Wave Life Sciences Q2 2023 Earnings Call Transcript

Quartr
Provided by Quartr
August 3, 2023

There are 11 speakers on the call.

Operator

Good morning, and welcome to the Wave Life Sciences Second Quarter 2023 Financial Results Conference Call. At this time, all participants are in a listen only mode. As a reminder, this call is being recorded and webcast. I'll now turn the call over to Kate Roush, Vice President of Investor Relations and Corporate Affairs. Please go ahead.

Speaker 1

Thank you, Haley. Good morning, and thank you for joining us today to discuss our recent business progress and review Wave's Q2 2023 financial results. Joining me today are Doctor. Paul Bono, President and Chief Executive Officer Anne Marie Li Kwaicheng, Chief Development Officer Kyle Moran, Chief Financial Officer and Doctor. Chandra Varghese, Chief Technology Officer.

Speaker 1

The press release issued this morning is available on the Investors section of our website, www .wavelifesciences.com. Before we begin, I would like to remind you that discussions during this conference call will include forward looking statements. 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. 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 ks for the year ended December 31, 2022, and our quarterly report on Form 10 Q for the quarter ended June 30, 2023. We undertake no obligation to update or revise any forward looking statements for any reason.

Speaker 1

I'd now like to turn the call over to Paul.

Speaker 2

Thanks, Kate. Good morning and thank you all for joining us on today's call. Today, I'll share highlights on our progress during the Q2 and then turn the call to Kyle to review our financials. Then we'll open up the call for questions. Anne Marie and Chandra are on the line today and will be available for Q and A.

Speaker 2

In the Q2, we continue to execute on our vision pioneering transformational RNA medicines using our multimodal platform. We remain on track to submit CTAs for our AATD program, The first RNA editing medicine to enter human clinical trials. We're accelerating work on a number of compelling targets in our collaboration with GSK And we continue to advance our clinical programs in DMD and HD. Today, I'll begin with AATD and RNA Editing, Then review our progress with GSK and building a sustainable pipeline. And finally, we'll end with an update on our clinical trial.

Speaker 2

As I speak with you today, we are preparing for the imminent submission of our first clinical trial applications or CTAs for WVE-six, the first RNA editing clinical candidate for the treatment of AATD. This milestone is important on multiple fronts. 1st, WVE-six signifies an entirely new modality moving into the clinic. We are incredibly excited about this milestone, which is an important advancement for the nucleic acid field For all patients who stand to benefit from RNA Editing Therapeutics. With AATD, our ability to utilize validated biomarkers in the clinic is expected to enable rapid delivery of proof of concept data for 6.

Speaker 2

This early clinical data set would increase the probability of Success with Wave's future RNA editing programs in the liver and beyond. 2nd, our path from targets to the clinic with 6 This reflects the translational speed of our platform. Upon first human dosing, we will demonstrate that we have expediently advanced this clinical candidate with a novel modality from the bench to patients at a remarkably fast pace. As we build our pipeline, we expect to drive further efficiencies with each new RNA editing clinical candidate. Importantly, 6 is not only first of its kind, but it's also best in class in AATP as supported by our robust preclinical data package.

Speaker 2

We are able to achieve remarkable potency and durability of editing with convenient subcutaneous dosing because of our unique fully chemically modified oligonucleotide. 6 is also compatible with GalNAc conjugation, a highly specific and elegant delivery tool that is well validated through multiple approved silencing For AATD, it is a significant advantage to have a stable and optimized candidate that can leverage GalNex and thereby avoid the nanoparticles which require intravenous doses. Among the AATD field, We continue to generate excitement for our RNA editing approach, which is a 1st in class therapy designed for restoration of both healthy hepatic and pulmonary function with a reversible redosable therapeutic agent. Our team is hard heard the enthusiasm firsthand from the community at the Alpha-1 National Conference Dallas, Texas in June, there is major unmet need in AATD with current therapies largely confined to treating either pulmonary or in the future hepatic manifestations of Nucyx. Despite the limitations of current therapy, AAPD already represents substantial pharmaceutical market with augmentation therapy alone currently accounting for about $1,300,000,000 in annual pharmaceutical revenue worldwide and this market is expected to grow.

Speaker 2

Our collaboration with GSK puts us in a strong position to execute on bringing our novel therapeutic option to this market. GSK has a long history and clear leadership in respiratory medicine, development and commercialization. And under the terms of our deal, Wave is eligible to receive As with ATB, our internal discovery work on the next wave of RNA medicine is substantially focused on 1st in class RNA editing therapeutics designed to repair and restore protein. With 8AR editing, we have a versatile modality that allows us to impact target biology in novel ways. As we look at the universe of genetic mutations driving disease, the majority of these mutations lead to a loss of protein function, meaning they can't be addressed with silencing tools such as siRNA or antisense.

Speaker 2

WAVE is best positioned to capitalize on these loss of function disease targets using our protein restoration and repair tools, including our leading RNA editing modality and validated pharmacological platform. We are not constrained by therapeutic area and have previously shown robust editing in extrahepatic tissues including CNS, kidney and lung. Beyond rare monogenic disorders, there is also a growing opportunity for RNA medicines with prevalent disease. With genetic insights being unlocked from large genome wide association studies, new druggable targets are rapidly becoming available. These targets have existing biological validation rooted in human genetics.

Speaker 2

GSK is at the forefront of investing in genetic discovery. Through our strategic collaboration, we are benefiting from their proprietary genetic insights, which augment our own internal data set and are informing and accelerating our next wave of programs, including partnered and wholly owned programs. We are rapidly building momentum within our collaboration and the WAVE and GSK teams are already actively working on multiple targets. Importantly, GSK pays 100% of the costs and expenses related to target validation for these partner programs. As a reminder, the GSK deal includes meaningful near term milestone payment opportunities beyond the clinical development milestones related to WB06, which has the potential to add substantially to our balance sheet in 2023 and beyond.

Speaker 2

We are planning to hold a virtual R and D Day on September 28, 2023, during which we will demonstrate how we are continuing to extend our leadership in RNA Editing. We will also discuss how we are uniquely translating genetic insights into internal wholly owned programs for both rare and more prevalent diseases. During the event, we will share new preclinical data for both hepatic and extrahepatic disease indications highlighting the potential depth and breadth of our next wave of pipeline programs. Moving on to DMD, we are on track to initiate Part B, a Potentially registrational Phase 2 study of WVN531, our exon 53 skipping candidate. This open label study will evaluate doses of 10 milligrams per kilogram of N531 administered every other week and we plan to assess dystrophin protein after 24 weeks and 48 weeks of treatment.

Speaker 2

Since our last update, our clinical development team has filed the clinical trial protocol with regulatory authorities and identified additional trial sites. We expect to share clinical data inclusive of dystrophin protein in 2024. If these data are supported, we intend to use them to file for accelerated approval in the U. S. As a reminder, our excitement for N531 is grounded in the proof of concept data from Part A of the study, which showed 53% exon skipping after just 3 biweekly doses, highest muscle tissue concentration and a favorable safety profile.

Speaker 2

We presented these results to the DMD community at the PPMD Conference in June, where they were met with excitement and optimism. With the extended dosing period in the forthcoming trial, we expect these high levels of skip transcript to result in downstream accumulation of substantial fully functional dystrophin protein. We know the DMD community is waiting for additional and better therapeutic options. With N531, we aim to provide a treatment option that delivers convenient, safe production of endogenous functional dystrophin and ultimately meaningful clinical benefit for all patients amenable to exon 50 free skipping. We are also planning a broad strategy to expand the number of exons we can address, which we would accelerate rapidly following positive dystrophin data for N531 to build the wholly owned GMV franchise.

Speaker 2

Turning to WVE-three, our 1st in class allele selective candidate for Huntington's disease or HD. HD patients have no disease modifying therapies available to them today and we believe 3 is the most promising HD compound in development. 3 takes advantage of broad delivery to the CNS, thereby reaching the variety of brain regions implicated in HTA. We've now confirmed the ability of oligonucleotide to distribute in the CNS in multiple NHP studies with our partner, including relevant concentrations in the cortex and striata. Therefore, we are confident that 3 is getting to the right part of the brain.

Speaker 2

It is also the most advanced approach designed to selectively knock down the toxic mutant huntingtin protein, while sparing the healthy wild type HTT protein. Biotype HTT is essential and plays several critical roles in the CNS, including regulation of the synaptic and protein transport, promoting neuronal survival and formation and function of cilia, which are essential to regulate CSF flow and reabsorption. This function in any of these pathways could be expected to adversely impact response and could potentially cause declines. With only single doses of WV003, we have already demonstrated positive initial mutant huntingtin reductions of approximately 35% compared to placebo in in the CSF with wild type HTT levels appearing consistent with omeleo selectivity. The select HD trial has continued to progress and In the Q2 of 2023, we initiated the multi ascending dose phase of the trial, dosing at 30 milligrams every 8 weeks.

Speaker 2

Given our robust and durable knockdown data observed in the multi dose cohort for the FOCUS C9 clinical trial of WVE-four, We believe the multi dose data for 3 will be most important to informing our next phase development. In the second half of twenty twenty three, We intend to share additional single dose biomarker and safety data along with any available multi dose data. With that, I'll now turn the call over to Kyle Moran, our CFO, for our financial update. Thanks, Paul. Turning to the financials.

Speaker 2

Our net loss for the Q2 of 2023 was $21,100,000 as compared to $41,300,000 in the prior year quarter. The decrease in net loss was primarily driven Revenue recognized under our collaboration with GSK. Under the GSK and JAKTA collaboration in the Q2 of 2023 was $22,100,000 In the prior year quarter, revenue of $400,000 was recognized under the Takeda collaboration. Research and development expenses were $33,300,000 for the Q2 of 2023 as compared to 29 point This increase in R and D expenses was primarily due to increased external expenses related to our clinical programs. GSK expenses slightly declined in the 2nd quarter sorry, G and A expenses slightly declined in the 2nd quarter to $12,300,000 as compared to $12,800,000 in the prior year quarter, primarily due to decrease in share based compensation.

Speaker 2

We ended the Q2 with $173,000,000 in cash and cash equivalents as compared to $88,500,000 as of December 31, 2022. The increase is primarily attributable to the upfront cash and equity investment of $170,000,000 received in the Q1 from our strategic collaboration with GSK. We expect that our cash and cash equivalents will be sufficient to fund operations since 2025. As a reminder, we do not include future milestones or opt in payments under our GSK or Takeda collaboration in our cash runway. As Paul stated earlier, we have the potential to receive meaningful near term milestone payments in 2023 beyond, including clinical development milestones related to WVE-six, our RNA editing candidate for treatment of AATV.

Speaker 2

I'll now turn the call back over to Paul. Paul? Thanks, Kyle. 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 to speaking with you at our R and D today in September.

Speaker 2

And with that, I'll turn it over to the operator for Q and A. Operator?

Operator

Thank you. We will now conduct a question and answer session. Please standby while we compile the Q and A roster. Our first question comes from the line of Steven Seedhouse from Raymond James. Go ahead with your question.

Speaker 3

Yes, good morning. Thanks so much for taking the question for the broad update. Paul, You mentioned rapid delivery of proof of concept data from the AATD study. I was hoping you could just expand on that, Comment on sort of the initial doses you'll be in the clinic with when gene editing went into the clinic at vivo. There were pretty profound editing rates already even at the lowest doses.

Speaker 3

Just curious if that's the type of thing You're expecting to sort of manifest here at the early doses in the study and what other other than Editing, what other sort of proof of concept features do you think you can generate pretty quickly?

Speaker 2

Wonderful. I'll take the question, Steve, and thanks for it and then hand I think when we talk about rapid proof of concept, our goal is, as stated, 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 treatment section. But the goal here is you bring up measuring editing efficiency. I think what's unique and really special about the ALPHA-one antitrypsin indication is that we can measure the most important Contribution of editing, which is protein formation. And so the biomarker we'll be able to measure in that study is The Alpha-one antitrypsin protein and we'll also be able to characterize how much of it is fixed corrected protein.

Speaker 2

So I think It gives us a really unique way of confirming preclinical studies in the clinic, both in the magnitude of production, but also the quality of production. Ann Marie, I don't know if you have other comments you want to make for the clinical trial design?

Speaker 4

No. Well, I would perhaps add that In the final stages before submitting ready almost ready to submit the CTAs and we'll comment further on the design once we're locked and loaded there.

Speaker 3

Okay, thanks. And just when you think about assessing off target RNA editing, Can you just describe, is this much different than you would do for an siRNA for instance? Is it any more onerous? What's What's your understanding of the sort of regulatory landscape for establishing an off target margin for RNA Editing Therapeutics?

Speaker 2

Yes. I mean, I think what's exciting about RNA editing as we think about a standardized oligonucleotide approach and looking at our experience in siRNA and antisense is the ability to assess normal what are the potential off targets in the same way we would do that for others. As you know and as we've shared previously, we've done the characterization to look for bystander edits and others on the transcript film and saw highly specific editing and therefore we did So in preparation for this submission, we obviously did a lot of that work to preempt that in terms of demonstrating as a new modality that We don't see by standardized as highly specific and behaves the same way as other oligonucleotides. And so I think we're excited about the prospect of thinking about this like Others as opposed to, as you alluded to, kind of the more onerous work that needs to be done on DNA editing. I mean, I think The other point is, I think it really reflects the ability and the importance of reversible editing, the idea that we're working on the transcript and not Inducing permanent genetic mutations on DNA.

Speaker 2

So I think as we approach this, particularly as we think about prevalent diseases, We think it's an important contribution that we get to make to the space of really thinking about how do you go after not just devastating rare diseases, but actually apply these technologies to Broad chronic diseases, which is important obviously to ourselves and to our partner, GSK.

Speaker 3

Yes. And just lastly for me, I appreciate that. This is maybe thinking a little bit ahead, but as you think about initial patient selection for AATD, how broad is that demographic going to be? And Like will you be looking for patients with lung and liver involvement right away to sort of show the power of this approach and specific genotypes that Would be early targets, any comments there would be appreciated. Thanks so much.

Speaker 2

Yes. I mean, I'll hand it over to Ann Marie in a second on the clinical side, but I think it is As we think about the application initially where we're pursuing, which is if you think about the homozygous disease patients, it's both liver and lung. And so as we think less about Where the manifestation is, the actual driver of that disease is in the underlying genetics. And therefore, it's about correcting those ZZ patients to MZ patients And therefore following the protein relative to that. So it's much more about selecting for the genotype and demonstrating evaluating the Protein and the constitution of that protein in this initial period.

Speaker 2

Later we can then say, look, we can drive that to the lung and think about where Protein infusions have been developed and thinking about achieving threshold levels of apple and antitrypsin protein and looking at liver demographics. But I think initially the proof of concept really is focused on demonstrating that translational potential Of both for AATP with this particular medicine, but even the RNA editing field more broadly and what's the impact as we think through other hepatic targets and beyond. I don't know if there's anything else you want to add to that in terms of the clinical trials and demographics?

Speaker 4

No. I mean, I think you hit it. We're focusing on GZ patients, Finotype patients for now and there'll be more details about the study once we're in full agreement with regulators.

Speaker 2

I think the other piece is, if we think about the ZZ population, the ZZ population by itself is about 100,000 patients in the U. S. So as we think about that, There is a consequential patient population to study. So we're not concerned that we'll be able to find the patients for the study.

Speaker 3

Thanks so much.

Operator

Thank you. Our next question comes from the line of Paul Matteis from CECL. Go ahead, Paul.

Speaker 5

Hi, this is Julian on for Paul. Thanks so much for taking our question. On AATD, I know you said for VOS VI, you're not constrained by therapeutic area. Just curious, regardless, is there anywhere else in particular that you find compelling beyond AATD to where You may be interested in establishing proof of concept moving forward. And then any other color also you could just provide in the GSK collaboration?

Speaker 5

I know you mentioned that you're currently working with them on numerous targets, but any other color you could provide on how that's coming along And how you plan on allocating your resources for joint programs versus your own moving forward would be super helpful. Thank you.

Speaker 2

Thank you, Julien. I'll take it from the beginning. And I think you set up a really important context at the very beginning, which is, Yes. I think you said AATD is not constrained by therapeutic area. I mean, AATD, you're right, liver and lung, but we're treating the liver to ultimately Create the protein that protects lung.

Speaker 2

So I think it's important in the context of AATD optimizes in a POC of down that What we've done and I think these are important data sets that we've previously shown and again as we said earlier That we plan to do the update on September 28 at our R and D Day is, we have shown data extrahepatic, meaning absent Galmec, the chemical modifications that we have So I think as we think about those therapeutic areas and what each of the potential within those I think what we're seeing is an expansion of indication. On a previous call and we'll obviously share more on R and D Day, I think we're also excited as we talk about not just as we said rare and prevalent, but really thinking about mechanisms. So in AATD, Here we're talking about the ability of a correction that actually changes a protein from a mutated form to a wild type or healthy form. There are applications in a number of tissues and therapeutic areas where we can apply that in developing meaningful therapeutics. What's been exciting and what we've shared previously some in vivo data on and we'll continue to share more on that is the ability to do up regulation.

Speaker 2

So to think about areas where you're under expressing a protein and then rather than trying to augment that by trying to deliver an mRNA therapeutic or other technology, which could be constrained even by mechanism of delivery. The ability to actually stabilize a transcript, increase its And therefore increase the protein that's produced, let's us think about other applications beyond just the base correction fixing the protein. And as we think about that area, We think that universe is really broad. It gives us a lot of opportunities to think about multiple therapeutic areas for us. So We are excited about sharing more data on programs in those areas and data that supports the growth of the RNA editing field and what it

Speaker 6

Excellent. Thanks so much.

Speaker 2

Sorry, last question. It was the GSK component. So as much as I'd love to be able to speak for a partner, I think we as we shared today, I think it's safe to say, there is an extraordinary amount of momentum. It was evident, anybody who attended the bio, We were on we were the participants with GSK as they were sharing kind of where they see the translational potential of their genetics investments and have really been highlighted by them as the opportunity that we provide with a multimodal platform. I think editing is 1.

Speaker 2

Importantly, as GfK looks across their universe, it's not just constrained to loss of function and editing. There are a lot of really prominent programs And silencing and we are partnering with them across silencing using siRNA and the data some of that basis of that data we shared last year As well as on the editing approach. And so really being able to think about diseases holistically where we're not constrained to either an upregulation gain of function disease or loss of function, So I can really pick the best tool for the right shot. 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.

Speaker 5

Excellent. Appreciate the color. Thank you.

Operator

Thank you. Our next call comes from the line of Eun Yang from Jefferies. Go ahead.

Speaker 7

Thank you. I have a couple of questions on RNA editing. So Obviously, you have the most advanced program in RNA Editing, but others are doing as well. So could you comment on Your technology, how you are better positioned for RNA editing compared to others, although There is not a lot of data out there from others. So that's question number 1.

Speaker 7

And second question is on AATV program. And obviously, you are going to be talking more about this at the R and D Day. But as you are very close to filing a CTA, When do you think we would be able to see the data? And in terms of serum AAT protein levels, You have shown remarkable increases in rodents. But how should we think about in humans?

Speaker 7

And how many fold of increase would be

Speaker 2

Great. We'll unpack that a lot. I think if we start with And then I'll move to your final question, which is really the translation of why are we leading in AAT. In editing, how does that translate into AAT and ultimately what do we expect to I think you said a lot at the beginning when you said why are we ahead of others. And I think you really brought up the important Which is there's not a lot of data out there from others.

Speaker 2

And I think what I'd like to say is this doesn't come from And immediately I'm saying we're interested in RNA editing. It comes from over a decade of investments in building an oligonucleotide chemistry engine. And what we were poised to do when we entered in the editing space was really bring together this convergence of best in class Nucleic acid chemistry, the how, how do you create guide trends that better interact with enzymes? How do we design that More specifically and enhance the opportunity set that we have with ADAR and ultimately how does that translate both in our non human primate studies In the liver using Galnex, in the liver not using Galnex and in other tissues beyond the liver. And I think if we get to the root of really how we approach things, It is a chemistry driven exercise.

Speaker 2

And I think in doing so, we've been able to get to short collinucleotides that aren't long, but don't require a Delivery vehicles, so we're not constrained to lipid nanoparticles that I do think ultimately complicate delivery and accessibility. That's important because I think a lot of times for those not familiar with LMPs, the chemistry that one would use to be compatible with an LMP versus what we can do to 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, but think of this 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 administration Being something that's potent and durable in terms of patients and safe as we think about being able to avoid off target at the day, bystander at the day and reversibility. So as 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 publication presentation, and I built that up through model.

Speaker 2

Now what's important in translation, you said, okay, well, how do we know this is And it translates what's giving us confidence is, I think the day to day, and I appreciate your recognition that that data is consequential that we've seen a post production. By starting in GalNec, what we're able to see is there is good precedence for that translation of thinking about human hepatocytes into rodent studies Into human, given that we've got a delivery agent in Galentech. And so we're going to learn a lot about the translational pharmacology, both on the disease and the new modality via that translation. And that's going to teach us 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 modalities in their translation to be able to start predicting where we think doses need to be as we get into the clinic.

Speaker 2

And that's important because as you said, we think about levels oftentimes of the protein in the in vivo studies like the fold increase off of baseline is the best way to start thinking about Relational potential and as we think about being able to increase the fold from baseline, so 7 fold from baseline. If we went back and looked at human studies, You're in the range of, I think, it's like 2.5 to 3 fold to 5 fold improvement that ultimately translate from these patients to Hematy. 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 the fold of editing is translating to fold protein production. That's giving us our confidence as we move into clinic. So like anything else, we do need to run that first study.

Speaker 2

I think we picked the right program With the right delivery tool to demonstrate 1st in class editing, but really excited as we go into September to talk about A multitude of opportunities beyond ATD, beyond just protein correction, beyond the liver That we're very excited to share with everyone and it will be a great opportunity to talk about the future of RNA aesthetic.

Speaker 7

Great. Can I have a follow-up question? So you have about $225,000,000 in development milestones from GSK on this AATV program. So starting Phase 1Q this year, How much of a milestone would you be expecting from that? Thank you.

Speaker 2

Great question on terms of as we alluded to We've got a number of development milestones beyond commercial milestones from GSK that come in over time. What we can't do obviously is break out those payments at various points. Obviously, as we receive them, there are opportunities where those are disclosed obviously in our financial statements. But Yes. Key is delivering this program into the clinic and beyond, which contributes milestone payments.

Speaker 2

Importantly, beyond AATD and I think that was another important feature is, there are a whole host of programs that are moving collectively with GSK beyond And it's important to note not only do we have those programs where GSK pays 100% of the R and D expenses as we're advancing them, But those also have milestones, both preclinical and clinical and commercial milestones. So as we think about the magnitude across the collaboration, There are multiple potential inflows coming from execution. And I think it's important as you said that those are not counted in our runway statement. So those would be accretive to our current cash position.

Speaker 7

Thank you.

Operator

Thank you. Our next call comes from the line of Asim Brana of Truist Securities. Go ahead.

Speaker 6

Good morning. This is Asim on for June. Thanks for taking the questions. My first question is, given that you've improved upon RNA Seemediate degradation, splice blocking ASOs, RNAi, RNA editing, all with your AIMIR platform. I'm just wondering if you have any plans to design guide RNAs with enhanced properties like stability and low off target cutting, basically to improve upon the hybrid DNA, RNA guide similar to those being used by Caribou.

Speaker 6

And as a follow-up question, just wondering, Maybe could you comment on the potential to use patients who've already received micro dystrophin gene therapy from a competitor for your N531 program? And I'm specifically referring to Sarepta's program. Thank you.

Speaker 2

Thank you. I mean, I think if we take the first question, as you pointed out, and I think it parallels Ian's question earlier, which is, we have made a substantial investment in building what we would view as best in class guidance. If we think about all of these opportunities And you've elegantly laid them out. All of them involve kind of this mechanism with RNA protein interaction, right? It's all about a guide RNA Interacting with a protein and exerting a biological and natural effect, whether that's cutting via RNA stage for 802, Whether that's exercising and utilizing the splicing machinery to generate protein correction or generate protein or RNA editing using Adar, I think the opportunity sets that's in front of us are a multitude.

Speaker 2

I think we're going to be focused on portfolio translation right now with this toolbox into meaningful medicine. However, as you've known in our history, we've always had through Various collaborations and internal research exercises, collaborations that have pushed us into new areas. So whether that's editing beyond data eye, whether or not that's Editing including as you said highly specific editing around other mechanisms whether it is DNA. While that's not our core capability, There are always opportunities that we have in being approached to by others and saying, what is the opportunity set that our proprietary chemistry can bring to other modalities. So we're not closed minded to say, this is all we do.

Speaker 2

We recognize that you can't always predict what's coming behind. But I think the key is and I think it's very important to say That we are focused on building out a therapeutic portfolio in the areas that we now want, particularly using our RNA and the capability. And that's where we're going to put our internal resources. Collaborations are great resources that we have in research payments that we can use into exploiting and exploring These other capabilities that our chemistry can present. Your last question, I would want a little bit of clarity because I think there are 2 Different components to it, which is where do we see N531 splicing and really exon skipping as we move it forward Relative to the newly approved gene therapy or whether or not it's potentially Combined, whether you can work in combination.

Speaker 2

So I think it's important as we think about demonstrating best in class editing, being able to deliver a highly specific, Stable, durable, skipping agent that doesn't require conjugates to get into cells to generate substantial amounts of exon skipping. Yes, I think we've got a very clear path in the exons that we hope to skip given our franchise. And I think seeing that translate and building that franchise is important. We know that gene therapy currently is only approved for 1 year of age for 4 to 5 year olds. So it's within that range And only in the U.

Speaker 2

S. Under an accelerated approval. So it's we're watching, we're paying attention to where that data is. There's kind of data for Coming at the end of this year really on the translation of that micro dystrophin. So I think like everybody else, while we all saw that 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.

Speaker 2

So I think there we're not going to take our eye off the ball and be distracted on not delivering functional dystrophin protein that we believe has based on our preclinical data, Based on following the Becker point, being able to ultimately see that the stacked protein when you create functional protein Demonstrates a benefit. Importantly as well as we think about the benefit of our skipping capability comes down to that question around our Which is different than others. I think sometimes within the enigma of talking about these companies, we think about Echolix on Skipping being kind of fairly similar. It's where it can go on There have been a number of companies trying to drive better distribution than skeletal muscle. What's important is that our construct Pre clinically, both in our double knockout model as well as non goparimate, actually have higher levels of exon skipping In the heart and the diaphragm.

Speaker 2

So as we think about ultimately being able to change the outcome for these boys' lives, it's not only by repairing and fixing muscle and improving What's most important to us is making sure we protect the heart and protect respiratory function. So as we think about the totality of what we can bring forward We're excited about what we can do with N531 and beyond and we'll continue to watch the field evolve in terms of micro dystrophin.

Speaker 6

Paul, thank you very much.

Speaker 2

Thank you.

Operator

Thank you. Our next call comes from the line of Salim Syed from Mizuho. Go ahead.

Speaker 8

Great. Thanks for the questions guys. Paul, just a few quick ones from us, just more clarification than anything here. So With the CTAs now being imminent, I'm sure you have some idea when we're getting data and I think folks have tried to ask it on the call, but I'll try to ask it maybe different. Is the baseline thinking here that we'll be able to get data in 2024?

Speaker 8

And also just curious when you'll be able to Is the Phase 1 trial design being shared this year or are we getting that also in 2024? On DMD, The functional endpoints that you've mentioned, do those have any bearing on whether this Phase 2 is registrational Or is it just going to be solely dependent on dystrophin levels? And then on 3, the wording in the press release, Seems like it changed a little bit versus the Q1. So I'm just curious, I think this time you guys added the word available Multi dose data versus last press release, the word available wasn't in the press release. This press release was additional single dose in any available multi dose.

Speaker 8

Last press release was additional single and multi dose. So curious what exactly has changed there in the multi dose side? Thank you. Excellent.

Speaker 2

All right. So if we start and thanks for the questions, Philippe. So we think about, and we'll just go right down in order, AATD, PMD, HD. So As it relates to the AATD timeline, as we said, the CTA submissions are imminent. Once we begin the trial, we can give a further update in terms of the Expectations for data.

Speaker 2

I think it's always important just to see that trial kick off. I think it's obviously safe to assume That data won't be in 2023 for that study. But looking forward, I think when you plan on what data we'll have as we move into 2024 It's something that we can provide updates on once that trial initiates. As it relates to DMD, you brought up the question on differentiation of Filing based on dystrophin and what functional data we have. I think 1st and foremost, and as we've seen from others, dystrophin will be a very important trigger for us in central filing, so getting that data is critical to us.

Speaker 2

What we have is the benefit and I'll let Anne Marie comment on As we think about function is the availability as we follow these boys not just from where the biopsies are, but really continue that study as we said both 24 weeks 48 weeks, we have an opportunity to measure a number of different functional endpoints and those don't only include the ambulatory, they include ability to look at respiratory So, Henry, I'll pause and let you answer any additional questions about potential filing around CMC data. And then I'll come back to H. D.

Speaker 4

Thanks, Paul. So, as you know, there is a well trodden regulatory pathway for filing with Dystrophin data, so we would expect that to be adequate. But of course, as Paul said, we're running the study through 48 weeks. So we'll of course be providing any of the Functional data available for that filing. Back to you, Paul.

Speaker 2

Great. And so on HD, On the call, we mentioned available data. I mean, the key is there's no change. Actually, we're excited that the multi dose is and that's the update is that the multi dose is underway in HD. So I think our update is being able to have available multi dose data while we have single dose data would be the update.

Speaker 2

I think it's Very big to say with that initiated that we would not expect full multi dose data in 2023. That's hence the available, But we'll be doing it better.

Speaker 8

Got it. Thanks guys. Just quickly, the Phase 1 trial my question was on the Phase 1 trial design. Are we getting that This year for 6 or is that something you also plan to share in 2024?

Speaker 2

No, I mean, we'll share the trial design once the study is Initiate, so that won't be it. That will be 2023. So I think that think about imminent filing and new updates, I think we'll be able to share the clinical trial plan, which to your questions will provide a lot more clarity as to timing of data as that study initiates.

Speaker 8

Perfect. Thanks so much guys.

Speaker 2

Okay. Thank

Operator

you. Thank you. The next call comes from the line of Jo Schwartz from Leerink Partners. Go ahead.

Speaker 9

Hi, it's Jenny on for Joe. Thanks for taking my question. I was just wondering if you guys have Commented on the stoichiometry of the antlers for RNA editing and how that compares to your other legos for exon skipping, molybdenum, etcetera. I guess what I'm really trying to get at is do you expect dosing to be in a similar range or higher, lower? And how does that influence how you guys are thinking about therapeutic index and any likelihood of potential dyssamine toxicity?

Speaker 2

Yes, I'll take the beginning and then I can turn some of that over to we'll see how I think as you mentioned, as we think about the stoichiometry, we just think about the pharma I think it's the better way of translational pharmacology of agar editing. It is a catalytic pathway. So we are able to harness the Catalytic mechanism within the enzyme. So to your point, we do see the advantages that come with that both on Being able to give smaller amounts of drugs that then be able to stay and that's where stability becomes such an important component of The drug is staying stable, not being degraded, staying in the cell and able to exert its effect. So it is catalytic as are a number of the mechanisms that we're utilizing.

Speaker 2

I think the other advantage as we think about AATD is by leveraging GalNec, we're getting we look at this a lot like other Yes. Potential siRNAs and approaches where you're using Galenic conjugated oligonucleotide to hepatocytes for the catalytic machinery. So I think we're seeing it Act very similar to other catalytic oligonucleotides in development. So this wouldn't be kind of Well, we don't get like, so key metric does where you have to give more and more drugs to try to exert an effect. So I think the catalytic efficiency of these enzymes is a huge advantage as We think about APeRS and we think about them a lot like we do RNAi.

Speaker 2

I don't know if there's other behavioral systematic

Speaker 10

No, this is a foundational technology benefit, right, looking at how you can use this Catalog machinery is to work to enable fast turnover kinetics. So that's really the basis. And to Paul's point, all these looking at catalytic issues, non stocking metrics.

Speaker 2

I think it's important too as we think about extra hepatic, We're not having to give large volumes to drug, particularly as we think too about being able to dose And other routes as we think about other tissues. So I mean, I do think that ultimately as we think about the AIMR platform, We should be thinking a lot like other financing capabilities like Martin.

Speaker 4

Great. Thank you. That's really helpful.

Speaker 2

Thank you.

Operator

All right. I'm showing no further questions at this Time, I would now like to turn the conference back to Doctor. Paul Bona for closing remarks.

Speaker 2

Thank you everyone for joining the call this morning. We've made significant progress advancing our pipeline and driving forward our leadership position in RNA medicines in the Q2. I am grateful to every Wave employee

Operator

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

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Earnings Conference Call
Wave Life Sciences Q2 2023
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