Q1 2023 REGENXBIO Inc. Earnings Call
Yeah.
Okay.
Good day, and thank you for standing by and welcome to the Virgin expires Incorporated's first quarter 2023 conference call.
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The speaker's presentation there'll be a question and answer session to ask a question. During the session you will need to press star one on your telephone you will then hear an automated message advising your hand this race to remove yourself from the queue. Please press star one or one one again. Please be advised that today's conference is being recorded I would now like to hand, the conference over to you.
Speaker today, Patrick Christmas Executive Vice President and Chief Legal Officer. Please go ahead Sir.
Good afternoon, and thank you for joining us today.
Earlier this afternoon, <unk> released financial and operating results for the first quarter ended March 31 2023.
Press release and data presentation are available on our website at www Dot orogenic style 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 expect plan will may anticipate believe should intend and other words of similar meaning.
Any such forward looking statements are not guarantees of future performance and involve certain risks and uncertainties. These risks are described in the risk factors and the management's discussion and analysis sections of <unk> annual report on Form 10-K for the full year ended December 31, 2022, and comparable risk factors section.
Regarding <unk> quarterly reports on Form 10-Q, which are on file with the Securities and Exchange Commission and available on the SEC's website.
Any information we provide on this conference call is provided only as of the date of this call may three 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 of the company.
Actual results may differ materially.
I'd now like to turn the call over to Ken Mills CEO of Virgin expire.
Thank you Patrick.
Good afternoon again, everyone. Thanks for joining us I'm pleased to begin today's call.
We're continue today's call with a recap of our recent business highlights as well as an update on our corporate goals.
Dr. Steve for Cole, our Chief Medical Officer will then provide an update on our clinical programs and get the system, Our Chief Financial Officer will provide an overview of financial results for the first quarter ended March 31 2023.
At the end of the call we will open up the line for questions.
<unk> bio 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 need we continue to be a leader in gene therapy with thousands of patients who had been dosed with AAV therapeutics derived from our NAV technology platform.
There is a meaningful progress in the gene therapy industry lately, including a growing understanding of gene therapy pricing models, and the FDA validation of surrogate markers as viable clinical endpoints.
<unk> continues to work closely with our regulatory partners to help advance and accelerate the development of gene therapies, particularly for rare diseases.
Today I'm pleased to discuss how organic spinal remains a leader in gene therapy as we share with you how our five by 'twenty five strategy is on track for advancing <unk> therapeutics from our internal pipeline and license program into pivotal stage for commercial products by 2025.
Our end to end capabilities continue to set us apart as a leader with our in house manufacturing Innovation Center running scalable commercial ready batches of our AAV therapeutics.
And our research and early development experts continuing to advance what's possible in gene therapy.
In fact, this week, we announced the summary of around 15 presentation at the upcoming <unk> conference, which reflect leadership in areas such as <unk>.
Engineering novel.
NAV cap seats for better targeting with <unk> therapeutics to clinically relevant tissue and organ.
Enhancing EV therapeutics tissue and cell types specificity and expression, including optimizing enhancer and promoter combination opt.
Optimizing devices and routes of delivery for AEP therapeutics and other proof of concept research that informs next steps in our pipeline strategy.
And today, we also announced significant update and progress in our global eye care collaboration with Abbvie.
Including the transfer of <unk> for all ongoing clinical trials for Abbvie as originally outlined in the collaboration agreement and the global expansion of pivotal trials atmosphere and a sense for the treatment of wet age related macular degeneration or wet AMD using sub retinal delivery.
Our investigational onetime gene therapy.
Formerly known as <unk> 314 also had been renamed ABV Rdx 314, and from now on by the way I'll refer to it as 314.
The new global site plans and expanded enrollment targets for atmosphere in a sense involve updates to our U S brands and new guidance for global regulatory milestone.
These trials are now expected to support regulatory submissions with the FDA and the EMEA in late 2025 through the first half of 2026.
Steve will share additional critical details, but first I wanted to frame our view todays update of the global expansion further optimizes the value and enhances the robustness of the 301 for our program.
I want to take the opportunity to make clear where we are today.
What is our clinical experience with 314.
We view the global commercial opportunity for Rdx <unk> four.
A major retinal vascular diseases, such as wet AMD. The current standard of care anti VEGF treatments require patients to receive injections every eye every four to 12 weeks for the duration of disease.
First generation anti VEGF treatment treatments are not good and emerging second generation anti VEGF treatments are making an impact for some patients with longer incremental acting mechanisms. However, real world evidence consistently shows us that vision improvements lagged behind the controlled clinical trial evidence.
Patients cannot be treated with the required frequency of both the first and second generation anti VEGF treatments.
And we do not control disease, well enough between doses.
Since doctors and clinics continue to struggle with the impact of the limitations of the current any emerging anti VEGF standard of care and under treatment is still the leader leading to disease progression damage to the retina tissue and loss of vision.
Together with Abbvie, we are developing 314 to be the first one time option and major retinal vascular diseases to address the significant unmet need in the treatment of wet AMD in diseases like diabetic retinopathy and other chronic retinal condition.
Our main goal in our partnering our gene therapy leadership.
With Abbvie as global infrastructure and leadership in eyecare with to expand beyond our U S footprint.
To bring 314 to patients worldwide.
We are pleased to see this vision coming to life with today's announcement and the forthcoming global expansion.
Where are we today, we think we're in a great position to optimize the opportunity for creating value with 314 for patients worldwide.
We have the largest global clinical program for onetime treatment option in major retinal vascular diseases. This involves seven ongoing clinical trials, including two pivotal trials global three phase II trials and we are studying two delivery devices for sub retinal and Super cradle delivery in two different.
Lead indications wet AMD and diabetic retinopathy with opportunities to expand further into several other adjacent retinal diseases.
Additionally, as I mentioned before a Virgin expired manufacturing innovation center, which is here in Maryland, It's fully operational state of the art GMP gene therapy manufacturing facility designed to meet global clinical and commercial regulatory standards.
Our NAV express platform process is already being used in the pivotal trials for 314.
And the <unk> manufacturing innovation center is on track to produce U S. Commercial supply operating in 500 liter level with bioreactors to support commercialization and with an option to expand up to 2000 meters as needed.
In 2023, we plan to use the manufacturing innovation center to produce that commercial scale GMP material for the entire 314 clinical program as well as performance qualification lots to support planned regulatory filings.
To summarize our clinical experience.
In total more than 600 patients have been dosed in the <unk> program, representing over 400 patient years of exposure across seven trials.
The totality of the clinical evidence shared to date shows the treatment of <unk> hundred one for using both sub retinal and <unk> delivery method is generally well tolerated patients are generally responding to onetime treatment of three one for long term follow up in our sub retinal studies has shown durability over four years.
With stable to improved <unk>, CVA and meaningful reduction in anti VEGF burden with the majority of patients injection free.
Sure.
Now real world evidence shows that patients with wet AMD or severely under treated due to the unsustainable burden of these frequent injections. We believe the profile of <unk> going forward. The potential one time treatment addresses this high unmet need and the majority of patients currently on hiring or the standard of care for transition to onetime gene therapy.
And there is opportunity to capital. Additionally, capitalize on additional market share for standard of care agents, biosimilars and emerging longer interval treatments.
Gather with Abbvie, we're developing 314 to be the first one time therapeutic option in major retinal vascular diseases to address significant unmet need for patients. This is a worldwide opportunity with a potential to reach over 30 million patients with high unmet need and what is already calculated to be over $14 billion global anti.
Jeff Mark.
Additionally today.
Frankly, the utilization of anti digest to treat diseases like early diabetic retinopathy as well.
The treatment burden is high less than 1% of patients with early disease are treated with one interim vitriol injections.
We believe that Theres a potential for <unk> four as a single in office injection to become a new standard of care for early diabetic retinopathy treatment to prevent vision loss.
An estimated 6 million patients have early Dr. In the U S alone.
And Dr is estimated to be a potential $15 billion global market in the next decade.
Supported with the right treatment profile, such as a one time treatment.
So with that I'm going to turn the call over to Steve. So he can get into greater depth on our three one for clinical progress and also discuss our rare disease pipeline and progress and updates Steve.
Thanks, Ken I'll.
I'll begin with an update on three one for.
<unk> uses the NAV <unk> vector to deliver a gene encoding a therapeutic antibody fragment to inhibit vascular endothelial growth factor or bad Jeff.
Building on what Ken shared I wanted to share more about 314 for the treatment of wet AMD using sub retinal delivery and the program. We are running to support new global registration plans.
<unk> bio and Abbvie have expanded enrollment in the ongoing atmosphere in our central <unk> the <unk>.
Two pivotal clinical trials evaluating <unk> in patients with wet AMD using sub retinal delivery to include patients in the U S Europe , Japan and Israel.
Atmosphere in ascent will enroll approximately 540 and 660 patients respectively.
This action will increase power of primary and secondary endpoints to enable these global regulatory submissions and labeling options.
Additionally, we shared interim data updates in February from the Phase II bridging study this.
This study is designed to evaluate the same dose levels being used in the two pivotal trials in.
In this trial material from our proprietary NAV Express platform manufacturing process was well tolerated with patients demonstrating stable to improve <unk> and central retinal thickness and meaningful reductions in anti VEGF burden.
The majority of patients were injection free following treatment with <unk> four.
Lastly, we also announced today that our fellow eye treatment study has been initiated as part of the pivotal program using sub retinal delivery.
This study will evaluate the safety efficacy and Immunogenicity of sub retinal three one for administration in the fellow eye of patients from atmosphere in ascent, who have bilateral disease and previously received a sub retinal injection of 314.
Data from patients enrolled in this study are expected to further support global regulatory submission plans.
We also continued to advance two additional three one for programs for the treatment of wet AMD and diabetic retinopathy using in office Super Choroidal delivery.
We completed enrollment of cohort six in the phase two trial, a randomized dose escalation study evaluating 314 in subjects with wet AMD.
<unk> is evaluating the third dose level with short course prophylactic ocular steroids. Following three one for administration to assess the ability to prevent or reduce the occurrence of mild to moderate intraocular inflammation seen in previous cohorts.
Patients were enrolled in cohort six regardless of neutralizing antibody or NAV status based on results from prior cohorts, showing similar safety and efficacy regardless of baseline nap status.
We continue to expect to report additional interim trial data from this trial, including initial data from cohorts six and the second half of 2023.
We also completed enrollment in cohorts four and five of the phase III altitude trial are multi center open label randomized controlled dose escalation trial evaluating supercoil delivery of 314 in patients with diabetic retinopathy.
Cohorts four and five are evaluating 314 at the higher third dose level with patient stratified by diabetic retinopathy severity scale or Dr. SaaS levels, and all receiving short course prophylactic ocular steroids following three one for administration.
Potentially prevent the observed incidence of mild iwai.
Therefore, we also continue to expect to report additional interim trial data from these cohorts in the second half of 2023.
Shifting to our rare disease portfolio rgs to owe to us or 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 C terminal or Cte domain founded naturally occurring dystrophin.
In preclinical studies the presence of the <unk> domain has been shown to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction induced muscle damage into strophic mice models.
Additional design features including codon optimization and reduced CPG content have the potential to improve gene expression increase translational efficiency and reduce immunogenicity.
<unk> 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.
We were pleased to participate in <unk> Futures conference and look forward to additional opportunities to engage with the duchenne community throughout the year.
We are actively recruiting patients in our phase <unk> affinity Duchenne trial, using commercial scale cgmp material from our manufacturing innovation Center.
Data collected in the trial include safety and Tolerability as well as micro dystrophin protein expression levels by three months and muscle strength and functional measures and muscle MRI at a later time points.
We expect to report initial data from this trial in the second half of 2023.
Improvements in Neurodevelopmental and daily activities skill acquisition words observed up to three years after our G X 121 administration.
We expect to complete enrollment in the first half of 2023 to support Ah BLA filing in 2024, using the accelerated approval pathway.
Moving to Rgs 111, an investigation on one time, a be therapeutic for the treatment of severe M. P. S. One using the NAV avianize vector to deliver the <unk> Jean.
We have completed enrollment of the phase one two trial of <unk> 111 for the treatment of M. P. S. One and plan to use commercial scale cgmp material being manufactured at our manufacturing innovation center using the NAV Express platform process to support its continued development.
We've recently announced additional positive interim data from the phase one to trial at the 2023 Worldsymposium in February .
Adminstration that Argy X 111 was well tolerated and an eight patients.
<unk> marker and Neurodevelopmental assessments indicated an encouraging CMS profile in patients dosed with <unk> 111.
We expect to share additional updates on plans for this program and the second half of 2023.
Following these two programs. We're also developing RG X 181 to treat neuro digit degenerative manifestations and <unk> 381 to treat ocular manifestations of <unk> or pattern disease.
We expect to initiate dosing in the first and human study of <unk> 381.
In the first half of 2023.
To conclude we have made significant progress with data updates and trial progression across all programs in our pipeline as we continue working toward our goal of five by 25.
At this time I'd like to thank the patients' families clinicians and patient advocacy representatives, who are involved in and support these trials without whom these advances in one time gene therapy development would simply not be possible.
And with that I turn the call over to visit to review our financial guidance.
Thank you Dr. Portola rejects bio end of the quarter on March 31st 2023, with cash cash equivalents and marketable securities totaling $474 million compared to $565 million.
As of December 31st 2022.
Decrease was primarily driven by cash used to fund operating activities during the first quarter of 2023.
R&D expenses were $59 million for the first quarter of 2023 compared to $56 million for the first quarter of 2022.
The increase was primarily attributable so personnel costs as a result of increased head count and laboratory and facilities cost driven primarily by the activation of the Regina <unk> manufacturing innovation center in mid 2022.
We expect the balance in cash cash equivalents and marketable securities of $474 million as of March 31st 2023 to fund our operations aimed to 2025.
This cash when we guidance is based on the company's current operational plans and excludes the impact of any payments that may be received from heavy upon the achievement of development or commercial milestones under R. Three one for collaboration.
With that I will turn the call back to Ken to provide final thoughts.
Thanks.
We continue to perform at a high level as we execute on our mission of improving lives for security as potential of gene therapy.
The updates from like Hurricane or collaboration with Abby today represent a serious and continued commitment and innovation involved in addressing unmet need and bringing a paradigm shift to the treatment of major retinal diseases worldwide.
We're focused on optimizing the value for the opportunity for 314 by expanding that global reach and supporting the profile of this potential one time treatment.
He did a great job of summarizing a lot of the progress we need here in the first quarter and looking ahead to the remainder of the year. We anticipate a number of key milestones that are going to continue to highlight the potential of our one tiny the gene therapies.
The interim update expected in the second half of the year for 88 and altitudes you prefer idol trials.
The initial data from the affinity Duchenne trial in the second half of the year completing enrollment in the first half of the year. The campsite trial for one to one to support the BLA submission in 2024, using the accelerated approval pathway and sharing additional updates on program plans for 111 181 and three.
<unk> one.
For Hurler syndrome in Baton disease are all important upcoming milestones.
We have a lot of important value driving catalysts ahead of us this year with a balance sheet to fund our mission in operations into 2025.
With a focus and a high performing team strong collaborators.
And the trust of clinical and patient community partners I believe we have a clear and definable path to achieve our find by 25 vision and continue to lead what's possible for AAV therapeutics.
And we look forward to providing you updates as we continue on this path throughout the upcoming year.
With that operator, I think we are ready to transition to Q&A.
Thank you.
As a reminder to ask a question you will need to press star one one on your telephone.
Question. Please press Star one one again, please wait for your name to be announced please stand.
Tell us Q&A roster.
Moment for your first question.
First question comes from the line of Genoa, Wang with Barclays Jetliners now open.
Thank you for the update I have two parts of our questions first one is the recording the atmosphere and <unk>.
Sizing by Abbvie. So wonderful can you remind us depaoli assumption for the Sweet cohorts study and it will increase the pilot was secondary and plan will be important for regulatory submission.
And related question for manufacturing process from the in house, and Netflix best platform, what percentage of patients need to be dosed in order to clear regulatory climate.
And my second question.
<unk> regarding the D. M D. My second half the <unk>. The safety also will be very important to update their what kind of a safety profile <unk> solares treatment.
Thanks, Gina I'm going to let Steve address the first question and circle back on that last year.
Hi, Gina thanks for the questions. So taking the first part of your your first question. The basically the powering concepts for the two pivotal studies, we have always has recently standard power.
Powered for the primary endpoint to have at least 90% power.
As we've.
And for an apartment in the press release.
Now that we have a global partner with Abbvie, we can think beyond the U S and really think of the tremendous opportunity. We have two globally develop to reach more patients and that's really the aspect where with more patients. We can increase power for also the secondary.
Points that.
That can be particularly important when thinking of labeling and associated health technology assessment negotiations that for example occur in in Europe . So for that reason, we are very excited about increasing the sample size as far as which endpoints secondary endpoints we achieve.
Greater power for of course with more patients, there's greater power across the board, but some of the ones that are potentially particularly interesting are the value drivers of decreased treatment burden. So with more patience. We can look across all these different cuts of treatment burden.
For example, what's the supplemental injection rate of patients after treatment with our G X 314, what's the reduction in that treatment Burton what proportion of patients required no injections, what proportion of patients require less than certain other thresholds and that's just the.
Name a few but again, we're excited at the opportunity that we have greater.
Power across the board for these to help us in our global registration plans.
The second part of your your first question I think related to the was it the <unk>.
Manufacturing Oh, Okay conclusion process I don't know do you know that we have a cut off for the percentage of patients that are required across the different global regulatory agencies. I think there's generally a perspective and we've already started to adopt the use of the process in the pivotal trials as well as.
The other global expansion trial like like the fellow I work and obviously the Bioreactor study is a direct inheritor of the original process to.
To the new process, we've also.
In the case of the Super Cruet, I'll actually been using bioreactor process almost out of the gate in aviate an altitude. So I think we feel like really great place really what we're focused on right now with respect to.
The manufacturing work is the qualification loss that will support a commercial inventory, which will begin in 2023.
And with respect to rdx too too.
We're early in the process of obviously evaluating safety and Tolerability. We said, we'll have our first updates in the second half of this year and I think you know.
Looking forward to reporting on information that would inform us not only about how to continue to navigate forward with respect to do with the expansion or dose escalation, but also to potentially.
It makes them more informed decisions with respect to some of the protocols that we have in place and the sort of early safety assessments right now it's too early to predict until we see the data Janet exactly.
How things will navigate forward from here, but we'll be relying on internal expertise and experience as well as the people that in the field guide us for the implementation of.
The use of the immune suppression protocols, including <unk> from a starting point I mean this was I think it is very important sort of multi stakeholder process that we went through to begin with and I think we'll we will continue to sort of inform forward looking decisions on the same basis.
Thank you very much.
Thank you.
One moment for our next question place.
And next question comes from the line of gain Leone with Raymond James Your line is now open.
Thanks for taking the questions. Congrats on the progress could you just maybe clarify for everyone. Whether there was actually an alteration in the agreement with Abby I think some of US had thought that there would be a transfer of the regulatory responsibilities as as a cost shift occurred in 20th.
Three.
So I'm just trying to understand the nuance of what May have changed in the agreement and then secondly can you just pine a little on some of the poster presentations that you have coming up the SEC K curious to know how serious we should take the G. A program that's being presented there and.
And you know if you do have a view on in terms of bringing that into the clinic, what the timeline might be for that thank you.
Thanks to him I appreciate the question I think on the agreement side.
I think the message is landing the way we intended it I mean, we said since the beginning of 2023 that under our original collaboration Abbvie is transitioning to taking on the majority of costs for the program overall and that it was also originally expected for the I M E transfer to.
Occur that that happens to now be overlapping with the announcement today of the global expansion work that we're doing with respect to atmosphere in a sense. But this is this is not anything that was new with respect to the original collaboration understanding. These are all sort of programmatic things that are being implemented now that we're about a year.
Over a year into the collaboration that of course took.
Time between the teams Q to execute on.
With respect to the AFC C T.
Presentations and posters were excited as always be able to share a lot about the research that goes on within <unk> file across multiple different therapeutic areas and we have been and continue to be focused on targets that has significant unmet need in our significant populations.
Obviously, we have a curiosity and a strong interest with respect you indications that can extend into areas that we already work in including in and around retina. So I don't think that.
We're saying anything more than that right now it's just that we have a really strong we search engine with respect to work that's led by Olivia and his team is very much in contact with work that we do in the clinic both on the device side on the technology side and on the clinical experience side, and we said all along that we're going to continue to look for her.
High value indications to add to our pipeline <unk>.
And this is an opportunity for us to show some of the basic research that's going on.
But certainly not any specific guidance about any new ind's that we're announcing today.
Thanks, if I could just add one follow up to that I was excited to see the addition of the bilateral cohort.
Being run is that is that an endeavor that would actually need a separate study or is the cohorts that you're going to be exploring fellow I treatment and could suffice for actually having a label at the end of atmosphere and the pivotal program to allow bilateral treat but thank you.
Hi, Dan.
Yeah. This.
Fellow Y protocol allows patients who've been treated in either atmosphere sent to have their fellow I'd treated.
With our Jack 314.
314, sorry.
This actually is as per plan from way back our interface to meeting.
Discussions.
With the FDA, where.
This was certainly part of the package that we have some exposures and fell Y. So that we've treated both eyes, so that that would be allowed in the label.
Excellent. Thank you.
Thanks.
Thank you one moment for our next question. Please.
And next question comes from the line of Vikram.
Brilliant with Morgan Stanley line is now open.
Hi, everyone. Thanks for taking my call. This is gospel on <unk>. So we have two questions. So the first one is how does the decision to expand enrollment and atmosphere.
Impact and can under registration pathway and I'll be able to study is 40 out several colorado delivery of what AMD.
And then the second one is 40 gx data expecting.
Second half of this year.
Would you expect to release this data to a top line release, all is a medical conference venue.
That would be suitable for it.
Okay.
I think yeah.
Thanks, Gospel I think I can hit these and then.
It has more to offer but I don't know that we see a direct impact with respect to the regulatory past were very advanced with Subretinal.
Retinal and I think as we were just talking with dean about including things like.
Hello, I studies and sort of preparations for.
Qualifying laps for supporting commercial manufacturing I think we're our view is that we're hurdling toward.
Important milestones for regulatory approvals that we've given guidance on now both in the U S and outside of the U S for the Subretinal approach.
With respect to Supercoil, we're gonna have we're still in sort of dose ranging mood and fees Jews I think the of course strongly influenced by the same pharmacology may NRG X 314, obviously is activity at the ability to show biological activity in treatment effect.
You know kind of first product with the sub retinal delivery I think has a strong indirect influence but.
Right now I don't see any direct relationship between are forward looking plans for how we complete the work to support the filings and approvals of Subretinal and where we are with Super provider again there.
They're related they're tethered of course because of the same pharmacological agents, but otherwise there as we've been guiding for the last.
<unk> and uhm with respect to aviate in altitude.
Usually those are decisions that are made closer to the point in time when the team has reviewed the data and is able to sort of assess opportunities for presentation I think our practice.
In our view has been to duties at medical conferences, and I think that would that be generally shares that view when we come together on these topics and I think that's the.
The most meaningful guidance. We can in addition give there right now.
Okay. Thank you.
One more question ask please plenty objects to a two data for sure I was wondering.
What is it a release.
It could be a top line release all medical conference.
Haven't decided yet so I think again it will differ.
And a little bit on the timing certainly we keep our eye on conferences that would be appropriate venues for that just just as we do for the retina work, but we will that will be a decision that will be made again, a little bit closer to him and frankly.
Thank you.
Thank you.
One moment for our next question.
And our next question comes from the lineup Alec Stranahan with Bank of America. Your line is now open.
Hey, guys. Thanks for taking our questions <unk>.
Two from US appreciate all the color 314, and the updates under the AD the.
Partnership and any additional details of the thought process that would go into moving 314 into total studies for supercoil delivery or or in D. R. <unk>.
Cisco Knogo now under at the sole discretion.
And secondly on on DMD, given the irick sitting patients into a Saturday beyond.
Is there an expectation that a subset of the M D patients step to your existing.
Antibodies that could lower efficacy of 202, and a refreshing I need us the mitigation steps that went into the design of two two with would be helpful. Thank you.
So thanks, Alec so on your your first question on 314, so for a Super Choroidal an office delivery.
We're making great progress in our phase two evaluation with these dose escalations in both of of the studies for wet AMD and D. R and we're learning a lot we've already learned a lot with these first ever supercoil deliveries of of gene therapy.
And we're excited that we have the opportunity to evaluate.
Short course ocular <unk>.
Steroid treatment to further mitigate any risks of of inflammation. So it's really going to depend on readouts from these existing cohorts that we're gonna disclose that at least initial results. Later later this year I think the process, we and Abby go through and it is a joint.
Process with our joint committees, where we collaborated very closely on.
Evaluating any new data cuts that come out and it really comes down to at what point do we feel we potentially could be meeting target profiles for either of these indications that then triggers when we believe we could go into.
Pivotal development for either of those indications.
Yeah, I think that we have you know of.
You that we're well aligned would that be at this stage in terms of.
Being incentivised to move.
As judiciously as quickly forward as we can based on the data that we see and we're in the process, having just fully enrolled both altitude and aviate with the expansion cohorts to have opportunities to look at new data from those cohorts as well as continuation of data we have already reported so I think well it'll be a good point in the second half of the year.
Here to.
To revisit that question and sort of establish where we are with respect to that process overall.
Two two side.
I think I understand your question, which was we've got this affinity beyond.
Study going on looking at incidents or prevalence of preexisting.
<unk> antibody titers, impatient and absolutely I think as a class.
Micro dystrophin products I think this is a focus for all of US we we notice from other experiences.
And other trials that we've run, including our EV intravenous trial in each of H and our peers are all generally in clinical fees screening out patients with measurable.
Or certainly above a certain threshold titers of preexisting antibodies to do their specific capsid and I think we're all looking to be able to characterize that and evaluated commercially. There's a lot known about aviate. It actually is already from studies that have been published in that we've worked on knowing that it's relatively low prevalence.
With respect to pre existing but we want to study specifically in this disease basis too, but I know that if you were working with 89 or another aviation.
You'd be focus on the same thing so right now our trial is excluding patients who might have antibodies too heavy for purposes of enrolling in the treatment study, but we're building this body of evidence to understand more both clinically and commercially how we keep navigating this program specifically with affinity beyond.
Very helpful. Thank you.
Thank you.
One moment for our next question.
And next question comes from early Merrill with UBS. Your line is now open.
Yeah. Thanks, so much for taking my question, just a little bit more color.
Me at modification, maybe can you just comment on any <unk> reset interactions and just the latest feedback.
Particularly any feedback on that thanks for expansion as long as the latest feedback on manufacturing after the bridging study.
And then just a broader question on the phase three trials I guess just.
According to the protocols I guess, what kind of monitoring.
Did you have ongoing in the study and just kind of curious has there been anything in terms of the data.
That may have <unk> the decision to increase the study scientists thanks.
Hi Alley.
So as far as any regulatory FDA or other interactions. This.
Opportunity and the action to increase the sample size was.
Not driven by any FDA interaction.
Though of course with any protocol amendment these get submitted so.
This is in line with the protocol and has been submitted to the FDA. So there's there's no issues there.
As far as the monitoring remind the this is a mast ongoing studies so.
There is certainly no opportunity to be looking at any any efficacy results in this and there's just really the standard medical monitoring that's applied in this kind of study.
I understand and then just a question in terms of at the empty can you maybe just comment how many patients you've enrolled in does so far.
We haven't updated on that today alley.
Okay.
Thank you.
One moment for our next question.
And our next question comes from the line of <unk> with I B C capital market your line of services.
Okay. Thanks for taking a question of the survey song to Luka Uhm first maybe one on the fellow I study. Just wondering is what bilateral does thing going to be done at the same time or is that going to be a stagger between the doses.
Subretinal administration.
And if there is a stagger what gives you the confidence at the <unk> have high levels of neutralizing antibodies against the Doctor and I have another follow up.
Yeah. So as part as you can imagine as part of clinical trials, we don't want to confound. The parents study evaluating the study by having a fellow I treated in any type of proximity so in the fellow I study this will general.
Really be patients who are are getting their fellow I treated some time later, maybe a year or two years.
After having their study I treated.
In the real World. We know for example, historically with luck, starting a totally different disease setting and other considerations the concept of timing them closer together.
Which can.
Have the added safety consideration of at least theoretically minimizing induced.
<unk>.
One of the benefits of Subretinal of course is the relative immune privileged status.
So we anticipate.
Good safety and Tolerability and a fellow why but you raise a good point, we have to actually demonstrate that given that treatment even with subretinal delivery you can have at least the asymptomatic.
Antibody response, so this will be our opportunity to to evaluate that.
That's that's helpful. Thanks, and then just maybe on Dandy, you know, giving your competitor hasn't gene therapy, that's close to approval.
How do you think this will impact Deregulatory path forward for your program, while it's still be possible to the last of the accelerated approval pathway with like a desk to find out the biomarker <unk> approval ended up being a dental T. Yeah competitor and you probably that might be helpful. Thanks.
Yeah. Thanks, Lisa I mean, I think it's.
It's really hard to speculate too much, especially in the rare disease areas and including in gene therapy, where it's going to be known that there are kids that are gonna be excluded from the potential to receive certain of the gene therapy because of the topic that we were talking.
Talking about with with one of the analysts before that <unk>.
Certain patients are gonna be food for accessing certain therapy, especially systemic therapies because of preexisting immunology and then they may be able to receive an alternative therapy, that's up for approval or in development. So.
And in General you know I think we've we've seen a agreed interest on the part of of regulators and the community to support many product alternatives in those types of circumstances, where you might see populations that have access issues or just generally with respect.
Two responsiveness.
Really excited and encouraged about the views that.
You know the agencies, taking on concepts of accelerated approval and the use of surrogate biomarkers to predict clinical benefit.
And we like the position that we're in with respect to being in a class of medicines that is under review because we are going to learn a lot.
Nowadays not even weeks or months anymore, but I I would I would say that there's a lot of options and they will be informed by some of the process and the decision but.
My sense is that it opens more doors than it closes.
But that's helpful. Thanks for taking my question.
Thank you.
Moments our next question.
And your next question comes from many.
With S V V Securities. Your line is open.
Good afternoon. This is living on the on some money just a question in terms of the partnership on 314, so regarding the development and regulatory milestone could you provide us an update an idea of where we are in terms of what potential to be received in terms of suppressing all of US is typical at all as well as what indeed.
N D N D N E.
Yeah, I don't think we've given too much specific guidance since we announced the collaboration I think we emphasize that.
There is about 1.3 or 1.4 billion of potential outstanding development and commercial milestones that remain with I think around half of that potentially being associated with development milestones for transitions into later stage development for new indications or including.
The Super Choroidal platform, So I think.
Knows we the things that would be opportunities for.
Near term access pre commercial in particular with respect to development milestones and you know I think as we get into periods of time, where those evaluations are ongoing uhm, we sort of update interpretations of data we can perhaps.
Give some more clarity, but at this time, we as I think Vince spoke to with respect to even our cash guidance, we're not including any of those milestones right now in any of our plans. It's not typical for us to do that so we're being very conservative about the cash guidance that we're giving even though we have known upcoming data readouts with rich.
<unk> certain of these programs that could inform these things.
Thank you.
Thanks. Thank you one moment for our next question.
And next question comes from Caroline Q withstand per capital market. Your line is open.
Hi, Thanks for taking my question Uhm I think Ken at one point, you mentioned that <unk> 14 had a sore ability of over four years, perhaps locations that have shown that level of durability and I'm. Just wondering is there.
Certain patient profile I mean aside from.
Negative that you can.
Speak to that tend to show a higher durability and then as a follow up to that can you speak to any.
F D. A guidelines on gene therapy, and the Doctor space that is there any discussion going on about what an acceptable threshold of durability is for approval. Thanks.
Yeah Carolina, when we're talking about Subretinal first of all these are all patients that we didn't even screen on the basis of preexisting immunity. So.
I'm not even sure that we know that these patients several of them are out.
Three four years with durability and then they could be NAV positive, we're not I don't even know that I've seen that data per se.
And so that's that's a very positive statement to make about the commercial opportunity by the way for Subretinal of that it has no impact. We later showed that it seems that Super Crowed also has not impacted by preexisting immunity said. This is all very different space than intravenous delivery I think with respect to threat.
<unk> in sort of interest that the agency has.
And I think that it's it's.
It's multilayered I think for approval.
Kind of durability is something that I think is you know kind of on a shorter interval.
I would say a year, which is basically the measures of our primary endpoints in our pivotal trials as well as.
How were studying things even in early phases is you accrue enough patients.
With respect to a year and both on a primary and a safety basis, I think you're setting yourself up for approval with respect to the agencies.
I think the question really comes to bear on.
The payers and the providers and the adoption of the treatment overall so.
And this is where highlighting today I think how much further along how much deeper how much broader our program is and we will continue to be.
In when AMD and in diabetic populations with respect to 314 across additional devices and how important that information is for global development and ultimately global commercialization so well.
While the FDA a group like the FDA I'm sure they're gonna be happy when a package comes in with three four year data and it'll give them more confidence I'm not sure it's going to be something that sort of it is heavily weighted but I think when we were in the payer environment and we're we're in the <unk>.
This globalization when we're in health technology assessment environment. These things are going to become I think incredibly important and I think the differentiation for where we are with three one for our view.
Is really meaningful.
<unk>.
One of confidence.
Great that's very helpful. Thanks.
Thank you. Thank you.
And I'm currently showing no further questions at this time. This concludes today's conference call. Thank you for your participation. You may now disconnect everyone have a wonderful day.
Mmm.
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