Q2 2022 WAVE Life Sciences Ltd Earnings Call
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Operator: Good morning and welcome to the WAVE Life Sciences second quarter 2022 financial results and the business update conference call.
Okay.
Good morning, and welcome to the wave life Sciences second quarter 2022 financial results and business update conference call. At this time, all participants are in a listen only mode.
Operator: At this time, all participants are on a listen only mode. As a reminder, this call is being recorded and webcast.
Operator: We'll pause for a moment while we compile our Q&A roster.
As a reminder, this call is being recorded and webcast I'll now turn the call over to Kate Rausch VP of Investor Relations and corporate Affairs at Wave Life Sciences. Please go ahead.
Operator: I'll now turn the call over to Kate Rausch, VP of Investor Relations and Corporate Affairs at WAVE Life Sciences.
Operator: Our first question comes from Salim Syed with Mizzou Hall.
Thank you operator, good morning, and thank you for joining us today to discuss our recent business progress and review our second.
Second quarter of 2020 financial results.
Joining me today are Dr. Pablo now President and Chief Executive Officer, Dr. Mike <unk>, Chief Medical Officer, and head of therapeutic discovery and development.
After Sandra Buggy, Chief Technology Officer, and head of platform Discovery Sciences, Moran Chief Financial Officer.
The press release issued this morning.
Slide presentation to accompany this webcast are available on the investors section of our website www dot we'd lifesciences dot com.
Before we begin I would like to remind you that discussions during this conference call will be forward looking statements.
These statements are subject to several restaurants certainties that could cause our actual results to differ materially from those described in these forward looking.
David.
The factors that could cause actual results to differ I discussed in the press release issued today and in our SEC filings, including our annual report on Form 10-K for the year ended December 31 2021.
Quarterly report on Form 10-Q for the quarter ended June 30th.
We undertake no obligation to update or revise any forward looking statements for any reason.
Operator: Please go ahead.
Salim Syed: Your line is open.
Now I'd like to turn the call over to Paul well. Thanks, Kate Good morning, and thank you all for joining us.
In the second quarter, we continued to make meaningful progress both on our therapeutic program and our platform.
I will start with some recent highlights I'll, then turn the call over to Mike who will provide updates on our innovative pipeline Chandra will then share. Some examples of how we continue to expand the addressable biological targets with our unique RNA based editing platform.
Finally, I will discuss our financials.
Kate Rausch: Thank you, Operator.
Salim Syed: Great.
I'm excited to begin today's call by announcing the selection of <unk> as our first RNA editing development candidate for Alpha one antitrypsin deficiency or AED.
We're also announcing that we expect to initiate clinical development of <unk>.
In 2023.
Oh six is a first in class RNA editing candidates and the most advanced therapeutic program currently in development the hardest in endogenous enzyme for editing there.
We're approximately 200000 people carrying almost that gets easy mutations in the U S and Europe and <unk> has the potential to transform how these patients are treated.
Demonstrating proof of clinical proof of concept in ACD with zero zero with zero to Derisk RNA editing for additional monogenic diseases as well as the open opportunities to address larger disease indication youre modulation of proteins, such as disruption a protein protein interaction and upregulation.
Kate Rausch: Good morning, and thank you for joining us today to discuss our recent business progress and review WAVE's second quarter 2022 financial results.
Continued investment in our prism platform has positioned us as leaders in the oligonucleotide innovation.
And we continue to be encouraged by the translation of our guide strength across multiple modality.
Kate Rausch: Joining me today are Dr. Paul Bolno, President and Chief Executive Officer, Dr. Mike Panzera, Chief Medical Officer and Head of Therapeutic Discovery and Development,
Earlier this year, we shared positive target engagement data from our ongoing focusing on clinical trials.
<unk> and Ft D, which demonstrated how our preclinical data are now translating in patients.
New pharmacokinetic data from our ongoing DMD and HD study, which Mike will share today further supports its clinical translation for differentiated pharmacology.
We remain on track to shared data from all three of our clinical studies this year.
Kate Rausch: Dr. Chandra Vargeese, Chief Technology Officer and Head of Platform Discovery Sciences, and Kyle Moran, Chief Financial Officer.
In June we completed a successful follow on offering which put wave and a strong well capitalized position entering the second half of 2022.
Kate Rausch: The press release issued this morning and the slide presentation to accompany this webcast are available on the investor section of our website, www.wavelifesciences.com.
We continue to execute on multiple pillars of value creation, including delivering clinical update and rapidly advancing our novel RNA based editing pipeline IWB or they are sick.
We also continue to advance discussions with potential strategic partners, who share our vision for broad application of wave platform and support the expansion of our pipeline, while unlocking value in GMP manufacturing.
Kate Rausch: Before we begin, I would like to remind you that discussions during this conference call will include forward-looking statements.
Now I'll turn the call over to Mike to provide an update on our pipeline Mike.
Kate Rausch: These statements are subject to several risks and uncertainties that could cause our actual results to differ materially from those described in these forward-looking statements.
Salim Syed: Good morning, guys.
Thanks, Paul and good morning to everyone on the call.
Kate Rausch: The factors that could cause actual results to differ are discussed in the press release issued today and in our SEC filings, including our annual report on Form 10-K for the year ended December 31, 2021, and our quarterly report on Form 10-Q for the quarter ended June 30, 2022.
Salim Syed: Congrats on the progress, and thanks for the question.
Kate Rausch: We undertake no obligation to update or revise any forward-looking statements for any reason.
Today I will discuss the continued progress of our therapeutic portfolio beginning with our CNS programs.
Kate Rausch: I'd now like to turn the call over to Paul.
But focusing on clinical trial for <unk> four in patients with benign or 72 associated Allison STB continues with administration of single and multiple dose is underway.
Paul Bolno: Paul?
Back in April of this year, we announced the first data update from our focused Jeannine program, which demonstrated robust dose related target engagement confirming translation of our preclinical work into the clinic.
Paul Bolno: Thanks, Kate.
Paul Bolno: Good morning, and thank you all for joining us.
I shared these data with the analyst community in June in an oral session at the conference of European Network secure Alister Npls could stop.
The presentation highlighted not only the clinical data soon here, but the wealth of information illustrating the differentiated preclinical profile of <unk> Airport.
We anticipate delivering an update with additional single and multi dose data for <unk> four in the second half of 2022 and are on track to initiate an open label trial in that same timeframe.
Paul Bolno: Paul, so I guess there's a lot of data coming between now and year-end, so I was hoping, if you could just tick through the three programs here, the DMD program, the HD program, and the ALS program, in terms of what do you perceive to be, you know, winning scenarios for these three programs, you know, biopsy, how much distribution production you expect to see on the knockdown data for Huntington's, how much, you know, mutant Huntington knockdown data do we expect to see, and then specifically, on the Huntington's, are we going to be getting single-dose data or multi-dose data, and for the two programs that you didn't specify, whether it's third quarter or fourth quarter, are we thinking more, you know, pumpkin spice latte time or eggnog time for the HD and the C9-ORF?
Moving onto Huntington's disease, WP easier zero three as our allele selective oligonucleotide currently being evaluated in select HD study targeting a polymorphism SNP three associated with the expanded <unk> transcript in certain patients with HD.
Paul Bolno: Thank you so much.
Paul Bolno: Thank you, Salim, and I'll start, and I'll transition to Mike as well, but just in no, particular order, and I think that's critical as we lay this out, but to start with your, – since you ended with SNP3, I'll start with SNP3.
Paul Bolno: So the SNP3 data will be single-dose, and I think stepping back 10,000 feet and looking, at all these data sets, I think they're important because they're going to give us, again, more indications, hopefully, of what we saw earlier this year with C9 on our single-dose, which is potent, durable target engagement.
Goal as we have said many times is to preserve production of wild type Huntington given the importance of this critical protein.
Preservation of Wild type Huntington continues to be a key objective that is supported by the community and by emerging preclinical and possibly clinical data.
Paul Bolno: So I think, firstly, as we think about preclinical translation to clinical translation, we'd, like to see the continuation of our preclinical data extending into clinical data readouts.
There is there are three of the only real plus program currently in clinical development.
Paul Bolno: So SNP3 is single-dose, the same evaluation that we had done on C9.
Similar to <unk>, we were able to leverage preclinical in vivo models to establish a starting doses zero-zero tree that was predicted to achieve CSF concentrations need to engage target and we designed and implemented an adaptive trial with the goal of accelerating time to approval.
Paul Bolno: It'll give us the opportunity to look at target engagement on the mutant protein, preservation, of wild type, which, as Mike alluded to earlier, continues to be an important metric to study, and other clinical biomarkers.
Paul Bolno: Again, it will be a biomarker-driven study.
Paul Bolno: As it relates to C9, we'll have continued data on both NEND multi- and single-dose to, again, continue to be able to look at the pharmacokinetics in target engagement.
The select HD study is progressing well and is already yielding interesting information from blinded assessments. The right hand side of slide nine shows the concentrations of <unk> III measured in patients three of our spinal fluid or CSF in the first cohort of patients dosed in the trial.
I'm the same graph, we have plotted the CSF concentrations observed following administration of 32 milligram.
<unk> <unk> hundred one <unk> to one or two which were the highest doses used in the precision HD studies, where reevaluate these first generation compounds for HD.
Approximately one month.
Single starting dose we are seeing CSF concentrations 20 fold greater than the maximum observed these previous compounds.
You may recall at the time, we just continue the precision AG program. We said the primary reason for doing so was modelling that indicated that we could not achieve CSF concentrations needed to engage target with those first generation compounds.
The profile of 003 appears quite different dose escalation continues in a select HG studying and we expect to share clinical data in the second half of 2022.
Paul Bolno: And DMD will give us the first opportunity, again, to look at preclinical to clinical, translation, as we shared today, based on tissue concentrations and exposure related to the DKO mouse model, where we did see a restoration of phenotype.
And as shown muscular dystrophy are open label clinical trial of <unk> three one for DMD patients with mutations amenable to exon 53 skipping is progressing well also.
Paul Bolno: That's going to give us an opportunity in muscle biopsies to look at tissue exposure, and target engagement.
Paul Bolno: Turn it over, Mike, for any additional follow-up on that.
You will recall in our preclinical studies and the decay or double knockout mouse treatment with an exon 23 surrogate of empires III. One resulted in a significantly prolonged survival at dose levels and frequencies achievable in human studies of course after converting to estimated human equivalent dose levels.
Paul Bolno: But that's going to be the key.
Paul Bolno: It's a robust data set across multiple programs, all related to PN, that answer key questions, related to target engagement in various tissues, the CNS versus muscle, as well as being able I think nothing really much to add other than to address the other question is the, you know, the DMV study, we've said the fourth quarter, that's open label, the patients are within those speculations, we have a good sense of when that's going to happen.
Paul Bolno: The other studies, as you know, are adaptive, they're driven by recruitment, timing of data, collection, and basically the timing of the reviews by the independent committee, so that's why we've been a little bit more, a little less definitive on the timing there, but it just really depends upon those factors because those are the blinded adaptive studies.
These data guided our target dose selection and escalation planning in our open label clinical trial on the right hand side of Slide 10, you can see some preliminary pharmacokinetic data from this study compared with data from Sumit <unk>, our first generation <unk> compound.
Paul Bolno: If I could follow up, guys, thanks for the call.
Paul Bolno: On the DMV specifically, do you have a number in mind in terms of distracted production, you're targeting on this particular readout?
Paul Bolno: I know it's single.
The figure shows plasma concentrations following single doses of <unk> three one at three dose levels compared with the top dose that <unk> used in our discontinued phase II III study.
What's clear is that approximately one week following dosing plasma concentrations of <unk> III, one we're already 40 fold greater than those achieved the souvenirs and dose escalation has yet to be completed.
The thing is underway at dose level, four and we look forward to data from muscle biopsies in the fourth quarter of this year.
Paul Bolno: So this particular readout, yeah, at this point in time, the target right now is being, able to evaluate the translation.
Yes.
I'll now give an update on our newest Kennedy <unk> fix for HEB.
Paul Bolno: I think the study is really determined to see, can we see the preclinical data and exposure, from the double knockout translate into humans?
Paul Bolno: So this time we're not laying out what a target exposure is, we'll continue to evaluate where, we are based, as Mike said, we're now into dose four, so there'll be more modeling as we get closer.
Paul Bolno: And the big factor, Slim, is does it look different from Zuberderson, right?
WV easier logistics is designed to address the therapeutic goal is essential when developing a novel therapy for HDD, namely restoration of circulating wild type.
Paul Bolno: Because, you know, you remember with Zuberderson, we just couldn't get into cells, we couldn't, engage target, we couldn't even see any transcript production at all with Zuberderson.
Paul Bolno: Here we have very different concentrations, as we've highlighted, and then we're going, to be looking at distribution, and if we see distro, it's going to be quite exciting.
Paul Bolno: So that's sort of how we're looking at that one.
Paul Bolno: Got it.
To address lung disease, and reducing the protein aggregation and liver to address liver disease.
Operator: Thanks so much.
Processes is that through RNA editing and homozygous for the <unk> patients one can ship the phenotype towards eight heterozygous for MZ phenotype, lowering the restaurant reviews of the product.
Operator: We'll move on to our next question.
Paul Bolno: In the second quarter, we continue to make meaningful progress, both on our therapeutic program and our platform.
Operator: Our next question comes from June Lee with Truist.
In the second quarter, we shared data using one of our lead <unk> to restore functional <unk> protein.
Paul Bolno: I will start with some recent highlights.
Operator: Your line is open.
Paul Bolno: I'll then turn the call over to Mike, who will provide updates on our innovative pipeline.
Operator: Hi.
At 19 weeks restored.
Operator: Good morning, and congratulations on the quarter.
Protein was determined to be functional as measured by robust inhibition of neutrophil elastase as well as pasty standing staining of liver biopsy, demonstrating reduced accumulation of Z <unk> aggregates over the duration of the study.
Operator: This is Mehdi on for June.
The selection of <unk> to take forward into IND, enabling toxicology studies, followed a thorough evaluation of multiple lead compounds each with potent editing capabilities in preclinical studies in mice and nonhuman primates in order to choose the molecule with the best overall profile.
Operator: So my question is related to the PN chemistry.
Operator: Recent studies in Angelman published, they show that these traditional POPS backbones, have sort of relatively limited penetration into deep brain tissues.
Operator: So could you provide some data on the function of PN chemistry in your studies, and which, type of tissues and which type of distribution you got with these versus the traditional, POPS backbones?
Operator: Thank you.
Operator: Yeah, no, it's a great question, because I think it's data that we've shared, and we're, happy to continue to share more.
Slide 13 shows the efficacy of <unk> in the <unk> mouse model, which is well established in this space.
Operator: What we have shared in the past is with the addition of PN chemistry, we do see much deeper, broader penetration across the CNS. So that's translating to uptake across tissues.
Operator: The data that we share related to mutant Huntington reduction from the back HD model in the corporate, deck is striatal data.
<unk> was administered subcutaneously following an initial loading dose.
<unk> certainly one RNA editing was approximately 50% and serum <unk> protein restoration ranged from four to seven fold higher than Pvs control remaining above.
11, micro molar level throughout the dosing interval.
Additional data supporting the favorable preclinical profile <unk> are shown on slide 14.
Operator: So what we've seen differently with the application of PN is broader, deeper penetration.
Mhm concentration dependent editing of circa <unk>, one was observed in primary human hepatocytes derived from a donor with the MD genotype, reaching as high as 80%, but the highest concentrations tested.
So where are we now have 006 IND, enabling activities are underway and we expect Cta submission next year.
In summary waves diverse portfolio of therapeutic candidates continues to advance through development as we are beginning to see our preclinical observations translate into clinic.
The data generated with each candidate continue to demonstrate the potential when principles of rational design and chemistry innovations our baidu oligonucleotides.
Novel approaches to complex disease biology.
Paul Bolno: Chandra will then share some examples of how we continue to expand the addressable biological targets with our unique RNA-based editing platform.
Operator: But ultimately, that is why, to Salim's earlier question, I think why the data for SNF3 is, going to be interesting.
Operator: Because one of the things that we can't do is C9, we're going to be looking is primarily, cortex, spinal cord.
Operator: And as it relates to HD, we know that that's cortex and deep gray structures like striatum.
With that I will turn the call over to China, China. Thanks.
Operator: So these data continue to help, will help clarify for us preclinical to clinical translation, as we measure this.
Mike.
Sand Hills progress to date with R. W. <unk>.
Fixed program.
<unk> demonstrates the potential of <unk> technology.
Operator: But we've seen that it's not tissue specific either.
Price correction of DTA driver mutation.
We like to think of <unk> as well.
Operator: We've seen deep penetration, as Mike was talking about, with looking at tissue concentrations, in DMD and muscle. And so we think not only is it helping with distribution, it's helping with retention, stability.
This army lights, and restoring our correctly protein function is only one example.
Operator: And we believe that's why we're seeing target engagement at low single doses that's also, durable.
How are we going to use the English to potentially treat diseases.
Recently, we have generated multiple proof of concept data said that demonstrate how <unk> can excavate pathways by modulating protein protein interactions and upwardly RNA expression by editing RNA binding protein market.
Operator: And so I think these data, being able to translate it from preclinical to clinical, is going, to be important.
Operator: I think to your point as well, being able to dose with lower doses, we think has a lot, of advantages as we're going forward to be able to explore a multitude of diseases.
These applications demonstrated the potential to design therapeutics precisely control.
Nation by Titrating, automate editing level and a mid dose.
I will review these in vitro and in vivo editing dataset on the next few slides.
We have used.
Q1 system before.
This shows the potential created a single site to activate a transcription factor.
I'll, probably bouncing gains.
Operator: And as we shared today, O06, our first aimer for alpha-1 antitrypsin deficiency, we had, shared that one of the advantages to being able to get potent, durable editing was a function of being able to apply PN chemistry on top of our chirality control models.
As shown on the right hand.
On slide 17, using <unk> Atlas, we achieve efficient editing.
Operator: Thank you.
<unk> in a dose dependent upregulation of <unk>, one again regulated by the Antarctic transcription factor in retail.
Operator: If I may, a very quick follow-up question.
We recently repeated this study in vivo and again saw.
Edited with multiple <unk> gain less and deliver Martin.
Let's hope it in downstream Dean of regulation.
Is it properly disrupted the Antarctic.
<unk> protein Saxon.
We would expect Upregulation of a key set of genes.
At our regulated by another two.
We successfully confirmed by automating transcriptome analysis as shown on the bottom right side of slide 18.
Yeah.
Another potentially disruptive application of ABR is to upgrade RMA compete happily sufficient diseases or diseases that require overexpression of target game.
We have now demonstrated the ability to upwardly several different target in <unk>.
<unk>.
Holly and immune target.
Editing automate motivated to regulate automate half life in vitro.
While much of our presentations today have focused on gallon conjugated design.
We also have.
<unk> substantial automated to date with systemic delivery of Unconjugated English.
We do not see to use complex delivery vehicle.
Lipid nanoparticles are viral vectors.
In in vivo mouse study, we have the editing of UGG to target across multiple tissues.
Including kidney adipose tissue and a range of liver cells with a single subcutaneous dose of Unconjugated.
Paul Bolno: And finally, Kyle will discuss our financials.
I'll now turn the call over to Carl Moran our CFO .
Paul Bolno: I'm excited to begin today's call by announcing the selection of WVE-006 as our first RNA editing development candidate for Alpha-1 Antitrypsin Deficiency, or AATD. We're also announcing that we expect to initiate clinical development of 006 in 2023. 006 is a first-in-class RNA editing candidate and the most advanced therapeutic program currently in development to harness an endogenous enzyme for editing.
Thanks Chandra.
Net loss for three months ended June 32022 was $41 3 million, we reported zero point $4 million in revenue for the second quarter.
R&D expenses were $29 7 million for the second quarter of 2012 June as compared to $31 $6 million for the same periods in 2021.
This was primarily due to decreased external expenses related to our previously discontinued clinical program.
Partially offset by increased share based compensation expense and increased external expenses related to our HCV program.
G&A expenses were $12 $8 million for the second quarter of 2022 as compared to $11 million last year.
Primarily due to increases in compensation related mainly from share based compensation offset by decreases in other external general and administrative expenses.
We ended the second quarter with 148.
$2 million in cash cash equivalents and short term investments.
This includes net proceeds for a $65 5 million up $65 5 million from our financing completed in June 2022.
This financing we extended our cash runway and we currently expect that our existing cash cash equivalents and short term investments.
It will enable us to fund our operating cap rate assumption expenditure.
Through the end of 2023.
As a reminder, we do not include potential milestones and upfront payments under our collaboration with our cash level.
I'll now turn the call back over to Paul Paul.
Paul Bolno: There are approximately 200,000 people carrying homozygous ZZ mutations in the U.S. and Europe, and WVE-006 has the potential to transform how these patients are treated.
Operator: Could you provide any high-level plans that you have for the design of WAVE-006, how this trial will be designed?
Thanks, Kyle over the past decade, we have established a disruptive oligonucleotide platform and are now seeing these innovations translate in the clinic.
Paul Bolno: Demonstrating clinical proof of concept in AATD with 006 would serve to de-risk RNA editing for additional monogenic diseases, as well as open opportunities to address larger disease indications through modulation of proteins, such as disruption of protein-protein interactions and upregulation.
Paul Bolno: Continued investment in our PRISM platform has positioned us as leaders in oligonucleotide innovation, and we continue to be encouraged by the translation of our guide strands across multiple modalities.
Our unique guide strength enable us to target diverse biology with multiple therapeutic modality.
In addition to what we have shared today around antisense slicing and RNA editing, we have previously demonstrated how prism can significantly improve SA RNA silencing in vivo over industry state of the art advanced DSP plus chemistry.
These capabilities together with our GMP manufacturing position us well to become leading a leading genetic medicines company.
Paul Bolno: Earlier this year, we shared positive target engagement data from our ongoing FOCUS C9 clinical trials in C9-ALS and FTD, which demonstrated how our preclinical data are now translating in patients.
Looking ahead, we expect several milestones in the second half of the year, including data from all three of our ongoing clinical trials.
Paul Bolno: New pharmacokinetic data from our ongoing DMD and HC studies, which Mike will share today, further supports this clinical translation of differentiated pharmacology.
Paul Bolno: We remain on track to share data from all three of our clinical studies this year.
Operator: I mean, what we'll do is, as we said, we're engaging in the IND-enabling studies.
We achieved our goal of selecting an HDTV development candidate and initiating IND, enabling studies in the third quarter and expect to submit multiple clinical trial applications for <unk> in.
Paul Bolno: In June, we completed a successful follow-on offering which put WAVE in a strong, well-capitalized position entering the second half of 2022.
In 2023 importantly.
Importantly, we are well capitalized to execute on all of these milestones and with that we'll open up the call for questions operator.
Paul Bolno: We continue to execute on multiple pillars of value creation, including delivering clinical updates and rapidly advancing our novel RNA-based editing pipeline led by WVE-006.
Operator: Planning will be underway as we think about 2023 clinical trial updates, and we'll definitely provide a full update on the Alpha-1 antitrypsin clinical program.
Paul Bolno: We also continue to advance discussions with, potential strategic partners who share our vision for broad applications of WAVE platform and support expansion of our pipeline while unlocking value in GMP manufacturing.
Paul Bolno: I'll now turn the call over to Mike to provide an update on our pipeline.
Mike Panzera: Mike.
Operator: And the only other thing I'd say to that is we've really been engaging outside experts in the community to sort of help us in that regard in terms of how we approach this and how we can do it in a way that accelerates time to proof of concept, as we have for each of our CNS folks.
Hello, Ladies and gentlemen, if you have a question or a comment at this time. Please press star one on your telephone keypad, we will pause for a moment, while we compile the Q&A roster.
Operator: I mean, we'll share, and, you know, there'll be more opportunities, I think, about the second half of the year.
Operator: The clinical community is extraordinarily excited about an RNA editing approach to being able to treat and restore protein function and protect liver.
Our first question comes from Salim Syed with Mizuho. Your line is open.
Mike Panzera: Thanks, Paul, and good morning to everyone on the call.
Mike Panzera: Today, I will discuss the continued
Operator: So it's an exciting time, I think, for the field to now have a candidate to be able to start exploring clinical trial design.
Great. Good morning, guys. Congrats on the progress and thanks for the question.
Operator: Awesome.
Paul So I guess theres a lot of data to come in between now and year end. So I was hoping if.
Operator: Thank you very much.
If you could just tick through the three programs here the DMD program the HD program.
Operator: One moment for our next question.
The ALS program in terms of.
What do you perceive to be winning.
Operator: Our next question comes from Paul Matias with Stiefel.
Winning scenarios for these three programs.
How much dystrophin production you expect to see.
Operator: Your line is open.
The knockdown data for Huntington's, how much maybe in Huntington knockdown data can we expect to see.
Operator: Great, thanks.
And then specifically on.
Operator: This is James on for Paul.
On the Huntington's or are we going to be getting single dose data and our multi dose data and for the two programs that you didn't specify whether its third quarter or fourth quarter are we thinking more.
Pumpkin Spice latte time or time for.
Mike Panzera: progress of our therapeutic portfolio, beginning with our CNS programs. The FOCUS-C9 clinical trial for WVE-004 in patients with C9-ORF72-associated
Operator: Maybe a quick one on ADAR and AAT.
C&I.
Thank you so much.
Thank you.
I'll start and I'll transition to Mike as well, but just in no particular order and I think that's critical as we lay this out but to start with your.
Mike Panzera: ALS and FTD continues with administration of single and multiple doses underway. Back in April of this year, we announced the first data update from our FOCUS-C9 program, which demonstrated a robust dose-related target engagement, confirming translation of our preclinical work into the clinic. I shared these data with the ALS community in June in an oral session at the Conference of European Networks to Cure ALS, or NCALS.
Mike Panzera: The presentation highlighted not only the clinical data seen here, but the wealth of information illustrating the differentiated preclinical profile of WVE-004.
Mike Panzera: We anticipate delivering an update with additional single and multi-dose data for WVE-004 in the second half of 2022, and are on track to initiate an
Since you ended with three I'll start with <unk>.
The <unk> data will be single dose that I think stepping back 10000 feet and looking at all of these data sets I think they are important because they're going to give us again more indication hopefully of what we saw earlier this year with benign on our single dose, which is potent durable target engagement. So I think firstly as we think about preclinical translation the clinical translation.
Wed like to exceed a continuation of our preclinical data extending into clinical data readouts. So SNP three a single dose of the liquid same valuation that we had done.
On <unk> nine.
US the opportunity to engage and look at target engagement on the mutant protein preservation of wild type, which as Mike alluded to earlier continues to be an important metric to study.
And other clinical Biomarkers again will be by a biomarker driven study as it relates to 59, we will have continued data on both net multi and single dose again continued to be able to look at the pharmacokinetics.
Target engagement.
And DMD will give us the first opportunity again to look at preclinical to clinical translation as we shared today based on tissue concentrations and exposure related to the Dk, Our mouse model, where we did see a restoration of phenotype that is going to give us an opportunity and muscle biopsies to look at tissue exposure to target engagement and turn it over to Mike.
For any additional follow up on that but that's going to be the key it's a robust data set across multiple programs all related to PM that answer key questions related target engagement in various tissues.
Versus muscle.
As well as being able to look at individual disease indications for cross silencing and slightly.
And I would say nothing nothing really much to add other than to address the other question is that.
Mike Panzera: open-label trial in the same timeframe.
The DMD study, we have said in the fourth quarter that said that's open label patients within dose escalation, we have a good sense of when that's going to happen. The other studies as you know our adaptive.
Mike Panzera: Moving on to Huntington's disease, WVE-003 is our allele selective oligonucleotide currently being evaluated in the SELECT-HD study, targeting a polymorphism, SNP3, associated with the expanded CAG transcript in certain patients with HD.
Mike Panzera: The goal, as we have said many times, is to preserve production of wild-type Huntington, given the importance of this critical protein. Preservation of wild-type Huntington continues to be a key objective that is supported by the HD community and by emerging preclinical and possibly clinical data.
They're driven by recruitment timing of data collection.
Mike Panzera: WVE-003 is the only allele-selective program currently in clinical development. Similar to WVE-004, we were able to leverage preclinical in vivo models to establish a starting dose of WVE-003 that was predicted to achieve CSF concentrations needed to engage target, and we designed and implemented an adaptive trial with the goal of accelerating time-to-approval process.
Basically the timing of that.
Mike Panzera: The SELECT-HD study is progressing well and is already yielding interesting information from blinded assessments.
The reviews by the independent Committee. So that's why we've been a little bit more.
Mike Panzera: The right-hand side of slide 9 shows the concentrations of WVE-003 measured in patient cerebral spinal fluid, or CSF, in the first cohort of patients dosed in the trial. On the same graph, we have plotted the CSF concentrations observed following administration of 32 milligrams of WVE-120101 and WVE-120102, which were the highest doses used in the PRECISION-HD studies, where we evaluated these first-generation PSPO compounds for HD. Possibly one month post this single starting dose, we are seeing CSF concentrations 20-fold, greater than the maximum observed with these previous compounds.
Mike Panzera: You may recall at the time we discontinued the Precision-AT program, we said the primary, reason for doing so was modeling that indicated that we could not achieve CSF concentrations needed to engage target with those first-generation compounds.
Little less definitive on the timing there but.
Is it just really depends upon those factors because.
Those are the blinded adaptive study.
If I could follow up guys. Thanks for the color on the DMD, specifically do you have a number in mind in terms of dystrophin production, you're you're targeting on this particular readout.
I know it's single this particular reader, yes at this point in time the target right now is being able to evaluate the translation I think the study is really determined to see can we see the preclinical data and exposure from the double knockout translate into humans. So this time, we're not laying out what a target exposure as we will continue to evaluate where we are based as Mike said, we're now.
And the dose for so there'll be more modeling as we get closer and the big factors limit.
Does it look different from superiors, alright, because when you remember with <unk> and we just couldnt get into.
<unk>, we couldn't engage target we couldn't even see any transcript production at all.
With Super garrison here, we have very different concentrations as we've highlighted and then we're going to be looking at distribution and if we see just drove going to be quite exciting so thats sort of how.
Looking at that one.
Got it thanks, so much.
One of them before our next question.
Mike Panzera: The profile 003 appears quite different.
Mike Panzera: Dose escalation continues in the SPECT-HD study, and we expect to share clinical data, in the second half of 2022.
Our next question comes from Joon Lee with <unk>. Your line is open.
Hi, Good morning, guys. Congratulations on the core focuses mainly on four June . So my question is related to the Pn chemistry.
Recent studies in Angelman published they show that is traditional P. O P. S backbones.
Sort of relatively limited.
Its ratio into deep brain tissues, so could you.
Some.
Data on.
The function of PM chemistry in your studies, and which type of tissues.
Type of distribution you cope with this versus the traditional kit.
Pete.
Yes.
<unk>. Thank you yes.
Yes, no. It's a great question, because I think it's data that we've shared and we're happy to continue to share more when we have shared in the past is with the Pn addition of Pn chemistry, we do see much deeper broader penetration across the CNS. So that's translating to uptake across tissue is the data that we share related to.
Mutant Huntington reduction in the back HD model in our corporate deck, Australia, it'll data. So what we have seen differently with the application of Pn is broader deeper penetration, but ultimately that is Y to liam's earlier question I think why the data for SNP three is going to be interesting because one of the things that we said two is benign.
We're going to be looking at primarily cortex spinal cord and as it relates to HD, we know thats cortex, and deep great structures like Australia. So these data continue to help will help clarify for us preclinical or clinical translation as we measure it but we've seen that it's not tissue specific either we've seen deep penetration as Mike was talking about.
We're looking at tissue concentrations in BMD in muscle and so we think not only is it helping the distribution.
Retention stability and we believe that's why we're seeing target engagement at low single doses at the hotel.
So durable and so I think these data being able to translate it from preclinical to clinical is going to be important I think to your point as well being able to dose with lower doses. We think has a lot of advantages as we're going forward to be able to explore a multitude of diseases and as we shared today, our fix our first amer for Alpha one antitrypsin deficiency.
We had shared that one of the advantages to being able to get potent durable editing was a function of being able to apply pn chemistry on top of our archival they control molecules.
Thank you.
A very quick follow up.
Other question is that could.
Could you provide any high level.
Plants that you have for that.
Design of but if over six.
This trial would be desired.
I mean, what we'll do is as we said where we're engaging in the IND, enabling studies planning will be underway as we think about 2023 clinical trial updates and we'll definitely provide a full update on the alpha one antitrypsin clinical program and the only other thing I'd say to that is we've been really been engaging.
Outside experts in the community to sort of help us in that regard in terms of how we approach best and how we can do it in a way that accelerates time to.
The concept that we have for each of our CNS.
I mean, we'll share and there'll be more opportunities I think about the second half of the year. The clinical community is extraordinary excited about an RNA editing approach.
To being able to treat and restore protein function and protect lever so.
It's an exciting time I think for the field and now have a candidate to be able to start exploring clinical trial design.
Awesome. Thank you very much.
One moment for our next question.
Our next question comes from Paul Matteis with Stifel. Your line is open.
Operator: Do you have a sense of how much endogenous ADAR is expressed in your animal model, and how does that compare to what we know about, you know, endogenous expression levels of ADAR in humans?
Great. Thanks. This is James on for Paul maybe a quick one on <unk>.
Do you have a sense of how much endogenous <unk> expressed in your animal animal model and how does that compare to what we know about.
Endogenous expression levels of ADR in humans. Thanks, so much.
Yes.
Jonathan.
The model and we've shown this across multiple models. We are using the standard model I don't know if you have a specific answer on the amount of aid are expressed in the in the animal model.
It's in the mouse model, we are using the bulk and Doug Peter.
And in the human <unk> mouse model that we described before the expression levels are very similar to what we've seen.
And we have.
<unk> provided the data in the previous session.
Presentations.
I think there was an old question existing of whether or not I think there was a question of whether or not the human model ahead of actually amplify that we've demonstrated and actually presented those data that is that there was not an over expression. So actually the amount of the amount of ADR actually correlate. We've also Sean that you don't exhaust data. So it's not a it's not an over expression and you don't know.
Exhaust the endogenous by Mylan.
Great. Thanks, that's very helpful.
And one moment for our next question.
Our next question comes from Luca <unk> with RBC. Your line is open.
Oh, great. Thanks, so much for taking my question congrats on the progress.
Maybe on AOS, we've always seen our tool first NDA getting accepted by the FDA based on NFL as a surrogate biomarker I'm wondering what was your reaction to that news and how are you thinking about implications for you and maybe for the field more broadly and then second on A&P circling back on a prior question again I know, it's super early days, but.
How are you thinking about the phase one study design what are the efficacy endpoint that you will be focused on in order to potentially capture benefits for both liver lung. Thanks, so much.
So I'll start with ACD, and then transition to Mike for your question, but as it relates to <unk>, obviously for the phase one study in the phase one two our goal will be to establish dose dose frequency like we have done for others driven primarily on the plasma biomarkers. So we're going to have the opportunity I think to do two things one is validation.
Adding in the production of protein.
See how that correlates again with our preclinical data that data again as we've shared on the call I think serves two purposes, one obviously incredibly exciting for the alpha one.
Community in terms of advancing a therapeutic program in designing a program for both lung and liver. We'll also be looking at biopsies that important point that the study of liver and editing and then secondly that really does unlock for us and once we've established that preclinical to clinical translation opens up modeling for us to be thinking much more broadly about our <unk>.
<unk> across multiple therapeutic areas.
I'll turn the call over to Mike now for a question related to Alex Yes.
Whenever FCA and a CNS disease.
Now starting to pay attention to.
Biomarkers like this CSF serum whatever.
It is a positive development.
This is these are very bad diseases or diseases that progress and progress has been limited. So the idea that there is the potential albeit easily.
Measurable biomarker that they may now be viewing as relevant.
From the standpoint of I should say reasonably likely to predict clinical outcomes.
<unk> is encouraging and we will be watching to see how this plays out both for us but for the community at large.
Got it thanks, so much.
And one of them are for our next question.
Okay.
Our last question comes from many for heart with SBB Securities. Your line is open.
Hi.
Sorry. Good morning, this is lending zongo on for Armani.
Just had a question regarding the novel Oh six programs would.
Would you be able to give us an overview of the expected commercial opportunity there. Thank you.
Yes, well, obviously, if you're buying a lot more but what's exciting for US is it is a consequential indications we have in one only needs to look at some of the programs that have faced challenges to see kind of what the market reaction to that so for us our focus has been on the 200000 patients in the U S and Europe .
The homozygous patients better amenable, so not we're not even looking at it the broader population beyond that but the 200000 patients that really have the opportunity to be corrected back to the MD phenotype. So consequential patient population. We've seen this play out in terms of the translation and other substantial.
Valuation program than other companies.
And it's attractive of a lot of interest both on the patient communities.
Investor community.
Our potential partners. So we think it's a really interesting space for us to be able to think much more broadly.
And be able to do it I should also remind people differently. So we've seen the silencing program is really focused on targeting SA RNA in the liver.
That's exciting to watch I think we've seen the protein replacement style companies generating commercial revenue in terms of protein replacement of IV infusion and I think our opportunity to supplant boat with a single subcutaneous injection.
That treats both liver and lung will be consequential to the field.
Mike Panzera: In Duchenne muscular dystrophy, our open-label clinical trial of WVE-N531 for DMD patients with mutations amenable to exon 53 skipping is progressing well also.
Thank you.
I'd now like to turn the call back over to Dr. <unk> for closing remarks.
Thank you and thank you everyone for joining the call. This morning is an exciting time for our organization and I am grateful to every wave employees for their dedication and unrelenting focus on our mission and the patients and families. We serve have a great day.
Ladies and gentlemen, this does conclude today's presentation. You may now disconnect and have a wonderful day.
Mike Panzera: You will recall in our preclinical studies in the DKO or double knockout mouse, treatment, with an exon 23 surrogate of N531 resulted in significantly prolonged survival at dose levels and frequencies achievable in human studies, of course, after converting to estimated human equivalent dose levels. These data guided our target dose selection and escalation planning in our open-label, clinical trial.
Operator: Thanks so much.
Mike Panzera: On the right-hand side of slide 10, you can see some preliminary pharmacokinetic data, from this study compared with data from suvidursin, our first-generation PSPO compound. The figure shows plasma concentrations following single doses of N531 at three dose levels, compared with the top dose of suvidursin used in our discontinued phase 2-3 study. What's clear is that approximately one week following dosing, plasma concentrations of, N531 were already 40-fold greater than those achieved with suvidursin, and dose escalation has yet to be completed.
Operator: I mean, the model, and we've shown this across now multiple models, we're using the standard model.
Mike Panzera: Dosing is underway at dose level four, and we look forward to data for muscle biopsies, in the fourth quarter of this year.
Operator: I don't know, Chandra, if you have the specific answer on the amount of ADAR expressed in the animal model.
Mike Panzera: I'll now give an update on our newest candidate, WVE006 for AATD. WVE006 is designed to address therapeutic goals essential when developing a novel therapy, for AATD, namely restoration of circulating wild-type MAAT to address lung disease and reducing VAAT protein aggregation in the liver to address liver disease.
Operator: Ladies and gentlemen, if you have a question or a comment at this time, please press star one one on your telephone keypad.
Operator: In the mouse model, we're using the mouse endogenous ADAR.
Operator: To raise your hand during Q&A, you can dial star 1 1.
The conference will begin shortly to raise Johan during Q&A, you can dial star one one.
Mike Panzera: Our hypothesis is that through RNA editing in homozygous or ZZ patients, one can shift, the phenotype towards a heterozygous or MZ phenotype, lowering the risk of disease pathology.
Operator: And in the human ADAR mouse model that we described before, the expression levels are very similar to what we've seen in humans. And we have actually provided the data in the previous presentations.
Mike Panzera: In the second quarter, we shared data using one of our lead AATD aimers to restore functional, AATD protein. In the first 15 weeks, restored AAT protein was determined to be functional as measured, by robust inhibition of neutrophil elastase, as well as past the staining of liver biopsies demonstrating reduced accumulation of VAAT aggregates over the duration of the study.
Operator: I think there was an old question existing of whether or not, I think there was a question of whether or not the human model had actually amplified it.
Mike Panzera: The selection of 006 to take forward into IND-enabling toxicology studies followed a, thorough evaluation of multiple lead compounds, each with potent editing capabilities. In preclinical studies in mice and non-human primates, in order to choose the molecule, with the best overall profile. Slide 13 shows the efficacy of 006 in the NSG-PIZ mouse model, which is well established, in this study.
Operator: We have demonstrated and actually presented those data that there is not an overexpression.
Mike Panzera: Space.
Operator: So actually the amount of ADAR actually correlates.
Mike Panzera: 006 was administered subcutaneously following an initial loading dose.
Operator: We've also shown that you don't exhaust ADAR.
Mike Panzera: At week 13, Serpent A1 RNA editing was approximately 50% and serum AAT protein restoration ranged from 4 to 7 volt higher than PBS control, remaining above an 11 micromolar level throughout the dosing interval.
Operator: So it's not an overexpression and you don't exhaust the endogenous endogenous.
Mike Panzera: Additional data supporting the favorable preclinical profile 006 are shown on slide 14.
Operator: Great, thanks.
[music].
Mike Panzera: Potent concentration-dependent editing of Serpent A1 was observed in primary human, peptides derived from a donor with the MZ genotype, reaching as high as 80% with the highest concentrations tested.
Operator: That's very helpful.
Mike Panzera: So where are we now with 006?
Operator: And one moment for our next question.
Mike Panzera: IND-enabling activities are underway and we expect CTA submission next year.
Operator: Our next question comes from Luca Issi with RBC.
Mike Panzera: In summary, WAVE's diverse portfolio of therapeutic candidates continues to advance through development as we are beginning to see our preclinical observations translate into clinics. The data generated with each candidate continue to demonstrate the potential when principles of rational design and chemistry innovations are applied to oligonucleotides, enabling novel approaches to complex disease
Operator: Your line is open.
Mike Panzera: biology.
Operator: Great, thanks so much for answering my question.
Mike Panzera: With that, I will turn the call over to Chandra.
Operator: Congrats on the progress.
Okay.
Chandra Vargeese: Chandra?
Operator: Maybe on ALS, we've obviously seen a 12% NDA getting accepted by the FDA based on NFL as a surrogate biomarker.
Yes.
Chandra Vargeese: Thanks, Mike.
Operator: I'm wondering what was your reaction to that news and how you're thinking about implications for you and maybe for the field more broadly.
Okay.
Chandra Vargeese: The substantial
Operator: And then second on AAT, circling back on a prior question.
[music].
Chandra Vargeese: progress to date with our WVE006 program for AATB demonstrates the potential of AMERS technology
Operator: Again, I know super early days, but how are you thinking about a phase one site design?
Chandra Vargeese: for precise correction of VTA driver mutations.
Operator: What are the efficacy endpoints that you will be focused on in order to potentially capture benefits for both liver and lungs?
Chandra Vargeese: We like to think of our AMERS as Swiss Army Knights and restoring or correcting protein function is only one example of how we can use, AMERS to potentially treat diseases. Recently, we have generated multiple proof-of-concept data sets that demonstrate how AMERS can activate gene pathways by modulating protein-protein interactions and upregulate RNA expression by editing RNA-binding protein motifs.
Operator: Thanks.
Chandra Vargeese: These applications demonstrate the potential to design therapeutics to precisely control, gene upregulation by titrating RNA editing levels and AMER dose. I'll review these in vitro and in vivo editing data sets on the next few slides.
Operator: So I'll start with AATD and then transition to Mike for your ALS question.
Chandra Vargeese: We have used the NRF keypoint system before.
Operator: But, you know, as it relates to AATD, obviously for the Phase 1 study and the Phase 1-2, our goal will be to establish dose frequency like we have done for others, driven primarily on the plasma biomarkers.
Chandra Vargeese: This system shows the potential to edit a single, site to activate a transcription factor and upregulate downstream genes.
Operator: So we're going to have the opportunity, I think, to do two things.
Chandra Vargeese: As shown on the right-hand side of slide 17, using GalNAC-AMERS, we achieve efficient editing, resulting in a dose-dependent upregulation of the NCO1, a gene regulated by the NRF2 transcription factor, in vitro. We recently repeated this study in vivo and again saw efficient editing with multiple GalNAC-AMERS in the liver of mice, which resulted in downstream gene upregulation.
Operator: One is validation of editing in the production of protein and to see how that correlates, again, with our preclinical data.
Chandra Vargeese: If we properly disrupted the NRF2 protein interaction, we would expect upregulation of a key set of genes that are regulated by NRF2, which we successfully confirmed by RNA-seq transcriptome analysis, as shown on the bottom right side of slide 18.
Operator: That data, again, as we've shared on the call, I think serves two purposes.
Chandra Vargeese: Another potentially disruptive application of AMER is to upregulate RNA to treat haploinsufficient, diseases or diseases that require overexpression of target genes.
Operator: One, obviously incredibly exciting for the Alpha-1 community in terms of advancing a therapeutic program and designing a program for both the lung and liver.
Chandra Vargeese: We have now demonstrated the ability to upregulate several different targets, including both, metabolic and immune targets, by editing RNA motifs to regulate RNA haploins in vitro.
Operator: We'll also be looking at biopsies, that important point to study liver and editing.
Chandra Vargeese: While much of our presentations today have focused on GalNac-conjugated designs, we also, have achieved substantial RNA editing with systemic delivery of unconjugated AMERS.
Operator: And then secondly, that really does unlock for us.
Chandra Vargeese: We do not need to use complex delivery vehicles such as lipid nanoparticles or viral vectors.
Operator: And once we've established that preclinical to clinical translation, opens up modeling for us to be thinking much more broadly about our aimers across multiple therapeutic areas.
Chandra Vargeese: In vivo mouse studies, we observed editing of UGP2 targets across multiple tissues, including, kidney, adipose tissue, and a range of liver cells with a single subcutaneous dose of unconjugated, AMERS.
Operator: I'll turn the call over to Mike now for a question related to ALS.
Kyle Moran: I'll now turn the call over to Kyle Moran, our CFO.
Operator: Yes.
Kyle Moran: Kyle?
Operator: You know, whenever FDA, in a CNS disease, now is starting to pay attention to biomarkers like this, CSF serum, whatever, it's viewed as a positive development.
Kyle Moran: Thanks, Chandra.
Operator: This is these are very bad diseases.
Kyle Moran: Net loss for three months ended June 30, 2022, with $41.3 million.
Operator: These are diseases that progress and progress has been limited.
Kyle Moran: We reported $0.4 million in revenue for the second quarter of 2022. R&D expenses were $29.7 million for the second quarter of 2022, as compared to $31.6 million, for the same period in 2021. This was primarily due to decreased external expenses related to our previously discontinued, clinical program, partially offset by increased share-based compensation expense, and increased external expenses related to our AATD program.
Operator: So, the idea that there is the potential of a easily measurable biomarker that they may now be viewing as relevant from the standpoint of, or I should say, reasonably likely to predict clinical outcomes is encouraging.
Kyle Moran: DNA expenses were $12.8 million for the second quarter of 2022, as compared to $11 million, last year. This was primarily due to increases in compensation related, mainly from share-based compensation, offset by decreases in other external, general, and administrative expenses.
Operator: And we'll be watching to see how this plays out, both for us, but for the community at large.
Kyle Moran: We ended the second quarter with $148.2 million in cash, cash equivalent to short-term investments. This includes net proceeds from our $65.5 million from our financing in June 2022. With this financing, we extended our cash runway, and we currently expect that our existing, cash, cash equivalent, and short-term investments will enable us to fund our operating capital expenditure to the end of 2023.
Operator: Got it.
Kyle Moran: As a reminder, we do not include potential milestones or opt-in payments under our Takeda, collaboration in our cash runway.
Operator: Thanks so much.
Paul Bolno: I'll now turn the call back over to Paul.
Operator: And one moment for our next question.
Paul Bolno: Paul?
Operator: Our last question comes from many for with security.
Paul Bolno: Thanks, Kyle.
Operator: Your line is open.
Paul Bolno: Over the past decade, we have established a disruptive oligonucleotide platform and, are now seeing these innovations translate in the clinic.
Operator: Hi, good.
Paul Bolno: Our unique guide strands enable us to target diverse biology with multiple therapeutic, modalities.
Operator: I'm sorry.
Paul Bolno: In addition to what we have shared today around antisense, splicing, and RNA editing, we have, previously demonstrated how PRISM can significantly improve siRNA silencing in vivo over industry state-of-the-art and advanced ESB plus chemistry.
Operator: Good morning.
Paul Bolno: These capabilities, together with our GMP manufacturing, position us well to become, a leading genetic medicines company.
Operator: This is living on for money.
Paul Bolno: Looking ahead, we expect several milestones in the second half of the year, including, data from all three of our ongoing clinical trials.
Operator: I just had a question regarding the novel program.
Paul Bolno: We achieved our goal of selecting an ADTB development candidate and initiating IND-enabling, studies in the third quarter and expect to submit multiple clinical trial applications for WVE-006 in 2023. Importantly, we are well capitalized to execute on all these milestones.
Operator: Would you be able to give us an overview of the expected commercial opportunity there?
Paul Bolno: With that, we'll open up the call for questions.
Operator: Thank you.
Operator: Operator?
Operator: Yeah, and we'll obviously be providing a lot more, but I mean, what's what's exciting for us is it is a consequential indication we have.
Operator: And one only needs to look at some of the programs that have faced challenges to see kind of what the market reaction has been to that.
Operator: So, for us, our focus has been on the two hundred thousand patients in the US and Europe that are the homozygous patients that are amenable.
Operator: So not we're not even looking yet at the broader population beyond that.
Operator: But the two hundred thousand easy patients that really have the opportunity to be corrected back to the MZ phenotype.
Operator: So consequential patient population.
Operator: We've seen this play out in terms of the translation and other substantial evaluation programs of the companies.
Operator: And it's attractive of a lot of interest, both from the patient community.
Operator: That's your community and our potential partners.
Operator: So we think it's a really interesting space for us to be able to think much more broadly at.
Operator: And be able to do it, I should also remind people differently.
Operator: So we've seen the silencing programs really focused on targeting SIRNA in the liver.
Operator: That's exciting to watch.
Operator: I think we've seen the protein replacement side of companies generating commercial revenue in terms of protein replacement, IV infusions, and I think our opportunity just to plant both with a single subcutaneous injection that treats both liver and lung will be consequential to the field.
Operator: Thank you.
Paul Bolno: I'd now like to turn the call back over to Dr. Paul Bolno for our closing remarks.
Paul Bolno: Thank you.
Paul Bolno: And thank you everyone for joining the call this morning.
Paul Bolno: This is an exciting time for our organization and I'm grateful to every WAVE employee for, their dedication and unrelenting focus on our mission and on the patients and families we serve.
Paul Bolno: Have a great day.
Operator: Ladies and gentlemen, this does conclude today's presentation.
Operator: You may now disconnect and have a wonderful day.
Operator: The conference will begin shortly.