Q4 2019 Earnings Call

Hi.

Operator: Good morning, and welcome to the WAVE Life Sciences 4th quarter and full year 2019 conference call. At this time, all participants are in a listen-only mode.

[music].

Good morning.

And welcome to the weight life Sciences fourth quarter and full year 2019 conference call.

At this time all participants are in a listen only mode.

Operator: As a reminder, this call is being recorded and webcast. I will now turn the call over to Kate Rausch, Head of Investor Relations at WAVE Life Sciences.

As a reminder, this call is being recorded and webcast.

We'll now turn the call over to cake Roush head of Investor Relations and wave Life Sciences. Please go ahead.

Kate Rausch: Thank you, Operator. Good morning, and thank you for joining us today to discuss our recent business progress and review WAVE's fourth quarter and full year 2019 Operating Results. With me here today is Dr. Paul Bolno, our president and CEO; Dave Guerrero, Interim CFO; and Dr. Mike Panzaro, WAVE Chief Medical Officer.

You operator.

Hi, good morning, and thank you for joining us today to discuss our recent business progress and review its fourth quarter and full year 2019 operating results.

With me here today is dr.

Couple Bono.

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Our president and CEO.

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And Dr. my friends airwaves Chief medical.

Right.

Kate Rausch: This morning, we issued a news release detailing our fourth quarter and full year results. Please note that this news release and the slide presentation that accompanies this webcast are available in the Investors section of our website, www.wavelife.org. 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 a number of risks and uncertainties that could cause our actual results to differ materially from those described in these forward-looking statements. 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, 2019. We undertake no obligation to update or revise any forward-looking statement for any reason. I'd now like to turn the call over to Paul Bolno, President and CEO of WAVE Life Sciences Ltd.

This morning, we issued a news release detailing.

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Corporate are in full year results.

Note that this news release and a slide presentation that accompanies this webcast.

The other one investor section other website www Dot Weve life Sciences Dot com.

Before we begin.

Okay.

I'd like to remind you that discussions during this conference call will include forward looking.

Okay.

These statements are subject to a number of risks and uncertainties that could cause our actual results.

I'll defer to.

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Those described these forward looking statements.

The factors that could cause actual results to differ are discussed in the press release issued today and then are I think he.

Excluding our annual report on form 10-K for year ended.

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Firstenergy.

We undertake no obligation to update or revise any forward looking statement for any.

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I'd now like to turn the call over the call Bono, President and CEO with my size Huh.

Thank you Kate good morning, and thank you for joining us today I'll start todays call with a few introductory remarks and a comp.

Paul B. Bolno: Thank you, Kate. Good morning, and thank you for joining us today.

Paul B. Bolno: Next, Steve Baiero will discuss our financial results, and then Mike Panzara will provide an update on our PrecisionHD development program. I'll conclude with an update on our ADAR-mediated RNA editing program and an outlook for 2020. WAVE is a genetic medicines company that was founded to design and develop novel oligonucleotide therapeutics using our proprietary PRISM platform. This unique platform enables us to design therapeutics in a rational way through a deep understanding of how the interplay among sequence, chemistry, and stereochemistry impacts key pharmacologic properties. Over the past decade, our chemistry has progressed and evolved, enabling us to build a broad pipeline that includes different modalities, a range of disease targets, and innovative properties such as unique backbone modifications, allele-selective designs, and novel modalities like RNA editing.

Okay.

Next Steve barrel will discuss our financial results and then Mike and zero will provide an update on.

Precision HD.

No.

Yes.

I'll conclude with an update on our eight our.

Arnie editing program at an outlook for 24.

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We have in genetic medicines company that was founded to design and develop novel Oligonucleotide therapeutics using our proprietary.

Okay.

Oh.

It's unique platform enables us to design therapies any rational way through a deep understanding of how the interplay among sequence chemistry.

That's true.

Yes.

Deep pharmacologic properties.

Over the past decade, our chemistry has progressed in evolve, enabling us to build the broad pipeline.

That includes.

Yeah.

Different modalities a range of disease targets.

And innovative properties, such as you need backbone modifications or wheel selective designs and novel modalities like Arnie editing.

Going forward, we will continue to innovate and expand our pipeline.

Paul B. Bolno: Going forward, we will continue to innovate and expand our pipeline. The foundation of this pipeline is our work in CNS, including Huntington's disease, ALS, and FTD, and several programs in collaboration with our partner Takeda. Over the course of our relatively short history, we've moved three programs into clinical development and have embraced and been humbled by the learnings that have come out of these and other programs along the way.

The foundation of this pipeline is our work in CNS, including Huntingtons disease, and less than FTD and several programs in collaboration with our partner Takeda.

Over the course of our relatively short history, we've moved three programs into clinical development and have embraced and been humbled by the learnings that have come out of these and other programs along the way.

Paul B. Bolno: Our dedicated and experienced team is actively preparing to advance two additional programs into clinical development in the second half of this year. Finally, we have established internal manufacturing capabilities that enable us to produce oligonucleotides to support our platform, preclinical work, and clinical development and provide us with increased control and visibility of our drug substance supply chain. Using PRISM, we leverage the ability to control stereochemistry of each backbone position of an oligonucleotide to rationally design potential therapeutics. Validating the importance of backbone structure to controlling RNA age activity, we have demonstrated the X-ray crystal structure, which we initially presented at our research day last October.

Our dedicated an experienced team is actively preparing to advance to additional programs into clinical development in the second half of this year.

Finally, we have established internal manufacturing capabilities that enable us to produce are going to be tied to support our platform preclinical work and clinical development and provide us with increased control and visibility of our drug substance supply chain.

Using prism, we leverage the ability to control Syria chemistry of each backbone position of an elegant nucleotides two rationally designed potential therapeutics.

Validating the importance of backbone structure to controlling Arnie age activity, we have demonstrated the X ray Crystal structure, which we initially presented at our research day last October.

Paul B. Bolno: As seen on the slide, the image depicts RNA phage bound to a heteroduplex containing a C9ORF72 mRNA target in red and a stereopure oligonucleotide in blue. Controlling the activity of RNase H is paramount to allele selectivity, the core differentiating feature in our Huntington's disease program, where we have designed compounds including WVE-120-101 and WVE Similarly, we have designed stereopure oligonucleotides with a transcript-selective approach for our C9ORG72 program aimed at treating ALS and FTD. During the fourth quarter and recent months, we have made important progress in advancing our two clinical programs for hunting, our CNS-focused pipeline of stereopure oligonucleotides, and our proprietary PRISM platform. Our Huntington's disease programs, Precision HD1 and Precision HD2, are the first and only in clinical development that are designed to selectively lower mutant Huntington protein while leaving wild-type Huntington relatively intact.

As seen on the side the image to pick R&D stage found to a head roads duplex containing 89 or 72, marni target and read any stereo pure really good nucleotide and blue.

Controlling the activity of our newest age is paramount to a wheel selectivity the core differentiated eating feature in our Huntingtons disease program, where we have designed compounds, including WB 121, or one and WB 121, or two to target single nucleotide polymorphism for Smith to select.

Typically lower than having to.

Similarly, we have design stereo pure oligonucleotides, where the transcript selective approach for our Cnine or 72 program aimed at treating Ala Moana TV.

During the fourth quarter and recent months, we have made important progress in advancing our two clinical programs for Huntingtons disease.

Our CNS focused pipeline of stereo pure oligonucleotides, and our proprietary prism platform.

First our huntingtons disease programs precision HD, one and persistent HD too are the first and only in clinical development that are designed to selectively lower using huntington protein, while leaving wild type Huntington relatively intact.

Paul B. Bolno: Wild-type Huntington is important for neuronal function, and there is increasing evidence that it is an essential protein for basic health, both in the central nervous system and in the systemic. At the end of last year, we reported the first results from our ongoing Precision HD2 clinical trial in Huntington, which demonstrated mutant Huntington reduction and no change in total Huntington as compared to placebo, as well as a safety profile that supported advancing to higher doses. Mike Pinzera will provide further updates on these programs later in the call.

Wild type Huntington is important for intermodal function and there is increasing evidence that wild type Huntington isn't a central protein for basic health, both in the central nervous system and systemically.

At the end of last year, we reported the first results from our ongoing precision AG two clinical trial in Huntingtons disease, which demonstrated mutant Huntington reduction and no change in total Huntington as compared to placebo as well as the safety profile that supported advancing to higher dose.

I couldn't there will provide further update on these programs later in the call.

Rounding out our HD portfolio is our son to three program, which is on track to initiate clinical development in the second half of the year.

Paul B. Bolno: Rounding out our HD portfolio is our SNP3 program, which is on track to initiate clinical development in the second half of the year. Approximately 40% of the HD population has a SNP3 mutation, and with overlap, up to 80% of the HD population carries at least one of SNP1, 2, and or 3. Last week, we presented our SNP3 preclinical, in vitro, and in vivo preclinical data at the CHDI, and we are excited to introduce this program into our portfolio. Our next program, also approaching the clinic, aims to address amyotrophic lateral sclerosis and frontal temporal dementia caused by mutations in the C9ORF72 gene. Our C9 program is designed to selectively and potently silence the transcripts that contain the hexonucleotide repeat, which drives the formation of toxic RNA and abnormal proteins in brain cells.

Approximately 40% of the age depopulation heavy snip, three mutation and with overlap up to 80% of the HD population carries at least one of snip, one two and two or three.

Last week, we presented our snip three preclinical in vitro and Invivo preclinical data at the CHD I'd conference and we're excited to introduce this program into our portfolio of clinical programs for the potential treatment.

Yeah.

Our next program also approaching the clinic aims to address it might trophic lateral sclerosis, and frontotemporal dementia caused by mutations in the C nine or 72 G.

Our Cnine program is designed to selectively and Potently silenced the transcript that contain the hickson nucleotide repeat which drives the formation of toxic, earning an abnormal proteins and brain tissue.

Paul B. Bolno: Like our SNP3 program, we have used transgenic mouse models to help guide our preclinical development. In these in vivo studies, we've shown potent knockdown of both the repeat-containing transcript and dipeptide while the C9ORF72 protein is present. We continue to advance our C9RF72 program and are on track to initiate clinical development in the second half of the year. Additionally, we continue to develop multiple preclinical CNS programs with our partner Takeda, targeting CNS diseases such as Parkinson's and Alzheimer's. As a reminder, our agreement with Decatur included $230 million in committed capital, which includes at least $60 million in research support to advance multiple preclinical targets over the term of the collaboration. Last year, we achieved target validation in vivo with a lead compound for one of the programs and expect two more in 2020. As shown on the slide, we highlight in vitro and in vivo results from an undisclosed target that we are working on in the collaboration. In vitro, we demonstrated that our compound is 16 times more potent than a stereo random record. In vivo, we've seen similar potent target knockdowns with good durability out to eight weeks of treatment.

Like our son of three program, we've used transgenic mouse models to help guide our preclinical development.

In these in vivo studies, we've shown potent knockdown of both the repeat containing transcript and that peptide while the Cnine hundred 72 protein is preserved we continue to advance our seen on or 72 program and are on track to initiate clinical development in the second after the year.

And we continue to develop multiple preclinical CNS programs with our partner Takeda targeting CNS diseases, such as Parkinsons and also numbers.

As a reminder, our agreement with Takeda included $230 million in committed capital, which includes at least $60 million in research support to advance multiple preclinical targets over the term of collaboration.

Last year, we achieve target validation in vivo with a lead compound for one of the program and expect to more in 2020.

As shown on the slide we highlight in vitro and in vivo results from an undisclosed target that we are working on it and the collaboration.

In vitro, we've demonstrated that our compound to 16 times more potent than these stereo random reference comes.

Nvvault, we've seen similar potent target knockdown with good durability out the research treatment.

Beyond CNS in 2019, we continue to work on two ophthalmology programs us to aid for ushers syndrome type two way and rupee 23 age for retinitis Pigmentosa.

Paul B. Bolno: Beyond CNF,

Paul B. Bolno: In October 2019, we presented in vitro and ex vivo preclinical data on our ASH2A program, which is designed to promote ASH2A exon 13 cells, and in vitro data on our Rho P23H program, which is designed to selectively silence Rho P23H transmission. We continue to explore opportunities to advance our work in ophthalmology. We have also continued to evolve our prison platform in 2019. Through PRISM, we can design and optimize a diverse set of stereopure oligonucleotides, which allows us to characterize and compare the behavior of various stereoisomers. With each target and a growing body of in vitro, in vivo, and clinical data from our programs, we gain insight into how the interplay between sequence, chemistry, including two prime modifications in backbone chemistry, and stereochemistry impacts activity.

In October 2019, we presented in vitro and ex vivo preclinical data on our us to a program, which is designed to promote attached to a Exxon 13 skipping.

And in vitro data on our ROE V 23 age program, which is designed to selectively silence rupee 23 age transcripts.

We continue to explore opportunities to advance our work in ophthalmology.

We've also continued to evolve our prison platform in 2019.

Through prism, we can design and optimized diverse set of stereo pure oligonucleotides, which allows us to characterize and compare the behavior of various stereo isomers.

With each target and a growing body of in vitro and vivo and clinical data from our programs, we gain insight into how the interplay between sequin chemistry, including two probably modifications and backbone chemistry and stereo chemistry impacts activity.

Paul B. Bolno: Most importantly, we build these learnings into future programs. For example, our SNP3 and C9-ORF72 programs are both designed with optimized chemistry off our platform. One of the exciting new developments to come out of our PRISM platform is our ADAR RNA editing modality, which I'll touch on more later in the call. While WAVE had many accomplishments in 2019, we also had an unexpected and disappointing setback in the fourth quarter with our DMV program. We are committed to better understanding the accompanying clinical data and incorporating any learnings into future programs. We are also committed to sharing these clinical data with the Duchenne community and others, and we'll have additional results analyzed in time for presentation at the Muscular Dystrophy Association Conference at the end of this month. In summary, WAVE has an innovative and differentiated pipeline led by our CNS development programs, including two Approaching the Clinic programs, which positions WAVE to potentially have four clinical programs in 2021. With that, I'll turn the call over to Dave Guerrero to review our fourth quarter and full year financial report. Okay.

Most importantly, we build these learnings into future programs for example, our snipped three and see nine or 72 programs are both designed with optimize chemistry our platform.

One of the exciting new developments to come off of our prison platform is our radar ornate editing modality, which I'll touch on more later in the call.

Well, we've had many accomplishments in 2019, we also had an unexpected and disappointing set back in the fourth quarter with our DMD program.

We are committed to better understanding the super nursing clinical data and incorporating any learnings into future programs.

We're also committed to sharing these clinical data with the Duchenne community and others and we'll have additional result, analyze and time for presentation at the muscular Dystrophy Association conference at the end of this month.

In summary wave has an innovative and differentiated pipeline led by our CNS development programs, including two approaching the clinics, which positions wave to potentially have four clinical program in 2021.

With that I'll turn the call over to Dave payer owed to review, our fourth quarter and full year financial results Dave.

Thanks, Paul for the fourth quarter 2019, we reported a net loss of $56.8 million compared to $37.9 million for the same period in 28.

Dave Guerrero: Thanks Paul. For the fourth quarter of 2019, we reported a net loss of 56.8 million dollars compared to 37.9 million dollars for the same period in 2018. We reported a net loss of $193.6 million for the year ended December 31, 2019, compared to $146.7 million for the year ended December 31, 2018. The increase in net loss in the fourth quarter and full year was largely driven by increased research and development efforts and continued organizational growth, both of which included costs and efforts, including manufacturing, in preparation for the potential commercialization of subadherence. Research and development expenses were $49.1 million in the fourth quarter of 2019 compared to $39.8 million for the same period in 2018. Research and development expenses for the full year were $175.4 million compared to $134.4 million for the prior year.

We reported a net loss of $193.6 million for the year ended December 31st 2090 compared to $146.7 million for the year ended December 30, Onest 28.

The increase in net loss in the fourth quarter and full year was largely driven by increased research and development efforts and continued organizational growth.

Both of which included cost and efforts, including manufacturing in preparation for the potential commercialization distributors.

Research and development expenses were $49.1 million in the fourth quarter 2019, compared to $39.8 million for the same period and 28.

Research and development expenses for the full year were $175.4 million compared to $134.4 million for the prior year.

The increase in research and development expenses in the fourth quarter and full year was primarily due to increased external expenses related to our clinical activity.

Dave Guerrero: The increase in research and development expenses in the fourth quarter and full year was primarily due to increased external expenses related to our clinical activities, including our HD programs and our now discontinued DMD programs, as well as increased investments in PRISM and other research and development experts. General and administrative expenses were $13.8 million for the fourth quarter of 2019, compared to $12.8 million for the same period in the prior year. General and Administrative Expenses were $48.9M in 2019, compared to $39.5M in 2018. The increase in general and administrative expenses in the fourth quarter and full year was mainly driven by our continued organizational growth to support WAVE's 2019 corporate goals. We ended 2019 with approximately $147 million in cash and cash equivalents.

Including our HD programs and are now discontinued DMD program.

As well as increased investments in prism and other research and development expenses.

General and administrative expenses were $13.8 million for the fourth quarter 2019, compared to $12.8 million for the same period in the prior year.

General and administrative expenses were $48.9 million in 2019 compared to $39.5 million in 2018.

The increase in general and administrative expenses in the fourth quarter and full year was mainly driven by our continued organizational growth to support waves 2019 corporate goals.

We ended 2019 with approximately $147 million in cash and cash equivalents.

While our cash utilization rate in the first quarter of 2020 will benefit from some wind down of Dnbi spend there will also be costs associated with the termination of this program in the first quarter 2020.

Dave Guerrero: While our cash utilization rate in the first quarter of 2020 will benefit from some wind-down of DMV spending, there will also be costs associated with the termination of this program in the first quarter of 2020. We expect to begin to realize the result of our overall cost reduction efforts, including our workforce reduction, in the second quarter of 2020. We expect that our existing cash and cash equivalents, together with expected and committed cash from existing collaborations, will enable us to fund our operating and capital expenditure requirements into the third quarter of 2021. I will now turn the call over to Dr. Michael Panzara, our Chief Medical Officer, who will provide an update on our clinical development program. Mike.

We expect to begin to realize the results of our overall cost reduction efforts, including our workforce reduction in the second quarter 2020.

We expect that our existing cash and cash equivalent together with expected and committed cash from existing collaboration will enable us to fund our operating and capital expenditure requirements into the third quarter of 2021.

I'll now turn the call over to Dr., Michael Pandora, Our Chief Medical Officer, who will provide an update on our clinical development program Mike.

Thanks, Dave and thanks to all of your for joining the call today.

Michael Linden: Thanks Dave, and thanks to all of you for joining the call today. From the start, we set out to develop an allele-selective approach to treat Huntington because we felt preserving wild-type Huntington was going to be essential to impacting clinical outcomes of the disease. As you know, patients with Huntington's disease have an expanded CAG triplet repeat in their Huntington gene, which results in the production of a mutant Huntington protein. However, Huntington's patients still possess wild-type or healthy protein as well, which is important for neuronal function, and some components of Huntington's disease are likely caused by the wild-type loss. Two recent publications over the past few months are worth highlighting today as they support wild-type Huntington's loss of function as a likely driver of HD pathogenesis.

From the start we set out to develop in a legal selective approach to treat huntingtons disease.

Because we felt preserving mild type huntington was going to be essential to impacting clinical outcomes of the disease.

As you know patients with Huntingtons disease have an expanded see AG trip repeat and their Huntington gene, which results in the production of the mutant Huntington protein.

However, huntingtons patients still possess well type are healthy hum healthy protein as well, which is important for neuronal function in some components in Huntington disease unlikely caused by the wild type loss of function.

Two recent publications over the past few months are worth highlighting today, they support wild type huntingtons loss of function as a likely driver of HD pathogenesis, specifically, one publication concluded that a steroid them specific.

Michael Linden: Specifically, one publication concluded that a striatum-specific defect in synaptic vesicle endocytosis was corrected by overexpression of wild-type Huntington, but not by lowering total Huntington. A second publication concluded that striatal projection neurons require Huntington for motor regulation, synaptic development, cell health, and survival during aging. Loss of hunting instruction could therefore play a critical role in hunting. Both of these publications support previous literature that we've discussed around the importance of wild-type hunting.

Defect and snapped Invesco Indosat ptosis was corrected by over expression of wild type huntingtown, but not by lowering total Huntington a second publication concluded that steroidal projection neurons require Huntington for motor regulation synaptic development sell health and survival during aging.

Loss of funding reduction could therefore play a critical role and chronic disease.

Both of these publications support previous literature that we've discussed around the importance of wild type Huntington.

Also just last week I attended the 15th annual CHS YOD Conference, where I was privileged to have the opportunity to meet with many of the world's experts in HD and you hear about much of the cutting edge research underway in this disease area.

Michael Linden: Also, just last week, I attended the 15th annual CHDI conference where I was privileged to have the opportunity to meet with many of the world's experts in HDI and to hear about much of the cutting-edge research underway in this disease area. During the meeting, an entire session was dedicated to understanding the importance of wild-type Huntington in the normal and diseased states and the effects of modulation in vitro and in vivo. From this session and the WAVE team's other discussions at the meeting, we gathered several critical takeaways.

During the meeting an entire session was dedicated to understanding importance of wild type Huntington and the normal and disease states in the effects of modulation in vitro and in vivo.

From this session and the wave teams other discussions at the meeting we gathered several critical takeaways.

Michael Linden: First, there were multiple presentations supporting that wild-type Huntington has numerous critical functions throughout life, such as intracellular trafficking, cell-to-cell adhesion, and BDNF transmission. Next, near-elimination of wild-type Huntington in mice was detrimental regardless of when suppression began, suggesting a critical role for the protein throughout life in addition to its well-known importance in embryonic and early development. Finally, in the study of non-HG patients, Huntington protein loss of function mutations are highly constrained, which suggests evolutionary pressure against such loss of function mutations, again speaking to the importance of the healthy Huntington protein. While we and the community continue to learn more about the many different roles of this essential protein, there is no doubt as to its importance.

First there were multiple presentations supporting the wild type that wild type Huntington has numerous critical function throughout life, such as films intra cellular trafficking cell to cell adhesion and bdnf transport.

Next near elimination of Wild type Huntington in mice was detrimental regardless of when suppression began suggesting a critical critical role for the protein throughout life. In addition to its well known importance and embryonic in early development.

Finally in the study of non agency patients Huntington protein loss of function mutations are highly constrain, which suggests evolutionarily evolutionary pressure against such loss of function mutations again speaking to the importance of the healthy coming through protests.

While we and the community continued to learn more about the many various roles of this essential protein there is no doubts as to its importance.

Michael Linden: Turning to an update on our clinical studies, beginning with the PRECISION-HD2 study of WAVE 120102. As a reminder, PRECISION-HT2 is our phase 1b2a multicenter randomized double-blind placebo-controlled trial that is evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of WVE120102 in adult patients with early manifest HD, euk The trial includes both single and multi-dose portions where patients are randomized to either WVE120102 or placebo and receive a maximum of four total intrathecal doses. After a single dose of treatment, patients undergo a washout period before entering the multi-dose portion of the trial.

Turning to an update on our clinical studies, beginning with the precision agency to study of wave, one two or one or two.

As a reminder, precision issue too is our phase one be to a multi center randomized double blind placebo controlled trial, which is evaluating safety tolerability pharmacokinetics and pharmacodynamics of single and multiple doses WV, one two or one or two adult patients with early manifest HD.

Who carrier targeted single nucleotide polymorphism Rs 306 to 331 that we referred to as snip too.

The trial includes both single and multi dose portions where patients are randomized to either WB, one two or one or two or placebo and receive a maximum of for total intrathecal doses.

After a single dose of treatment patients undergo a washout period before entering multi dose portion of the trial.

In December of last year, we announced initial data from this trial, which clearly demonstrated target engagement with an ability to dose higher to maximize the effects.

Specifically, there was a 12.4% reduction mutant hunting and protein into CSF when comparing all patients treated with multiple doses of one two or one or two to those treated with placebo.

Michael Linden: In December of last year, we announced initial data from this trial, which clearly demonstrated target engagement with an ability to dose higher to maximize the effect. Specifically, there was a 12.4% reduction in mutant hunting and protein in the CSF when comparing all patients treated with multiple doses of 120102 to those treated with placebo. These mutant Huntington reduction results, coupled with the favorable safety profile observed, supported continued dose escalation in the PRECISION HD2 study. In January, we initiated the 32 milligram cohort of the PRECISION-HG2 trial, and we look forward to sharing the results from this cohort, which is on track to be available in the second half of this year. The ability to go beyond this dose level will be determined by the single dose safety results of the 32 milligram cohort, as well as our existing preclinical data.

These mutant Huntington reduction results, coupled with the favorable safety profile observed supported continued dose escalation in the precision HD to study.

In January we initiated the 32 milligram cohort of the precision AG two trial and we look forward to sharing the results from this cohort which is on track to be available in the second half of this year.

The ability to go beyond this dose level will be determined by the single dose safety results of 32 milligram cohort as well as our existing preclinical data package.

And open label extension trial or oil Lee for the patients that participated in the precision issue to study is ongoing.

Based on the preliminary clinical data announced last year, we are working to amend the oily to enable all patients to receive the highest doses tested in our precision HG to study.

The precision AG.

One study comes next turning to one to a 101, which is being investigated in the ongoing precision AG one trial.

This trial also enrolled early manifest HD patients, who carry different snip Rs 306 to three or seven or us snip one.

Michael Linden: An Open-label Extension Trial, or OLE, for the patients that participated in the PRECISION-HG2 study is ongoing. Based on the preliminary clinical data announced last year, we are working to amend the OLE to enable all patients to receive the highest doses tested in our PRECISION-HG2 study. The PRECISION-HD1 study comes next, turning to 120101, which is being investigated in the ongoing PRECISION-HD1 trial. This trial also enrolled early manifest HG patients who carry a different SNP, RS-362307, or SNP1. Based on the PRECISION-HT2 initial results, PRECISION-HT1 has remained blinded, and we are working diligently to initiate a 32-milligram cohort. We remain on track to deliver top-line results for PRECISION-HT1, including those from the 32-milligram cohort, in the second half of 2020. NOLE for patients who participated in the PRECISION-HD1 trial was just initiated in February for patients who, similar to patients, as I mentioned, who participated in this trial. Similar to the Precision HD2 OLE, our goal is to enable patients with Precision HD1 OLE to be treated with the highest possible doses tested in the PrecisionHD1 study.

Based on the precision issue to initial results precision AG. One has remain blinded and we're working diligently to initiating 30 milligram cohort we remain on track to deliver top line results for precision AG, one, including those from the 32 milligram cohort in the second half of 2020.

And I'll leave for patients who participated in the precision AG. One trial was just initiated in February for patients that persist similar.

For patients as I mentioned to participate in this trial.

Similar to the precision AG two overly our goal is to enable patients and the precision 81 overly to be treated with the highest possible doses tested.

In the precision HC one study.

With that I'll hand, the call back over to Paul Paul Thanks, Mike.

Latest modality, earning editing, which we initially announced that our research day last year continues to advance.

We have developed this program over a relatively short period of time and while it's still early we believe our technology can for several advantages over other players in the emerging Arnie editing field.

Michael Linden: With that, I'll hand the call back over to Paul. Okay?

2019, our team evaluated more than 1000, oligonucleotides assessing a variety of sugar or based modification backbone chemistry, and stereo chemistry as well as other parameters to gain insight into the relationship between an elegant nucleotide structure and its eight our activity.

Paul B. Bolno: Thanks.

Paul B. Bolno: Thanks, Mike. Our latest modality, RNA editing, which we initially announced at our research day last year, continues to advance. We've developed this program over a relatively short period of time, and while it's still early, we believe our technology confers several advantages over other players in the emerging RNA editing field. In 2019, our team evaluated more than 1,000 oligonucleotides, assessing a variety of sugar or base modifications, backbone chemistry, and stereochemistry, as well as other parameters to gain insight into the relationship between an oligonucleotide WAVE's approach to RNA editing has several advantages over... First, our oligonucleotides freely enter cells and do not require lipid nanoparticles for viral delivery. Second, our oligonucleotides are based on prisms, so they are fully chemically modified and stereopure.

Waves approach to Arnie editing has several advantages over others first our oligonucleotides freely cancer cells and do not require liquid nanoparticles for viral delivery.

Second our oligonucleotides are based on prism. So they are fully chemically modified and stereo pure.

And finally, our holdings of nucleotides recruit in darkness, Arnie editing enzyme eight are no exception is proteins, such as casnine or comerica eight are needed.

Most recently our team presented a poster at the inaugural International conference on base editing enzymes and application.

These results have demonstrated that we can achieve editing efficiencies of up to 70% across primary human cell line can be true.

Paul B. Bolno: And finally, our oligonucleotides recruit the endogenous RNA editing enzyme, ADAR, so no exogenous proteins such as Cas9 or chimeric ADAR are needed. Most recently, our team presented a poster at the inaugural International Conference on Base Editing Enzymes and Applications. These results demonstrated that we can achieve editing efficiencies of up to 70% across primary human cell lines. Additionally, as seen on the right side of the slide

Additionally, as seen on the rate of side of the side.

We've achieved editing across several distinct R&D transcript validating the technology across multiple sequences in vitro.

We will begin in vivo studies in the near future for this program and look forward to sharing results. This year, which will guide our initial therapeutic program.

Importantly, we believe these will be the first in vivo Arnie editing data using endogenous aydar with Galnac conjugate.

Paul B. Bolno: We've achieved editing across several distinct RNA transcripts, validating the technology across multiple sequences. We will begin in vivo studies in the near future for this program and look forward to sharing results this year, which will guide our initial therapeutic program. Importantly, we believe this will be the first in vivo RNA editing data using endogenous ADAR with Galnet content. In summary, 2020 is a year of execution.

In summary, 2020 of the year of execution in the first months of this year. We've initiated the 32 milligram cohort for precision HD to study and right size our organization, ensuring that we have the right team in place to continue and expand clinical development advance our preclinical portfolio and sustain a leading nucleic.

Acid discovery engine.

In this first half our team is focused on completing the preclinical and manufacturing activities required to submit to clinical trial application in the second half of the year.

Paul B. Bolno: In the first months of this year, we initiated the 32 milligram cohort for our Precision HD2 study and right-sized our organization, ensuring that we have the right team in place to continue and expand clinical development, advance our preclinical portfolio, and sustain a leading nucleic acid discovery. In this first half, our team is focused on completing the preclinical and manufacturing activities required to submit two clinical trial applications in the second half of the year. As I just discussed, we'll have data to share from our first in vivo studies for our ADAR RNA editing program. Moving to the second half of the year, we'll have data readouts from the 32 milligram cohorts of our PRECISION-HD1 and PRECISION-HD2 trials. We continue to explore opportunities to advance our two ophthalmology programs and look forward to sharing our progress.

As I just discussed will have data to share from our first in vivo studies for our eight R&D editing program this year.

Moving to the second half of the year, we'll have data readouts from the 32 milligram cohorts of our precision HD, one and persistent HC two trial.

We continue to explore opportunities to advance our two ophthalmology programs and look forward to sharing our progress with you.

We'll also continue to events multiple preclinical CNS programs in collaboration with Takeda.

Looking to 2021, we anticipate having four clinical programs ongoing including the potential for pivotal trials within our HD portfolio.

In 2022, and beyond we and our partner Takeda will be positioned to deliver multiple potential DTA filings each year.

We will also have the first clinical data from our Sixthree Cnine or 72 program, both of which have been optimize without prism chemistry.

Paul B. Bolno: We'll also continue to advance multiple preclinical CNS programs in collaboration with the CADA. Looking to 2021, we anticipate having four clinical programs ongoing, including the potential for pivotal trials within our HG portfolio. In 2022 and beyond, we and our partner Takeda will be positioned to deliver multiple potential CTA filings each year. We'll also have the first clinical data from our SNP3 and C9-ORF72 programs, both of which have been optimized with our PRISM chemistry. In addition, we expect to transition ADAR RNA editing from a platform capability to delivering multiple programs by that time. Finally, we are capitalized to accomplish this exciting and innovative work ahead of us. And with that, we'll open up the call for questions. Operator?

In addition, we expected transition eight our R&D editing from a platform capability to delivering multiple programs by that time.

Finally, we are capitalized to accomplish this exciting and innovative work in front of them.

And with that we'll open up the call for questions operator.

At this time I would like to inform everyone. If you would like to ask a question. Please press Star then the number one on your telephone keypad.

Well pause for just a moment somehow the Ken a roster.

Your first question comes from the line of step Kids Pepper dining A.H.C. Wainwright.

Good morning, Thanks for taking the call. This is airing on for Debjit I just wanted to ask how many patients would you need dose at the 32 milligram dose cohort to escalate and how many patients in that cohort might we expect an update on in the second half.

So hi, this is Mike.

From the as you know each cohort has 12 patients a plan to be dose and we would expect that in the second half of this year. We present the full data set from all cohort.

Operator: At this time, I would like to inform everyone that if you would like to ask a question, please press star, then the number 1 on your telephone keypad. We'll pause for just a moment to compile the Q&A roster. Your first question comes from the line of Debjit Chappadaye with HC Wayne White.

Okay.

And on the first part how many would would you need to dose do you need dose everyone in the cohort to escalate work based on our intention is to our intention is to dose the complete cohort were not going to be.

Aaron: Morning. Thanks for taking the call. This is Aaron from DebJet.

Dosing less than what we are intended to.

Okay, all right great. Thank you.

Michael Linden: I just wanted to ask, how many patients would you need to dose in the 32 mg dose cohort to escalate, and how many patients in that cohort might we expect an update on in the second half?

I'll get back into queue.

Your next question comes from the line of Whitney I can with Guggenheim Securities.

[laughter].

I mean on for Whitney.

Hi, good on the pursued an answer to your question trials.

Michael Linden: So hi, this is Mike. From, as you know, each cohort has 12 patients planned to be dosed, and we would expect that in the second half of this year, we would present the full data set from all cohorts.

Do you feel you providing more information on you guys. That's hard on very generic update.

Turning to make dose and as you guys hopefully provide safety update servier.

I I you broke up there in your call. This is Mike again, I believe you were asking if we'd be providing interim updates throughout the year in the 32 or if we go higher our intention as I said is too.

Michael Linden: And on the first part, how many would you need to do?

Michael Linden: Our intention is to dose the complete cohort, so we're not going to be dosing less than we intended to.

Second half of this year provide you with an update on the progress of the stuff.

Aaron: Okay. All right. Great. Thank you. I'll get back in the queue.

Got it and then one follow up on the Essen Pete three Centsthree trial can you guide can you provide more details around trial design. There I guess, how do you plan to design a trial versus an HD studies.

Operator: Your next question comes from the line of Whitney Igen with Guggenheim Securities.

Evan: This is Evan speaking on behalf of Whitney. Just again, on the PrecisionHD trials, will UBI be providing more information on if you guys dose higher than 32 mg? And as you dose up, will you provide safety updates through the year?

Hi, This is Mike again, I mean, what we're doing now is I'm obviously the.

Designing that trial will be based upon the final profile that we evaluate with preclinical work, which is ongoing so more to come later in the year on that.

Got it thank you.

Your next question comes online as many for Harwood SVB lingering.

Michael Linden: I you broke up there in your call. This is Mike again. I believe you're asking if we'd be providing interim updates throughout the year in the 32 or if we go higher. Our intention, as I said, is to provide you with an update on the project in the second half of this year.

Hi, guys. Thanks for taking my question I got two quick ones. So does the oligo for snips three use a similar or not identical backbone chemistry as the first two steps.

Michael Linden: And then one follow-up, on the SNP3, SNP3 trial. Can you provide more details around trial design there? I guess, how do you plan to design this trial versus precision HD studies?

Are there any my been many modifications that you've made the you did you continue to extract some learnings from that program.

And then the second question.

Michael Linden: This is Mike again. What we're doing now is obviously the design of that trial will be based upon the final profile that we evaluate with preclinical work, which is ongoing. So more to come later in the year.

How should we think about the tempo of preclinical assets in the Takeda partnership moving into the clinic do you anticipate advancing all six targets other sort of like.

Gauge the state stake eating the getting.

Evan: Got it. Thank you.

How do you have to do I, just trying to think about the timeline of those getting in the clinic.

Operator: Your next question comes from the line of Mani Foroohar with SVB Linguistics.

And the scale of any potential milestone cash flows as they've become early clinical assets.

Mani Foroohar: Hey guys, thanks for taking my question. I have two quick ones.

Paul B. Bolno: So does the oligo for SNP3 use a similar or identical backbone chemistry as the first two SNPs? Are there any modifications that you've made as you continue to extract some learnings from that program? And then, the second question, how should we think about the pace of preclinical assets in the Takeda partnership? Moving into the clinic, do you anticipate advancing all six targets? All this sort of like that.

So to answer your first question relating to the design of Symthree I mean, as we said on the call. We've we've leveraged what we've learned around the prison platform with new to prime modification backbone designs in the interplay with Sarah chemistry, and so the three has a different design than that for one and two.

And that gives a different profile pharmacologically to mikes point, we have one I understand that and with the Nvvault datasets that we're able to run and transgenic model, we have much better visibility into helping to design that study. So we're very excited about the implementation not just in how we're using that in that three but didn't see nine and to your next question with the Qaeda.

Paul B. Bolno: Stage gating studies you have to do, and just try to think about the timeline of those getting into the clinic and the scale of any potential milestone cash flows as those become early clinical assets.

Paul B. Bolno: So to answer your first question relating to the design of SNP3, I mean, as we said on the call, we've leveraged what we've learned around the PRISM platform with new two-prime modification backbone designs and the interplay with stereochemistry. And so SNP3 has a different design than SNP1 and 2, and that gives a different profile pharmacologically. To Mike's point, we want to understand that. And with the in vivo data sets that we're able to run in transgenic models, we have much better visibility into helping to design.

Across the multiple programs.

What's interesting in a dedicated collaboration as we've said and you alluded to it there is up to six programs and the collaboration.

Those are moving forward.

We are generating datasets and as data gets generated.

We provide guidance as we just did around the transition of those programs starting with the first program.

That we identified and we'll have it as we said expect to more this year.

We haven't guided beyond that.

And Thats the best way to think about it if you think about this category to structure, we have the potential for over 2 billion in milestones pre commercially than in other I've got sorry billion pre commercially at about another.

Paul B. Bolno: I'm very excited about the implementation, not just in how we're using it in SIFT 3, but in SIFT 9, and to your next question with Dakeda, across the multiple programs. What's interesting about the DECADA collaboration, as we've said, and you alluded to it, there are up to six programs in the collaboration. Those are moving forward. We are generating data sets, and as data gets generated, we provide guidance, as we just did, around the transition of those programs, so starting with the first program that we identified, and we'll have, as we said, expect two more this year. We haven't guided beyond that, and that's the best way to think about it. If you think about this Category 2 structure, we have the potential for over $2 billion in milestones pre-commercially, and another, sorry, $1 billion pre-commercially, and about another post-commercial with a 15% loyalty. So pretty substantial in terms of the activities. We're excited about the progress of the collaboration, and we will keep things moving.

Most commercial with.

15% royalty loyalty.

So pretty substantial in terms of the activities were excited about the progress of the collaboration.

And we will keep things.

Great. Thanks, Thanks for taking my question guys.

Your next question comes from the line immune Yang with Jefferies.

Thank you based on the summit to date on last December.

Does that somebody Tim and the Glenn infinitely one is from the Q and starting to the permanent second half of this year. How do you think a year patient enrollment will be based on the data.

Yeah, Hi, this is Mike.

I have to say for the snip.

Two let's start with snow to the release of the bid at the end of last year actually helped our recruitment a fair amount simply because.

You know target engagement and good tolerability tend to peak interests and physicians and patients. So we're not having any issues with identifying patients.

And that will drive this cohort in any additional cohorts that are required now the the interesting thing Thats net three is that when when you have the.

Mani Foroohar: Great. Thanks for taking my question, guys.

Operator: Your next question comes from the line of Eun Yang with Jeffreys. Thank you. Based on the SNP2 data last December, as you upped the dose to 32 mg in SNP1 and SNP2 and started the SNP3 program in the second half of this year, how do you think your patient enrollment would be based on the data?

The screening person appointed slip to complete you also have samples that allow you to assess versus three.

It's the same type of technology. So we're starting in a very good place.

With the sites, who are already involved and the ability for those patients who might not have qualified for sniff cornerstone of two to be potentially eligible for since three so that's how we're going to start and then where they're going to go from there on it and we'll see where it goes but what we have no I have no concern about identification of patients.

Eun Kyung Yang: Yeah, hi, this is Mike. Well, I have to say for the snip. Let's start with SNP 2. The release of the data at the end of last year actually helped our recruitment a fair amount, simply because target engagement and good tolerability tend to pique interest in physicians and patients. So we're not having any issues with identifying patients, and that will drive this cohort and any additional cohorts that are required. Now the interesting thing about SNP 3 is that when you have the screening for SNP 1 and SNP 2 complete, you also have stampouts that allow you to assess for SNP 3. It's the same type of technology. So we're starting in a very good place with the sites who are already involved and the ability for those patients who might not have qualified for SNP1 or SNP2 to be potentially eligible for SNP3. So that's how we're going to start, and then we're going to go from there, and we'll see where it goes, but we have no, I have no concern about the identification of patients in the group.

Thank you for Threed, one incentive to data in second half of this year are those data coming out at the same time or data coming out as they become available.

We haven't really provided guidance about the timing of that we've just said the second half this year that we will be actually providing both.

Study result.

Thank you My last question is on the same insurance. So based on Kashi guidance is it reasonable to think could that potentially collaboration milestones payments from park in Brazil to be around 7 million present Melanie.

So we have not broken out the individual cash payments from the R&D expenses, but we do expect those R&D expenses being the contributing factors to the bench.

Thank you.

Your next question comes on the line of Sterling favorite Mizuho Securities.

Michael Linden: Thank you. For SNP1 and SNP2 data in the second half of this year, are those data coming out at the same time, or are they coming out as they become available?

Hi, Good morning, this is going up from selling team I mean, so thanks for thanking our questions just a couple of quick ones for us.

Regarding this nine or 72 program is there any pressure on the door to planning to Champaign telephone Colleen, Thailand thing and then from the preclinical studies do you find any off target gene silencing.

Michael Linden: We haven't really provided guidance about the timing of that; we just said in the second half of this year that we will be actually providing both study results.

Eun Kyung Yang: Thank you. My last question is on financials. So, based on the cash guidance, is it reasonable to think that potential collaboration milestone payments from partners would be around $30 million in 2020?

Thanks.

So I think I'll take the first part of the question first part of the question in terms of.

Good level is not a threshold correct do you think there two things we're looking at it threshold because there is and we think they're both important and treatments one is potency and obviously that.

Dave Guerrero: So we have not broken out the individual cash payments from the R&D expenses, but we do expect those R&D expenses to be contributing factors to the expenses.

The level of knockdown and we want to see as much knock down as possible, we haven't guided to a specific threshold, but we'd be substantial knock down has demonstrated on the slides we showed earlier.

Eun Kyung Yang: Thank you. Your next question comes from the line of Salim Syed with Mizzou Health Securities.

I think the second piece that that we think is important beyond potency of durability, so reducing the frequency of those injections as we saw out at eight weeks, we still saw durable knockdown of targets. So again the potential not just for potent knockdown, but durability as both being equivalent and thirdly again being variance specifics so again take.

Operator: Hi, good morning. This is Bennett from Salim's team at Mizuho. Thanks for taking our questions. We have just a couple of quick ones for us. Regarding the C9-ORF72 program, is there any threshold that you are planning to achieve in terms of silencing? And then, from the preclinical studies, did you find any off-target genes silenced?

Salim Qader Syed: Thanks.

Michael Linden: So I think I'll take the first part of the question first part of the question in terms of the Good level of the threshold there. Correct.

Good leaving beyond.

The non Texas nucleotide repeat containing transcripts and tax so when we think about building the program and have run our in vivo models to demonstrate that we look at potency durability and selectivity as kind of the three critical thresholds of the program and again why we're excited about the program that that's currently advancing into the clinic. Yes. This is Mike just.

Michael Linden: There are two things we are looking at at thresholds, and we think they're both important in treatments. One is potency, and obviously that's the level of knockdown. And we want to see as much knockdown as possible, and we haven't gotten to that yet.

Paul B. Bolno: demonstrated on the slides we showed earlier. I think the second piece that we think is important beyond potency is durability. So, reducing the frequency of those injections, as we saw, out of eight weeks, we still saw durable knockdown of targets. So, again, the potential not just for potent knockdown but for durability is both being equivalent. And thirdly, again, being variant-specific. So, again, leaving the... the non-hexanucleotide repeat-containing transcripts in TACC. So when we think about building the program and have run our in vivo models to demonstrate that, we look at potency, durability, and selectivity as kind of the three critical thresholds of the program. And again, while we're excited about the program, that's currently being developed.

Round that out I mean transition to those criteria I'm, obviously that we are very sensitive during the design process in the and the in the and the preclinical process any sorts of off target effects, there might be because that would manifest as either specific or non specific tolerability. So obviously balancing all of those criteria are important for the molecule.

All that we attach them actually take forward I mean, as we demonstrated the follow up on that and the fiber we showed the crystal structure and kind of our first crystal structure, we're able to look at that engagement.

That that degree of specificity as a key criteria and our designs and we think accord that program before.

Alright, Thank you very much I was helpful.

Your next question comes from Paul Matteis people.

Hey, Thanks for taking my questions.

Michael Linden: Yeah, this is Mike. Just to round that out, obviously, we are very sensitive during the design process and the preclinical process to any sorts of off-target effects there might be, because that would manifest as either specific or nonspecific tolerability. So, obviously, balancing all those criteria is important for the molecule that we eventually take from.

So I think when the original sneak one snap to data came out there were a couple controversies on the wall Street side related to dose response and also related to the data from the mutant versus total Huntington assets I guess in the latter point do you have any updated thoughts on you know how why you saw mutant change.

But no change in total Huntington.

Paul B. Bolno: I mean, as we demonstrated, and just to follow up on that in the slide where we showed the crystal structure and kind of our first crystal structure, we were able to look at that engagement. That degree of specificity is a key criteria in our designs and we think a core advantage of the program going forward.

And secondarily is there any more granularity you can give us on what you saw it that 16 make dose because I feel like that's kind of the main question I get as it relates to how can we be confident that 32 makes well look better. Thanks, so much.

Hi, Paul.

You know regarding the.

First question about total and how to assess the total versus the mutant as we said at the time, which was only a couple of months ago. We did see this reduction in Newton, we didnt see a big change.

Salim Qader Syed: Thank you very much. That was very helpful.

Operator: Your next question comes from Paul Mathias with Stifel.

Total assay, meaning no change from placebo, we're trying to understand what that means as we said that that could be related to again, a differential effect between you and wild type you could something that as we increase the dose we'd see clearer on those questions still remains so theres no update to provide our.

Paul Mathias: Hey, thanks so much for taking my questions. So I think when the original SNP1, SNP2 data came out, there were a couple of controversies on the Wall Street side related to dose response and also related to the data from the mutant versus total Huntington assays. I guess on the latter point, do you have any updated thoughts on why you saw mutant change but no change in total Huntington? And secondarily, is there any more granularity you can give us on what you saw at that 16 mg dose? Because I feel like that's kind of the main question I get as it relates to how can we be confident that 32 mg will look better?

On that and in terms of the dose response as we said also all along that what we did see with this when you look at pulled active versus placebo, we saw an effect and we saw based on analyses.

Just another dose effect and it was that suggestion of the dose effect on that led us to be plan.

Michael Linden: Thanks so much.

Michael Linden: Hi Paul, it's Mike. Regarding the first question about the total and how to assess the total versus the mutant, as we said at the time, which was only a couple months ago, we did see this reduction in the mutant. We didn't see a big change in the total assay, meaning no change from placebo. We're trying to understand what that means, as we said that it could be related to another differential effect between mutant and wild type. It could be something that as we increase the dose, we'd see clearer. But those questions still remain, so there's no update to provide on that.

That we're now executing to increase the dose I mean, we had a statistical evidence of a dose effect. That's we've guided us and that's why we're comfortable that increasing the dose is going to give us a great.

Okay. I guess was with numerically was 16 better than a better than four or.

So what we said is that I think we knew it is safe to assume that when you look at some of the individual comparisons they're not going to each be statistically significant we've said that previously but what we did say is by looking across all the dose cohorts pooling all of the data.

Michael Linden: And in terms of the dose response, as we said also along that, you know what we did see was this when you look at pooled active versus placebo, we saw an effect, and based on analyses, we saw a suggestion of a dose effect. And it was that suggestion of a dose effect that led us to the plan that we're now executing to increase the dose. I mean, we had statistical evidence of a dose effect. That's what guided us, and that's why we're comfortable that increasing the dose is going to give us a greater effect.

What you do when you have a small dataset that's variable you look across the dose cohorts and at the highest doses tested we see a statistically significant effect, that's what we said and that's why we're comfortable increasing the dose.

Alright, Thanks, Mike I appreciate entity or as we get to the ended the year will be breaking all that out for you I mean, I think is yes. There and then just maybe one more question is are there any place a present this had a medical meeting I think it's great. You guys are presenting the Super nursing data I know you presented snip three step in CHD I. It seemed like that would've been a great opportunity to show more color here or what are your thoughts.

Michael Linden: Okay, I guess numerically, was 16 better than 8, better than 4, or...?

Michael Linden: So what we said is that it is safe to assume that when you look at some of the individual comparisons, they're not going to each be statistically significant. We've said that before. But what we did say is by looking across all the dose cohorts, pooling all of the data, what you do when you have a small data set that's variable, you look across the cohorts, and at the highest doses tested, we see statistically significant benefits. That's what we said, and that's why we're comfortable increasing the dose. As we get closer to the end of the year, we'll be breaking all that down for you.

On that I mean, you've got a and is another opportunity as well were Roche had some data last year.

Yeah, I mean, we have all intention just like with Sudarsan of presenting us at a medical meeting, but we also don't want to present partial datasets at a medical meetings at Super Dursun dataset will be a complete assessment of what we have so that is the approach we'd like to take with HD and there are medical meeting.

Yes that we're thinking about that would where we would present these data, but the intention is to show the complete dataset not an interim analysis from the ongoing study and I think all that with some of the discussion as you said, maybe there's some contra revenue. This was an interim update on an ongoing study so to that end, we provided that interim update because we wanted to be.

Paul Mathias: And then maybe one more question, are there any plans to present this at a medical meeting? I think it's great you guys are presenting the Stupert-Urson data; I know you presented SNP3 stuff at CHDI.

Transparent shared share that study was progressing but we will present the full data when the full data is complete.

Michael Linden: It seemed like that would have been a great opportunity to show more color here. What are your thoughts on that? I mean, you've got AAM as another opportunity as well, where Rausch had some data last year.

Fair enough. Thanks, so much.

Your next question comes on line up you around wherever it with Cowen.

Hi, guys the spread it out for your own thanks very much for taking the question just two quick ones from us.

Paul B. Bolno: Yeah, I mean, we have every intention, just like with Suva Durson, of presenting this at a medical meeting, but we also don't want to present partial data sets at a medical meeting. The Suva Durson data set will be a complete assessment of what we have, so that is the approach we'd like to take with HD, and there are medical meetings that we're thinking about where we would present these data, but the intention is to show the complete data set, not an interim analysis from the ongoing study.

Lets pilot on the 30 to make just what I was actually just wondering.

How you came to actually decide on that 32 milligrams. If there was any preclinical work you felt correlated well that dose and why maybe you didn't think to go even higher when I guess would you to that effect would you consider adding another dose cohort if.

Safety looks good down the line you think you can get back can get better knockdown.

Paul Mathias: And I think, Paul, that was some of the discussion, as you said, maybe there was some controversy. This was an interim update on an ongoing study. So to that end, we provided that interim update because we wanted to be transparent, share that the study was progressing, but we will present the full data when the full data is available.

And then one other question just on the Cnine or of 72, obviously, a pretty exciting target.

Just in terms of timing for the year or you kind of looking at the snips reprogram and see nine or moving roughly in parallel at this point.

Now are you may be thinking to focus on either LSR FTD first as you move that went into the clinic. Thanks very much.

Operator: Fair enough. Thanks so much.

Yaron Werber: Your next question comes from the line of Yaron Werber with Cowen.

Hi, This is Mike.

So first of all starting off with a 32 milligram.

Brendan: Hi guys, this is Brendan on for you alone. Thanks very much for taking the time.

As you'll recall.

Our preclinical work we had in vitro evidence in fiber glass of differentiation between Union Wild type and that was what we had when we started and as we've gone along now we've collected human data, which then has guided us in terms of the dose escalation as I've described though jump from 16 to.

Brendan: Thank you very much for taking the questions. I'm about to pile on the 32 mg dose, but I was actually just wondering how you came to actually decide on that 32 mg, if there was any preclinical work you felt correlated well with that dose, and why maybe you didn't think to go even higher when, I guess, would you consider adding another dose cohort if safety looks good down the line and you think you can get better knockdown? And then one other question just on the C9-ORF-72, obviously a pretty exciting target. Just in terms of timing for the year, are you kind of looking at the SNP3 program and C9-ORF moving roughly in parallel at this point? And are you maybe thinking to focus on either ALS or FTD first as you move that one into the CLIC? Thanks very much.

32 was after seeing that the 60 milligram cohort.

Was safe at a single dose and that started the process going up to 32 purely based upon safety and we thought a doubling from 16 to 32 was reasonable and probably the most that and ethics committee and the regulatory or you want doubling as a pretty big increase so that was sort of what guided the 32.

Whether we go to whatever double bass from there whatever I mean, that's going to be dependent upon what we see with the 32 and in this case, we'll have more human data human safety data human Pharmacogenetics Pharmacodynamic data that will then guide what that now.

Michael Linden: Hi, this is Mike. So first of all, starting off with the 32 milligram dose, as you'll recall, for our preclinical work, we had in vitro evidence in fibroblasts of differentiation between mutant and wild type, and that was what we had when we started. And as we've gone along now, we've collected human data, which then has guided us in terms of the dose escalation, as I've described. The jump from 16 to 32 was after seeing that the 16 milligram cohort was safe at a single dose. And that started the process of going up to 32, purely based on safety. And we thought a doubling from 16 to 32 was reasonable and probably the most that an ethics committee and a regulatory authority would want. Doubling is a.

Next dose level should be so that's where it will go and that's our intention assuming that supported by the 32.

So that's the intention for HD in terms of Cnine or 72 versus snipped three as it is now teams are working diligently to move those along in parallel.

Obviously thats all guided upon the data that you generate we look.

Forward late to engaging regulatory authorities in the community on the best ways to develop those in light of the data that we're generating from our preclinical studies and as of now our intention is to approach FTD and they are less I'm in a similar way and figure out again.

Michael Linden: Bye. Bye. Bye. Bye. Bye. Bye. Bye. Bye. Bye. Bye. Bye. Bye. [inaudible] We're going to move on. Thank you. All right. So, thank you so much for that. We're going to talk about the best ways to develop those in light of the data that we are generating from our pre-clinical studies. As of now, our intention is to approach FQG and ALS in a similar way.

Best way to develop them as close to parallel as possible.

Michael Linden: Thanks very much.

Got it thanks very much.

Brendan: Thank you.

Thank you.

Paul B. Bolno: And At this time, there are no further questions. I would like to turn the call back over to Dr. Paul Bolno.

And at this time there are no further questions I would like to turn call back over to Dr. Paul Bono.

Paul B. Bolno: Great. Thank you again, everyone, for your time today and for your interest in WAVE Life Sciences. Have a great day. Take care.

Yes.

Great. Thank you again, everyone for your time today and for your interest in way of life Sciences have a great day take care.

This concludes today's conference you may now disconnect.

Operator: This concludes today's conference. You may now disconnect. Goodbye.

Good bye.

[music].

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