Q2 2023 Wave Life Sciences Ltd Earnings Call

Good morning, and welcome to the wave Lifesciences second corner of 2023.

As well as a conference call at this time all participants are malicious.

As a reminder, this call is being recorded.

Now turn the call over to Kate Rash, Vice President of the rest of your relation incorporated.

Please go ahead.

Did you really good morning, and thank you for joining us today to discuss a reason for this progress or do you wait a second quarter of 2023 financial results join.

Joining me today, a doctor <unk>, President and Chief Executive Officer, Henry We quite Chung Chief Development Officer, <unk>, Chief Financial Officer, and Dr. <unk> Chief Technology Officer.

Release issued this morning is available on the Investor section of our website Www Dot wave life Sciences Dot com.

Before we begin I'd like to remind you that discussions during the conference call work with forward looking statements.

These statements are subject to several risks and uncertainties that could cause our actual results to differ materially from those describe any forward looking statements.

The doctors that could cause actual results to differ are discussed in the press release issued today and then S as in violin, including our annual report.

Severe ended December 31st 2022, and according to report on form. Thank you for the quarter ended June 30th My 23, when did take no obligations update revived me forward looking statement for any visa and now like to turn the call over to pump escape. Good morning, and thank you all for joining us on today's call today.

Sure highlight put our progress during the second quarter, and then turn the call to Kyle to review, our financial and will open up the call for questions.

Emery and Sandra are on the line today and will be available for two and a.

And the second quarter, we continued to execute when our vision pioneering transformational already medicine, using our multimodal platform we remain on track.

For a T V program.

First ornate editing medicine to enter human clinical trials were accelerating work on a number of compelling targets that our collaboration with yesterday and we continue to advance our clinical programs B M B and H D.

I'll begin with a T V and already editing and review our progress at G. S. K and building a sustainable Piper finally will end with an update on a clinical trial.

And they speak with you today, we are preparing for the imminent permission of our first clinical trial applications are C. P. H W. V 006 at first Arnie editing clinical candidate for the treatment of a T J.

Okay. One is important on multiple drugs first W. V E O six signifies an entirely new modality moving into the correct.

Incredibly excited about this milestone, which is an important advancement nucleic acid sealed it for all patients who stand to benefit from RNA editing therapeutics.

With a P D. Our ability to utilize validated biomarkers in the clinic is expected to enable rapid delivery up for the account.

The data for Oh is there.

There's early clinical data that would increase the probability of success with waves future aren't editing program in the liver and beyond.

Second our past some targets the clinic with all those extra reflects the translational feet of our platform.

Upon first human dosing, we will demonstrate that we have expediently advances clinical candidates with a novel modality from the bench the patient at a remarkably fast paced.

We built our pipeline Rebecca drive further efficiencies with each new or an eight editing clinical Canada.

Importantly, oh sacred not only first of its kind, but it's also best in class and a T. A S supported by a robust preclinical data package, we are able to achieve remarkable.

Ability of editing convenient.

So think because of our unique elite chemically modified I'll, let me repeat that.

Oh six is also compatible with Garnet conjugation are highly specific an elegant delivery. So it is well validated your multiple approved therapeutics on the market.

For a T D. It is a significant advantage to have a stable and after my candidate that can leverage cowlneck and thereby avoid lipid nanoparticles, which required intravenous doses.

Among b a D D field, we continue to generate excitement for RNA editing approach, which is the first in class therapy designed for restoration of both healthy a paddock and pulmonary function with a reversible redose double therapeutic nature.

Our team is heart or.

The enthusiasm first hand from the community the Alpha one national comfortably Dallas, Texas, Jane There's major I might need an a T V with current therapies largely confined to treating either pulmonary.

Or in the future of Paddick manifestations of your day.

The limitations of current therapy.

P D already represents a substantial pharmaceutical market with augmentation therapy alone currently accounting for about $1.3 billion in annual pharmaceutical revenue worldwide. In this market is expected to grow our.

Our collaboration with G. M. K put this in a strong position to execute on bringing a novel therapeutic option to this market.

G S K, the long history, and clear leadership in respiratory medicine development and commercialization and under the terms of our D. A wave is eligible to receive substantial development launch and failed milestone payments, including meaningful near term clinical milestones as well as significant royalties.

As with ATT.

Our internal discovery work on the next wave of irony medicine substantially focus on first in class or in a editing therapeutic.

Nine to repair and restore budget.

With eight or editing, we have a versatile modality that allows us to impact target biology in novel ways.

As we look at the University of genetic mutations driving disease. The majority of these mutations lead to a lot of protein function, meaning they can't be addressed with violence tools, such as <unk> or empty said.

Wave is best positioned to capitalize on the loss of function disease targets, using our protein restoration and repair tools, including our leading already at any modality invalidated pharmacological platform. We are not constrained by therapeutic area and a previously shown robust editing and extra padding tissues C N S kidneys and lungs.

Beyond rare monogenic disorders, there's also a growing opportunity for aren't a medicine, so prevalent disease.

With genetic inside being unblocked from large genome wide Association study.

<unk> <unk> target are rapidly becoming available.

Targets have existing biological validation rooted in human genetics.

G. S. K is at the forefront of investing in genetic discovery.

There are strategic collaboration we are benefiting from their proprietary genetic insight, which augment our own internal dataset at our informing and accelerating our next wave of programs, including partner and hallway on programs.

We are rapidly building momentum within our collaboration and the wave and G. S. K teams are already actively working on multiple park.

Importantly, she had paid 100% of the cost and expenses related to target validation for these partner programs as.

As a reminder, <unk> include meaningful near term milestone payment opportunities beyond the clinical development milestones related to W. V O six which has the potential to add substantially to our balance sheet in 2023 M. B R.

We are planning to hold a virtual R&D day on September 20th 2023, during which we will demonstrate how we are continuing to extend our leadership and already out of date.

We will also discuss how we are unique retranslating genetic insight into internal fully on programs for both rare and more prevalent diseases.

The event, we will share new preclinical data for both a paddock an extra hepatic disease indication highlighting the potential depth and breadth of our next wave of pipeline programs.

Moving onto the D. M V. We are on track to initiate heartbeat potentially registration fees to study at W. V N Y three 150.

53 skipping Canada.

Is open label study will evaluate doses of 10 milligrams per kilogram of N 531 administered every other week and we plan to assess dystrophin protein after 24 and 48 weeks of treatment.

Since our last update or clinical development team has filed a clinical trial protocol regulatory authorities and identified additional trial sites. We expect to share clinical data includes a dystrophin protein 2024. If these data are supported we intend to use them to file for accelerated approval in the U S.

As a reminder, or excitement and 531 is grounded in the proof of concept data from part of the study, which showed 53 per cent Exxon skipping. After just three biweekly Joseph Haydn muscle tissue concentration and a favorable safety profile.

We presented these results to the D. M V community at the P. P. M E covered June where they were met with excitement and optimism.

With the extended dosing period in the forthcoming trial, we expect these high level of us skipped transcript to resolving downstream accumulation of substantial fully functional dystrophin perfect.

We know the D. M V community is waiting for additional and better therapeutic options with N 531, we aim to provide a treatment option that delivers convenient date production of endogenous functional dystrophin and ultimately meaningful clinical benefit for all patients the medical the Exxon 50 prescribing.

We're also planning a broad strategy to expand the number of Exxon, we can address which we would accelerate rapidly falling positive district and data for N factory, one <unk> G. M D franchise.

Turning to W. V 003.

First in class proactive candidate for Huntington's disease or H T.

H D patients have no disease modifying a therapy available to them today and we believe 003 is the most promising H D compound and development.

Oh, three takes advantage of broad delivery to the VNS, thereby reaching the variety of brain region is located in nature.

We've now confirmed the ability of our nuclear guide to distribute and the C. N S and multiple NH beef patties with our partner, including relevant concentrations in the court Texans writer.

Therefore, we are confident that O three is getting to the right part of the brain.

It is also the most advanced approach design to selectively knocked down the toxic Huntington protein sparing the help that you filed type H y.

<unk> H D T as essential and played several critical roles in the CNS, including regulation of the synaptic and protein transport <unk>.

Promoting neuronal survival.

And formation and function of Sylvia, which are essential to regulate VSS Lola Henry absorption.

The function in any of these pathways could be expected to adversely impact response essentially caused the cards.

With only single doses W. V O. Three we have already demonstrated positive initial huntington reductions of approximately 35% as compared to placebo M. S. D. S. S with wild type H T T level of appearing consist of Italy also activity.

H D trial had continued to programmes and in the second quarter of 2023, we initiated the multi attending doses of the trial dosing at 30 milligrams every eight weeks.

Given a robust and durable knockdown data observed in the multi dose cohort perkasie nine clinical trial W. B E 004, we believe in a multi dose data for O three will be most important to informing our next space available.

And the second half of 2023, we intend to share additional single dose biomarker safety data along with any available more details data.

With that I'll now turn the call over to Kyle Moran are CFO Friday until update.

Thanks, Paul.

Turning to the financials alright, let lost for the second quarter of 2023 was $21.1 million as compared to $41.3 billion in the prior year quarter.

The decrease in that loss was primarily driven by revenue recognized under our collaboration with G. S. K.

Under the G. S. K indicated collaboration for the second quarter of 2023 was $22.1 million.

Prior year border revenue zero point $4 million was recognized under vindicated collaboration.

Research and development expenses for $33.3 million for the second quarter of 2023.

Compared to $29.7 million prior to your order.

This increase in R&D expenses, primarily due to increased external expenses related to clinical program.

G S K expenses.

Slightly decline in the second quarter, sorry, G N a S.

They didn't find the the second order to $12.3 million as compared to $12.8 billion prior to your order.

Primarily due to decrease in Sharebait a consultation.

We ended the second quarter with $173 million in cash cash.

Compared to $88.5 billion December 31st 2022.

The increase is primarily attributable to the upfront cash equity investment $170 million received in the first order from a strategic collaboration with G. S. K.

We expect that our cash and cash equivalents will be sufficient funds operations such 2025.

As a reminder, do not include future milestones are often payments under R. G. S. K eight a collaboration cashback.

As Paul stated earlier, we have the potential to receive meaningful near term milestone payments of 2023 N P R, including clinical development milestones related W. V E.

R RNA editing Kelly the treatment.

<unk>.

Announced during the call back over the phone.

Thanks <unk>.

We are well positioned to execute on multiple upcoming milestones across our pipeline in 2023 and beyond I look forward to seeing many of you at upcoming Investor conferences, and you're speaking with you at our R&D, a better day than in September and with that I'll turn it over to the operator for Q&A operator.

Thank you now conduct a question and answer session.

To ask a question. Please press style one one on your telephone and wait for your name to be and asked you. A question. Please press star one went against.

<unk> has a Q and a rash.

Our first question comes from the line Steven She has her maiden name go ahead.

With your question.

Good morning. Thanks, so much for taking my question for the brought update Paul you mentioned rapid delivery of proof of concept data from the a T. D studied I was hoping you could just expand on that.

Uhm comment on sort of the the initial dosage is you'll be in the clinic with when gene editing when will the clinic and <unk>.

They were pretty profound editing raised already even at the lowest dose is I'm just curious if that's the type of thing.

You're expecting to.

Sort of manifest here at the early doses and studying and what other other than.

<unk>, what other sort of proof of concept features do you think you can generate pretty quickly.

It's wonderful I'll take the question is Steven Thanks for it and then having to call the emirate, but I I think what we talk about rapids proof of concept. Our goal is at eight it as quickly as possible get to a measurement of protein go through as we stated before the study rapid healthy human volunteer section and then treat infections or the <unk> you bring up measuring.

Editing efficiency I think what's unique and really special about to be alpha one antitrypsin indication is that we can measure the most important hunter.

Contribution, Nevada name, which is protein information and so the biomarker will be able to measure that study.

Is the alpha one antitrypsin protein and will also be able to characterize how much of it is.

Fixed corrected protein. So I think it gives us a really unique way of confirming preclinical studies in the clinic, but with the nets. The magnitude of production, but also the quality of production Emory I don't know if you have other comments you Wanna make me proud of that.

No well I would perhaps add that and.

The final stages before submitting ready almost ready to submit the C th and will comment further on design months were locked tonight at that.

Okay sanction and just when you think about assessing off target RNA editing.

Can you just describe is much different than you would you would do for an S. I R and a for instance is it any more onerous what what <unk>, what's your understanding of the sort of regulatory landscape for establish.

Establishing.

And off target margin for her in a editing therapeutics.

Yeah, I mean, I think what's exciting about RNA editing as we think about a standardized oligonucleotides approach and looking at our experience N F. I R and a an empty sense is the ability to assess normal you know what <unk> what are the what are the potential on target in the same way, we would do that for others. As you know ended up we've shared previously we've done the characterization.

So look for <unk> and others on the transcript of them is a highly specific anything and therefore, we didn't see by standard. So in preparation for the mission. We obviously did a lot of that work to preempt that in terms of demonstrating at a new modality that we don't see by Sandra is highly specific can behave the same way another alligator.

And so I think we're excited about the prospect of thinking about this like others as opposed to it as you as you alluded to kind of add some more onerous uhm.

Work it needs to be done on DNA anything I mean, I think to the other point is I think it really reflects the ability and the importance of reversible at at the idea that we're working on the transcript and not inducing permanent genetic mutations on DNA cause I think as we approached as particularly as we think about prevalent diseases, we didn't get the important cause.

Tribute and that we get to make the space. It really thinking about how do you go after not just devastating.

Devastating rare diseases, but actually apply these technologies too.

Broad chronic diseases, which is important obviously to ourselves and to our partner Joseph.

Yeah, just just last week for me I appreciate that.

This is maybe taking a little bit ahead, but did you think about initial patient selection for a G b.

How broad is that demographic gonna be in.

Like will you be looking for patients with lung and liver involvement right away.

Sort of.

Show the power of this approach in specific genotype.

Would be early targets any comments or it would be appreciate it. Thanks so much.

Yeah, I mean, I out to hand, it over to Emory and a second on the clinical side, but I think it is important as we think about the application initially where we're pursuing it which is you think about the homozygous D. C patients, it's liver lung and so as we think less about where the manifestation is the actual driver of that disease is <unk>.

Underlying genetics and therefore, it's about correcting nosy the patient and the patient and therefore following the protein relative to that so it's much more about selecting for the genotype and demonstrating evaluating the protein in the constitution of that protein in this initial period later, we can <unk>.

We can drive that to the lung and think about where.

Protein infusion been develop and thinking about achieving threshold level was available and it drips, a protein and looking at liver demographics, but I think initially the proof of concept really is focused on demonstrating that translation of essential both for a G. B with this particular medicine, but even the RNA editing feel more broadly.

And what's the impact as we think through other targets and beyond and re enter if there's anything else you want to add to that in terms of clinical trial, the new graphics.

No I mean, I can't I can't with five to seven GT patient finish that patience now and there'll be more details about the study <unk> in front of a number recognizes.

I think the other pieces you know if we think about those easy population is easy population by itself is about 100000 patients.

So as we think about that there is a consequential patient populations to study. So we're not concerned that we'll be able to find the patience for this study.

Alright, thanks, so much.

Thank you our next question.

Comes from the line.

Tommy T S M C dot com.

Hi. This is Julian also Paul Thanks, so much for taking a question on a T. D. I know you said for so six you're not constrained by therapeutic area. I'm. Just curious you know regardless is there anywhere else in particular that you find compelling uhm.

B R. A T D as to where you may be interested in you know establishing proof of concept moving forward and then any other color. You also you can just provide in the G. S. K collaboration Uhm I know you mentioned that you're you're currently working with them on numerous targets, but you know any other color you can provide on how that's coming along.

And how do you plan on allocating you know your resources.

For.

For a joint programs versus your own moving forward would be super helpful. Thank you.

Oh, Thank you join up I'll I'll take it from the beginning and you know I think you you.

Set up a really important contacts at the very beginning which is yeah I think.

You said a T V is not concerned by therapeutic <unk>, you're right, they're very long, but for treating the liver to ultimately.

Create the protein that protect a lot. So I think it's important in the context of a T D optimize it in a P. O C. A gallon that conjugation and what it can do across functions. What we've done and I think these are important datasets that we previously shown and again as we said earlier that we plan to do the update on September 28th at our D. J as we have.

Sean data extra Paddick meeting <unk> chemical modifications that we have distribute to a number of issues CNN lung kidney and others. So I think if we think about those therapeutic area than what you should've essential within the tissues unlock heading what we're seeing is an expansion of indication on a previous call in.

Well, obviously share more on our a D day I think we're also excited as we talk about that just as we said a prayer prevalent but really thinking about mechanisms. So in a T. D. Here, we're talking about the ability of a correction that actually trained as a protein from a mutated form to a wild type you're healthy.

There are applications and a number of tissues and therapeutic areas, where we can apply that developing meaningful therapeutics.

With the exciting won't be sure previously so I'm in vivo data on and will continue to share more on that is the ability to do upregulation. So to think about areas, where you're under expressing a protein and then rather than trying to augment that buyer tried to deliver it M. R. A therapeutic or other technology, which we could could be constrained even by mechanism of delivery the ability.

To actually.

Stabilize the transfer increases expression and therefore, increasing protein. That's produced led to think about other applications beyond just the base correction fixing a protein and as we think about that area see we didn't got universes is really brought gives us a lot of opportunities to think about you know multiple uhm therapeutic areas for so we are excite.

And about sharing more data on programs in those areas and data that supports the growth of the RNA editing field and what it can do beyond Alpha one antitrypsin.

Excellent. Thank you so much Oh, alright last question <unk> with a G. S. K component. So you know as much as I'd love to be able to see for apartment I agree you know as we share today I think it's safe to say there is an extraordinary amount of per month it was evident.

Uhm anybody who attended by out we were on where the participants with G. M. K. If they were sharing kind of where they see the translation of potential of their genetics and best minutes and it really been highlighted by then there's the opportunity that we provide with a multimodal platform I think editing as one importantly is.

You have cable cause across their universe, you know, it's not just some strange the loss of function and editing there are a lot of really prominent program in silencing and we are partnering with them across silencing using S. I R. A and the date of the some of that based on for that data, we shared last year as well as on the editing approaches so really being able to think about diseases Holistically where.

We're not constrained to either Upregulation, Dana function disease or lots of perfect. If it can really pick the best tool for the right job. So I think there's a lot of momentum on the collaboration across programs and we're excited to continue to provide updates where we can.

Excellent I appreciate the color. Thank you.

Thank you <unk> <unk>.

<unk> from Jeffrey So go ahead.

Thank you I have a couple of questions <unk>. So I'd actually you have <unk> advanced program.

Any any editing.

<unk> could you come in on.

Your technology, how you are better positioned.

<unk> <unk> <unk> <unk> <unk>.

There is not a lot of data from auto I just had that question number one.

Question is on a T. A a T V program and I must say you are gonna be talking more about <unk>, but as you are very close to filing a C. T. A when do you think <unk> would you be able to say that data and then tell me some of us here.

<unk> you haven't shown remarkable increase <unk>, but how how much did anything covering him and can have any for the other inquiries or would it be.

You are a a chapter thank you.

Great Uhm will impact that a lot I think if we start with the front and then I'll move to Europe . Your final question is it really the translation of why are we leading an aide in editing how does that translate to a D D and ultimately what what do we expect to see in the translation.

I think he said a lot at the beginning when you said you know why why are we ahead of others and I I think you really brought up the important piece, which is there's not a lot of data out their mothers and I think.

What I'd like to say is this does.

Come from you know immediately saying well we're interested in already editing it comes from over a decade of investment in building and Halligan nucleotide chemistry ancient and what we are poised to do when we entered in the editing space was really bring together this convergence the best in class nucleic acid chemistry, how.

How do you create guidance Tran, that's better interact with enzymes, how do we design that some more specific plan enhance the opportunities that that we have with a dark and ultimately how does that translate both in a nonhuman primate study.

In the liver, you know using <unk> and live or not using yandex and another tissue beyond the liver and I think if we get to the root of really how we approach thing. It is a chemistry driven exercise and I think in doing so we've been able to get too short how long <unk> long, but don't required delivery vehicles. So we're not can <unk>.

Trained to lipid nanoparticles that you I do do you think ultimately complicate delivery inaccessibility, that's important because I think a lot of times for those not familiar with L. M P.

A mystery that when would you have to be compatible with an L. M. T vs. What we can do to not be in one means that we can focus on really enhancing not just potency, but stability and durability. So as we think about optimizing pharmacology as we transition program I think it is not as.

A science experiment on editing, but ultimately translating into a human therapeutic means we are thinking about what's going to be a best in class therapeutic infrequent subcutaneous uhm.

Uhm.

Administration.

Being something that's potent and durable in terms of patience and faith, you know as we think about being able to avoid target at a date by Sandra day and reverse the bill payment. So we put that whole profile together. We built this program systematically from the beginning off of our chemistry engine in a data driven way through our application presentation.

And I feel better after model that what's important in translation you said, okay, well how was how do we know this is gonna translate what you know what what's giving a confidence is I think the date of the day like you know I. Appreciate your recognition that that data is consequential that we've seen approached production.

By you starting in down there what we're able to see is there is good precedence for that translation I'm thinking about human a padded sites into road in studies into human given that we've got it delivery agent in Gallup I can so we're gonna learn a lot about the translational pharmacology, both on the disease and the new modality buyer that translation and that's gonna <unk>.

Teachers, obviously, a lot about preclinical modeling as we think about subsequent programs as they go forward the benefit of all of that is we can look to other modality their translation.

Be able to start predicting where we think joseph need to be as we get at the clinic and that's important because as you said, we think about level is often times with the protein in the in vivo studies like the full of increase off a baseline is the best way to start thinking about translational potential and as we think about being able to increase the hold per data sauce seven fold from based on.

We went back and looked at human study you are in the range of about two and a half to rebuild to five fold improvement that ultimately translate from the the the patience to empty. So you know it's not just a measurement of the protein that's being produced in the rodent model, but ultimately in the translation of how much support of editing is translating protein production.

Giving us our confidence as we move into clinic, so like anything else, we do need to run that first study I think we'd pick the right program with the right Uhm delivery talk to demonstrate first in class editing, but really excited as we go into September to talk about a multitude of opportunities beyond a T D beyond.

Just protein direction beyond the liver that you know, we're very excited to share with everyone and there'll be a great opportunity to talk about the future of of Arnie.

Alright can I have a follow up question. So you have about 225 of <unk> G. S. K.

Yeah.

T V program, so studying favorite one slash Q V C. R. How much of a <unk> would you be expecting from that thank you.

Great question on in terms of you know it has to be alluded to before that we've got a number of development milestones beyond commercial milestones from G. S. K that come in overtime, what we can't do obviously his breakout those payments at various points, obviously as we received.

There are opportunities where those are disposed obviously.

Financial statements, but yeah. She is delivering this program into the clinic and beyond which contributes milestone payments importantly, beyond a T D and I think that was another important feature is.

There are a whole host of programs that are moving collectively with G. M. K beyond a T V and it's important to know not only do we have those programs, where you have K paid 100 per cent of the R&D expenses were advancing though but those also have milestones both preclinical and clinical and commercial milestones. So as we think about the magnitude of crossed.

The collaboration there are multiple potential.

Influence coming from execution and I think it's important as you said that those are not counted our runway statements. So those would be uhm freedom to our current cash.

Thank you.

Thank you our next call comes online.

<unk> ask you a security sky.

Good morning. This is awesome <unk>, thanks for taking the questions.

Uhm. My first question is keeping that you've been proved upon our nation you needed degradation.

<unk> R E I or any editing all with your email platform.

<unk> if you have any plan to design guide, our niece with enhanced properties like stability and low off trying to cutting basically to improve upon the high ratieni earn a guy so much <unk>.

And as a follow up question. Just wondering you know maybe could you comment on the potential to use patience.

Uhm who've already received my condition and gene therapy from a competitor for Ya and 531 program.

And I'm, specifically, referring to start this program. Thank you.

Thank you I mean, I think if we take the first question as you pointed out and you know I think it parallels funes question earlier, which is you know we have made a substantial investment in building. What we would do is best in class <unk>, We think about all of these opportunities.

Elegantly laid the mouse all of them involve kind of this mechanism with RNA protein interactions right. It's all about you know a a guide RNA interacting with a protein and exerting a biological gotcha back whether that's cutting fire alrighty states for able to whether that's exercising and utilizing a slice of machinery to generate.

Protein corrections or generate protein or are in a at at and using <unk> I think the opportunity said that's in front of US are you know a multitude I think we're going to be focused on portfolio construction in translation right now with this whole back into meaningful medicine. However, as you've known in our history, we've always had.

Through various collaborations and internal research exercises <unk>.

Collaboration that have pushed up and send you area. So whether that's editing beyond data I, whether or not the editing, including as you said highly specific editing around the other mechanisms whether it <unk>, but that's not our core capabilities. There are always the opportunity that we have been in being approached you by others and bedding what are the opportunities that that.

Our proprietary chemistry can brings leather modality. So we're not close minded to say this is all we do we recognize that you can't always predict what's coming behind but I think the key is in no way that I think it's very important to say that we are focused on building out a therapeutic portfolio in the area that we've album, particularly you think are already authenticated.

<unk> and that's where we're gonna put our internal resources collaborations are great resources that we haven't researched payment that we can <unk> exploiting and exploring these other capabilities that are chemistry <unk> for example.

The last question and I, you know I I wouldn't want a little bit of card cause I I think there are two different components to it which is.

Where do we C N 531, slicing and really excellent skipping as we move it forward.

<unk> relative it too.

The newly approved gene therapy, or whether or not it's potentially.

By it you know whether you can work in combination so.

I think it's important as we think about demonstrating best in class at at at being able to deliver a highly specific stable durable skipping agent that doesn't require conjugates to get into Dallas to generate substantial amounts of Exxon.

Exxon skipping you I think we've got a very clear path and the Exxon that we hope this gift given our branch I said I think seeing that translate in building that franchises important we know that gene therapy. Currently it's only approved for one year of age for four to five year old so within that range and only in the U S under an accelerated approval.

So.

It's we're watching we're paying attention to where that data. There's I know data forthcoming at the end of this year really on the translation of that micro district been so I think like everybody else, while we all saw that reached.

Recent accelerated approval I think there's a lot to continue to follow on the benefit of micro dystrophin and whether or not it's functional. So I think there we're not gonna take our eye off the ball and be distracted on not deliberate functional dystrophin protein that we believe has based on our preclinical data based on following the Becker uhm.

Point being able to ultimate we see that these that protein when you can create functional protein demonstrate a benefit importantly, as well as we think about the benefit of our skipping capability comes down to that question around our chemistry, which is different than others I think sometimes.

Within the Enigma talking about the company as we think about alcohol iPhone skipping being kind of fairly similar right where it can go on our distribution meetings and there've been a number of companies trying to drive better distribution skeletal muscle what's important is that our construct pre clinically both in our double knockout model as well as another primary actually up higher.

What was of Exxon skipping and the heart and the diaphragm. So as we think about ultimately being able to I'll change the outcome for these boys lives not.

Not only by repairing and fixing muscle and improving emulation.

What's most important to us is making sure we protect the heart and protect respiratory function. So do we think about the totality of what we can bring forward essentially for Exxon skipping you know.

We're excited about what we can do within 531 and beyond and will continue to watch the deal with the bottle of it services like or just.

Well, thank you very much.

Thank you.

Thank you.

Ah next call comes out from the line <unk> <unk> go ahead.

Great. Thanks for the for the questions guys. Paul just a few quick ones from us just to.

Clarification than anything here, so with the suitcase now being eminent I'm sure you have some idea when we're getting data and I think folks I tried to ask it on the call, but I'll try to ask it made me <unk> is the baseline thinking here that will be able to get data in 2024, and also just curious when you'll be able to.

Based on trial design be insured this year or are we getting that also in 24.

On D M B.

The functional end points that you've mentioned you don't have any bearing.

On whether this phase two is registrational.

Or is it just gonna be solely dependent on district and levels.

And then on 003, the wording in the press release, it seems like it's changed a little bit versus the first quarter. So just curious I think this time you guys out of the word available mall diagnose date of birth is plus press release the word available wasn't in the press like there was this pessimism additional single dose in any available.

Multi the last part please with additional single and multi desk. So curious what.

What exactly has changed during the multi notified thank you.

Excellent alright, so if we start and thanks for the questions. So we think about mobile just spell it right down and order a C. D. C. M D. H D. So is it real estate ATT timelines.

Have you said the CPA submissions are emitted once we begin the trial, we can give up further updated insurance expectations for data I think it's always important.

That trial kickoff.

And obviously safe to assume that data won't be in 2023 for that study, but looking forward I think when you went and what data will have as we move into 2024, it's something that we can provide updates on once that trial initiate it.

As it relates to D. M. D brought up the question on differentiation of filing based on dystrophin functional data we have.

First and foremost in it as we've seen from others dystrophin will be a very important trigger for us central violence or getting that data is critical to us where.

What we have is the benefit and I'll, let emery comment on as we think about function is the real ability as we follow these boys not just from where the biopsies are but really continue that study as you said, it's about 24 weeks of 48 weeks, we have an opportunity to measure a number of different functional uhm, an appointment and they've done only include the ambulatory they incur.

<unk> ability to look at respiratory function in other so in real pause and let you answer any additional questions off the central filing around C. M. D data and then I'll come back K H D.

Thanks, Paul <unk> actually noticed that reset well trodden regulatory pathway for finding with dystrophin data <unk> of course.

And I suppose that were running the study three four to eight weeks I will of course be providing any of the <unk>.

<unk> are available for that finding.

At T. Paul.

Great and so on H D. On the call. We mentioned available data I mean, the key if there's no change actually we're excited that there won't be Joseph that'd be updated that that won't be noted underway and H D. So I think are are outdated.

Being able to have available will be dose data, while we have single those data would be the update I think it's very safe to say with that initiated that we would not expect full details data in 2023.

The available will be Dorothy.

Mmm got it thanks, guys just quickly the phase one trial. My question was on the face on trial design or when you're getting that this your 4006 or is that something you also plan to share in 24.

Oh no you I mean, what is that the trial design once the study initiated so that won't be a that'll be 2023, so I I think that it you think about imminent filing in.

New updates I think we'll be able to share that clinical trials, which to your questions will provide a lot more uhm clarity as to the timing of data cause that study initiates.

Perfect. Thanks, so much guys.

Got it thank you.

Thank you. The next call comes from the line at Joshua <unk> go ahead.

Hi, Jenny insurance <unk>, Thanks for taking my question.

Just wondering if you guys have commented on most of the geometry of the email for Ya, Alright, I editing and how that compares to your other really goes for Exxon skipping or a sign up for <unk>.

I guess, what I'm really trying to get <unk>.

Or higher lower and how did that influence how you guys are thinking about therapeutic came back from any likelihood of potential.

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Yeah, I'll I'll take the beginning and then I can turn some of that over to.

We'll see how it I think.

I think as you mentioned as we think about this stoichiometry or are we just think about the pharmacology.

Better way of translational pharmacology.

<unk> headache is it is it is a catalytic pathway. So that we are able to harness the catalytic mechanism within the enzymes at your point reached.

We do see the advantages that come with that boat on being able to give smaller amounts of drug that then be able to stay in that sort of stability become such an important component of the drug thing stable not being degraded thing and the bill is able to it started the back. So it is catalytic as are a number of the mechanism that that.

We're utilizing I think.

The other advantage as we think about a T. D is by leveraging down that we're getting you know we need to get this a lot like other potential.

Potential S irna as it approaches where you're using down that conjugated oligonucleotides two hepatocytes for the catalytic Sharon So I think we're seeing it.

Very similar to other <unk> other catalytic oligonucleotides and development. So this wouldn't be kind of.

You'll be you'll get there. So we can metric dose, where you're gonna be getting more and more drugs to try to insert into back. So I think the catalytic efficiency of these enzymes is is a huge advantage as we think about a person you know we think about the Ah locked like we do our new high under if there's other behavioral symptomatic feature that you think about the neighbors first the others.

<unk>.

No. This is a foundational technology benefits I'm looking at how you can use this catalytic mission is to to work to enable them fast down <unk>.

So that's really the basis and to pause while I'm you know I'm looking account, let it <unk> sounds stopped on Netflix.

And I think it's important to US do you think about extra paddick that without having to get a large volumes of drug, particularly as we think too about being able to dose.

Q another route as we think about other tissue. So I mean, I I do think that ultimately as we think about the neighbor platform, we should be thinking a lot like other silencing capabilities black market.

Alright. Thank you that's very helpful.

Thank you.

Alright, I'm showing no further questions at this time I would now like to turn the conference back to Dr. Pamona cause you're going back.

Thank you everyone for joining the call. This morning, we've made significant progress advancing our pipeline and driving forward our leadership position and are in a medicine in the second quarter I am grateful to every wave employee for their dedication and focus on our mission and on the patients and families be Sir have a great day.

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

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