to assess her ability out to a year later this year.

And then have express side of it I think that we have.

Started the process in 2023 of creating.

Process qualification lots around the planning of Vla's for voting R. G X 121, and Archie X 314, and so we've had the opportunity to have a lot of dialogue with FDA I'm running over 12 clinical trials, but referred to late stage.

Studies 121314 with the sub retinal approach we've had more advanced discussions with FTA. 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 capabilities when it comes to high quality high yield commercial ready cgmp facilities that exists.

Great. Thank you.

One moment for our next question.

Our next question comes from Andreas artery, so what for security <unk>.

Yeah. Thanks for taking my questions here just to from US for for R. G X 121 M. P. S who can you elaborate on your interactions with the F D. A and how they came to support the show the time frame for accelerated pool versus the competitors and then.

What additional data <unk>, probably second part of the questions that need to collect you feel comfortable.

Dancing 314.

Pivotal trials for <unk> cause decision ended up <unk>. Thanks.

So I I, Hey, Andrew I as I can I can take the second one first so.

I guess the generic answer as we obviously take into account all data updates that 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 the indications we have very clear noninvasive ways to assess.

Four response and also potential dose response.

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 of other than the.

Suggestion I gave in terms of at least efficacy on on diabetic retinopathy.

And to your related question of who who makes the decision.

Work very closely and collaboratively with Abby and we have the traditional joint committees like joint development and joined commercial committees that work together and cross functionally evaluate.

All the data.

Really compare that against our target product profile to make such decisions.

Yeah, and then with respect to the first question about one to one.

There really is not a close competitor to the target product profile of Archie X 121, which is a one time therapy to address <unk>.

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.

Standing on top of the.

The unmet need for CNS features of M. P. S. Two because of the existing standard of care treatments in the U S like <unk>.

Not being able to address those features and I think that the FTA designation of the arm at is supportive of the fact that they are encouraged by the clinical data that has been reported so far such that they wanted designated as you know.

A program that has the type of status that is meant to be accelerating so I think that we feel really good about our data we feel good about the unique one time profile of the treatment that.

Addresses CNS manifestations of Hunter and we feel good about the data that we've reported in the support that we're seeing from stakeholders and regulators.

Alright, thanks for starting to color their and congrats on all the progress we can follow up on that.

One of them.

Four next pressure.

And next question comes from ready for harvest <unk>.

Hi, Good afternoon. This is learning so I'll go on some money I know you know you have touched a little bit on the infringement low sets and I was wondering if you could provide <unk>. If there are any updates available in terms of the timing for a second losses as well as kind of potential level of damages that is spelled out and the potential.

Division between the company and the University of Pennsylvania.

So we don't have any update on the timing of the second lawsuit as I <unk>.

<unk> to the first case is scheduled to go to trial in early 2000 2004 and that's the.

Otherwise the exact timing of the second lawsuit is not yet no.

Thank you and <unk>. So far. The addition program. So what do you expect to the Sept is Alvin it's based on a total but just think that would have to be on potential of a quick mental enrollment.

In your study as well as the potential impact Sunday and I study results that are expected date of this year.

And again I think an important feature that everyone.

I understand AVG therapy is that.

There continue to be voice kids and some of our trials and another trials that are unable to access therapy for a variety of reasons, even sometimes commercial therapy because of the pre existing immunology. They can maybe achieve treatment from a certain type of sector because the serology, but.

Not another <unk>.

A rare disease, but as a larger incidence and prevalence in 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 RG X two two program that clinical stage right now and as we go forward.

Think additional data for.

Micro distributing class of products on the basis of.

The fact that our product is not that class.

When we had the opportunity to show our Micra dystrophin data Emphasising that are micro dystrophin is.

Potentially better form of and more similar to full length of <unk> or more naturally biologically active forms a truncated dystrophin I think should be really exciting because you could show that there is evidence of incremental improvements with existing technology, but really I think we.

Should be thinking about RG X. Two two is an improvement to the first generation of micro dystrophin, 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 gonna be boys that are going to be able to access the other treatment.

Thank you and actually speaking of the potential of differentiation in terms of potency should we expect to see them put on muscle function almost on strikes maybe earlier than the other program, saying you know, let the six months uhm right out.

I think that it's.

It's hard to assess that from the animal models, because they're very different in certain forms than than the human aspects of the disease.

As you get later in in the progression.

Animal models can be fragile in different types of ways and so you can't always collect that scene longitudinal data.

Think on the basis of our understanding I think we would expect to see more clear separation at something like the one year time point, but I think it could be possible for certain types of measures to distinguish themselves between the sixth in 12 months time points as well.

We certainly wouldn't expect it would be something that would accompany the micro dystrophin measures from the biopsy the three months.

Thank you so much for your clarification.

Thanks again.

Again, ladies and gentlemen, if you have a question or comment at this time. Please press star one what on your telephone one moment for our next question.

Our next question comes from Caroline <unk> burden for a capital markets. Your line is open.

Hi, Thanks for taking my question. So on our checks for 14 for some writing on <unk>, what <unk> are there any updates and enrollment from Abby a pivotal trials will set atmosphere, especially since they increase the number of patients as well as the trial sites in the study.

<unk>.

Hi, Carolyn.

So we don't have any change in our guidance, so everything's going very well post the expansion the global expansion of the pivotal program.

And we continue on track.

Complete these studies so that we can achieve b L. A N.

And European regulatory submissions in late 2025 through the first half of 2026.

Yep.

Trucking along.

Great. Thanks.

And I'm not showing any further question at this time and this does conclude today's presentation. You may know disconnected have a wonderful day.

Mmm.

[music], Okay [music].