Q2 2022 Regenxbio Inc Earnings Call
The conference will begin shortly to raise your hand during Q&A you can dial star one one.
[music].
Okay.
Good day, ladies and gentlemen, ending by welcome to the second quarter 2022 rejects bio incorporated earnings conference call. At this time all participants are in a listen only mode. After the Speakers' remarks, there will be a good question answer session to ask a question during the session you will need to press.
Star one one on your telephone keypad.
At this time I would like to turn the conference over to Mr. Victor <unk>, Chief Financial Officer, <unk> Bio Sir please begin.
Good afternoon, and thank you for joining us today with US today are Ken Mills, <unk>, President and Chief Executive Officer, Dr. Steve <unk>, our Chief Medical Officer.
Earlier this afternoon, <unk> released financial and operating results for the second quarter ended June 32022 of the press release reporting our financial results is available on our website at Www Dot <unk> Dot Com today's conference call.
Forward looking statements regarding our financial outlook.
Jason to regulatory and product development plans. These forward looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted and can be identified by words, such as expect plan will may anticipate believe.
Should enhance 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 30 <unk>.
2021, and comparable risk factors section.
In <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 August <unk> 2022, 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 extraordinary and does not purport to project financial positions or operating results of the company.
Actual results may differ materially.
I would like to now turn the call over to Ken Mills Ken.
Thank you good afternoon, everyone and thanks for joining us I'm pleased to begin today's call with a recap of our recent business highlights as well as an update on our corporate goals.
He will then provide an update on our clinical programs and will provide an overview of financial results for the second quarter ended June 32022 at the end of the call. We will open up the line for questions.
Before Steve gets into the pipeline progress in detail I'd like to provide some context on the gene therapy industry.
Last quarter I mentioned, how encouraged I was about the future of the industry. In this past June I believe we witness the impact of many effects, including with the FDA Advisory Committee unanimously endorsing two new gene therapies for the treatment of rare diseases.
Clearly this is great news for the gene therapy industry, and most importantly for patients needing these potentially life saving therapies.
I believe the panels approach to reviewing the risk reward profile of these products and the communities acknowledgment for the products construct and its role in both safety and efficacy highlights the willingness to these experts to take a more flexible approach when evaluating products for patients with large unmet need.
In addition in the past couple of months the European Commission has granted marketing authorization for one <unk> therapeutic in the EMA has also adopted a positive opinion recommending conditional market approval for another AAV therapeutic both indicated for rare diseases.
So overall I find these endorsements encouraging for the industry as well as for <unk> as we advance our AEP therapeutics for patients with large unmet need.
Moving on to some of our internal highlights for the quarter. We continue to make excellent progress advancing <unk> hundred one for using both sub retinal and Super choroidal delivery with.
With <unk> 314 for the treatment of wet age related macular degeneration using sub retinal delivery, we remain on track for a BLA filing in 2024 based on two pivotal trials atmosphere and ascent.
We've also progressed, our rdx <unk> four trials using supercritical delivery for the treatment of wet AMD and diabetic retinopathy or Dr.
And in May we announced completion of enrollment of the phase II <unk> trial evaluating our DXP one four for the treatment of Dr and more recently in July we announced completion of enrollment in cohort five of our phase III <unk> trial evaluating <unk> for in the treatment of wet AMD.
We plan to present additional Super correlated data later this year and we're pleased with the progress we've made across the entire <unk> programs. This quarter. We continue to take full advantage also of our global partnership with Abbvie to bring <unk> to market.
Taking a moment to update on <unk>, our candidate for the treatment of Duchenne last quarter, we announced that we made the difficult decision to delay dosing of patients in our first in human Duchenne clinical trial.
Decision was due to an unexpected isolated observation the final vial filling stage of the manufacturing process at a third party contract manufacturer that didnt meet our quality criteria.
The unexpected delay among other things reinforced the importance of investment towards in house, GMP manufacturing capabilities and the facility.
This is why I would like to highlight that this past quarter, we celebrated the opening of our new cgmp manufacturing facility called the <unk> bio manufacturing innovation Center.
It's 21000 square foot facility is located in our headquarters building in Rockville, Maryland.
This marks our successful expansion into a company with full end to end capabilities from research and development to commercial scale infrastructure.
We are one of only a few gene therapy companies worldwide with a cgmp facility capable of production that scales up to 2000 liters.
The first run and our manufacturing innovation center support our clinical supply for the RG <unk> program.
New process improvements that we plan to use in our facility are expected to produce for example in <unk> and approximately fivefold improvement in vector yields perhaps than previously used processes.
I want to reiterate our strong commitment to the Duchenne community preparation for the initiation of our first in human trial with <unk> two continues including ongoing manufacturing of additional clinical supply for the trial. We continue to anticipate dosing. The first patient in this trial in the first half of 2023.
Finally, our newest update comes from earlier this morning, when we announced that the pivotal program in <unk> is now active and enrolling patients and our intention to file a BLA in 2020 for using the accelerated approval pathway.
NPS fewer hunter syndrome is a debilitating disease with a large unmet need that significantly impacts the child's daily life and life expectancy.
Adequately treated by any drugs on the market today.
We're developing <unk> one a potential first in class onetime AED therapeutic for the treatment of Mps's due to treat the CNS manifestations of MPS SKU for which there are currently no available treatment options.
Discussions with the FDA support this plan the accelerated approval pathway with created to allow for expedited development of drugs to treat serious conditions and provide a meaningful advantage over available therapies based on a surrogate endpoint.
I would note that following our announcement in November 2021 at the launch of the pathway development consortium co founded by <unk> and solid Biosciences, which brings together key stakeholders, including the FDA with the goal of expediting patient access to AED Therapeutics, we have seen an increased interest in accelerated approval pathway across the <unk>.
Therapy industry.
This is an important advancement for rare disease communities, and especially those like the <unk> community our.
Our pivotal program will measure gags in the CSF, which we believe can be considered a surrogate biomarker that is reasonably likely to predict clinical benefit in NPS to disease under the accelerated approval pathway as the buildup of gags or glycosaminoglycan in the central nervous system of MTS to patients.
<unk>, the clinical manifestations, including neuro developmental deficits, we believe the accelerated approval pathway will allow us to advance <unk> one as quickly as possible with the aim of providing a much needed new treatment option for the <unk> community.
So with that I will now turn the call over to Steve to talk in greater detail about the internal program.
Thank you Ken.
I'll begin with an update on our <unk> 314, which is being developed in collaboration with Abbvie to treat multiple ocular indications, including wet AMD and diabetic retinopathy RJ.
<unk> 314 uses the NAV <unk> vector to deliver a gene encoding a therapeutic antibody fragment to inhibit vascular endothelial growth factor or a bad job.
Wet AMD is a leading cause of vision loss in people over 60.
<unk> more than 2 million patients in the U S Europe and Japan.
The current standard of care for wet AMD patients are anti VEGF treatment, which require patients to receive frequent injections into the eye.
Real World evidence shows that patients with wet AMD are severely under treated due to the unsustainable treatment burden of these frequent injections.
As a result, the majority of wet AMD patients experienced significant vision loss over time.
<unk> hundred 14 is being developed as a onetime treatment for wet AMD that has the potential to reduce the frequency of anti VEGF treatments and preserve vision for wet AMD patients.
We continue to enroll patients in the atmosphere on ascent, our two pivotal clinical trials evaluating the efficacy and safety of <unk> 314 in patients with wet AMD using the sub retinal delivery approach.
Buying these two pivotal trials will enroll approximately 765 subjects.
And evaluate for non inferiority, the mean change in BC VA for <unk> 314, compared to repeated <unk> injections of anti VEGF treatment at one year. These two trials are expected to support a BLA submission for our JAK $3 14 and 2024.
Overall, we believe our JAK $3 14 represents a significant potential advancement for the treatment of wet AMD.
We are also advancing two additional <unk> 314 programs that are part of our collaboration with Abbvie for the treatment of wet AMD and diabetic retinopathy using in office Super Choroidal delivery approach.
In wet AMD, we recently announced that we completed enrollment in cohort five of our phase III trial, a randomized dose escalation study evaluating the efficacy safety and Tolerability of <unk> 314, and 95 subjects with wet AMD.
To date, we have presented six month data for the first two cohorts that demonstrated evidence of the emerging clinical profile of <unk> 314, using super choroidal delivery with the most recent data from cohort two showing stable visual acuity in retinal thickness as well as a 72% reduction in anti <unk>.
Hi, Jeff treatment burden compared to the mean annualized injection rate during the 12 months prior to receiving <unk> 314.
The safety profile for <unk> 314 across all cohorts as of the last update from November four 2021 was reported to be well tolerated in 50 patients with no drug related serious adverse events mild and track their inflammation was observed on slit lamp examination at similar incidents across.
Both dose levels in cohorts, one and two and four out of 15 patients in cohort one and three out of 15 patients in cohort two and resolve quickly with topical corticosteroids.
Patients in this trial did not receive prophylactic steroids before or after administration of <unk> $3 14.
Moving to <unk> 314 for the treatment of Dr.
<unk> is a complication of diabetes and is the leading cause of blindness in adults between the age of 24 75 worldwide and.
An estimated 27 million patients are affected by this debilitating disease worldwide.
Dr is a slowly progressive disease that can lead to vision, threatening complications, including diabetic macular edema, or <unk> and neovascular innovation that can lead to blindness.
Like in wet AMD patients with Dr can be treated with anti VEGF therapy, which is proven to reduce the risk of developing vision threatening complications.
However, due to the unsustainable treatment burden using anti VEGF therapies, primarily the result of the frequent injections required with today's available treatments.
Many people with this condition either elect to forgo treatment or put off receiving any treatment until symptoms become unavoidable.
We believe that gene therapy, like <unk> 314 could potentially overcome this hurdle and provide an important therapy for patients to significantly alter their disease progression.
We recently completed enrollment of the phase II <unk> trial, a randomized dose escalation study in 60 subjects across three cohorts to evaluate the efficacy safety and Tolerability of <unk> hundred 14 in subjects with Dr.
The trial's primary efficacy endpoint is the proportion of patients achieving at least a two step improvement and Dr measured by the <unk> scale at one year.
Six month data from cohort one demonstrated after a single Super Choroidal <unk> 314 administration are clinically meaningful to step improvement from baseline on the <unk> scale and 47% of the <unk> treated patients compared to zero percent in the observational control.
As of the data cutoff of January 18th 2022, <unk> hundred 14 was reported to be well tolerated in the 15 patients dose.
With our <unk> 314 in cohort one with no drug related SAE and no intra ocular inflammation observed.
We're encouraged by what we're seeing at this stage.
Shifting to our rare disease portfolio portfolio <unk> 202, our potential onetime gene therapy for the treatment of Duchenne is 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> terminal or <unk>.
<unk> domain founded naturally occurring dystrophin.
In preclinical studies the presence of the Cte domain has been shown to recruit key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction induced muscle damage and distressed dystrophic mice models.
Additional design features including codon optimization and reduced CPG content, which has the potential to improve gene expression increase translational efficiency and reduce immunogenicity.
<unk> is designed to support the delivery of targeted expression of genes throughout skeletal and heart muscle using our NAV AAV vector and a well characterized muscle specific specific promoter SBC $5 12.
The affinity Duchenne phase one two trial will measure safety and Tolerability of <unk> 202, as well as micro dystrophin protein expression levels muscle strength and functional assessments, including the Northstar ambulatory assessment and muscle MRI.
Preparation for this trial is ongoing including readying clinical trial sites for the upcoming trial, which we anticipate dosing in the first half of 2023.
Finally, as Ken mentioned earlier, we are pleased to announce that the ongoing phase one two trial of <unk> hundred 21 has been expanded into a pivotal phase 123 trial called camp site.
Our campsite trial, which is now active is a multi center open label trial enrolling boys with NPS to H four months up to five years of age.
The trial is expected to include up to 10 NPS to patients to support the BLA filing using the accelerated approval pathway with the potential to enroll additional patients.
These patients will receive a dose of $2 90, <unk> GC per gram of brain mass of <unk> 121, using commercial scale cgmp material, which is the same dose being evaluated in cohort three of the phase <unk> trial.
The BLA BLA filing is expected to support be supported by endpoints in the pivotal program <unk>.
Including changes from baseline of glycosaminoglycan or gags in the cerebrospinal fluid or CSF at four months.
The trial will also continue to collect neuro developmental data and caregiver reported outcomes.
The camp site trial is a global trial and is expected to include sites in the U S, Brazil, and Canada, we have begun dosing patients in this pivotal program.
Behind <unk> hundred 21, we are developing <unk> 111 for the treatment of severe NPS, one or Hurler syndrome, where we continue our ongoing phase two open label trial, we continue with plans to enroll additional patients in a cohort two expansion arm of this trial.
And tomorrow, our team is proud to join the National NPS societies 36, anecdotal family conference taking place in Nashville. This is one of the largest NPS advocacy conferences and is held each year to support research education and awareness for this debilitating.
Both diseases.
Look forward to connecting with the NPS community and discussing our <unk> 121 pivotal program plan with more physicians caregivers and patients stakeholders.
So to conclude we have made significant progress in the first half of 2022, and we look forward to further progress over the course of the rest of the year.
Now I turn the call back to Ken.
Thank you Steve for the good updates into the entire team for the progress over this past quarter and throughout the entire year so far.
I'm really proud of how our company has been advancing our pipeline and I believe that the fundamentals that <unk> have never been stronger we put into place are five by 'twenty five strategy to progress five AAV therapeutics from our internal pipeline and licensed program into pivotal stage or commercial products by 2025.
With these updates I hope you can all see how important progress we've made in executing on this plan.
And beyond the internal programs five by 'twenty. Five May also include programs being developed through our NAV technology licensees. Our NAV technology platform is driving the field of AAV gene therapy forward with over 60 clinical trials utilizing that vectors registered in the national Institutes of health clinical trial database since 2015.
Overall, I believe we have laid out a clear and definable path to achieving this goal by advancing our key programs that have the potential to treat very high unmet need in areas, where our NAV technology platform can be used to develop and potentially commercialize <unk> therapeutics as soon as possible.
So with that now I'm going to turn the call over to Dave who will review our financials and guidance.
Thank you Ken quarter ended on June 30 of 2022, <unk> with cash cash equivalents and marketable securities totaling $692 million compared.
$849 3 million as of December 31, 2021. The decrease was primarily the result of cash used to fund operating activities and capital expenditures as well as temporary unrealized losses on marketable debt securities during the first six months.
We ended June 32022.
R&D expenses were $61 million for the quarter ended June 32022, compared to $45 9 million for the quarter ended June 32021, the increase was primarily attributable to personnel costs and expenses associated with clinical trials and.
<unk> related activities for our lead product candidates and was partially offset by <unk> through important development cost reimbursable by Abbvie under our eye care collaboration.
<unk> with the collaboration agreement with <unk> firewall are continuing to fund certain ongoing clinical trials for <unk> hundred one for through the end of 2022, while other three one important development costs are shared with Abbvie beginning in 2023 as he will be responsible for funding.
The majority of all <unk> and <unk> development expenses.
So on our current operating plan, we expect the balance in cash cash equivalents and marketable securities of $682 million as of June 32022 to fund our operations into 2025.
Ken I will turn it over to you.
Thanks.
Overall I'm incredibly encouraged about how <unk> continues to perform at a very high level and I'd like to take this time to thank our entire <unk> team, our investigators and the patient communities for their commitment and involvement in the development of our innovative <unk> therapeutics.
To summarize what you've heard from us today.
We continue to be a leader in gene therapy.
Thousands of patients who have been dosed with AED therapeutics derived from our NAV technology platform and hundreds more are receiving treatment every quarter.
We have an amazing team of scientists and engineers dedicated to expanding the understanding and application of AAV vectors applying differentiated capabilities of NAV technology platform and exploring the potential to generate new innovative AAV therapeutics for diseases that have the potential to significantly impact patients lives.
Global eye care collaboration with Abbvie continues to advance and is on track for the first BLA filing in 2020 for progress in trial enrollment and emerging clinical trial data supports excellent progress in our supercoil delivery programs.
Preparation for the initiation of the first in human trial for Rdx. Two to continue we are readying clinical trial site and manufacturing additional critical supply for the trial, including the first batches to be produced at our manufacturing innovation Center in Rockville, We continue to anticipate dosing. The first patient in this trial in the first half of 'twenty.
23.
Our manufacturing innovation center, and our GMP capability remains a key differentiator for <unk> bio and the key element of our strategy already house facilities cutting edge allows us to move quickly from candidate selection to the production of clinical grade material, which supports accelerating the early development of AED Therapeutics. Additionally, we.
Leave our approach focuses on early product quality and process control, which lessens the need for changes during clinical development to enable efficient transition from clinical trials to commercial readiness.
We're excited to be advancing <unk>, one into pivotal stage, making this our second active pivotal program and another opportunity for a BLA filing by 2024.
We feel that our intention to use the accelerated approval pathway for <unk>, one positive positive implications for the rare disease community. It signifies the ability to leverage FDA regulatory tools to facilitate and expedite drug development and offers hope for rapid access to new therapies for patients living with the more than 7000.
Rare diseases.
Our plan for accelerated approval is supported by our NAV Express process and our manufacturing innovation center designed for the high yield manufacturing quality of AED therapeutics at scale necessary to support clinical development and commercialization.
And as required under the accelerated approval pathway. We are and we will continue to be committed to conducting post approval confirmatory trials to verify that <unk> provides the expected clinical benefit.
And lastly, as you heard from it we have a foundation of capital over $680 million to fund our mission and operations into 2025 and through multiple filings and other anticipated data milestones that leave us well positioned to execute our five by 'twenty five strategy of advancing five AED.
Therapeutics to late stage development and commercialization by 2025.
So with that I will turn the call over operator for questions.
Yes.
Thank you ladies and gentlemen, if you have a quick question.
Right.
One one on your telephone.
Good morning.
At this time please star one.
One one.
Please standby, while we compile the Q&A roster.
Our first question or comment comes from the line of <unk> Wang from Barclays. Your line is open.
Thank you for taking our question for Gina.
I have two questions one for arch X 100 to one gather full arch acts sorry, one four so for the one to one.
Since you announced the pivotal.
Program have you online fully aligned with FDA on the primary endpoint like SaaS of gags and.
Follow up duration and comparatively for the phase III trial, and if not what's your base case assumption.
For the 314.
Youll have dose if you Nab patient plus positive patients have you seen the toxicity profile any different than what we have seen what has been reported so far.
Hey, Tom as Ken Thanks for the question I'll take one in Q1, and maybe turn it through in for question over to Steve.
As we alluded to the announcement this morning about moving into a pivotal phase following the accelerated approval pathway with unencumbered with communication with FDA and the trial design that Steve outlined for campsite.
Does it include a comparator arm and involves measurement of gags in CSF that four months.
Which we believe is an opportunity to represent a surrogate endpoint in the accelerated approval pathway. So really excited to make this announcement today and that the structure of the campsite study is not only.
Amendment to the existing IND.
Also as active and we've been enrolling patients as part of our pivotal program.
Great. Thanks.
Thanks for the question on <unk> 314 regarding nabs are neutralizing antibody status and any impact in the two trials that we're running with supercoil delivery.
As you know with sub retinal delivery, we already know that neutralizing antibody status of patients doesn't impact.
The safety and efficacy that we see.
We are excited that we are at April to characterize.
Super Choroidal delivery of gene therapy, with our NAV technology with our <unk> hundred one for where we can answer the question that you've asked and we've gone about this very methodically both in terms of dose escalation, but also looking at.
Both Nab negative and Nab positive cohorts of patients.
At dose level, two and dose level, three and the aviate wet AMD study and at dose level two.
The alpha to Dr study.
And in the data releases.
As we've discussed previously we've actually not seen any evidence of impact we're not seeing for example, any greater safety.
Safety or inflammatory findings in patients who are Nab positive and then the data cuts, where we can look at Nab negative in that positive like.
In aviation, we're able we're going to be able to assess this over time.
But to date in the releases that we've had we've been very pleased with the lack of any clear differentiation in terms of <unk>.
Safety between nap negative in that positive.
Thank you.
Thank you.
Our next question or comment.
Dan <unk> from Raymond James.
Your line is open.
Thank you for taking the questions and congrats on the progress.
Just two.
<unk> kind of anything to confirm for me.
Can you just confirm that you will have an update on aviate altitude in the back half of this year.
And then secondly can you just walk us through.
The camp site requirements from the FDA in terms of the primary endpoint I think I misheard, but I thought you said.
The requirement is 10 patients and the primary analysis that with a.
Measurement of gag reduction in the CSF at month four.
Again, I, probably misheard that but if you could just clarify thank you.
Hey, Deane it's Ken.
I can take both of these actually you can expand on it if you could.
No Thats right. We plan, we announced that we will have <unk> data from the ongoing trials. Later this year that would include <unk> at an altitude updates.
With respect to one Q1, no you're being a great listener I think you actually heard the information that we communicated that.
<unk> is a trial that is.
Our pivotal phase expansion of what was the ongoing phase <unk> trial, where we continue to.
Collect a number of endpoints across the entirety of the trial with point that enroll but with respect to the accelerated approval plan. We've been focused on and have alignment that gags in CSF at an endpoint of four months, we'd have the opportunity to support an accelerated approval.
<unk> as a surrogate endpoint and so that's.
That's what we're executing on now in order to achieve what we think is an exciting timeline for the BLA in 2024.
Okay. Thank you I guess.
If I can ask a follow up to that I mean.
Can you rank your level of confidence here I guess why youre getting the question is this doesn't seem to be in line again different Mac.
Different mechanism, but it doesn't seem to be in line with what JCR Denali I understand to be the requirement to hunter.
For a regulatory approval.
Obviously can't speak to other People's programs, Dane and as you pointed out.
We don't know of another program that uses AAV therapeutic technology to focus on Hunter syndrome delivered directly to the CNS.
What we can communicate as we are in terms of an understanding of the opportunity for accelerated approval for <unk> one.
And our degree of confidence is such that we announced this morning and follow up this afternoon that we're going to execute on this plan.
And I think this is a really encouraging thing for patients.
Okay. Thank you very much.
Thanks.
Thank you.
Our next question or comment comes from the line of Alex Stranahan from Bank of America.
Mr Stranahan.
A question or comment comes from the line of Alex Stranahan from Bank of America.
Mr. <unk> your line is open.
Hey, guys. This is John I'm on for Alex Thanks for taking our question just a follow on from Us.
In terms of manufacturing what does the economics look like right now in terms of moving things.
In house versus.
Going with the contractor if you can put like a specific percentage of cost savings.
Moving things and how that will be.
Really helpful and second part to that would be.
What are we looking at in terms of expecting all the pipelines to fully and completely move in house.
How long are we expecting.
<unk>.
It's still going partial external production to continue thanks.
Hey, John Thanks for the questions. So.
As we've announced we.
I've opened the facility here in Rockville, and we've started to make the first batches to support program work here at <unk>. We highlighted the fact that we prioritize the first batches to support the clinical supply for RG <unk>.
We continue to have material need.
On bulk.
Cereal in particular made at the CDMA sites that we used principally Fuji film down in Texas, and I think that your question about kind of the future focus here.
Is a good one but we're still in the early phases of kind of.
Utilization of the new facility and the planning overall is something that is as you can expect sort of multi variable we've got clinical supply needs in the immediate for rdx <unk> I should point out that we actually have the inventory that we need in place made with the.
Now have express bioreactor process to support the Rdx, one Q1 pivotal phase.
We have a lot of inventory in place of course, we've been continuing to expand the.
The inventory and then use it with respect to execution of atmosphere.
As well as aviate and altitudes and when it comes to <unk>. We're in a very dynamic process and now that's starting to include Abbvie with respect to that planning. So I don't know that we have a finite answer at this point, John but what I can say is that the plan in terms of the investment was to rely more and more on ourselves to.
To deliver material for all of the needs that we have across the pipeline as well as through commercialization and we think that the capacity is there in rockville to achieve that the absolute timeline I rely on the expertise of our highly capable technical operations team to work on those transitions of processes.
Here to support our need and balance that with continuing to have sort of backup options in the <unk> space. So in terms of the cost component of it.
I don't know that we would project right now any sort of material changes to our.
Our P&L and R&D expenses with respect to how we're thinking about.
Use of our new facility. In addition to the ongoing <unk> relationship use what I would say is we're making a lot of material. We have a lot of programs. We have two programs that are now in digital feet and so I think we probably have among the sort of highest use of.
Any of the gene therapy companies that I can think of particularly honor diversity program basis, I feel really well positioned with where we are right now for our needs.
Alright, Thank you Ken Thanks for the color.
Thank you our next question or comment.
Comes from the line of Ellie Merle from UBS standby.
Okay.
Hey, guys. Thanks for taking my question.
<unk> 111, NPS one I.
I guess after the update on the Registrational study for NPS and how are you thinking about the potential path and MTS, one and if the design with look relatively similar and the initial FDA feedback on that or any timeframe under which we can.
To learn more feedback and then just a follow up question on the MBS. Two study I guess in terms of the endpoint any sort of magnitude of effect or effect size that was discussed.
With the regulators and then just last question on <unk>.
314, I know you haven't given sort of direct guidance in terms of the timing, but any kind of high level. How we should think about certain medical meetings that could be good candidates for learning more.
Just anything to help us think about when we could kind of learn more about some of these higher dose and Nab positive cohort.
Thanks Ali good robust set of questions. There so I'll try to tick through a few of them and.
Certainly going to involve Steve here as well.
The focus with respect to one Q1 juxtaposed with 111 for <unk>.
Certainly been affected by the fact that we've.
Accumulated more patients in the <unk> phase one two trial, we've gone through additional dose escalation being able to go through additional longer term safety assessments for certain of the patients with MTS too and so conversations around the concept of the accelerated approval pathway.
We're frankly, just supported by more data, particularly on the safety side, but also on kind of the dose responses that we saw with respect to the biochemical markers.
As we've reported the emergence of.
Kind of understanding of correlations in certain patients with respect to the clinical outcomes as well and.
I think speaking to the point that Dean had raised and I think you're bringing up again with respect to <unk>.
Some of the robustness of that data and where we were.
We were beginning to report.
As early as February of this year that with the dose level three and the phase <unk> study, which is the pivotal dose now it's part of the pivotal program expansion as Steve alluded to the $2 911 dose is one where we began to see normalization of certain gags in the CSF and so I think we're.
We're thinking about these diseases thinking about surrogate biomarkers for approvable endpoints in things like the accelerated approval pathway and thinking about how to make not just the logical scientific arguments, but scientific arguments connected with a biomarker argument that's going to connect with confirmatory studies that.
We also believe are part of the process of kind of dynamically engaging in our accelerated approval pathway program.
Really saw the totality of that with respect to <unk> one.
We know and acknowledge that <unk> hundred 11 in MTS one is.
Closely related disease adjacent to NPS too.
But we're not where we were with one to one or are with one to one with respect to the levels of enrollment and the robustness of the data set at this time so.
We'll continue to expand the 111 program, but absolutely right now the focus for US is on accelerating the <unk> program against this new timeline, which we're really encouraged about.
On <unk> for Steve.
So on your question about any more granularity on.
Updates on aviate altitude on the back end of this year and medical meetings or not.
As you mentioned we're not.
Able to give any more specifics and it's the type of thing that we work on.
Planning with our strategic partner Abbvie as well, but we do share the view that it is good to be opportunistic and try to take advantage of the typical big meetings that.
Happen.
On the usual cadence around the year, so that would be in the mix of what we're thinking about but.
Certainly we look forward to giving an update on on both programs in the second half of the year.
Thanks.
Okay. Thank you.
Our next question is coming back.
Okay.
From the line of Lisa Walter from RBC capital markets.
Yes.
Oh perfect. Thanks for taking my question.
Hi, This is Lisa for Linzess.
So sorry.
Three for me relating to the accelerated approval.
Potential accelerated approval path for Rgs once your line.
Alright.
The new FDA Commissioner has been supportive of their farming the accelerated approval pathway.
So that approval can only.
Once the confirmatory phase three is already ongoing.
Just wondering how confident are you that this will not.
Applied to our <unk> line.
And question number two assuming you can file rdx lunch on early how are you thinking about the actual primary endpoint for a confirmatory phase III trial later on.
And one last question just on Cam site.
Just wondering if you could provide more color on the trial design well.
Will patients be allowed to be on background enzyme replacement therapy.
Good set of questions.
Yes.
So I think one of the benefits here as Ken mentioned is right from the beginning we are committed to a confirmatory study.
Four.
Complying with the accelerated approval pathway.
And with the goal of 2020 for BLA via accelerated approval pathway.
We're now just approaching second half of 2022, I think that gives a lot of time in terms of.
Fine tuning the actual confirmatory aspect I think the benefit is we believe.
In the reasonably likely to predict clinical benefit, particularly in this disease with.
Replacement of the enzyme via gene therapy directly to the CNS.
And that's really going to put us in a good position to as rapidly as we can get this product to patients in need and in parallel plan for that confirmatory study one of the realities. We know with this disease in a lot of these rare diseases for which accelerated approve.
<unk> pathway is intended that the actual demonstration of the clinical benefit.
Just takes up more patients and longer follow up given the inherent variability in these different diseases, including NPS too.
Certainly we feel confident we can do a confirmatory study, but with more patients.
And longer follow up where we'll be able to look at neuro cognitive.
Outcome measures like the ones that we do include in our ongoing study. So we feel very good in terms of the first two parts of your tier three part question.
<unk>.
So I think we're in a really good place now that we have campsite ongoing.
Hitting the pivotal part of the program.
Sure.
Yes, and I think that.
<unk>.
With respect to some of the earlier questions.
<unk>.
This is an accelerated approval plan approach, we wanted to sort of accelerate the use.
Of the Biomarkers that we think have shown evidence of correlating to clinical outcomes that we've shown in our data. We also believe that those biomarkers have been things that have been strongly associated with good scientific understanding including in animal models of the disease.
<unk>.
And we think that.
At this stage.
Have a really robust safety data set not just <unk>.
Frankly in patients that are an extension of the phase <unk> study, but we also have to acknowledge that we have.
Over the last year or so also set up additional phase <unk> study for <unk>, five and older with respect to <unk> as well. So there was a lot to draw firm in terms of the communications and the interactions that we had with stakeholders. Both in the patient communities. We brought our investigators for we talk.
Physician experts, who were not investigators in currently Rdx <unk> studies to bear on conversations with the FDA and others about how to accelerate the development of <unk> one.
I would say one point, Lisa Im not sure that I have heard or here.
The same thing that you are kind of representing about what the new commissioner of the FDA is saying about confirmatory studies, we certainly.
Have a commitment to running confirmatory studies, we expect to bring confirmatory evidence forward as Steve alluded to I think it's pretty straightforward with respect to Hunter syndrome, we need to see the neurodevelopmental outcome and we want to see a lot of important caregiver reported outcomes as well when you talk to the field.
Just sort of a singular perspective on what are the outcomes because theres so much heterogeneity in a small population.
I think those types of conversations falling on the years of leadership at FDA and regulators has a profound impact on sort of how they think about the need and the kind of interest behind accelerating a gene therapy for Hunter syndrome, So for us.
It is more dynamic than saying, we're going to run a confirmatory study and we have to figure out what that design is going to be it's actually built into the development plan and the program even through camp cited as Steve alluded to we're still collecting all of these other measures we're going to be relying most heavily on this.
Irrigate biomarker to support the accelerated approval then.
The boys that have already been enrolled boys that are enrolled through this accelerated approval plan fees.
The trial is actually opens you enrolling boys. In addition to the 10 that we would associate with the accelerated approval band to be able to continue to collect evidence and have that apply as part of the confirmatory evidence. So I think.
There is no reason to sort of put.
Any of this into a box that my view is that what's been most encouraging about these discussions is that there is a lot of confidence in it.
Ada that we brought forward in terms of the safety the correlation of the potential surrogate biomarkers in animal in the human data, we've shown to the disease process to the outcomes that we've shown with respect to things like the neuro developmental outcomes.
Caregiver reported outcomes already and so it just shepherding that to something that makes it accessible to patients.
As efficient a way as possible and I think thats been on what we've seen over the last quarter or two emerge in conversations with all stakeholders.
Well. Thank you. Thank you a lot for that.
A thorough answer and then.
I guess just on the enzyme replacement therapy are you, including or excluding patients.
Yes, we are.
As we've done in the phase <unk> study, we've always continued to enroll patients on <unk>.
Acknowledge that in.
The background developing doesn't affect is known not to have any effect on the neurodegenerative pathology associated with NPS too. So we've shown that in the data that we presented to date in the phase one two study from cohort one to cohort three and occasionally we have had enzyme naive patients enrolling the study.
<unk> from certain sites, but in general, especially in the U S. Lisa we see patients coming in on <unk>, IV and they get <unk> on top of it and Thats been.
The expected continue approach on camp site.
I just want to thank you for taking taking a question.
Thank you.
Our next question or comment comes from.
Our garage from what Bush Securities Mr. <unk>. Your line is open.
Hi can you guys hear me via operator cut out.
Yes.
Okay great.
Yes, thanks for taking my questions Congrats on the progress as well.
So for the MTS to program just a couple of.
Follow up questions here.
In line with the previous question.
And this has to do with your interactions with the FDA and how important that they consider this correlation between biomarker then I guess the functional measures.
I don't believe we saw the functional measures from cohort three in the February update so one might think that that data has yet.
Peter.
Can you remind us.
What <unk> seen to date, what's really informed the phase two dose and then on 314 Super Choroidal just to clarify.
The press release, it says that no patients were treated.
Previously treated or treated after dosing.
Is that from all of the remaining cohorts as well.
Thank you.
I'm not sure I understood. The last part of the question Andreas.
Yes.
Yes, just to clarify sorry, if I wasn't clear.
The way it was worded.
Implied at least from.
My reading of it that you have not seen none of the patients that receive prophylactic steroids prior to or after being dosed and all of the cohorts.
Yes, that's correct so.
Sure.
As we've discussed.
Previously for for both studies, both aviate and altitude and all of the cohorts we have not.
Included prophylactic steroids, either before or after the administration of <unk> three one quarter.
Okay and does that have.
I'm trying to understand it.
That has anything to do with R&D research.
Observations inflammation.
Additional cohorts you can speak to that.
Well right from the initial cohorts in both studies, we did not have a prophylactic steroids, either before or after and as we've dose escalated.
In both studies given excellent Tolerability, we did not institute.
Prophylactic steroids at the higher doses.
And so with respect to the <unk> Q1 program question I think.
Just continuing to.
Support.
The understanding here that the dynamic conversations with FDA are certainly included the data that we have presented on podium.
As well as <unk>.
Information that we've included in both the amendment with respect to the campsite study and conversations that we have multiple of these.
Designations, including things like fast track that allow for a dynamic interaction with respect to FDA on this topic.
It's.
Something that also has.
Been part of <unk>.
Paul I'd say interactions that we've had with.
Stakeholders, including FDA on the topic.
Accelerated approval for things like.
Hunter and Hurler syndrome, I think I alluded to in my remarks.
Our initiation with solid biosciences, and the formation of the pathway development consortium, which is something that we announced late in 2021.
Actually started out with working group focused in Duchenne and talking about concepts of how to accelerate <unk> therapeutics in the background of Duchenne later that group came together and issued a white paper that was more broad spectrum, but identify categories of different types of diseases and how.
You would come forward and think about acceleration of development based on the science or the pathology of the disease or kind of the residency with respect to tissue type.
And some of that white paper work landed on <unk>.
NPS diseases, or neurodegenerative diseases, including MTS diseases.
Were evident.
From those discussions and I think validated through the announcement today is that there is.
Support for accelerated approval to rely on adjusted viable endpoint something like gags in CSF based on the emergence of <unk>.
FDA leadership allude to animal data and support is we've certainly seen them be supportive of human clinical data and the reconciliation of those thing in terms of the correlation to where the confirmatory evidence is going to come from I think it's.
It's inherent in the biomarker.
From my perspective that when especially in the case of <unk>.
Gags in CSF, when Youre talking about the substrate of the enzyme that's deficient in the disease that its going to quarterly has correlated with changes in pathology in animal model and going to correlate with changes in pathology in the humans and eventually be confirmed in things like the neurodevelopmental.
Mental outcomes in the.
Caregiver reported outcome. So I think there is.
<unk>.
A unique space in my view for the MTS CNS diseases and their relationship with respect to AED therapeutics that had been part of many discussions including for diseases that are more rare than the <unk> as well of course <unk>.
And many other companies are part of this other paradigm approach for bespoke AAV gene therapies, where I've.
Observe there have been similar conversations about how do we exceed the and accelerate the development of the therapeutics once we have safety and sort of stable manufacturing capabilities for patient so.
For me I think we've been talking with all of you about our involvement in a lot of those different consortiums and groups. We've been talking about the interest that we've had in sort of finding pathways for acceleration of rare disease.
Obviously, we've announced work in Duchenne, but most of our clinical data of course in rare diseases in <unk>, one in Hunter syndrome, and I think just based on a very.
Mature kind of and sort of longitudinal set of conversations and regulatory interactions that have gotten us to this point.
And really encouraged and pleased with this outcome because it sets us up to file the BLA.
SaaS the timeline as.
Probably our team can handle and we're up to the task for execute.
Alright, Thanks Nicole.
Thank you.
Our next question or comment comes from the line of Mani <unk> from <unk> Securities standby.
Okay. Thanks for taking the question a lot of the colleagues other firms have dug out clinical data et cetera, I wanted to revisit another topic, that's been discussed a little bit on this call around.
Our wholly owned manufacturing in the value of manufacturing for AAV specifically.
The specific question I have is.
As how you see the expansion in capacity, obviously has been tremendous investment.
The <unk> community.
And are the face of <unk>.
Blowing investment into AEP development.
Adventure in Lockstep pharma give us a sense of where we are in terms of the available capacity.
And what that means about the value of our investments in wholly owned manufacturer.
Okay.
Money I don't I don't know that.
We.
We are the company that sort of maybe Beth to give give the overview of what the entire CMO landscape is like at this moment I think.
And we've talked with you for a while and I think others on this call about our journey.
Started four or five years ago, when we had no need for high quality clinical material.
We experienced a lot of things with a lot of different <unk>.
And up to and most recently, including our experience with this final fill finish third party in the CDMA network.
I think with respect to capacity.
<unk>.
It may be there it may not be I don't know its a really hard thing to establish when I think about the capex investment in particular like you I think we see a lot of announcements about new facilities being invested in and built perhaps.
But what I can say about our interest in our approach and that's really came from.
The leadership team here and some of the most experienced people that we have in the company when it comes to manufacturing is.
That really to be able to.
Scale high quality manufacturer, especially in a new area you need real continuity with respect to the quality team and with respect to the floor operations team and that was something that I would say, we certainly observed with respect to this dynamic change in demand.
For the CDMA space is that there has been there's been the potential for a lot of movement in people and in expertise and that was something that I would say it was a driver for.
Our investment in something that was making us uncomfortable.
Now we are more comfortable with and I think one that we are priced will about that we have an excellent quality team and excellent operations team and a team that.
We think is really connected to the mission of <unk> Island, one that appear in our building where the research labs or in.
Where I work and others work.
And having that type of opportunity at this time and place I think establishes that it wasn't just about the capex investment, but it was about the people investment, making it something that was going to last and a sort of continuously for us and look we've got designs on peaking now two pivotal programs to BLA in 2000.
24, and we've got the five by 'twenty five strategy, we want to commercialize so having that responsibility means having a stable not just set of equipment, but a set of people as possible as well and I think thats been.
If it's there.
One of the big priorities of our focus on investment.
Great and if I could ask a separate question.
Scott earlier, but I'm not sure if the answer what complete or maybe I missed it because of the call.
But because of the quality audio and all we could you.
Give us a little more detail on where you think exactly the requirement for milestones on the Bayley score.
And a little bit of detailed quantitative.
Okay.
Didn't address any sort of specific quantitation with respect to the neurodegenerative outcome requirements.
On a confirmatory study I think the way that I address that is when we've engaged with.
The physician clinical experts in MTS, when we talked with the patient family stakeholders and brought them together in circumstances, where we're able to do so with the FDA and with our own data and assessment.
There is no absolute hard cutoff on any one measure domain for any of that so what we've seen and what we've continued to do in our clinical program is to collect all of that data collect all of the domains of things like.
Bailey and Thats sort of equivalent assessments on an age adjusted basis include caregiver reported outcomes include the biochemical measures and the other measures that are sort of evidence of the gene therapy, turning on the gene therapy, having both biochemical and sort of cellular morphological changes occurring in that.
The confirmatory evidence is actually going to be something that's going to be.
I think a journey that is going to.
A lot more patients to sort of grow that understanding against the heterogeneity of the disease in general.
So what I can say is that we're really encouraged about everyone recognizing that and recognizing that there are sufficient changes occurring in the boys on the basis of our gene therapy approach for something like NPS too that there is interest in the opportunity and wanting to accelerate its access to more fan.
These employees and that our commitment to continue to sort of grow that understanding that understanding of what are the different types of neurological outcomes that we're going to see in different types of employees at different ages against the heterogeneity of the disease is going to be something that I think is also going to leave its mark, but that's not going to be something.
That can be achieved by 2024 and thats something that is going to take many more years of confirmatory commitment to achieve and we'll be there to do that as well.
Okay. Thanks.
Our next question or comment comes from the line of Caroline.
<unk> Your line is open.
Alright, Thanks for taking my question I just had a quick question.
If you could provide some guidance on the R&D and G&A expense I'm. Just wondering if you just expect them to keep trending up in the near term.
To get a little more color on that.
Great.
Okay.
Okay.
I think we've seen R&D expense grow as we've expanded into pivotal phase of development and sort of increase.
Manufacturing and supply requirements for things.
<unk>.
Duchenne muscular dystrophy program, which obviously is larger quantities of AAV that we need on a per patient basis. So.
So moving into continuing.
First in human development of RG <unk>, two pivotal feeds with RG <unk>. One is going to have some increased costs, we're going to have increased costs with respect to the expansion of all the work around our Jeff two and four yes, we would continue to see.
R&D increase although has been alluded to there is going to be some continuing to offset it.
<unk> continues to shoulder more and more of the.
Clinical trial and development expense, however, with a 2020 for BLA filing tier G&A point, we will also be transitioning into pre commercial readiness modes with things like Rdx three one for sub retinal so I think that is.
<unk> added growth will be something that.
On a year to year basis, well continue to see increases in as we head towards these BLA filings for <unk>.
Two pivotal phase programs.
We continue though to support the guidance that the cash on hand will.
Afford us the opportunity to execute on all of these milestones the regulatory achievements as well as the clinical development milestones into 2025 and.
Part of our 2025 strategy I think this is.
All rather consistent.
That's helpful. Thanks.
Thank you.
I'm showing no additional questions in the queue at this time I would like to turn the conference back over to Mr. Ken Mills for any closing comments.
Yes.
Thanks, everyone for listening today. Thanks for all the great questions. We really are excited about the advancement of all of the programs, particularly the events of the announcements of the active pivotal program for <unk>, one looking forward to engaging with all of you more on updates throughout this year.
<unk>.
Have a good rest of your summer.
Ladies and gentlemen, thank you for participating in today's conference. This concludes the program you may now disconnect everyone have a wonderful day.
Yes.
The conference will begin shortly to raise your hand during Q&A you can dial one one.
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Okay.
Yes.
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