Q1 2022 Regenxbio Inc Earnings Call

May 4, 2022

Okay.

Yes.

Good day and thank you for standing by welcome to the Q1 2022 <unk> by incorporated earnings Conference call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During this session you will need to press star one.

One on your telephone if you require any further assistance. Please press star zero I would now like to hand, the conference over to our speaker today, Mr. Patrick Christmas Chief Legal Officer. Please go ahead.

Good afternoon, and thank you for joining us today.

With us are Ken Mills, <unk>, President and Chief Executive Officer, Dr. Steve Nicola, our Chief Medical Officer, and our Chief Financial Officer.

Earlier this afternoon, <unk> released financial and operating results for the first quarter ended March 31, 2020 to the press release reporting our financial results is available on our website.

At Www Dot <unk> Dot Com today's conference call will include forward looking statements regarding our financial outlook. In addition to regulatory and product development plans. These.

Forward looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.

And can be identified by words, such as expect plan will may anticipate believe should intend.

In 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, 2021 in the comparable risk factor sections of <unk> <unk>.

<unk> quarterly reports on Form 10-Q, which will be 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 four 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.

The audited 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 would now like to turn the call over to Ken Mills Ken.

Thank you Patrick good afternoon, everyone and thanks for joining us.

Pleased to begin today's call with a recap of our recent business highlights as well as an update on our corporate goals Steve.

Steve will then provide an update on our clinical programs and will provide an overview of financial results for the first quarter ended March 31 2022.

At the end of the call we will open up the line for questions.

<unk> gets into the pipeline progress in detail I would like to provide some context on the gene therapy industry.

Despite the recent market performance of the sector I cannot help but be optimistic for the future of gene therapy.

Over the years, we've seen a high level of investment in people quality and safety monitoring and have developed a deeper understanding of the science across the industry.

Recent challenges experienced across the industry are not history tells us as the guide uncommon for novel modalities like gene therapy <unk>.

LNG is creating opportunities in a relatively new field like gene therapy. The recent challenges have led to greater collaboration and involvement with key leaders, including regulatory agencies and I believe will better define the path towards getting gene therapies to patients with unmet needs as efficiently as possible.

While this past year has led to a difficult decision for a number of gene therapy companies I'm encouraged as Virgin expire in the field of gene therapy had deeper into 2022 and beyond.

So Nathan I'm.

I'm incredibly proud of how our company has been advancing our pipeline during these times and I believe our fundamentals have never been stronger. This is why we felt this past quarter was the right time to announce our five by 'twenty five strategy to progress Fine E therapeutics from our internal pipeline and licensed program into pivotal stage or commercial products by two.

25 <unk>.

The goal is defined by 'twenty five strategy was to lay out a clear and definable plan to advance key programs that have the potential to treat very high unmet need in areas, where we and our partners can use our NAV technology platform to develop and potentially commercialize <unk> therapeutics as soon as possible.

One of the leading candidates to meet our five by 'twenty five strategy as Rdx 314 for the treatment of wet AMD and diabetic retinopathy.

As you know we have a global partnership with Abbvie to bring <unk> forward to market for which we have received a $370 million upfront payment and are eligible to receive up to $1 3 billion in additional milestone.

We believe this deal not only validates <unk> bio as a leading player in the gene therapy space and also validates Rdx 314, and its broad opportunity in ophthalmology.

While the landscape for therapies being developed in both wet AMD and in diabetic retinopathy has changed over the past few months with some new product launches and also high profile setbacks in the field. We believe the opportunity for RG <unk> four has improved based on the encouraging interim safety and efficacy data presented for both wet AMD.

And diabetic retinopathy.

Overall, we plan to take full advantage of <unk> leadership in eyecare and its commercial strength as we work together to advance <unk> hundred one for for both the treatment of wet age related macular degeneration and diabetic retinopathy.

And our five by 'twenty five strategy. We also expect to include candidates from our other internal program such as <unk> for the treatment of Duchenne and <unk> one for the treatment of Hunter syndrome.

This quarter, we presented positive interim data at the World Symposium for neuro degenerative lysosomal storage disorder program.

<unk> one for the treatment of Hunter syndrome, and <unk> 111 for the treatment of Hurler syndrome. We believe the data update highlight the potential of both programs to alter the course of these debilitating diseases and deliver improved patient outcome.

Moving to <unk>.

Today, we announced that we made a difficult decision to delay <unk> dosing of patients in our first in human Duchenne clinical trial. This was a proactive step we elected to take in consideration of patient safety. This decision was due to an unexpected and isolated observation in the final vial filling needs of the manufacturing.

Contract manufactured it didnt meet our quality criteria.

We've informed all key stakeholders and are investigating the situation based on this update our current expectation is to be able to dose patients in the first half of 2023.

Work preparing for trial initiation, continuing including readying clinical trial sites and manufacturing additional clinical supply importantly, this recently unexpected events highlight the importance of having our own in house manufacturing capabilities I view this as a key to our longer term success.

This will delay our current development plan, certainly does not impact our strong commitment to developing <unk> for patients with Duchenne, which continues to be a key element of our five by 'twenty five strategy.

Beyond our internal programs five by 'twenty. Five May also include program developed by our NAV technology licensees.

Our NAV technology platform is driving the field of AAV gene therapy forward with over 66 zero clinical trials utilizing <unk> registered and the National Institutes of health clinical trial database since 2015.

Technology is also the basis for us it'll genmar one of two FDA approved gene therapies in the United States today.

With a number of additional AAV <unk> therapeutic being developed over a broad range of therapeutic areas and disease indications iron NAV technology licensees. We believe these programs will also contribute key gene therapy products to meet our $5 25 strategy.

With that.

Let me turn the call over to Steve now to talk in greater detail about the internal program.

Thanks, Ken.

I'll begin with an update on <unk> hundred 2014, which is being developed in collaboration with Abbvie to treat multiple ocular indications, including wet AMD and diabetic retinopathy.

<unk> hundred 14 uses the NAV AAV vector to deliver a gene encoding a therapeutic antibody fragment to inhibit vascular endothelial growth factor or bet Jack.

AMD is a leading cause of vision loss in people over 60 affecting more than 2 million patients in the U S Europe and Japan.

Current standard of care for wet AMD patients are anti VEGF treatments, which required patients to receive injections into the eye every four to 12 weeks.

You'll 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> three <unk> 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 loss for patients with wet AMD.

Data presented to date part.

Four.

Our phase one two clinical trial of <unk> 314 for the treatment of wet AMD using the sub retinal delivery approach is demonstrating a durable treatment effect over three years now, including mean improvement in vision and stable retinal thickness and reduction in anti VEGF treatment burden.

We believe our JAK $3 14 represents a significant potential advancement for the treatment of wet AMD.

We continue to enroll patients and atmosphere.

Our two pivotal clinical trial evaluating the efficacy and safety of <unk> 314 in patients with wet AMD using <unk>.

<unk> delivery approach.

Our sense is the first trial to be initiated under our eye care collaboration agreement with Abbvie. These.

These two trials are expected to support a BLA submission for our Gen $3 14 and 2024.

We are also advancing two additional programs are part of our collaboration with Abbvie are Jack <unk> in wet AMD and <unk> 314 in diabetic retinopathy and are both being developed using an in office Super Choroidal delivery approach.

In wet AMD, we are presenting the six month data for the first two cohorts in our phase III <unk> trial, demonstrating 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 the 72.

2% reduction in anti VEGF treatment burden compared to the mean annualized injection rate during the 12 months prior to receiving <unk> three <unk>.

Looking at the safety profile across all cohorts as of November 4th of last year. Our JAK $3 14 was reported to be well tolerated in 50 patients with no drug related serious adverse events mild and trochlear inflammation once observed slit lamp examination at similar incidents across both dose levels.

That is four out of 15 patients in cohort, one and three out of 15 patients in cohort two and resolve quickly with topical corticosteroids.

We expect to complete enrollment in 88 in the first half of 2022.

Patients in this trial did not receive prophylactic steroids before or after administration of <unk> three 2014.

Moving to our Gen $3 14 for the treatment of D. R.

Dr is a complication of diabetes and is the leading cause of blindness in adults between the ages of $24 75.

An estimated 27 million patients are affected by this debilitating disease worldwide.

Dr is a slowly progressing disease than in a large proportion of Dr. Patients leads to vision, threatening complications, including diabetic macular edema, or <unk> and Neovascular innovation that can lead to blindness how.

However, many with this condition do not receive anti VEGF treatments are proven therapy to reduce the risk of developing these vision threatening complications due to the unsustainable treatment burden.

<unk> three <unk> could potentially overcome this hurdle and provide an important therapy for patients to significantly alter their disease progression.

We recently presented six month data from our phase II <unk> trial at the Angiogenesis conference in February that demonstrated a clinically meaningful two step improvement from baseline on the <unk> scale. After a single Super Choroidal <unk> three one for administration and 47% of the 15th.

<unk> treated patients in cohort one.

<unk> zero percent in the observational control.

Importantly, this was an increase from 33% observed at three months.

We are encouraged by what we're seeing at this stage.

Furthermore, as of January 18th our JAK $3 14 was reported to be well tolerated in the 15 patients dose in cohort one with no drug related Aes and no intra ocular inflammation.

Enrollment is complete and the altitude trial in patients in this trial did not receive prophylactic steroids before after administration of <unk> 314.

Shifting now to our rare disease portfolio and <unk>, our potential onetime gene therapy for the treatment of Duchenne.

We are developing <unk> E X 202 to be a highly differentiated product and have designed it to deliver a transgene for our novel Micro dystrophin that includes the functional elements of the C terminal RCT domain founded naturally occurring dystrophin.

In preclinical studies the presence of the Cte domain has been shown to recruit several 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 include codon optimization and reduced CPG content, which has the potential to improve gene expression increase translational efficiency and reduce immunogenicity.

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

As Ken discussed earlier, we continue to prepare for trial initiation, including ready and clinical trial site and manufacturing additional supply we remain fully committed to initiating this trial as soon as possible.

Earlier this year at the World Symposium, we presented data from the ongoing trials for both <unk> hundred 21 for the treatment of NPS to or Hunter syndrome.

And <unk> 111 for the treatment of severe NPS, one or Hurler syndrome.

Demonstrating emerging evidence of CSF biomarker activity, along with neuro developmental assessments, indicating an encouraging potential CNS profile for both clinical candidates.

As of December 20th.

Of last year, <unk> 121, and <unk> hundred 11 were both well tolerated with no drug related aes.

We continue plans for enrolling patients in the expansion arm of both trials.

Overall, we have already made significant progress in 2022, and we look forward to providing further updates throughout the year.

Now I'll turn the call back to Ken.

Thanks, Steve for the good updates and to the team for the progress we've made over this past quarter.

In the first part of this year.

Before turning the call over to Vince I would like to highlight our progress that we mentioned about manufacturing as you know we begun utilizing our new headquarters in Rockville, Maryland houses, our new cgmp manufacturing facility.

I am excited to share that this facility is now operational allowing for high yield production of NAV vectors at scale up to 2000 meters using our platform suspension cell culture process.

With the new headquarters and GMP manufacturing facility, we are continuing to expand our capabilities from basic research and development to commercial scale infrastructure we.

We have over 21000 square feet of our corporate headquarters dedicated to our in house GOP pilot plant advanced analytic slab multiple 2000 liter bioreactor suites for GMP manufacturing of bulk drug substance and flexible state of the art fill finish suite to support multiple programs.

This capability remains a key differentiator for <unk> bio and a key element of our strategy our facility is cutting edge.

As us to move quickly from candidate selection.

Production of clinical grade material, which supports accelerating the early development of our <unk> therapeutics.

Additionally, we believe 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.

Furthermore, our manufacturing team is formulated AAV therapeutics can be used with a number of innovative delivery device solutions and techniques, including pioneering the clinical use of the Super Choroidal technique any intracisternal intervention that Steve alluded to.

We believe being a leader in innovative device delivery of AAV therapeutics distinguishing competency for regenerative filings.

So at this stage I'm going to turn the call over to Nick for a review of our financial guidance.

Thank you Ken <unk> ended the quarter on March 31, 2022, with cash cash equivalents and marketable securities totaling $764 8 million compared.

Fair to $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 quarter ended March 31 2022.

R&D expenses were $55 6 million for the quarter ended March 31, 2022, compared to $39 $7 million for the quarter ended March 31 2021.

The increase was primarily attributable to personnel costs and costs associated with clinical trials and manufacturing related activities for our lead product candidates and was partially offset by organic through important development cost reimbursable by Abbvie under our eye care collaboration in accord.

With the collaboration agreement with <unk>, we will continue to fund certain ongoing clinical trials for <unk> hundred one for through the end of 2022, while other 314 development costs are shared with Abbvie beginning in 2023, Abbvie will be responsible for funding the majority.

All our gx ruling for development expenses.

Based on our current operating plan, we expect the balance in cash cash equivalents and marketable securities of $764 8 million as of March 31, 2022 to fund our operations into 2025.

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

Thank you Ben.

Overall <unk> continues to perform at a very high level and I would like to take this time to thank our agenda by our team our investigators and patient communities for their commitment to the development of our innovative <unk> therapeutics.

Taking just one moment to circle back on <unk>.

I wanted to reiterate our strong commitment to the Duchenne community.

Unexpected delay reinforces the importance of our in house GMP manufacturing facility.

We plan for the first runs in this facility to support our clinical supply for RG <unk> and RG <unk> program. We're also able to begin to install new process improvements that we plan to use in our facility that will be expected to produce for example in the case of RG X two to approximately five <unk>.

<unk> improvements in vector yield per batch and previously used processes.

So to summarize what you've heard from us today and my views on the overall status of our progress. So far this year, we continue to be a leader in the field of AAV therapeutics.

There are over 2000 patients dosed with <unk> therapeutics derived from our NAV technology platform.

Our global eye care collaboration with Abbvie continues to advance and is on track for the first BLA filing in 2024.

Emerging clinical trial data and an expanded trial enrollment mentioned by Steve supports excellent progress in our Super colloidal delivery program to unlock additional value.

We have strong science and clinical data behind our rare disease pipeline of AAV <unk> therapeutics, when we look to take advantage of accelerated pathways to address high unmet need.

Our internal GMP capability is operational.

Putting the high yield manufacturer of quality <unk> therapeutics across the diverse range of program and has the scale necessary to support clinical development and commercialization.

We also have an amazing team of scientists and engineers dedicated to expanding the understanding and the application of AAV vectors.

Applying the differentiated capabilities of the NAV technology platform and exploring the potential to generate new innovative AED therapeutics.

In fact on that point this week, we announced the summary of around 15, one five presentations at the Ash TCT Conference next week, which reflects leadership in areas such as evaluating are now vectors to identify and characterize more clinically relevant features and benefits.

Engineering novel Capsid.

Enhancing <unk> therapeutic tissue and cell types specificity and expression, including optimizations of Enhancers and promoter combination.

Expertise in designing delivery device systems for use with <unk> therapeutics.

From concept research that informs the next step in our pipeline strategy and innovative manufacturing process development and analytical capabilities.

And all of this.

<unk> on the foundation of the capital to fund our mission and operations into 2025.

We believe that we remain on track to execute on our five by 'twenty five strategy to advance <unk> therapeutics to late stage development and commercialization by 2025, we're more confident than ever in our science, our people and our capabilities to support developing AAV therapeutics for diseases that have the potential to significant.

<unk> impact patients' lives.

And with that.

A portion of the call is over I will turn it over to the operator for questions.

Secondly, as a reminder to ask a question you will need to press star one on your telephone to withdraw your question press the pound key.

Our first question comes from Alex Stranahan of Bank of America. Your line is open.

Hey, everyone. This is John on I'm on for Alex.

Thank you for taking my questions.

Just a couple from US I think the first question could you just elaborate a little bit more on the decision to delay the 202 program.

Exactly what the issue that you ran into.

How do you how do you think this delay will affect kind of the.

Overall competitiveness.

202.

Field.

That's the first question second question.

It's also on DMD. So how do you with recent news on the obviously safety issues ran into by other companies.

Or do you wish to kind of learn from all of that and kind of.

And eliminate the concerns of those issues in your study.

The second question third question, just a short one on manufacturing.

Obviously your in house manufacturing is very promising.

What do you think are the challenges going forward with regards to that.

Thank you.

Okay, John Thanks for the questions.

Start I'll, let Steve comment on that.

Clinical trial comparisons and also circle back on in House manufacturing. So as I reported we had this unexpected isolated observation in the very final stages of manufacturing process for our gx <unk> clinical supply and.

The unexpected nature of this in the late stage nature of this caused us to have to report this delay and re guide first patient dosed to the first half of 2023, which is.

I think telegraphing that we have a six to 12 month delay this was something that was.

Reported at a third party contract manufacturer of ours and that Didnt meet our quality criteria. So that relates to your third question, John which is that we've been looking at the landscape for a while we've been communicating with all of you about how important we think it is to bring the quality and <unk>.

Availability of clinical supply and commercial supply for our pipeline in house, we started that investment pre COVID-19 with the build out of our headquarter facility and the intend to bring online the GMP facility and we announced today that the GMP facility is operational so for us.

A key element of the five by 'twenty five strategy to be able to be a company with five programs in pivotal feeds order commercialized by 2025. It was imperative for us to bring those in house capabilities for GMP manufacturing here to Rockville and enable our team that level of support.

With respect to the 200 to.

Comparisons to other trials in our approach I'll turn it over to Steve.

Hey, John Thanks for the good questions.

On the <unk>.

Historical.

Data sets that we can look at in AAV field.

We do have the benefit of all of our licensees in all of our.

Collective understanding in the field both in Duchenne, but also other programs.

And I think we got to take advantage of all of this and I think it's been very collaborative in the field.

<unk> appropriately so where we get to take advantage of what's been learned I think each program is specific though and you can't really.

Carry too much forward from one program to another because of all the different aspects. So for example.

<unk>.

Versus a benign so some of the programs.

Same complement activation for example.

With a benign.

<unk> nine at <unk>.

Higher doses.

And the other finding a potential transgene immunogenicity, but we've taken advantage of the learnings from that and our AEP.

Eight program, where clinically complement activation hasnt been.

A real issue in the same way that it's been seen with high dose.

AAV nine nevertheless out of an abundance of caution for first in human study Werent being.

Very robust and how we look at this initially where we're for example, including complement inhibition with alcoholism App just a short course as well as other typical immune suppression.

Regimens to really cover.

For that aspect.

We feel very excited both.

Based on that as well as our preclinical package, where we've seen very good.

Safety at doses, including the very first dose that we're looking at clinically by the way we see very good.

Clinical and.

Pathophysiology.

Proof of concept in our model. So all of this ties together make us feel very good about our.

Innovative trans gene promoter.

Within.

<unk> eight <unk>.

Really an exciting program to advance on.

Sure. Thanks for the color. Thank.

Thank you. Thank you.

And our next question comes from Vic ramp Euro hit of Morgan Stanley . Your line is open.

Good day everyone.

Vikram. So we have two questions. The first one is <unk>.

Dosing has begun for the objects to achieve program.

Many patients what data on how much follow up do you think.

You would need prior to sharing our initial outlook at the data.

And then on the funding for the initial data set that is initially generated what do you aim to see to establish that <unk> has a competitive safety and efficacy profile.

Thanks, <unk>. This is Ken I'll start and let Steve provide some more color if necessary. So we have reported that the trial design at this stage includes two dose levels with a basic three plus three design 1014, moving up to 2014 and each one is.

Those dose cohort has the potential for expansion as well.

When it comes to the profile of RG <unk> and the execution of the design, we'd be looking to complete the initial cohorts of three patients.

Look at some of the primary safety evidence as well as the secondary endpoints that we'll be measuring such as micro dystrophin expression at.

90 days as well as.

Intermediate measures of things like functional outcomes and imaging on the order of three months six months and beyond.

Looking for there to be.

Similarity parity if you will to existing treatments that are micro dystrophin AAV gene therapy based candidates being studied clinically and look for a safety profile that is similar to improved micro dystrophin levels that are similar to improve to continue to support.

Evidence that we see a place for <unk> in the treatment paradigm.

I think the points to emphasize about differentiating aspects that we think are key in addition, our we're using a different capsid.

And to the extent that we see the same types of evidence that I think others have demonstrated to work and continue to demonstrate with micro dystrophin based AAV gene therapy, we believe that there could be a place in the market for patients who couldnt access because of preexisting immune status other types of products using <unk> nine or other capsid that.

Would be able to access <unk> two for instance, because of its differentiating immunological profile with 88.

In addition, we think the <unk> terminal domain is likely to provide opportunities for us to look for longer term functional outcome improvements things that may be comfortable we wouldn't pick up in the first 90 days or six months, but at a year at 18 months or two years wed start to show a longer term differentiating profile and that would be meaningful not only for our <unk>.

<unk> long term follow up in clinical development, but also in the marketplace and then finally on the.

Manufacturing side the emphasis today.

Sort of lesson learned on the importance of having control over the quality as well as the control of the process itself here at our manufacturing facilities that are of Paramount importance.

Having control over that supply being able to advance with our people our processes and with improvements to those processes that we plan to bring to our new facility as well, we think that being a major contributor to supplying the market and with higher yields processes potentially have an advantage on cost of goods.

We will be things that in addition to those early looks are meaningful long term contributions to helping patients with duchenne and having a differentiated profile.

Got it thank you very much.

Yes.

Thank you.

And our next question comes from Gena Wang of Barclays. Your line is open.

Thank you.

We have at this time for China, we have three questions.

First one is about the 314, so as you completing the ring moment to Super quality. The trials thinking when can we expect to see the protein level data.

Second is regarding to the cgmp facility.

Just to clarify beyond the analytic go wrong that you're managing.

Are there any other or what are the other steps to go through to get fully ready for clinical supply and.

For the Duchenne program the last question.

Is Q I saw the <unk>.

Abstract you showed the higher AAV mediated gene expression, the second skeleton muscle.

Disease model versus a normal mice, driven by downregulation of known factors.

Wondering how relevant is defining to human and how does this help you to refine the dose escalating strategy and also dose vaccine strategy in a clinical study.

Thanks for the question queue underground three one for sure so.

On 314 as you mentioned, we have the two Super <unk> and office delivery studies, one in wet AMD. The other in diabetic retinopathy, where we have clinical proof of concept.

In both studies and we continue to evaluate dose response.

And both indications we have.

Very good noninvasive ways to assess clinic.

Clinical response.

Your question on aqueous humor protein we did choose to include.

Measurement of aqueous humor protein.

With this new route of administration as these were the first studies ever done with Supercoil deliveries just to include that for for assessment and we haven't given any guidance on.

When we have data for that in these ongoing studies.

Our focus, particularly now that we actually have.

Clinical signal and even clinically meaningful signal and even <unk>.

In the case of diabetic retinopathy on the endpoint variable that's used for actual approval.

Focus as heavily there.

I think your second question related to.

Bioreactor clinical supply.

Fortunately that's not on the critical path.

As far as how we would advance there so.

As Ken mentioned, we continue to be on track with our plan to have a BLA submission in 2024, and that's really driven on completing the two pivotal studies.

With respect to the.

Question relating to the preclinical work done.

Turning around candidates for Duchenne, including <unk>.

Yes, there is the totality of evidence that obviously went into support our IND for.

The purposes of selecting doses and for FDA granting a safe to proceed we certainly looked at disease models as well as different types of background models with respect to evaluating things like transaction efficiency and safety and bio distribution I think it's.

The people in our research and development organization as well as people in the space have learned that there are differences across animal models with respect to a disease model and what you may see in terms of transaction and what you might find in black six mics or other types of models. So we reconciled all of those things built the appropriate package.

To be able to inform the doses that Steve alluded to today, starting at 2014 planning for dose escalation to <unk> 14. This we're continuing to rollout over time different parts of the package that went into the IND EBIT, but the totality of evidence has been there since we filed the IND at the end of last year.

Thanks for the questions.

Operator.

Thank you.

And our next question comes from Manny Forehearth of SVP Securities. Your line is open.

Hey, Good afternoon. This is Rick on for Marty Thanks for taking our questions.

So given there is roughly six months to 12 months delay in the dosing of <unk> 202 could you just walk us through some of the steps that need to take place before you can initiate dosing.

Is it simply that you have to produce a new batch of clinical product from your in house facility or would you potentially have to revise manufacturing protocols.

Third party manufacturer or any other potential steps.

So I think the essence of the six to 12 month delay is that we have to reestablish.

Reestablish our clinical supply and the primary plan for doing so is using the new GMP capabilities here in Rockville, I think we will have strategies like we always do to sort of mitigate different potential outcomes from that but I think the essence of the box hitting that re guided point is going to be.

<unk> on the great capabilities, we have here to make that bulk drug supply get it filled and get it prepared for patients that will be done.

Under and sort of as part of the IND that was filed at the end of last year that we announced was safe to proceed early this year as we continue to make progress on that and get closer to that next milestone we'll update something in addition to that first.

First half of the year guidance, but this is a recent and unexpected event for us at this stage so.

This is where we are guiding right now.

Alright, that's it from US thanks for taking the question.

Thanks.

Certainly ladies and gentlemen, if you do have a question. Please press Star then one.

If you'd like to remove yourself from the queue. Please press the pound key our next question comes from Andreas <unk> of bed, which securities. Your line is open.

Yes, good afternoon, and thanks for taking a question.

<unk> also got one until to.

You guys have an abstract that is GCT talks.

Talks about the recruitment.

So just a quick question.

As to how.

202 may differentiate from other competitors on targeting unannounced binding domain.

Yes, Thanks Andreas.

Glad you raised that we should have brought the R&D team that this call apparently but I'll try to field. These.

You talked about the fact that we think that the C terminal domain and other elements of the Rgs to construct which again was selected from sort of a multi year effort on the part of our scientists to select the candidate that with differentiated based on science based on manufacturer ability based on on safety.

As we got closer and closer to selecting the final candidate that became our gx two O. Two we were looking at the entirety of things that contributed to improvements in the structural integrity of the truncated dystrophin units function as well as the ability of the the biology to recruiting including in NAS, but.

Limited too I think in that abstract in another circumstances, we have published data that shows that there are other aspects of the dystrophin associated protein complex that we view are being recruited are essential to have the C terminal domain as part of the expressed protein in order to recruit and stabilize that complex and so we think that.

<unk> and Nossa among them, which we know has been something that has been talked about as part of <unk>.

For instance, the construct that we know solid biosciences has brought into the clinic. Our view is that that is a good direction to go and always has been making improvements to the science. The biology of the C terminal domain components of dystrophin has been a key component for us.

Evaluation and candidate selection.

Great and congrats on growing lives Rockville vertical.

And our next question comes from Daniel Donlan of Chardan. Your line is open.

Hi, and thank you all for taking the question.

While along with tier two lenders as well.

Actual posture for tier two.

At the newest framework the other programs into.

And then those other programs will be affected.

And the third party manufacturer for this program is not a group that we use for any of the other programs that <unk> bio as part of our pipeline.

Okay. Thank you.

I am showing no further questions at this time I would now like to turn the conference back to Mr. Ken Mills for closing remark.

Thanks, Operator again, just wanted to reiterate thanks, everyone for the time today continue to be excited for the field of gene therapy for the progress, we're making here at <unk> bio and the capabilities, we have to help as many patients as possible. So thanks for everyone's questions and support and we'll look forward to seeing you all soon and have a good day.

Okay.

This concludes today's conference. Thank you for participating you may now disconnect.

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Good day and thank you for standing by welcome to the Q1 2022 region expire incorporated earnings Conference call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During this session you will need to press star one on your.

Telephone if you require any further assistance. Please press star zero I would now like to hand, the conference over to our speaker today, Mr. Patrick Christmas Chief Legal Officer. Please go ahead.

Good afternoon, and thank you for joining us today.

With us are Ken Mills, <unk>, President and Chief Executive Officer, Dr. Steve Nicola, our Chief Medical Officer, and deficit, our Chief Financial Officer.

Earlier this afternoon, <unk> released financial and operating results for the first quarter ended March 31, 2022 press release reporting our financial results is available on our website.

At Www Dot <unk> Dot com today's.

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 forecast.

Can be identified by words, such as expect plan will may anticipate believe should intend.

In other words of similar meaning.

<unk> quarterly reports on Form 10-Q, which will be on file with the securities and Exchange Commission and available on the SEC's Web site.

Please be advised that today's call is being recorded and webcast. In addition, any on already.

On the audited 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 would now like to turn the call over to Ken Mills Ken.

Thank you Patrick good afternoon, everyone and thanks for joining us.

Pleased to begin today's call with a recap of our recent business highlights as well as an update on our corporate goals.

I will then provide an update on our clinical programs and it will provide an overview of financial results for the first quarter ended March 31 2022.

At the end of the call we will open up the line for questions.

Firstly it gets into the pipeline progress in detail I would like to provide some context on the gene therapy industry. Despite.

Despite the recent market performance in the sector I cannot help but be optimistic for the future of gene therapy.

Over the years, we've seen a high level of investment in people quality and safety monitoring and have developed a deeper understanding of the science across the industry.

Recent challenges experienced across the industry are not history tells us as the guide uncommon for novel modalities like gene therapy challenges create opportunities and a relatively new field like gene therapy. The recent challenges have led to greater collaboration and involvement with key leaders, including regulatory agencies and I believe.

We will better define the path towards getting gene therapies to patients with unmet needs as efficiently as possible.

While this past year has led to a difficult decision for a number of gene therapy companies I'm encouraged as <unk> bio and the field of gene therapy had deeper into 2022 and beyond.

To this end I'm incredibly proud of how our company has been advancing our pipeline. During these times and I believe our fundamentals have never been stronger. This is why we felt this past quarter was the right time to announce our five by 'twenty five strategy to progress 580 therapeutics from our internal pipeline and licensed program in <unk>.

It'll stage or commercial products by 2025.

All of the $5 25 strategy was to lay out a clear and definable plan to advance key programs that have the potential to treat very high unmet need in areas, where we and our partners can use our NAV technology platform to develop and potentially commercialize AAV therapeutics as soon as possible.

One of the leading candidates to meet our five by 'twenty five strategy as Rdx 314 for the treatment of wet AMD and diabetic retinopathy.

As you know we have a global partnership with Abbvie to bring <unk> forward to market for which we have received a $370 million upfront payment and are eligible to receive up to one 3 billion in additional milestone.

We believe this deal not only validates <unk> bio as a leading player in the gene therapy space and also validates Rdx 314, and its broad opportunity in ophthalmology.

And diabetic retinopathy.

Overall, we plan to take full advantage of the <unk> leadership in eyecare and its commercial strength as we work together to advance <unk> hundred one for for both the treatment of wet age related macular degeneration and diabetic retinopathy.

In our five by 'twenty five strategy. We also expect to include candidates from our other internal program such as <unk> <unk> 202 for the treatment of Duchenne and <unk> one for the treatment of Hunter syndrome. This.

This quarter, we presented positive interim data at the World Symposium for neuro degenerative lysosomal storage disorder program.

<unk> Q1 for the treatment of Hunter syndrome, and <unk> 111 for the treatment of Hurler syndrome. We believe the data update highlight the potential of both programs to alter the course of these debilitating diseases and deliver improved patient outcome.

Moving to <unk>.

Today, we announced that we made a difficult decision to delay patient dosing of patients in our first in human Duchenne clinical trial. This was a proactive step we elected to take in consideration of patient safety. This decision was due to an unexpected and isolated observation in the final vial filling age of the manufacturing.

And third marine contract manufacturer that Didnt meet our quality criteria.

We've informed all key stakeholders and are investigating this situation based on this update our current expectation is to be able to dose patients in the first half of 2023.

Work preparing for trial initiation continues including readying clinical trial sites and manufacturing additional clinical supply importantly, this recent and unexpected events highlight the importance of having our own in house manufacturing capabilities I view this as a key to our longer term success.

While this will delay our current development plan, certainly does not impact our strong commitment to developing <unk> for patients with Duchenne, which continues to be a key element of our five by 'twenty five strategy.

Beyond our internal programs five by 'twenty. Five May also include program developed by our NAV technology licensees.

Our NAV technology platform is driving the field of AAV gene therapy forward with over 66 zero clinical trials utilizing NAV vectors registered and the National Institutes of health clinical trial database in 2015, our NAV technology is also the basis for the Gen. One.

<unk> has two FDA approved gene therapies in the United States today.

With a number of additional AAV therapeutics being developed over a broad range of therapeutic areas and disease indications by our NAV technology licensees. We believe these programs will also contribute key gene therapy products to meet our five by 'twenty five strategy.

With that.

Like to turn the call over to Steve now to talk in greater detail about the internal program.

Thanks, Ken.

I'll begin with an update on our <unk> hundred 14, which is being developed in collaboration with Abbvie to treat multiple ocular indications, including wet AMD diabetic retinopathy.

<unk> hundred 14 users than NAV AAV vector to deliver a gene encoding a therapeutic antibody fragment to inhibit vascular endothelial growth factor or bet Jack.

At AMD is the leading cause of vision loss in people over 60 affecting more than 2 million patients in the U S Europe and Japan.

Current standard of care for wet AMD patients are anti VEGF treatments, which required patients to receive injections into the eye every four to 12 weeks.

You'll 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> three <unk> 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 loss for patients with wet AMD.

Data presented to date part.

Or.

Our phase one two clinical trial of <unk> 314 for the treatment of wet.

AMD using the sub retinal delivery approach is demonstrated a durable treatment effect over three years now, including mean improvement in vision and stable retinal thickness and reduction in anti VEGF treatment burden.

We believe our JAK $3 14 represents a significant potential advancement for the treatment of wet AMD.

We continue to enroll patients and atmosphere in.

Our two pivotal clinical trial evaluating the efficacy and safety of <unk> in patients with wet AMD using <unk>.

<unk> delivery approach.

Our sense is the first trial to be initiated under our eye care collaboration agreement with Abbvie. These.

These two trials are expected to support a BLA submission for our Gen $3 14 and 2024.

We are also advancing two additional programs that are part of our collaboration with Abbvie Rgs <unk> in wet AMD and <unk> hundred 14 in diabetic retinopathy that are both being developed using an in office supercoil delivery approach.

In wet AMD, we have presented six month data for the first two cohorts in our phase III <unk> trial, demonstrating 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 the <unk> 72.

2% reduction in anti VEGF treatment burden compared to the mean annualized injection rate during the 12 months prior to receiving <unk> three 2014.

Looking at the safety profile across all cohorts as of November 4th of last year. Our JAK. Three 2014 was reported to be well tolerated in 50 patients with no drug related serious adverse events.

<unk> and track their inflammation was observed on slit lamp examination at similar incidents across both dose levels that is in four out of 15 patients in cohort one and three out of 15 patients in cohort two and resolved quickly with topical corticosteroids.

We expect to complete enrollment in aviation in the first half of 2022.

Patients in this trial did not receive prophylactic steroids before or after administration of <unk> 314.

Moving to our Gen $3 14 for the treatment of Dr.

Dr is a complication of diabetes and is the leading cause of blindness in adults between the ages of $24 75.

An estimated 27 million patients are affected by this debilitating disease worldwide.

However, many with this condition do not receive anti VEGF treatments are proven therapy to reduce the risk of developing these.

And threatening complications due to the unsustainable treatment burden.

<unk> three <unk> could potentially overcome this hurdle and provide an important therapy for patients to significantly alter their disease progression.

We recently presented six month data from our phase II <unk> trial at the entry Genesis Conference in February that demonstrated a clinically meaningful two step improvement from baseline on the <unk> scale. After a single Super Choroidal <unk> three one for administration and 47% of the <unk>.

<unk> treated patients in cohort one compared to zero percent in the observational control <unk>.

Importantly, this was an increase from 33% observed at three months.

We are encouraged by what we're seeing at this stage.

Furthermore, as of January 18th our JAK $3 14 was reported to be well tolerated in the 15 patients dose in cohort one with no drug related Aes and no intra ocular inflammation.

Enrollment is complete and the altitude trial in patients in this trial did not receive prophylactic steroids before after administration of <unk> 314.

Shifting now to our rare disease portfolio and <unk>, our potential onetime gene therapy for the treatment of Duchenne.

We are developing <unk> E X two or two to be a highly differentiated product and have designed it to deliver a transgene for our novel Micro dystrophin that includes the functional elements of the C terminal or Cte domain.

Rounded naturally occurring dystrophin.

Additional design features include codon optimization and reduced CPG content, which has the potential to improve gene expression increase translational efficiency and reduce immunogenicity.

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

As Ken discussed earlier, we continued to prepare for trial initiation, including reading and clinical trial site and manufacturing additional supply we remain fully committed to initiating this trial as soon as possible.

Earlier this year at the World Symposium, we presented data from the ongoing trials for both <unk> hundred 21 for the treatment of NPS to or Hunter syndrome, and <unk> hundred 11 for the treatment of severe MTF, one or Hurler syndrome.

Demonstrating emerging evidence of CSF biomarker activity, along with neuro developmental assessments, indicating an encouraging potential CNS profile for both clinical candidates.

As of December 20th.

Last year, <unk> 121, and <unk> hundred 11 were both well tolerated with no drug related aes.

We continue plans for enrolling patients in the expansion arm of both trials.

Overall, we have already made significant progress in 2022, and we look forward to providing further updates throughout the year.

Now I'll turn the call back to Ken.

Thanks, Steve for the good updates and to the team for the progress we've made over this past quarter and in the first part of this year.

Before turning the call over to Vince I would like to highlight our progress that we mentioned about manufacturing as you know we began utilizing our new headquarters in Rockville, Maryland houses, our new cgmp manufacturing facility.

I am excited to share that this facility is now operational allowing for high yield production of NAV vectors at scale up to 2000 meters using our platform suspension cell culture process.

With the new headquarters and GMP manufacturing facility, we are continuing to expand our capabilities from basic research and development to commercial scale infrastructure.

We have over 21000 square feet of our corporate headquarters dedicated to our in house GMP pilot plant advanced analytic slab multiple 2000 liter bioreactor suites for GMP manufacturing of bulk drug substance and flexible state of the art fill finish suite to support multiple programs.

This capability remains a key differentiator for <unk> bio and a key element of our strategy our facility is cutting edge.

Cause us to move quickly from candidate selection.

The production of clinical grade material, which supports accelerating the early development of our <unk> therapeutics.

Furthermore, our manufacturing team is formulated AAV therapeutics can be used with a number of innovative delivery device solutions and techniques, including pioneering the clinical use of the super choroidal technique any interest external intervention that Steve alluded to.

We believe being a leader in innovative device delivery of AAV therapeutics distinguishing competency for regenerative filings.

So at this stage I'm going to turn the call over to Nick for a review of our financial guidance.

Thank you Ken <unk> ended the quarter on March 31, 2022, with cash cash equivalents and marketable securities totaling $764 8 million.

Compared to a $149 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.

Quarter ended March 31, 2022.

R&D expenses were $55 6 million for the quarter ended March 31, 2022, compared to $39 $7 million for the quarter ended March 31, 2021 bakeries.

The increase was primarily attributable to personnel costs and costs associated with clinical trials and manufacturing related activities for our lead product candidates and was partially offset by <unk> strong forward development cost reimbursable by Abbvie under our eye care collaboration in accord.

With the collaboration agreement with <unk> will continue to fund certain ongoing clinical trials for <unk> hundred one for through the end of 2022, while other 314 development costs are shared with Abbvie beginning in 2023, Abbvie will be responsible for funding the majority.

All our gx ruling for development expenses.

Based on our current operating plan, we expect the balance in cash cash equivalents and marketable securities of $764 8 million as of March 31, 2022 to fund our operations into 2025 with that I will turn the call back to Ken to provide final thoughts.

<unk>.

Thank you.

Overall <unk> continues to perform at a very high level and I would like to take this time to thank our <unk> team, our investigators and patient communities for their commitment to the development of our innovative <unk> therapeutics.

Taking just one moment to circle back on <unk>.

I wanted to reiterate our strong commitment to the Duchenne community. This unexpected delay reinforces the importance of our in house GMP manufacturing facility.

We plan for the first runs in this facility to support our clinical supply for RG, <unk> and RG <unk> program.

We're also able to begin to install new process improvements that we plan to use in our facility that will be expected to produce for example in the case of <unk> to approximately five times improvement in vector yield per batch and previously used processes.

So to summarize what you've heard from us today and my views on the overall status of our progress. So far this year, we continue to be a leader in the field of AAV therapeutics.

There are over 2000 patients dosed with <unk> therapeutics derived from our NAV technology platform.

Our global eye care collaboration with Abbvie continues to advance and is on track for the first BLA filing in 2024 emerging clinical trial data and expanded trial enrollment mentioned by Steve supports excellent progress in our Super colloidal delivery program to unlock additional value.

We have strong science and clinical data behind our rare disease pipeline of AAV Therapeutics, where we look to take advantage of accelerated pathways to address high unmet need.

Our internal GMP capability is operational supporting the high yield manufacturer of quality <unk> therapeutics across the diverse range of program and has the scale necessary to support clinical development and commercialization.

We also have an amazing team of scientists and engineers dedicated to expanding the understanding and the application of AAV vectors.

The differentiated capabilities of the NAV technology platform and exploring the potential to generate new innovative AAV therapeutics.

In fact on that point this week, we announced the summary of around 15, one five presentations at the <unk> Conference next week, which reflects leadership in areas such as evaluating are now vectors to identify and characterize more clinically relevant features and benefits.

Engineering novel Capsid.

Enhancing AAV therapeutic tissue and cell types specificity and expression, including optimizations of Enhancers and promoter combinations.

Expertise in designing delivery device systems for use with AAV therapeutics proof of concept research that informs the next step in our pipeline strategy and innovative manufacturing process development and analytical capabilities.

And all of this.

Stands on the foundation of the capital to fund our mission and operations into 2025.

Really impact patients' lives.

And with that.

A portion of the call is Hoover I'll turn it over to the operator for questions.

As a reminder to ask a question you will need to press star one on your telephone to withdraw your question press. The pound key our first question comes from Alex Stranahan of Bank of America. Your line is open.

Hey, everyone. This is John on I'm on for Alex.

Thank you for taking my questions.

Just a couple from US I think the first question could you just elaborate a little bit more on the decision to delay the 202 program.

Exactly what the issue that you ran into.

How do you how do you think this delay will affect kind of the overall competitiveness of the 202.

Yield of DMD.

That's the first question second question.

It's also on DMD. So how do you with recent news on the obviously safety issues ran into by other companies.

Do you wish to kind of learn from all of that and kind of.

And eliminate the concerns of those issues in your study.

The second question third question, just a short one on manufacturing.

Obviously your in house manufacturing is very promising.

What do you think are the challenges going forward with regards to that.

Thank you.

Okay, John Thanks for the questions.

Start I'll, let Steve comment on that.

Clinical trial comparisons and also circle back on.

In house manufacturing, so as I reported we had this unexpected isolated observation and.

Very final stages of <unk>.

Manufacturing process for our Gx <unk> clinical supply and.

The unexpected nature of this in the late stage nature of this caused us to have to report this delay and re guide first patient dosed to the first half of 2023 witches.

I think telegraphing that we have a six to 12 month delay this was something that was.

Of the five by 'twenty five strategy to be able to be a company with five programs in pivotal fees or commercialize by 2025, Linda imperative for us to bring those in house capabilities for GMP manufacturing here to Rockville and enable our team that level of support.

With respect to the 202.

Harrisons to other trials in our approach I'll turn it over to Steve.

Hey, John Thanks, Thanks for the good questions.

On the.

Historical.

Datasets that we can look at in AAV field.

We do have the benefit of all of our licensees in all of our.

Collective understanding in the field both in Duchenne, but also other programs.

And I think we got to take advantage of all of this and I think it's been very collaborative in the field.

<unk> appropriately so where we get to take advantage of what's been learned I think each program is specific though and you can't really.

Carry too much forward from one program to another because of all the different aspects. So for example.

88.

Versus a benign so some of the programs.

Same complement activation for example.

With AAV nine.

Nine.

Higher doses.

And the other finding.

Potential transgene immunogenicity, but we've taken advantage of the learnings from that.

Our AAV.

Eight program, where clinically complement activation hasnt been.

A real issue in the same way that it's been seen with high dose.

A benign nevertheless out of an abundance of caution for first in human study we're being.

Very robust and how we look at this initially where we're for example, including complement inhibition with alcoholism App just a short course as well as other typical immune suppression.

Regimens to really cover.

For that aspect so we feel very excited both.

Based on that as well as our preclinical package, where we've seen very good.

Safety at doses, including the very first dose that we're looking at clinically by the way we see very good.

Clinical and.

Pathophysiology.

Proof of concept in our model. So all of this ties together make us feel very good about our.

Innovative trans gene promoter.

Within.

AAV eight.

Really an exciting program to advance arc.

Sure Thanks for the color.

Thank you.

Yes.

And our next question comes from Vic ramp Euro hit of Morgan Stanley . Your line is open.

Good day, everyone. This industrial et cetera. So we have two questions. The first one is once dosing has begun for the objects to achieve program.

How many patients what up data and how much follow up do you think.

You would need to sharing our initial outlook at the data.

And then on the funding for the initial data set that is used to generate what you aim to see to establish that 202 has a competitive safety and efficacy profile.

One of those.

Dose cohort has the potential for expansion as well.

When it comes to the profile of RG <unk> and the execution of the design, we'd be looking to complete the initial cohorts of three patients.

Look at some of the primary safety evidence as well as the secondary endpoints that we'll be measuring such as micro dystrophin expression at.

90 days as well as.

Intermediate measures of things like functional outcomes and imaging on the order of three months six months and beyond will.

We will be looking for there to be.

Similarity parity, if you will to existing treatments.

That our micro dystrophin AAV gene therapy candidates being studied clinically.

And look for a safety profile that is similar to improved micro dystrophin levels that are similar to improve to continue to support evidence that we see a place for <unk> in the treatment paradigm I think the points to emphasize about differentiating aspects that we think are key.

In addition, our we're using a different capsid and so the extent that we see the same types of evidence that I think others have demonstrated or can continue to demonstrate with micro dystrophin base AAV gene therapy, we believe that there could be a place in the market for patients who couldnt access because of preexisting immune status other types of.

Using <unk> nine or other capsid that would be able to access <unk>. Two for instance, because of its differentiating immunological profile with 88.

In addition, we think the <unk> terminal domain is likely to provide opportunities for us to look for longer term functional outcome improvements things that may be gospel, we wouldn't pick up in the first 90 days or six months, but at a year at 18 months or two years wed start to show a longer term differentiating profile and that would be meaningful not only for our <unk>.

<unk> long term follow up in clinical development, but also in the marketplace and then finally on.

Manufacturing side the emphasis today.

Sort of lesson learned on the importance of having control over the quality as well as the control of the process itself here at our manufacturing facilities that are of Paramount importance.

We will be things that in addition to those early looks are meaningful long term contributions to helping patients with duchenne and having a differentiated profile.

Got it thank you very much.

Yes.

Thank you.

And our next question comes from Gena Wang of Barclays. Your line is open.

Thank you.

We have at this time for China, we have three questions.

First one is about the 314, so as you completing the ring moment.

Two super quality their trials thinking when can we expect to see the protein level data.

And second is regarding to the cgmp facility.

Just to clarify beyond the analytic turnarounds that you mentioned.

Are there any other or what are the other steps to go through to get fully ready for clinical supply.

For the Duchenne program the last question.

As you saw the eight.

<unk> abstract you showed the higher AAV mediated gene expression in the skeletal muscle.

Disease model versus a normal mice, driven by downregulation of real factors.

Wondering how relevant is defining into human and how does this help you to refine the dose escalating strategy and also dose vaccine strategy in a clinical study.

Thanks for the question do you want to address three one for sure. So.

On 314 as you mentioned, we have the two Super corridor and offer this delivery studies one in wet AMD. The other in diabetic retinopathy, where we have clinical proof of concept.

In both studies and we continue to evaluate dose response.

And both indications we have.

Very good noninvasive ways to assess Clint.

Clinical response.

Your question on aqueous humor protein we did choose to include.

Measurement of aqueous humor protein.

With this new route of administration as these were the first studies ever done with Super Broyhill delivery just to include that for for assessment and we haven't given any guidance on.

When we'd have data for that in these ongoing studies.

Our focus, particularly now that we actually have.

Clinical signal and even clinically meaningful signal and ive been a signal on in the case of diabetic retinopathy on the endpoint variable that's used for actual approval and our focus as heavily there.

I think your second question related to.

Bioreactor clinical supply.

Fortunately that's not on the critical path.

As far as how we would advance there so as.

As Ken mentioned, we continue to be on track with our plan to have a BLA submission in 2024, and Thats really driven on completing the two pivotal studies.

With respect to the.

Question relating to the preclinical work done.

Turning around candidates for Duchenne, including <unk>.

Yes, there is the totality of evidence that obviously went in to support our IND for the purposes of selecting doses and four FDA granting a safe to proceed we certainly looked at disease models as well as different types of background models with respect to evaluating things like transaction efficiency in <unk>.

<unk> and bio distribution I think it's.

The people in our research and development organization as well as people in the space have learned that there are differences across animal models with respect to a disease model and what you may see in terms of transduction and what you might find in black six mics or other types of models. So we reconciled all of those things built the appropriate package to be.

To inform the doses that Steve alluded to today, starting at 2014 planning for dose escalation to TV 14. This we're continuing to rollout over time different parts of the package that went into the IND EBIT, but the totality of evidence has been there since we filed the IND at the end of last year.

Thanks for the question.

Operator.

Thank you.

And our next question comes from Manny Forehearth as SVP Securities. Your line is open.

Hey, Good afternoon. This is Rick on for Marty Thanks for taking our questions.

So given there is roughly a six to 12 months delay in the dosing of <unk> 202 could you just walk us through some of the steps that need to take place before you can initiate dosing.

Is it simply that you have to produce a new batch of clinical product from your in house facility or would you potentially have to revise manufacturing protocols.

Third party manufacturer or any other potential steps.

So I think the essence of the six to 12 month delay is that we have to you.

Reestablish our clinical supply and the primary plan for doing so is using the new GMP capabilities here in Rockville.

We will have strategies like we always do to sort of mitigate different potential outcomes from that but I think the essence is about hitting that re guided point is going to be relying on the great capabilities. We have here to make that bulk drug supply get it filled and get it prepared for patients that will be done.

Under and sort of as part of the <unk> that was filed at the end of last year that we announced was safe to proceed early this year as we continue to make progress on that and get closer to that next milestone we'll update something in addition to that.

First half of the year guidance, but this is a recent and unexpected event for us at this stage so.

This is where we are guiding right now.

Alright, that's it from US thanks for taking my question.

Thanks.

Certainly ladies and gentlemen, if you do have a question. Please press star then one if you'd like to remove yourself from the queue. Please press the pound key. Our next question comes from Andreas <unk> of bed, which securities. Your line is open.

Yes, good afternoon, and thanks for taking a question. We've also got one until to.

You guys have an abstract.

<unk>.

It talks about the recruitment.

So just a quick question.

As to how.

202 may differentiate from other competitors on targeting announced binding domain. Thanks.

Thanks Andreas.

I'm glad you raised that we should have brought the R&D team to this call apparently but I'll try to field.

We've talked about the fact that we think that the C terminal domain and other elements of the rgs to construct which again was selected from.

With a multi year effort on the part of our scientists to select the candidate that with differentiated based on science based on manufacturer ability based on on safety, but as we got closer and closer to selecting the final candidate that became our gx two O. Two we were looking at the entirety of things that contributed to improved.

<unk> and the structural integrity of the truncated dystrophin and its function as well as the ability of the biology to recruiting including in NAS, but not limited to I think in that abstract in another circumstances. We have published data that shows that there are other aspects of the dystrophin associated protein complex that we view are being.

<unk> recruited are essential to have the C terminal domain as part of the expressed protein in order to recruit and stabilize that complex and so we think that and not among them, which we know has been something that has been talked about as part of.

For instance, the construct that we know solid biosciences has brought into the clinic. Our view is that that is a good direction to go it always has been making improvements to the science. The biology of the C terminal domain components of dystrophin has been a key component for us.

Evaluation and candidate selection.

Great and congrats on growing lives Rockville very cool. Thanks. Thank you.

And our next question comes from Daniel Donlan of Chardan. Your line is open.

Hello, and thank you all for taking the question.

All along.

Well.

The manufacturing parts of <unk>.

The industry will be other programs, so that any of those other programs will be affected.

And the third party manufacturer for this program is not a group that we use for any of the other programs that <unk> bio as part of our pipeline.

Okay. Thank you.

I am showing no further questions at this time I would now like to turn the conference back to Mr. Ken Mills for closing remark.

Thanks, Operator, again, just want to reiterate thanks, everyone for the time today continue to be excited for the field of gene therapy for the progress, we're making here at <unk> bio and the capabilities, we have to help as many patients as possible. So.

For everyone's questions and support and we'll look forward to seeing you all have a good day.

This concludes today's conference. Thank you for participating you may now disconnect.

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