Q2 2020 WAVE Life Sciences Ltd Earnings Call
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Operator: Good morning, and welcome to the WAVE Life Sciences second quarter 2020 conference call. At this time, all participants are in a listen-only mode.
Good morning, and welcome to life, We life Sciences second quarter tiny tiny conference calls.
At this time all participants are in addition, the mountain.
Operator: As a reminder, this call is being recorded and webcast. I'll now turn the call over to Kate Rausch, Head of Investor Relations at WAVE Life Sciences. Please go ahead.
As I remind you just called is being recorded and bad.
I'll now turn the call already to keep our.
Head of Investor Relations said to me bite size.
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 second quarter 2020 operating results. On the call with me today are Dr. Paul Bolno, our President and CEO; Dr. Mike Panzera, our Chief Medical Officer, Head of Therapeutics Discovery and Development; David Guerrero, Interim CFO; Dr. Chandra Vargeese, Chief Technology Officer; and Dr. Ken Rhodes, SCP Therapeutics Discovery. Paul and Mike will provide opening remarks, after which Dave will discuss our second quarter financial report. This morning, we issued a news release detailing our second quarter results. Please note that this news release is available in the after section of our website www.waveslifesciences.com. The slide presentation that accompanies this webcast will also be available on our website following this call.
Thank you operator good morning, Thank you for joining us today to discuss our recent business progress there you wait a second quarter 2020 operating results.
On the call with me today are Dr. awful.
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Hi, Mike will provide opening remarks, after which Steve will discuss our second quarter financial results.
This morning issued a news release detailing our second quarter results.
Please note that this news release is available in the Investor section of the website Www Dot life Sciences dotcom.
Slide presentation that accompanies this webcast will also be available on our website. Following this call.
Kate Rausch: Before we begin, I would like to remind you that the discussions during this conference call will include forward-looking feedback. These statements are subject to a number of risks and uncertainties that could cause their actual results to differ materially from those described in this forward-looking statement. The factors that could cause actual results to differ are discussed in the press release issued today and in our SEC filings, including our annual report on Form 10-K for the year ended December 31st, 2019, and our quarterly report on Form 10-Q for the quarter ended June 30th, 2020. We undertake no obligation to update or revise any forward-looking statements for any... Now, I'd like to turn the call over to Paul Bolno, President and CEO of WAVE Life Sciences.
Before we do again I would like to remind you that discussion. During this conference call will include forward looking statement.
These statements are subject to a number of risks and uncertainties that could cause our actual results to differ materially from most describe them as forward looking statements.
The factors that could cause actual results to differ are discussing press release issued today and I see filings, including our annual report on form 10-K for the year ended December 31st 2019.
Quarterly report on form 10-Q for the quarter ended June Thirtyth 2020.
We undertake no obligation to update or revise any forward looking feeling for anything.
Now I'd like to turn the call over to Paul Bono, President and CEO, we'd like I said Oh.
Paul B. Bolno: Thanks, Kate. Good morning to everyone on the call, and thank you for joining us. I hope you and your families are staying healthy and safe during these challenging times. While we have been impacted by the global COVID-19 pandemic, we have continued to advance our clinical and preclinical neurology pipeline. Since the declaration of the pandemic in the United States back in March, we, like others, have been navigating a fluid and unprecedented environment and recent outbreaks.
Thanks, Kate good morning to everyone on the call. Thank you for joining US today I Hope you and your families are saying Oh PNC during these challenging times.
Well, we've been impacted the global Cobot 19 pandemic, we've continued to advance our clinical and preclinical neurology pipeline.
The declaration of depend demick in the United States back in March we like others have been navigating a fluid and unprecedented environment and recent outbreaks around the world remind us well be in certain keep it is likely to persist well into the second after this year.
Paul B. Bolno: and outbreaks around the world.
Paul B. Bolno: Please join me in a moment of silence as I remind us of the uncertainty that is likely to persist well into the second half of this year. Built from our PRISM platform, our pipeline addresses a wide range of neurology, and includes 11 programs that span discovery through clinical phage development. Since our last update, both our precision HD clinical trials for patients with Huntington's disease have continued, with patients advancing through the 32 milligram dose cohorts. We now expect to report data from these trials in the first quarter of 2021.
So from a prison platform our pipeline addresses a wide range of neurology.
And includes 11 programs that span discovery through clinical stage development.
Since our last update.
Our precision H.D. clinical trials for patients with Huntingtons disease have continued.
Patients advancing through that 32 milligram dose cohorts, we now expect to report data from these trials in the first quarter 2021.
Paul B. Bolno: We have also continued to successfully advance the work required to submit the clinical trial applications for our SNF3 program for Huntington's disease in the fourth quarter of this year. This third allele-selective program incorporates all of our learnings from our SNP1 and SNP2 programs, as well as the advancements in our platform, including new chemistry. Importantly, targeting SNP3 increases the number of Huntington's disease patients who could potentially benefit from a new allele-selective HD therapeutic. In addition, we are all excited about the progress that we are making to advance our C9-ORF72 program for ALS and FTD. These are two devastating diseases with high unmet need, and our approach has the potential to target one mutation.
We've also continued to successfully advanced the work required to submit the clinical trial applications for our Snam Rete program for Huntington disease in the fourth quarter of this year.
Third a wheel selective program incorporate all of our learnings from arsenic, one and two programs as well as the advancements in our platform, including your chemistry.
Importantly, targeting three increases the number of Huntingtons disease patients.
Could potentially benefit from me do a wheel selected H.D. therapeutic.
In addition, we're all excited about the progress that we're making to advance our see nine or 72 program for analysts and of TD.
These are two devastating diseases with high unmet need and our approach has the potential to target one mutation within both diseases.
Paul B. Bolno: Like SNP3, this program is designed with new chemistry off the platform, and the variant selective strategy was optimized with our PRISM technology. We remain on track to submit a clinical trial application for our C9 programs in the fourth quarter of this year. Lastly, our collaboration with Takeda for multiple CNS indications, including Alzheimer's disease and Parkinson's disease, continues to yield new compounds with target validation for a third program expected to be achieved by the end of this year. With regard to our PRISM platform, we have a lot of exciting work ongoing, much of which will be discussed during our upcoming Analyst and Investor Research Webcast at the end of this month. We continue to generate promising data with our new ADAR-mediated RNA editing capability, and we expect to present additional in vivo editing data during this upcoming webcast, as well as discuss the opportunity to apply this modality to neurology. The ability to edit RNA-transmitted...
No. Three this program is designed with new chemistry off the platform and the very selective strategy was optimized without prism technology.
We remain on track to submit a clinical trial application Percy nine programs in the fourth quarter of this year.
Lastly, our collaboration with Takeda for multiple CNS indications, including Alzheimer's disease, and Parkinson's disease continues to yield new compounds with target validation for the third program expected to be achieved by the end of this year.
With regards to represent platform, we have a lot of exciting work going on going much of which will be discussed during our upcoming analyst and investor research webcast at the end of this month.
We continue to generate promising data with our new eight our mediated arnie editing capability and we expect to present additional in vivo editing data during the upcoming webcast.
As well as discussed the opportunity to apply this modality to urology targets.
The ability to edit Arnie transcript significantly expand our targetable landscape and adds to our existing two bucks the modalities for the design of novel R&D Therapeutics.
Paul B. Bolno: Targetable landscapes, and as...
Paul B. Bolno: Modalities for the Design of Novel RNA Therapeutics. We also expect to present ADAR editing data at multiple scientific meetings this fall, including the Oligonucleotide Therapeutic Society, or OTS, annual meeting and the Keystone Symposium on RNA Editing and Modification, as well as announce our first RNA-ADAR editing program later this year. We have implemented novel chemistry enhancements
We also expect to present eight aren't editing data at multiple scientific meeting its Paul including be Oligonucleotide Therapeutics Society or oats, Yes annual meeting and the Keystone Symposium on Arnie.
Locations as well as announced our first ornate eight arc editing program later this year.
More broadly we've implemented novel chemistry enhancements across our plot pipeline and our next wave of neurology programs, including the United Works 72, three and our Arnie editing.
Paul B. Bolno: Transcripts provided by Transcription Outsourcing, LLC.
Paul B. Bolno: are all designed with this new chemistry in mind. We will discuss more details on our new PRISM chemistry platform for the first time during our research webcast.
Our all designed with this new chemistry.
We will discuss more details on our new prism chemistry platform.
For the first time during a research webcast.
Paul B. Bolno: I would like to provide a brief update on our operations amidst the ongoing pandemic. In the second quarter, we shifted from responding to the COVID-19 restrictions to developing and implementing a robust business continuity plan, enabling us to resume many of our critical on-site activities. We expanded the number of on-site laboratory and manufacturing staff over the past couple of months while maintaining strict protective measures to ensure their health and safety.
I would like to provide a brief update on our operations admit the ongoing pandemic in the second quarter, we shifted from responding to the coping 19 restrictions to developing and implementing the robust business continuity plan, enabling us to resume many of our critical onsite activities.
We expanded the number of on site laboratory manufacturing staff over the past couple of months, while maintaining strict protective measures to ensure their help them take.
Paul B. Bolno: Today
To date more than 60% of our employees are now trained on these protective measures can eligible to work on site.
Paul B. Bolno: More than 60% of our employees are now trained on these protective measures and eligible to work on-site. The remainder of our team has adapted well to working from home. Overall, everyone at WAVE has embraced and excelled in new ways of working, and their flexibility and ingenuity also mirrors what we are seeing among the broad network of researchers and patients who are participating in our studies. Furthermore, our supply chain has remained intact, ensuring we have sufficient material to drive our preclinical and clinical pipeline forward.
There are many of our team has adapted well to working from home.
Overall, everyone has embraced and excelled in new ways of working and their flexibility and ingenuity also mirrors, what we are seeing among the broad network of researchers and patients who are participating in our studies.
Our supply chain has remained intact, ensuring we have sufficient material to drive our preclinical and clinical pipeline forward.
In the month of May Dr., Ken roads joined our team a senior Vice President Therapeutics discovery and I'm very excited to have them on board and comes to wave with decades of experience discovering and advancing therapeutic candidates in neurology space. He will help build our pipeline by identifying new targets and therapeutic areas of focus and guiding the reach.
Paul B. Bolno: In the month of May, Dr. Ken Rhoades joined our team as Senior Vice President, Therapeutics Discovery, and I am very excited to have him on board. Ken comes to WAVE with decades of experience discovering and advancing therapeutic candidates in the neurology space. He will help build our pipeline by identifying new targets and therapeutic areas of focus and guiding the research needed to advance candidates. You will hear from Ken at our upcoming Analyst and Investor Research Webcast. I'd now like to turn the call over to Dr. Michael Panzara for an update on our clinical and preclinical neurology programs.
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You will hear from Ken at our upcoming analyst and Investor Research webcast.
I'd now like to turn the call over to Dr., Michael pens era for an update on our clinical and preclinical urology programs like.
Thanks, Paul.
Today, I will begin with an update on our precision AG, one and precision AG two clinical trials for the treatment of Huntingtons disease.
During the cold in 19 pandemic, we've remained keenly focused on ensuring the safety of our studies him patients in investigators well both clinical trials have continued to advance clinical trial type patients and investigators are facing new or continued restrictions.
Michael Linden: Thanks, Paul. Today I will begin with an update on our PRECISION-HG1 and PRECISION-HG2 clinical trials for the treatment of Huntington's disease. During the COVID-19 pandemic, we have remained keenly focused on ensuring the safety of our study teams, patients, and investigators. However, while both clinical trials have continued to advance, clinical trial sites, patients, and investigators are facing new or continued restrictions. Progress has continued, and we have been successful at identifying the patients needed to complete the 32 mg cohorts for both studies. While we are working to enroll these patients as safely and efficiently as possible, we now anticipate being able to share data from all treatment cohorts for both SNP1 and SNP2 studies, as well as data from our open-label extension trials in the first quarter of 2021.
Progress has continued and we have been successful at identifying the patient needed to complete the 32 milligram cohort for both studies.
While we are working to enroll these patients as safely and efficiently as possible, we now anticipate being able to share data from all treatment cohorts for both if one instead of two studies as well as data from our oil or open label extension trials in the first quarter of 2021.
At the beginning of the pandemic and the time of our last update we were hopeful that we could keep our studies on track because of the prioritization disease modifying studies by health authorities infrequent dosing regimen of precision AG trials and based on the location of our clinical trial sites. While this has certainly been helpful.
Ongoing impact to the client of ours has been unavoidable.
We believe that selectively lowering of mutant Huntington will be critical to achieving long term clinical benefit with any therapeutic in HD.
Michael Linden: At the beginning of the pandemic and the time of our last update, we were hopeful that we could keep our studies on track because of the prioritization of disease-modifying studies by health authorities, the infrequent dosing regimen of the PRECISION-AC trials, and based on the locations of our clinical trials. While this has certainly been helpful, the ongoing impact of the coronavirus has been unavoidable. We believe that selectively lowering mutant Huntington will be critical to achieving long-term clinical benefit with any therapeutic in HD, which is why we are expanding our commitment to HD patients with the development of our third allele selective program, SNP3. Preparations continue towards beginning clinical development with the submission of a clinical trial application, or CTA, for SNP3, which is expected to occur in the fourth quarter of 2020.
Which is why we are expanding our commitment to 80 patients with the development of our third a wheel selective program snip three.
Preparations continue towards beginning clinical development with the submission of the clinical trial application or C.T.J. fortunate three which is expected to occur in the fourth quarter 2020.
We have leveraged the learnings from both our first HD clinical programs in terms of Kennedy screening identification in vivo target validation as well as advancements in our platform when designing our snip three compound, which incorporate a novel chemistry advancement from our prism platform.
Beyond the advances in developing our lead snthree compound over the past several years, we have significantly evolved our methods to identify patients eligible for eligible for statthree targeting and measurement fluid biomarkers.
Michael Linden: We have leveraged the learnings from both our first HD clinical programs in terms of candidate screening, identification, and in vivo target validation, as well as advancements in our platform when designing our SNP3 compound, which incorporates a novel chemistry advancement from our PRISM platform. Beyond the advances in developing our LEAD SNP3 compound, over the past several years, we have significantly evolved our methods to identify patients eligible for SNP3 targeting and measure fluid biomarkers. When we started this journey, we were told that identifying patients with relevant SNPs through a process called SNP phasing was not possible or too burdensome to be practical for therapeutic development. Since then, we have clearly proved SNP phasing can be accomplished successfully and efficiently.
When we started this journey, we were told that I don't think patients with relevant snips through a process called snip facing what not possible or two burdensome to be practical for therapeutic development.
Since then we have clearly proved snip phasing can be accomplished successfully and efficiently.
We not only confirmed the feasibility of phasing it in a prospective observational study, which was recently published in neurology genetics, but we have successfully phased in identified more than enough patients appropriate for our studies it make timeline to enable enrollment.
Taking this approach to the next level last year, we entered into a collaboration with assure region for the development and commercialization of potential companion diagnostic for each of our snip. One is the two programs.
Just recently, we expanded disagreement to enable us to use their scalable technology for patient selection and our upcoming clinical trial for snip three.
Michael Linden: We not only confirmed the feasibility of SNP phasing in a prospective observational study, which was recently published in Neurology Genetics, But we have successfully phased and identified more than enough patients appropriate for our studies in a timeline to enable and, Taking this approach to the next level, last year, we entered into a collaboration with Asuragen for the development and commercialization of a potential companion diagnostic for each of our SNP1 and SNP2 programs. Just recently, we expanded this agreement to enable us to use their scalable technology for patient selection in our upcoming clinical trial for SNP.
Our three program has the potential to also broaden our reach into the HD population.
This program addresses a significant portion of the Huntingtons disease population on zone as approximately 40% of the H.T. population has no treating an observation we have confirmed using patient samples from our observation of study.
Today together with arsenic wanting snip two programs, we have the potential to address up to 80% of the H D population.
To remind you why we believe a wheel full activity matters patients with huntingtons disease have approximately half the level of wild type Huntington protein as healthy patients and there was a growing understanding around the importance of minimizing any effect on wild type Huntington given the role it plays and so many critical biological functions both in the San.
Michael Linden: Our SNP3 program has the potential to also broaden our reach into the HD population. This program addresses a significant portion of the Huntington's disease population on its own, as approximately 40% of the HD population has SNP3, an observation we have confirmed using patient samples from our observational study. Today, together with our SNP1 and SNP2 programs, we have the potential to address up to 80% of the HD population. To remind you why we believe allele selectivity matters, patients with Huntington's disease have approximately half the level of wild-type Huntington protein as healthy patients, and there is a growing understanding around the importance of minimizing any effects on wild-type Huntington, given the role it plays in so many critical biological functions, both in The supporting data not only continues to grow, but so does the recognition of this fact in conversations with the HD community.
Nervous system and systemically.
Supporting data not only continues to grow as does the recognition of this fact in conversations with CHP community.
I'm sure those of you who listened in on the virtual Huntingtons disease Society of America, or 80, I say Congress in June noticed this.
We've also been told that it would never be possible to measure wild type Huntington CSFP of HD patients.
We have turned our focus to the scientific challenge and have made progress. We believe that is critical to understand the impact of potential treatments on wild type Huffington I look forward to keeping you updated as we strive to complete this work in time for our data readout.
Now turning focus to our she nine or 72 program targeting the most frequent genetic cause the familial forms of mountrail pick lateral sclerosis, Wes and fruchter temporal dementia or FTD.
True true neuro degenerative diseases that are both devastating and field.
No no 72 genetic mutations are also a strong genetic risk factor for sporadic forms of these diseases.
Our seen IR 72 targeting compound is designed to selectively in Potently silence. The hexis nucleotide repeat contained transcripts, which drives the formation of toxic are named proteins in the central nervous system.
Dave Guiero: I'm sure those of you who listened in on the Virtual Huntington's Disease Society of America or HTSA Congress in June noticed that we have also been told that it would never be possible to measure wild-type Huntington in the CSF of HD patients. We have turned our focus to this scientific challenge and have made progress. We believe that it is critical to understand the impact of potential treatments on wild-type Huntington and look forward to keeping you updated as we strive to complete this work in time for our data. Now turning the focus to our C9R72 program, targeting the most frequent genetic cause of the familial forms of myotrophic lateral sclerosis, or ALS, and front of temporal dementia, or FDM. Two neurodegenerative diseases that are both devastating and fatal.
Our clinical candidate heads had striking effects and transgenic animal models with potent and durable knockdown of both the repeat contain transcripts and associated died peptide while levy CNR 72 protein levels relatively intact.
The ability to measure Doug peptide repeat in the CSF avail, Lesniewski patience is a critical biomarker target engagement as well those other biomarkers and your generation will afford us the opportunity to rapidly assessed for signs of efficacy in the clinic.
We plan to include both LS enough PV patients in our clinical trial with the intention to advance development in both indications we hope to share more details on this clinical trial design later this year once the details or agreed upon with key stakeholders, including regulatory authorities.
Dave Guiero: C9R72 genetic mutations are also a strong genetic risk factor for sporadic forms. Our C9R72 targeting compound is designed to selectively and potently silence the hexonucleotide repeat-containing transcripts, which drive the formation of toxic RNA and proteins in the central nervous system. Our clinical candidate has had striking effects in transgenic animal models with potent and durable knockdown of both the repeat-containing transcripts and associated dipeptides while leaving C9R72 protein levels relatively low. The ability to measure dipeptide repeats in the CSF of ALS and FTD patients, a critical biomarker of target engagement, as well as other biomarkers in neurodegeneration, will afford us the opportunity to rapidly assess for signs of effic We plan to include both ALS and FTD patients in our clinical trial with the intention to advance development for both indications.
We continue to expect to some of the Cts in the fourth quarter. If this year.
Similar to our Snip three program RC nine program takes advantage of innovations from or prison platform that have led to a compound with the potential to be highly differentiated from other therapeutic approaches Dr., Ken Roche will discuss this program in more detail during our upcoming research webcast.
So with that I'll turn it over to date got Euro for a review of our financials.
Thanks, Mike.
For the second quarter 2020, waved reported a net loss of $40.5 million compared to $41.9 million for the same period in 2019.
Research and development expenses were $31.5 million and the second quarter 2020, compared to $41.6 million for the same period in the prior year.
The decrease in research and development expenses in the second quarter.
It's primarily due to decreased external expenses related to Super Dursun due to our December 2019 decision to discontinue the program.
Dave Guiero: We hope to share more details on this clinical trial design later this year once the details are agreed upon with key stakeholders, including regulatory authorities. We continue to expect to submit a CTA in the fourth quarter of this year. Similar to our SNP3 program, our C9 program takes advantage of innovations from our PRISM platform that have led to a compound with the potential to be highly differentiated from other therapeutic approaches. Dr. Ken Rhodes will discuss this program in more detail during our upcoming research webinar. So with that, I'll turn it over to Dave Guiero for a review of our financials.
Partially offset by increased external expenses related to our clinical and preclinical activities.
Including our HD programs NRC, nine or 72 program for LS in a PD.
General and administrative expenses were $10.2 million for the second quarter of 2020 compared to $11.6 million for the same period in the prior year.
The decrease in general and administrative expenses in the second quarter of 2020 was mainly driven by decreased head count, resulting from the workforce reduction implemented in February 2020.
Wave ended the second quarter of 2020 with approximately $94 million in cash and cash equivalents.
Paul B. Bolno: For the second quarter of 2020, WAVE reported a net loss of $40.5 million compared to $41.9 million for the same period in 2019. Research and development expenses were $31.5 million in the second quarter of 2020 compared to $41.6 million for the same period in the prior year. The decrease in research and development expenses in the second quarter was primarily due to decreased external expenses related to Suvidersan due to our December 2019 decision to discontinue the program, although partially offset by increased external expenses related to our clinical and preclinical activities, including our HD programs and our C9-ORF72 program for ALS and FTD. General and administrative expenses were $10.2 million for the second quarter of 2020 compared to $11.6 million for the same period of the prior year.
We expect that our existing cash and cash equivalent together with expected in committed cash from our existing collaboration.
Will enable us to fund, our operating and capital expenditure requirements into the fourth quarter of 2021.
As a reminder, we do not include potential milestone payments and other uncommitted payments related to works Qaeda collaboration and our cash runway.
I'll now turn the call back over to fall for closing remarks, Paul.
Thanks, Dave we've made significant progress this year despite challenges posed by the global kind of them, we continue to advance or neurology pipelines, which you see t. submissions expected in the fourth quarter and data read outs from our precision each de trial expected in the first quarter next year.
In the near term we have several updates planned to be included in our upcoming research webcast presentation, including seemed nine or 72 preclinical data in vivo data on our eight our editing modality and data highlighting our new chemistry enhancements from our platform. The research webcast will be held August 25th and we hope you can tune it.
Paul B. Bolno: The decrease in general and administrative expenses in the second quarter of 2020 was mainly driven by decreased headcount resulting from the workforce reduction implemented in February 2020. WAVE ended the second quarter of 2020 with approximately $94 million in cash and cash equivalents. We expect that our existing cash and cash equivalents, together with expected and committed cash from our existing collaboration, will enable us to fund our operating and capital expenditure requirements into the fourth quarter of 2021. As a reminder, we do not include potential milestone payments and other uncommitted payments related to our CADA collaboration in our cash runway. I will now turn the call back over to Paul for his closing remarks. Okay, Paul? Thank you.
With that.
Well open up the call for questions operator.
Thank you at this time you would like to take any questions. You might have first study is reminder to ask a question you will need to press Star then the number one on your telephone.
Once again, please press star one to ask the question.
Do we do our request you me press the pound or hashed.
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We have our first question comes from the line of human Young from Jefferies. Your line is open. Please go ahead.
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I'll pass the call to Mike, but just did begin I think it was clear what Mike was saying was that it was presented to US is this would be a challenge we have been able to do that from the beginning and have continued to provide enhancement to that I'll, let Mike continues.
Operator: WAVE has made significant progress this year despite challenges posed by the global pandemic. We continue to advance our neurology pipeline with two CTA submissions expected in the fourth quarter and data readouts from our PrecisionHD trials expected in the first quarter next year. In the near term, we have several updates planned to be included in our upcoming research webcast presentation, including C9-ORF72 preclinical data, in vivo data on our ADAR editing modality, and data highlighting our new chemistry enhancements from our platform. The research webcast will be held on August 25th, and we hope you can tune in. With that, I will open up the call for questions.
Comment on the phasing out there.
Yeah, Hi that it's exactly what Paul said basically what I had said is bad we were always told when we started this process of identifying patients to have this I'll deal specific approach that there would be a lot of burden and it wasn't really feasible.
Got to do any practical way to do clinical trial.
[laughter], but from the beginning we managed to to do that we've managed to do this study that I mentioned published we managed to do it in the trials and the new.
Operator: Thank you. At this time, we would like to take any questions you might have for us today. And as a reminder, to ask a question, you will need to press star, then the number 1 on your telephone keypad. Once again, please press star 1 to ask a question. To order a request, you may press the pound or hash key.
Approach will be working with our partner sure again to develop sort of a next generation phasing approach that allows us more amenable to a companion diagnostics. So shall we moved it along we've managed to use it efficiently and were looking for we're just continuing to do that.
Operator: We'll pause for a moment to compile the Q&A list. Our first question comes from the line of Eun Yang from Jeffries. Your line is open. Please go ahead. Hi, this is Suji Dowling for Eun. Thanks for taking the time to answer my question. So I have a question about the SNF basing that Paul mentioned. You mentioned that SNF basing was burdensome earlier. Does it mean that the SNF-3 clinical trial will use a different protocol for SNF basing compared to the earlier HB1, HB2 program?
And I think the second part of your question was about enrollment we don't give specifics about enrollment for what I can say is luckily we've been able to identify.
Patients the for it for the killing of the cohorts, including their snipped phasing and we're just working to get them into the study.
Yeah.
We have our next question comes in light of many through higher from SVB, you'll be hearing your line is open. Please go ahead.
Hey, guys. Thanks, taking the question a couple of quick ones, we'll start with boring finance question.
Operator: And then could you-
Paul B. Bolno: I'll pass the call to Mike, but just to begin, I think it was clear what Mike was saying was that it was presented to us as this would be a challenge. We have been able to do that from the beginning and have continued to provide enhancements to that. I'll let Mike continue. Comment on the SNF phasing out there. Mike
I'm looking at how you got some fairly rapidly reduce your cash burn in the in the and the follow on to the stupid or send data should give us a sense of how much of your spend this quarter last quarter I'm with separation cost regarding oh, and how much incremental cost there is to come out I'm struggling a little.
Michael Linden: Yeah, hi. It's basically what Paul said, basically. What I've said is that when we started this process of identifying patients to have this allele-specific approach, we were always told that there would be a lot of burden, and it wasn't really feasible to do in a practical way to do clinical trials. But from the beginning, we've managed to do that. We've managed to do the study that I mentioned published. We've managed to do it in the trials. And the new approach will be working with our partner, Shurigen, to develop sort of a next-generation phasing approach that allows it to be more amenable to a companion diagnostic. So we've moved it along. We've managed to use it efficiently, and we're looking forward to just continuing to do that. And I think the second part of your question was about enrollment. We don't give specifics about enrollment, but what I can say is luckily, we've been able to identify patients for the filling of the cohorts, including their SNP phasing, and we're just working to get them into the study.
The challenge is yet to your Fourq you 21 onto your Fourq you 21 cash runway Guy that's for US and I think we're happy over modeling it moving too.
Clinical trial operation you haven't seen a series of delays in your Huntingtons enrollment and taking your published data versus what we nobody ideology of Huntington you should have been able to enroll assuming year old somewhere near the speed that Roche I haven't said.
Essentially the entire study from one or two large size human epidemiological data you've given up on regarding the prevalence of snips. So what do you think the reasons are the patients are avoiding your study are there and as you can make to your to either your R&D leadership or to your R&D strategy and then to avoid.
Future underperformance in enrollments be it in clinical development. Thanks.
Thank you. So we'll take the first question person that and I'll, let Dave follow up with some of the the financial guidance, but yes. As you pointed out there with the substantial reduction related to E commerce as well as operating costs related to see Patersons, Dave you want to speak to that the finances.
Operator: We have our next question comes in the line from Mani Foroohar from SVB Learning. Your line is open, please go ahead.
Operator: Hey guys, thanks for taking the question. A couple quick ones.
Sure Paul So as you saw we did have reduced cashman cash from Q1 to Q2. In addition, as we reported in our 10-Q. This morning. We've also we've also earned approximately 20 million on our ATM.
Operator: We'll start with a boring finance question. I'm looking at how you guys have fairly rapidly reduced your cash burn in the follow-on to the Suva Durson data. Can you give us a sense of how much of your spend this quarter compared to last quarter was separation costs related to that and how much incremental costs there are to come out? It's going to be a little bit challenging to get to your 4Q21, to your 4Q21 cash runway guidance for us, and I think we might be over-modeling it.
Since March of this year and so that's also adding to our son to cash runway.
And the second part of question, Mike you want to talk about the speed of enrollment.
Yeah, I mean, I think that you know there are patients out there we've managed to identify them. We've actually started to be able to you know work with the site to get through this pandemic, but let's just remember we we have we have this pandemic going on and just give me I'll.
Operator: Moving to clinical trial operations, you guys have seen a series of delays in your Huntington's enrollment, and taking your own published data versus what we know about the epidemiology of Huntington's, you should have been able to enroll, assuming you enrolled somewhere near the speed that Roche Aionis did, essentially the entire study from one or two large sites, given the epidemiological data you've given us regarding the prevalence of SNPs. So what do you think the reasons are that patients are avoiding your study? Are there changes you can make to either your R&D leadership or to your R&D strategy and execution to avoid future underperformance in enrollment speed and clinical development?
Give you a concrete example, I mean, we have you're right we have.
Half of our sites are out there in and it's certainly not in Australia just to give you. An example half that many of our sites are in Australia, and you know we had a whole group of patients scheduled to come into the study.
I'm beginning on last Wednesday, and then Monday.
Melbourne announced a sudden mark down and not just centrally wiped out a whole group of patients that could have gone into the study.
Operator: Thanks. Thank you.
Dave Guiero: So we'll take the first question first, and I'll let Dave follow up with some of the financial guidance. But yes, as you pointed out, there was a substantial reduction related to FTE costs as well as operating costs related to Suviderson. Dave, do you want to speak to the finances?
At that point because of a the locked down in Melbourne, and so we had to redirect that for extend to other places. So I mean this is a very complex in fluid environment.
I'd say the issues of this year are certainly very different things should just last year and I think that we have adapted we made changes last year.
Dave Guiero: So, as you saw, we did have reduced cash from Q1 to Q2. In addition, as we reported in our 10Q this morning, we've also earned approximately $20 million on our ATM since March of this year, and so that's also adding to our extended cash runway.
To improve upon our recruitment this year, but it's not a patient interest issue not a patient interest issue at all we actually had there's a lot of interest in the community and I think that I'm wearing a we're just right now trying to navigate a very complex situation.
Michael Linden: And the second part of the question: Mike, do you want to talk about the speed of enrollment?
That makes a lot of sense to me, but given the severity and the relentless decline associated hunting unsurprisingly. There is a lot of patient interesting any potential therapy I get that but again what are the structural changes Paul that you're thinking of making in Europe.
Michael Linden: Yeah, I mean, I think that, you know, there are patients out there. We've managed to identify them, and we've actually started to be able to work with the sites to get through this pandemic. But let's just remember we have this pandemic going on, and just give you, I'll give you a concrete example. I mean, we have half of our sites are out there in Australia. Just to give you an example, half, many of our sites are in Australia.
Research leadership head count et cetera to avoid delays like this for example, one could have chosen for one Asia Pac enrollments I Wonder could have chosen for four places like New Zealand, which has much less of a cobot impact or other places where you would have expose yourself to less of this risk.
Michael Linden: And, you know, we had a whole group of patients scheduled to come into the study beginning last Wednesday. And then on Monday, Melbourne announced a sudden lockdown, and that just essentially wiped out a whole group of patients that could have gone into the study at that point because of the lockdown in Melbourne. And so we had to redirect efforts then to other places.
Given if anything going on for a couple of years I would've thought you'd consider that.
Well, so again, yeah. When you think engineering research leadership strategy, Yeah and.
Our personnel if necessary.
Yeah. So I think the key is prior to that you know your point on on New Zealand, we only knew about that news dealing with less impacted more recently, so getting getting sites up and running during a pandemic and shifting that wasn't there I mean, I think we had the diversity of clinical trial sites that earlier this year have things going on a positive trajectory.
Michael Linden: So, I mean, this is a very complex and fluid environment. I'd say the issues of this year are certainly very different from the issues of last year. And I think that we have adapted. We made changes last year to improve upon our recruitment this year. But it's not a patient interest issue. It's not at all about patient interest.
I think that Mike point, we didn't make changes both in our operating relationship internally with our global sea our own networks, we enhanced our clinical development team, adding additional positions more recently to again continued to focus on delivering and executing on the study as Mike said the patients are identified.
Michael Linden: We actually have, there's a lot of interest in the community. And I think that we're in a, we're just right now trying to navigate a very complex situation.
Operator: That makes a lot of sense to me. But given the severity and the relentless decline associated with hunting, unsurprisingly, there is a lot of patient interest in any potential therapy.
This is an identification issue, it's now just closing it out and that chip.
Operator: But, again, what are the structural changes, Paul, that you're thinking of making in your research leadership, headcount, etc., to avoid delays like this? For example, one could have chosen for one's APAC... Enrollment sites, one could have chosen a place like New Zealand, which has much less of a COVID impact, or other places where you would have exposed yourself to less of this risk. Given the study has been going on for a couple of years, I would have thought you would have considered that. So again, how are you thinking about changing the research leadership strategy?
Okay, that's taking the questions guys.
With that.
I said, thanks for taking my question.
You month.
We have our next question comes in light of savvy.
The roll your line is open. Please go ahead.
Hey, Paul Hey, Mike Hi, Dave Thanks for all the color guys I'm just a few for me if that's okay. All on all in the Huntingtons program.
So Paul or Mike could you, maybe just give us some color. How you guys are thinking about the bogey here I'm going to given Roshe units is 46 sprint, 60% knock down on both.
<unk> and the wild type what do you think you need to have in if you're just knocking down the meeting in order to <unk>, you know quote unquote successful.
Paul B. Bolno: [inaudible] Yeah, so I think the key is prior to that. Your point on New Zealand, we only knew about that New Zealand was less impacted more recently. So, you know, getting sites up and running during a pandemic and shifting that wasn't there. I mean, I think we had the diversity of clinical trial sites that earlier this year had things on a positive trajectory. I think to Mike's point, we did make changes in both our operating relationship internally with our global CRO network and in our clinical development team, adding additional physicians more recently to, again, continue to focus on delivering and executing on the study. As Mike said, the patients are identified, so this isn't an identification issue.
Sure a in the upcoming dataset number two is when we looked at the pooled the data from the bid you disclosed in December which included the 60 milligram err on the 95% confidence interval you went up as high as 25% knocked down on the meat in Huntington.
And I'm just wondering here if there's anything to suggest that the 16 milligram.
It's actually hitting close for the 25%.
Then something you know lower than that weather was the 12 or closer to the the zero in the lower end of the confidence interval and then lastly.
Just give us some color on any data that you maybe getting into blinded aggregate and sending a if you have access to NFL data, perhaps or or or if there's anything you're you're looking out there in the blinded aggregated data. Thank you.
Operator: It's now just closing it out, and hence that shift. Okay, thanks for taking the questions, guys. What's that? Thanks for taking my questions.
Now I'll pass the call on some I can answer the question, specifically, but it's an interesting transition over because I think we are excited to have continued our lead data in that first quarter as well to review at the time, we had the that 32 milligram data. So in aggregate a lot of data to evaluate Mike do you want to speak to the.
Operator: We have our next question comes in the line from Salim Syed from Mizzou. Your line is open, please go ahead.
Operator: Hey, Paul. Hey, Mike. Hey, Dave. Thanks for all the color guys.
Operator: Just a few from me, if that's okay, all on the Huntington's program. So, Paul or Mike, could you maybe just give us some color on how you guys are thinking about the bogeyman here, you know, given Roche Iones is 46%, 60% knockdown on both The mutant and the wild type, what do you think you need to have if you're just knocking down the mutant in order to be, you know, quote unquote, successful here in the upcoming data set? Number two is when we looked at the pooled data from the study that you disclosed in December, which included the 16 milligram on the 95% conference interval, you went up as high as 25% knockdown on the mutant Huntington. And I'm just wondering here if there's anything that suggests that the 16 milligrams is actually hitting closer to the 25% than something, you know, lower than that, whether it was the 12 or, you know, closer to the zero on the lower end of the confidence interval. And then lastly, if you could just give us some color on any data that you may be getting in the blinded aggregated setting, if you have access to NFL data, perhaps, or if there's anything you're looking at there in the blinded aggregated data. Thank you.
The numbers.
Yeah, I, so I I mean, I think that in terms of it I mean as you all know I think that what is a meaningful production and you know Huntington is is really not from we've been established I mean, if you think about watch you mentioned, the 40% to 60% knock down that's often quoted.
The actual study that's being conducted this essentially if you if you already HD meetings last 18 eating really where anybody could depend was the 50 I'm meeting Palm Springs, the target of 20, 25% was being spoken about essentially by.
Roche in terms of what they felt was that minimum meaningful when you're considering a knock down that includes both mutant and Huntington. So so that's the number that's actually been out there, but you hear people talking about as meaningful I'm. So we would think that if it's meaningful in the setting of nonspecific knock down certainly that's gonna be meaningful in the south.
Adding of a selective knocked down so I think tree answer to that until you have clinical effect and see how that all translate it's really not clear I'm. So were obviously, we said many times that we were dissatisfied with the interim analysis that we saw we wanted to go higher we have gone higher and now that's.
Michael Linden: I'll pass the call on to Mike to answer the question specifically, but it's an interesting transition over because I think we are excited to have continued OLE data in that first quarter as well to review at the time we have the 32 milligram data. So, in aggregate, a lot of data to evaluate. Mike, do you want to speak to the...
Looking forward to seeing that data in terms of ongoing and now in terms of ongoing assessment of Biomarkers and those types of things. We are the the assayed that type of stuff is very tightly held and restricted and we share safety data with our safety monitoring committee that is on blue.
Michael Linden: Well, yeah, I so I mean, I think that in terms of, as you all know, I think that what is a meaningful reduction in mutant Huntington is really not firmly established. I mean, if you think about what you mentioned, the 40 to 60% knockdown that's often quoted, the actual study that's being conducted is essentially if you are at HD meetings, the last HD meeting really where anybody could attend was the CHDI meeting in Palm Springs, the target of 2025% was being spoken about, essentially, by Roche in terms of what they felt was the minimum meaningful when you're considering a knockdown that includes both So, that's the number that's actually been out there, but you hear people talking about it as meaningful. So we would think that if it's meaningful in the setting of nonspecific knockdown, it's certainly going to be meaningful in the setting of select.
And then where they go in named after each cohort as we've talked about talk about dose escalation. We review blinded information, but we do not review by blinded biomarker information that is not a.
Standard review process said Wade.
Got it thanks, Mike Mike I don't know, maybe I missed that the I'm on the 16 made.
Can you mean.
But finding that a little bit.
Oh, I mean again, we've we've been clear that we've shared that interim analysis, which was pooled data.
The cooled active cohorts versus the pool placebo cohorts, we've never really gotten into the individual knocked down is that of the of each cohort separately, that's all going to be part of the data readout in the first quarter.
Okay. Thanks, very much interesting early in a single data as well.
So we'll have more opportunities for continued dosing so wanting something thanks Paul.
Michael Linden: But the true answer to that, until you have clinical effects and see how that all translates, is really not clear. So we're, obviously, we said many times that we were dissatisfied with the interim analysis that we saw. We wanted to go higher, we have gone higher, and now that's, you know, we're looking forward to seeing that data.
Your next question comes into line of Paul Matteis from Stifel. Your line is open. Please go ahead.
Hey, Thanks for taking the question is is Alex on for Paul I'm, just a couple shame on us and I guess Im curious for your next clinical programs Snips degree and seen a horse programs you mentioned the DTA firing Fourq you just wondering if you could give us an idea when you think you could start dosing if that.
Michael Linden: In terms of ongoing assessments of biomarkers and those types of things, we are, the assay, that type of stuff is very tightly held and restricted, and we share safety data with our safety monitoring committee that is unblinded, where they go, and they, after each cohort, as we've talked about, talk about dose escalation. We review blinded information, but we do not review blinded biomarkers. That is not a standard review process at WAVE.
I'm going to be ex U.S. or if you're thinking about fivenine de sometime soon as well and then on your where 80 in PD programs curious if you could give us anymore color on those sorts of targets that you're you're looking at Ah. Thanks.
That's great for the as it relates to see night and three update regarding the Cts, Mike do you want to comment on.
Michael Linden: Got it, thanks Mike. Mike, I don't know if, maybe I missed it, on the 16 meg. Can you maybe... I'll be replying to that in a little bit.
Sure sure I mean, typically you know I'm once you get your Cts cheap Ctr yen.
Michael Linden: Again, we've shared that the interim analysis was pooled data, the pooled active cohorts versus the pooled placebo cohorts. We've never really gotten into the individual knockdown of each cohort separately, but that's all going to be part of the process.
Obviously it depends upon when you get your sites up and everything but generally we like to think about a quarter. After he or she ta is and you begin to be able to dose. So that's about what we've been finding of course you know.
Operator: Thank you very much.
Operator: Thanks, Paul.
That was certainly and that's typically when there is no cobot going on so we'll have to see how that goes but we're going to be targeting countries, where we can do it despite coated and so on which again is a glut, we're going to take this globally and our our intention to get this off the ground inside and outside of.
Operator: Thanks, all.
Operator: We have our next question comes from the line of Paul Matisse from Spitho. Your line is open. Please go ahead.
Operator: I guess I'm curious about your next clinical program, SNP3 in the C9-ORF program. You mentioned the CTA filing 4Q. Just wondering if you could give us an idea of when you think you could start dosing, if that's all going to be XUS, or if you're thinking about filing IND sometime soon as well. And then on your AD and PD programs. Curious if you could give us any more color on the sorts of targets that you're looking at. Thanks.
As it relates to the 80 PD and other targets from Takeda. Unfortunately, we're not at.
Liberty to disclose the confidential targets as part of the collaboration but as they make progress.
We are working with them to be able to share more around those programs, but the team continues to push forward.
Paul B. Bolno: That's great. As it relates to the C9 and SNP3 updates regarding the CTA, Mike, do you want to comment on that?
And then as we said we've been able to implement using our new chemistry similar to those that were using person to threed see nine in those programs as well and we're excited to provide data update on what's happening on the research side of wave during our upcoming research day.
Michael Linden: Sure. Sure.
Michael Linden: I mean, typically, once you get your CTA in, obviously, it depends upon when you get your sites up and everything. But generally, we like to think about a quarter after your CTA is in, you begin to be able to dose. So that's about what we've been finding. Of course, you know, that was certainly when there was no COVID going on. So we'll have to see how that goes. But we're going to be targeting countries where we can do it, despite COVID. And so, which, again, is global, we're going to take this global, and our intention is to get this off the ground, inside and out.
Yeah, Thanks, and I guess, one one quick follow up there I could you give us a quick update on the ophthalmology program I don't know if I saw that in the press release, just curious where that stands thanks.
Yes, so as it relates to the ophthalmology, we had done a lot of work looking at target engagement. Both in the back of the <unk> on the right now around Australia, and ROE P 23, H., we haven't provided additional.
Updates related to those programs as we look at the collaborative path forward to advance those programs.
Great. Thank you.
Your next question comes in light of Yaron Werber from Cowen. Your line is open. Please go ahead.
Once again the anniversary your line is open. Please go ahead.
Paul B. Bolno: As it relates to the ADPD and other targets from Takeda, unfortunately, we're not at liberty to disclose the confidential targets as part of the collaboration, but as they make progress, you know, we are working with them to be able to share more around those programs, but the team continues to push forward, and as we've said, we've been able to implement using our new chemistry similar to those that we're using for SNP3 and C9 in those programs as well, and, you know, we're excited to provide that update on what's happening on the research side of WAVE during our upcoming research day.
Hi, guys, it's Brendan unfair.
It's from us.
Mostly on H.D. and kind of different dosing cohorts here. So you mentioned that the Q1 read out will include data through the 30 to make a much even considering maybe higher I just know doses. So I guess.
First I was hoping to see like what can we expect them to read out in Q1 in terms of time after treatment I guess, namely how far.
Out after the treatment will the read out included at that point and then also you know how how do you think we should think about the timeline for these programs would you potentially wait to proceed to pivotal until the additional higher dose cohorts are fully enrolled and read out.
Operator: Thanks, and I guess one quick follow-up: could you give us a quick update on the ophthalmology program? I don't know if I saw that in the press release; just curious where that stands. Thanks.
And then I have one follow up it that's all right. Thanks.
Mike, which I can take the C.C. question.
Yes. So again you would expect at the time of the of the read out in the first quarter, you're going to get the as you remember the design that whole full four doses of the 32 milligram dose level plus.
Paul B. Bolno: Yeah, so as it relates to ophthalmology, we have done a lot of work looking at target engagement both in the back of the eye and the retina around ASH2A and RhoP23H. We haven't provided additional updates related to those programs as we look at the collaborative path forward to advance those programs. Great, thank you.
Basically all the lower dose cohorts. So that'll all be part of that it'll include the key Biomarkers, we talked about mutant it'll include.
Operator: We have our next question comes from the line of Yarin River from Colin. Your line is open, please go ahead. Once again, you are on a river. Your line is open, please go ahead.
We're work striving to get our assessment of Wild type done by then and actually you'll have clinical and you know safety and those types of things at that point you know after we're done with our after we're done with that 32 milligram. We're also going to understand at that point, you'll understand why.
Operator: Hi guys, this is Brendan on for your [inaudible]. First, I was hoping to see, like, what can we expect in the readout in Q1 in terms of time after treatment? I guess, mainly how far...
Whether we are going to a higher dose and we'll have all of that I'm able to discuss that with you. In addition, you'll have the open label extension study data Snip, one incident to whatever we have after a certain number doses similar to what were dosing in the precision HD. So you'll have law.
Operator: How do you think we should think about the timeline for these programs? Would you potentially wait to proceed through Pivotal until the additional high-risk cohorts are fully enrolled in Readout? And then, I have one follow-up. Thanks.
Michael Linden: Mike, would you like to take the ASP question?
Longer term dosing, then you'll have with precision and some patience with similar dosing. So it's a fairly large dataset.
Michael Linden: Yeah, so again, you would expect at the time of the readout in the first quarter, you're going to get, as you remember the design, the whole full four doses of the 32 milligram dose level plus basically all the lower dose cohorts. So that'll all be part of that.
That will be sharing and that first quarter and the you know with us with the hope of again sharing with all of you are thinking about what the next steps would be in terms of the steps towards a pivotal that'll be driven by the degree of knocked down that we see across.
Michael Linden: It'll include the key biomarkers we talked about, mutant. It'll include, you know, we're striving to get our assessment of wild type done by then, and actually, you'll have clinical and, you know, safety and those types of things. At that point, you know, after we're done with our 32 milligrams, we're also going to understand at that point whether we are going to a higher dose, and we'll have all of that, able to discuss that with you. In addition, you'll have the open-label extension study data, SNP1 and SNP2, whatever we have after a certain number of doses, similar to what we do in the Precision So you'll have longer-term dosing than you'll have with Precision and some patients with similar dosing.
So all the full cohorts remember the interim was only a partial you know cohort in that and that not everybody had gotten out the day 140. So once we look at all of that once we look at the or at least once we look at the 32 milligram knockdown that'll put us in a bit better position to determine next steps towards.
Towards our pivotal study, which we would anticipate given where we are that we should be able to begin those steps. Once we see that 32 milligram knocked down if that level is at a level that we feel is meaningful. So we're we're already beginning to thinking on how we do that.
Okay, great. Thanks, very much and just really quickly I was also hoping you know as you kind of mentioned a you know you get there working to optimize a wild type.
Michael Linden: So it's a fairly large data set that we'll be sharing in that first quarter and with the hope of, again, sharing with all of you our thinking about what the next steps would be. In terms of the steps toward a pivotal, that'll be driven by the degree of knockdown that we see across all the full cohorts. Remember, the interim was only a partial cohort in that not everybody had gotten out to day 140. So once we look at all of that, once we look at the OLE, once we look at the 32 milligram knockdown, that'll put us in a better position to determine the next steps toward our pivotal study, which we would anticipate, given where we are, that we should be able to begin those steps once we see that 32 milligram So we're already beginning the thinking on how we will do that.
Detection at that I I was hoping that we could maybe get a little bit more color I'm kind of where that stands and maybe what's just left optimizing how you might be and if you are looking to implement said differently than you have previously or kind of just where that is at this point.
No definitely handsets and Mike it's an exciting amount of work on the research side to answer a really important question for the fields, Mike would you like yeah, no. Thanks for that and so as we discussed at the interim analysis on the mute NAFTA is an assay that is.
Similar to whatever others are using to measure mutant and at that time. We also discussed how we looked at the total Huntington Amin CSF samples, but we also said at the time that there were pretty significant limitations to that in terms of how you look at the mutant versus the total and the difficulties measuring.
Operator: Okay, great. Thanks very much. And just really quickly, I was also hoping, you know, as you kind of mentioned, you guys are working to optimize the wild type detection assay. I was hoping that we could maybe get a little bit more color on kind of where that stands and maybe what's just left to optimize and how you might be and if you are looking to implement it differently than you have previously or kind of just where that is.
On the wild type because some indirect measurements what we're talking about now is wanting to I'm specifically focus.
On measuring the wild type portion of that total pool. This is something that we've been spending a lot of time thinking about we actually are looking on implementation of that and we're striving that when we revealed the data in the first quarter, we'll have an assessment using.
Paul B. Bolno: No, I'll definitely hand this to Mike. It's an exciting amount of work on the research side to answer a really important question for the field. Mike, would you like to? Yeah.
A new approach that will allow people to understand whether what is being measured in that total last a what piece of that is wild type what piece of that is mutant and then make that our intention is to sort of work with community to make that a little bit more while.
Michael Linden: Now, thanks for that. So, as we discussed at the interim analysis, you know, the mutant assay is an assay that is similar to whatever others are using to measure mutants. And at that time, we also discussed how we looked at the total Huntington score in CSF samples. But we also said at the time that there were pretty significant limitations to that in terms of how you look at the mutant versus the total and the difficulties measuring the wild type because it's an indirect measurement. What we're talking about now is wanting to specifically focus on measuring the wild-type portion of that total pool. This is something that we've been spending a lot of time thinking about. We actually are looking to implement that, and we're striving that when we reveal the data in the first quarter, we'll have an assessment using a new approach that will allow people to understand whether what is being measured in that total assay, what piece of that is wild-type, what piece of that is mutant, and then make that, our intention is to sort of work with the community to make that a little bit more widely available should we be successful, because We think this is something that's important and the community that the partners we're working with are quite excited about.
Widely available should we be sticks out because we.
We think this is an important thing that needs to be looked at and we don't think this is something that we alone should be.
Should be using we think this is something that's important and community that partners, we're working with our quite excited about.
About the approach.
Yes, Greg I mean, moving away from that kind of dynamic range and ratios it kind of them more more concrete numbers is obviously the direction that we said at the beginning we would move to in the team has been working extraordinarily hard to advance. It. So we're excited to keep pushing that forward.
Okay, great. Thanks, guys.
Thank you.
Never in my last question comes in July of Human Yang from Jefferies. Your line is open. Please go ahead.
On that.
Yeah.
Next year.
Yes.
Right.
Yes.
The second question I had wise.
<unk>.
I'm going to be similar to just wanted to.
Sorry.
Yes.
Yes.
Yeah, I'll pass the question to Mike, but that the the phase one two study incident free will be in patients, but I'll, let Mike continue to answer questions around the Orleans.
Thanks.
Yes, so the only the way the doses are so everybody in the open label extension study is getting active drugs and the way. The study is designed is that once a cohort.
Operator: Yeah, it's great. I mean, moving away from this kind of dynamic range and ratio to kind of more concrete numbers is obviously the direction that we said at the beginning we would move to. And the team's been working extraordinarily hard to advance that. So we're excited to keep pushing that forward. Okay, great. Thanks, guys. Thank you.
Is shown to be safe and the precision AG study patients are migrated up to whatever the highest dose the highest safe dose has been in the in the precision HD studies show patients are migrating up to the highest doses tested in that study and watched what we'll see in the.
Operator: We have our last question, which comes from the line of Eun Yang from Jeffries. Your line is open, please go ahead. I have a quick question on OLE data here.
Operator: Our website, www.wavelife.org.au, The second question I had was... This is the first trial that you are going to start. Is the design going to be similar to the first one? For more information, visit www.wavelife.org
In the first quarter are the basically the safety and the biomarker results of those patients over the over the duration that they've been exposed the other thing in terms of the three trial and adverse similarities to sneak one incident to certainly there'll be a lot of similar.
Paul B. Bolno: I'll pass the question to Mike, but the Phase 1-2 study in SNF 3 will be in patience, but I'll let Mike continue to answer questions around the OLE and the SNF 3 design.
Charities, but there's also had a lot of learnings from the precision AG, one and actually two studies that will be incorporated into the precision HD well would likely be the precision AG three study and this study in terms of phasing as I mentioned earlier, we'll be using the new technology for snip facing through our partnership with assure agent.
Michael Linden: Yeah, so the OLE, the way the doses are, so everybody in the Open Label Extension Study is getting active drug. And the way the study is designed is that once a cohort is shown to be safe in the Precision HD study, patients are migrated up to whatever the highest dose, the highest safe dose has been in the Precision HD study. So patients are moving up to the highest doses tested in that study. And what we'll see in the first quarter are basically the safety and biomarker results of those patients over the duration that they've been tested. In terms of the SNP3 trial versus similarities to SNP1 and SNP2, certainly, there will be a lot of similarities, but they've also had a lot of learnings from the PrecisionHD1 and PrecisionHD2 studies that will be incorporated into the PrecisionHD, what would likely be the PrecisionHD3 study. And this study, in terms of phasing, as I mentioned earlier, will be using new technology for SNP phasing through our partnership with Asuragen.
Thank you.
You have another question from the line of Veggie Chapel Cotai from <unk> Wainwright. Your line is open. Please go ahead.
Hi, guys Hi, good morning, Thanks for the data updates and then sorry about that delays.
So I wanted to ask Oh and by the way. This is Eric on for Debjit and wanted to ask are the newly identified patients for the precision studies all at the same site or are they geographically diverse.
And you have more patients identified that are needed to fill out the cohort or is it exactly the number of patients are required.
And then finally, if your patient Mrs and injection or a follow up or they totally excluded or is there an and a new patients needed or is there how much flexibility is there.
Operator: Great, thank you.
Mike would you like it goes yeah, I mean, all I will say is that we have multiple sites with patients in multiple backups. So there's no.
Operator: We have another question from the line of Bajaj Chappopadhyay from A.C. Wayner. Your line is open; please go ahead.
There is no exact here because you.
Operator: Hi guys, good morning.
Operator: Thanks for the data updates, and I'm sorry about the delays. So I wanted to ask, oh, and by the way, this is Aaron on behalf of DevJet. I wanted to ask, are the newly identified patients for the precision studies all at the same site, or are they geographically diverse? And do you have more patients identified than are needed to fill out the cohort, or is it exactly the number of patients that are required? And then finally, if your patient misses an injection or a follow-up, are they totally excluded, and a new patient is needed, or how much flexibility is there? Mike, would you like to take these?
You know, we're starting to think about additional cohorts and additional patients. So yeah I Oh, we have more patients that have been phase that we need and then more I'm sites than we need to do it.
Okay, great. Thank you and then and then a quick follow up so would dose escalation beyond the two milligrams be dependent on.
How helpful Dataset do you need.
To justify escalation down 32 milligrams do you need though the full patient.
Data dataset at 32 milligram.
Michael Linden: Yeah, I mean, all I will say is that we have multiple sites with patients and multiple backups, so there's no exact number here because, you know, we're starting to think about additional cohorts and additional patients. So, yeah, we have more patients that have been phased in than we need and then more sites than we need to do it.
And up to 182 days or is there some sort of.
Partial no that's how we've never we've never waited for the full hundred 96 days. It is actually to be able to make that decision. If you recall going from eight to 16 and 16 to 32 was made before we had any biomarker data or had complete safety data was based upon.
Operator: Okay, great. Thank you. And then, and then a quick follow-up. So, with dose escalation beyond 32 milligrams, will it be dependent on how full of a data set you need to justify escalation beyond 32 milligrams? Do you need the full patient data set at 32 milligrams, and out to 192 days?
The safety of the a couple of the of the single dose cohort and review of an independent safety Committee. So we haven't weighted to completion before making those decisions.
Okay, great. Thanks, guys.
Good day.
There are no questions at this time, Oh, now I turn the call back over to Dr., Paul Ball mill.
Operator: We've never waited for the full 196 days it takes to be able to make that decision. If you recall, going from 8 to 16 and 16 to 32 was made before we had any biomarker data or had complete safety data. It was based on the safety of the single-dose cohort and the review of an independent safety committee.
Thanks, everyone for joining the call. This morning to review, our second quarter update and thanks to our employees for their hard work and commitment to patients. We look forward just speaking to you again soon and our upcoming research webcast, having like day. Thank you.
Ladies and gentlemen that does conclude your conference for today. Thank you all through participating and you may now disconnect have a good thing.
Operator: Okay, great. Thanks, guys. Thank you.
Paul B. Bolno: There are no questions at this time. I will now turn the call back over to Dr. Paul Bolno.
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Paul B. Bolno: Thanks, everyone, for joining the call this morning to review our second quarter update. And thanks to our employees for their hard work and commitment to patients. We look forward to speaking to you again soon on our upcoming research webcast. Have a nice day. Thank you.
Operator: Ladies and gentlemen, that does conclude our conference for today. Thank you all for participating, and you may now disconnect. Have a great day.
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