Q3 2019 Earnings Call
Good morning, and welcome to the Voyager Therapeutics third quarter 2019 financial results and corporate highlights conference call.
Operator: Good morning, and welcome to the Voyager Therapeutics 3rd Quarter 2019 Financial Results and Corporate Highlights conference call. At this time, all lines are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star 1 on your telephone. If you require any further assistance, please press star zero. Please be advised that this call is being recorded. At this time, I'd like to turn the call over to Vasilis Kariolis, Voyager's Assistant Controller. Please proceed.
Finally, participants' lines are in listen only mode.
The speakers presentation, there will be a question and answer sorry to ask a question during the session you'll need to press star one on your telephone.
If you require any further assistance please press star zero.
Please be advised that this call is being recorded at this time I'd like to turn the call over to the smallest curios wagers assistant controller. Please proceed.
Vasilis Kariolis: Thank you. Good morning, and thank you for joining us. With me on the call today are Andrei Teren, our President and Chief Executive Officer, Omar Khawaja, Chief Medical Officer and Head of R&D, and Matt Otmer, Chief Operating Officer. Earlier today, we issued a press release that outlines the financial results and corporate highlights for the third quarter of 2019. The release is available at voyagertherapeutics.com. Before we begin, just a reminder that the forward-looking statements included in this call represent the company's view as of today, November 6, 2019. Voyager disclaims any obligation to update these statements to reflect future events or circumstances except as required by law. Please refer to today's press release as well as Voyager's filings with the SEC for information concerning risk factors that could cause actual results to differ materially from those expressed or implied by such statements. With that, I'll pass the call over to Andre.
Thank you good morning, and thank you for joining US with me on the call today Andre trends, our president and Chief Executive Officer.
Mark Khwaja, Chief Medical Officer, and head of R&D and not partner Chief operating officer.
Earlier today, we issued a press release, which outlines the financial results in corporate highlights for the third quarter of 2019.
Releases are available at Voyager Therapeutics Dot com.
Before we began just a reminder that the forward looking statements included in this call represent the company's view as of today November six 2019.
Where is your disclaims any obligation to update these statements reflect future events or circumstances, except as required by law. Please refer to today's press release as well as voyagers filings with the FCC for information concerning risk factors that could cause actual results to differ materially from those expressed.
Or implied by such statements.
With that I'll pass the call over to Andre.
Vasilis Kariolis: Thank you, Vasili, and good morning, everyone. Welcome to our Q3 earnings and Corporate Highlights call. Our CFO, Alison Dorval, is unable to participate in the call this morning due to a death in her immediate family, which sadly occurred on Sunday.
Thank you have a silly and good morning, everyone welcome to our Q3 earnings and corporate highlights call.
Our CFO Allison Dorval is unable to participate in a call. This morning news about that dinner immediate family, which sadly occurred on Sunday or heartfelt thoughts are without said in her family.
Andrei Teren: Our heartfelt thoughts are with Alison and her family. I thank Vasili, our assistant controller, for stepping in and covering our financial highlights. I'll begin today by walking you through some of our recent corporate developments. Omar will then provide a pipeline update, and Vasily will wrap up with the financial results. Once we've concluded our remarks, we'll have some time to take your questions.
Hi, Thanks have a silly our assistant controller for stepping in and covering our financial highlights.
I'll begin today by walking you through some our recent corporate developments.
Mark will then provide a <unk> pipeline update.
That's still a well wrap up.
With the financial results once we've concluded at all remarks, WAF, sometimes take your questions.
Andrei Teren: We've had another productive quarter in Q3 at Voyager, building on a transformative first half of the year during which we entered into two important collaborations and a restructured one. It's an exciting time at Voyager as we gain momentum and expand on our foundation. Voyager sits squarely at the intersection of gene therapy and neuroscience. This dual focus on AV gene therapy and neurological diseases provides us with several advantages.
We've got another productive quarter injuries, we at Voyager building on a transformative first half the year during which we entered into two important collaborations and restructured one.
It's an exciting time at Voyager as we gain momentum and expand on our foundation.
Voyager sits squarely at the intersection of gene therapy, a narrow science.
They will focus on a the gene therapy and neurological diseases provides us with several advantages for one as we've continued to hire key talent, we've been able to add the colleagues with specialized expertise precisely in our chosen area.
Andrei Teren: For one, as we've continued to hire key talent, we've been able to add colleagues with specialized expertise precisely in our chosen area. Their experience is already proving to add significant value to our efforts. Another benefit of our focus as we keep advancing our pipeline is that we're finding invaluable learnings translating from program to program. We're seeing this, for example, as we've begun planning for the rapid transition from IND to first patient treated in our Huntington's disease program. Given the similar nature of the neurosurgical procedure involved in the one-time HD treatment and the one-time PD treatment, we expect to more rapidly enable sites to enroll study participants than would otherwise be possible without our prior experience. The benefits of our FOCUS experience also apply to our earlier stage programs. Our work on a vectorized antibody against pathological species of alpha-synuclein with our partner AbbVie is progressing faster than expected in light of the early learnings from our anti-Tau vectorized antibody efforts.
Their experience is already proving to add significant value to our efforts.
Another benefit of our focus as we keep advancing our pipeline is that we're finding invaluable learnings translating from program to program.
We're seeing this for example, as we began planning for rapid transition from mine D to first patient treated in our Huntingtons disease program.
Given the similar nature of the neurosurgical procedure involved for the onetime HD treatment and the onetime NPD treatment, we expect to more rapidly enable sides to enroll study participants then or whatever the otherwise been possible what out or prior experience.
The benefits of our focus experience also apply to our earlier stage programs.
Our work on a victory is anybody against pathologic all species of Alpha Synuclein, what our partner Abbvie is progressing faster than expected in light of the early learnings from our anti tile victories anybody efforts.
These learnings intern are now being applied to our own additional efforts in fact rise antibodies.
Andrei Teren: These learnings, in turn, are now being applied to our own additional efforts in vectorized antibodies. Moving forward, we'll continue to rigorously apply our learnings and those from others working in the space as we further advance our pipeline and platform. Regarding our lead program, BYDC for Parkinson's Disease, which is partnered with Nurkirin, we expect to present final three-year data from all three cohorts of the 1101 phase one trial at a medical conference in 2020. 2020 is also expected to be an important year for Huntington's program as we anticipate filing an IND application and beginning screening and enrollment into the clinical trial.
Moving forward will continue to rigorously apply or learnings and those from orders working in a space as we further advance our pipeline and platform.
Regarding our lead program at the why do you see for Parkinsons disease, which is partnered with aircraft. We expect to present final three or data from all three cohorts of the live in a one phase one trial at a medical conference in 2020.
2020 is also expected to be an important here for Huntingtons program as we anticipates filing an R&D application and beginning screening and enrollment into the clinical trial.
Andrei Teren: As we announced in a press release this morning, we presented some positive data on VYHTT01 at ESGCT last month. Omar will share more details on this shortly. Finally, we're pleased to announce today that Alan Nunley has been promoted to the position of Chief Business Officer from his previous role as VP of Corporate and Business Development. Allen has been a key collaborator in my first year at Voyager, and I look forward to his continued success in his new role. I'll now turn the call over to Omar to provide more detail on our pipeline programs.
As we announced in a press release. This morning, we presented some positive data on the wide steel one at U.S.J.C.T. last month Omar we'll share more details on this shortly.
Finally, we're pleased to announce today that I'm not only has been promoted to the position of Chief business officer from his previous role as VP of corporate and business development.
And it's been a key collaborator in my first year at Voyager and I look forward to its continued success in his new role.
I'll now turn to call over to Omar to provide more detail on our pipeline programs.
Omar Khawaja: Thank you, Andre. First, I'll go through recent updates on our Parkinson's disease program. As Andre mentioned, the collaboration with Neurocrin, which we entered into earlier this year, is off to a good start. We've agreed to the proposed statistical analysis plan for Restore 1 and are requesting feedback from the FDA before year-end. Steady progress continues to be made towards enrollment in the Restore One trial. We'll provide a more detailed update on Restore One after we receive feedback from the agency.
Thank you on dry so that's all day two recent updates on our Parkinson's disease program.
As Andres mentioned, the collaboration with New York, written which we answered earlier. This year is off to get stuff. We've agreed to the proposed statistical analysis plan for is still one under a costing feedback from the FDA the full year and.
Study progress continues to be made towards enrollments at this Bristol one trial.
To provide a more detailed updates on we're still one after we receive feedback from the agency.
As a reminder, our approach to Parkinson's disease with the being like 80, 80 see pipe bomb it's highly differentiated.
Omar Khawaja: As a reminder, our approach to Parkinson's disease, with the VAEADC program, is highly differentiated. It consists of the targeted delivery of a small volume of gene therapy to the region of the brain where it is needed for motor function. The result is a regulated system controllable by the standard of care oral medication. This ability to regulate the transgene activity is highly desirable and a rather unique feature for AAV gene therapy.
It consists of the targeted delivery of the small volume as gene therapy. So the region of the brainwashed as needed some nice a function.
The result is a regulator school system controllable by the standard of care oral medication.
This ability to regulate the transaction activity, it's highly desirable I'd, rather unique feature threaten the hazy gene therapy.
By creating a reservoir of a b C. The ends I needed to convert leave it there, but that doesn't mean in the putamen, where bypassing die increase I don't think neurons and introducing AIDC into healthy position not signal runs right and then be used to produce doesn't mean.
Omar Khawaja: By creating a reservoir of AADC, the enzyme needed to convert levodopa to dopamine in the putamen, we're bypassing dying presynaptic neurons and introducing AADC into healthy postsynaptic neurons, where it can then be used to produce dopamine. AEDC delivered into the Putamen will do nothing on its own, but AODC in combination with levodopa will produce dopamine.
AIDC delivered into the P type and we'll do nothing on it side.
The AIDC in combination with leave it that will produce does mean.
Our approach gets the patient the exogenous control a the amount that they needed.
Omar Khawaja: Our approach gives the patient exogenous control over the amount of dopamine needed to manage their motor function and the ability to avoid the negative impacts of too much dopamine in brain regions where it is not needed. The phase 1b trial was initiated in 2014, so we're now starting to see longer-term results that may speak to both the durability of effect and, in the context of a progressive degenerative disease, contrast against the predicted course of disease progression. We expect to present 36-month data from all three cohorts of PD1101, as well as two-year data from PD1102, at scientific meetings in 2020. Patients completing the three-year protocol on PD1101 and PD1102 are now enrolling in our longer-term extension study. This will eventually provide us with over five years of data in addition to the placebo-controlled data at the time of the PLA filing and payer discussions.
To manage that motor function and the ability to avoid the negative impacts of too much that's the main and brain regions, where theres not needed.
Phase one be trial was initiated in 2000, Fourteens, having now starting to see longer time result that nice bike speech by securing those either side and in the context of that progressive degenerative disease.
The trust against the predictive course of disease progression.
We expect to present 36 months data from all three cohorts MPD 11, I, one as well as to your data from P.D. 11 attitude at scientific meetings and 2020 .
Patients completing the three opposed to call them PD 11, I won on PD 11, I too are now enrolling in our longer term extension study.
It will eventually provide us with over five years of data. In addition to the placebo controlled data at the time as would be I like filing.
I had discussions.
Oh Huntingtons disease program is also progressing well, we've held advisory meetings with buys neurologists and neurosurgeons and have received positive feedback on our delivery approach as well, it's all proposed clinical trial design and biomarker assessment.
Oh deliberately a patch leverages, our learnings from the talking tens pipeline with local delivery a fee like http. Yarwun into the putamen.
The Huntingtons disease were also delivering directly into the tightness.
Omar Khawaja: Our Huntington's disease program is also progressing well. We've held advisory meetings with both neurologists and neurosurgeons and have received positive feedback on our delivery approach, as well as our proposed clinical trial design and biomarker assessment. Our delivery approach leverages our learnings from the Parkinson's program with local delivery of VYHTT01 into the putamen. For Huntington's disease, we're also delivering VYHTT01 directly into the thalamus. We chose this delivery approach based on our understanding of the disease pathology and the importance of delivering Vector to the striatum as well as to the cortex. Pathological changes in Huntington's disease are evident first in the striatum, with changes in the cortex becoming noticeable as the disease progresses. In fact, certain areas of the brain of a patient with Huntington's disease are deteriorating well before symptoms appear.
We chose this delivery approach based on our understanding of the disease pathology.
Important delivering back to this triton as well as to the cool tax.
Pathological changes of Huntingtons disease, I evident earliest in this triton with changes in the quarter, becoming noticeable at the disease progresses.
In fact certain areas, that's the brain as a patient huntingtons disease.
Oh deteriorating well before the Simpsons, Japan.
The following us in contrast, as a lot sheet present structure in the early stages of Huntingtons disease.
Delivery of how gene therapy to the Solidness as well as to the be time and should allow us to deliver enough back into the impact to strengthen as well as leverage the rich connections between the following this and the cool types to reach the out to brain.
Last month, the European Society of gene and cell therapy meeting in Barcelona, We presented an update on all the white https. Every one program during an oral platform presentation.
We previously presented data on dice dependent back to buy a distribution.
That's why does HCT and Lauren I know down in the brains of non human primate.
Omar Khawaja: The thalamus, in contrast, is a largely preserved structure in the early stages of Huntington's disease. Therefore, delivery of our gene therapy to the thalamus, as well as to the putamen, should allow us to deliver enough vector to impact the striatum, as well as leverage the rich connections between the thalamus and the cortex to reach the outer brain. Last month, at the European Society of Gene and Cell Therapy meeting in Barcelona, we presented an update on our VYHTT01 program during an oral platform presentation. We previously presented data on dose-dependent vector biodistribution, as well as HTT mRNA knockdown in the brains of non-human primates.
Our recent presentation, we provided new evidence that the why HCT easier at one also especially lets Huntington probably team.
On the Huntington, probably seen reduction in commensurate with the M&A lowering and back to genome distribution in the NHP brain regions analyze.
These findings provide further evidence that all gene therapy deliver to the soundness and be time and result in significant reductions in HCT and Laura <unk> and in Huntington protein levels that are predicted to be clinically efficacious.
We now expect filing an IP for B y axis easier I want the huntingtons disease during the first half 2020 .
As the kinetic some Huntington knockdown appeared to be difference in non human primate spend in right and we plan on submitting a nine de application with final one year data from a preclinical studies instead of the previously planned interim six months days huh Okay.
Omar Khawaja: In our recent presentation, we provided new evidence that VYHGT01 also efficiently lowers Huntington's protein, and that Huntington's protein reduction is commensurate with the mRNA lowering and vector genome distribution in the NHP brain regions analyzed. These findings provide further evidence that our gene therapy delivered to the thalamus and butamen results in significant reductions in HDT, mRNA, and in Huntington protein at levels that are We now expect to file an IND for VYHTT01 for Huntington's Disease during the first half of 2020. As the kinetics of Huntington knockdown appear to be different in non-human primates than in rodents, we plan on submitting an IND application with final one-year data from our preclinical studies, instead of the previously planned interim six-month data. Our goal is to minimize the amount of time between IND acceptance and the first patient dose. We will be leveraging our related clinical experience in Parkinson's disease to achieve this. Activities towards site selection engagement have already begun and will continue to take place in the fourth quarter and beginning of 2020.
Our goal is to minimize the amount of time between R&D acceptance in fast patient nice we will be leveraging all related clinical experience in Parkinson's disease to achieve this.
Activities towards site selection engagement have already begun and we'll continue to take place in the fourth quarter and the beginning of 2020 .
We continue to expect screening and dicing assess patients on clinical study during 2020 .
Our other pipeline programs, including the Friedreichs ataxia program with your question I know two back twice antibody programs with Abbvie continue to progress.
Working on studies to support lead candidate selection for Friedreichs ataxia and continue to deliver on or ahead of schedule against how what kind on the I'd be collaborations.
Additionally, we've agreed on the two discoveries listener crane and are working on Orion discovery efforts against new targets.
With our focus and expertise and neurological disease.
With the sitting several opportunities that are compelling target say the gene therapy.
We expect to provide more information on new pipe and during 2020 .
I'll now pass the call onto the Celestica the financial update.
Thank you Omar.
Voyager reported net loss of 15 million or 41 cents per share for the third quarter ended September Thirtyth 29 team compared to net loss of 20.3 million or 63 cents per share for the third quarter of 2018.
Collaboration revenues of 20.4 million for the third quarter ended September Thirtyth 2019, compared to collaboration revenues of 2.1 million for the third quarter of 2018.
These 2019 revenues reflect the recognition of noncash amounts for research services that were formed for various programs under the Abbvie Neurocrine collaboration agreements. In addition to amounts expected to be reimbursed by NERC trend as per that collaboration agreement.
Phyllis: We continue to expect screening and dosing of the first patient in a planned clinical study during 2020. Meanwhile, our other pipeline programs, including the Friedrichs-Ataxia program with Neurocrin and our two vectorized antibody programs with AbbVie, continue to progress. We're working on studies to support lead candidate selection for Friedrichs hytaxia and continue to deliver on or ahead of schedule against our work plans for the ADVI collaboration. Additionally, we've agreed on the two discovery trips with Neurocrin and are working on our own discovery efforts against new targets, with our focus and expertise in neurological disease. We're pursuing several opportunities that are compelling targets for AAV gene therapy. We expect to provide more information on new programs during 2020. I'll now pass the call on to Phyllis for the financial update.
Amounts can vary based on quarterly assessments of our efforts under each of these collaborations.
The increase in collaboration revenue during the third quarter of 2019 compared to the same period in 2018, primarily relates to the recognition of amounts from the NERC trend and Abbey Alpha Synuclein collaboration both of which were entered into in Q1 2019.
Additionally, revenue related to the Abbvie Tao collaboration increased year over year as our efforts continue to increase.
These increases were offset by a reduction in collaboration revenue from our collaboration with Sanofi Genzyme, which was restructured in June 2019.
R&D expenses of 29.8 million for the third quarter ended September Thirtyth 2019, compared to 16.6 million for the third quarter of 2018. These expenses include costs incurred under the Neurocrine collaboration which are expected to be reimbursed.
Phyllis: Thank you, Omar. Voyager reported a net loss of $15 million, or $0.41 per share, for the third quarter ended September 30, 2019, compared to a net loss of $20.3 million, or $0.63 per share, for the third quarter of 2018. Collaboration revenues of $20.4 million for the 3rd quarter ended September 30, 2019, compared to collaboration revenues of $2.1 million for the 3rd quarter of 2018. These 2019 revenues reflect the recognition of non-cash amounts for research services that were performed for various programs under the AbbVie and Neurocrin collaboration agreements in addition to amounts expected to be reimbursed by Neurocrin as per that collaboration agreement. These amounts can vary based on quarterly assessments of our efforts under each of these collaborations. The increase in collaboration revenue during the third quarter of 2019 compared to the same period in 2018 primarily relates to the recognition of amounts from the Neurocrin and AbbVie Alpha-synuclein collaborations, both of which were entered into in Q1 2019.
The increase in R&D expenses in the third quarter of 2019 related primarily to external research and development costs and increased employee related and facility costs to support the advancement of our pipeline programs, including our restore one phase two clinical trial for Vyšehrad C.
General and administrative expenses of 8.5 million for the third quarter ended September Thirtyth 2019, compared to 6.6 million for the third quarter of 2018 increase in gene expenses in the third quarter of 29 team is primarily due to an increase in employee related and facility.
Cost to support the advancement of our pipeline programs and growing operations.
At September Thirtyth 29 team, we had 307.4 million in cash cash equivalents and marketable debt securities compared to 155.8 million at December 31st 2018.
Operating expenses are anticipated to be 150 million to 155 million exceeding our previously forecasted range of 140 million to 150 million largely as a result of higher than planned noncash expenses.
Nevertheless, we continued to project yearend cash cash equivalents and marketable debt securities to be in the previously forecasted range of 280 million to 290 million based on our current operating plans. We expect these amounts to be sufficient to meet our operating needs and capital expenditure requirements and.
Phyllis: Additionally, revenue related to the AbbVie Tau collaboration increased year over year as our efforts continued to increase. However, these increases were offset by a reduction in collaboration revenue from our collaboration with Sanofi Genzyme, which was restructured in June 2019. R&D expenses of $29.8 million for the third quarter ended September 30, 2019, compared to $16.6 million for the third quarter of 2018. These expenses include costs incurred under the Neurocrine Collaboration, which are expected to be reimbursed.
Mid 2022.
With that we would like to now open the call up for questions operator.
Ladies and gentlemen to ask a question you'll need to press star one on your telephone to withdraw your question first the pound.
And the interest time, we ask that you. Please limit yourself to one question and one follow up if you have any additional questions you may rejoin the queue. Please standby what we've compiled if you want a roster.
And our first question comes from Phil Nadeau with Cowen and company. Your line is now open.
Good morning, Thanks for taking my question my questions on the audience program you mentioned in your prepared remarks that pick one year data is necessary for the R&D given the difference in connection that knock down between rodents and non human primates, you talk a little bit more about the difference.
Phyllis: The increase in R&D expenses in the third quarter of 2019 related primarily to external research and development costs and increased employee-related and facility costs to support the advancement of our pipeline programs, including our RestoreOne Phase II clinical trial for VYAADC. General and administrative expenses of $8.5 million for the third quarter ended September 30, 2019, compared to $6.6 million for the third quarter of 2018. The increase in G&A expenses in the third quarter of 2019 is primarily due to an increase in employee-related and facility costs to support the advancement of our pipeline programs and growing operations. As of September 30th, 2019, we had $307.4 million in cash, cash equivalents, and marketable debt securities compared to $155.8 million at December 31st, 2018.
What exactly you're seeing and wise, one year data more informative and six month it.
Yeah. Thanks, Phil for that question, Scott Omar to address it.
Yeah. So in a back in 2017 voyage I had a pre I'd meeting with FDA and in the discussion around that the Senator toxicology and patient study.
That was a.
The feedback from the FDA.
Was that like to time points for assessments of toxicology.
Should match the kinetics tons. Your next question and specific requests.
I would have been sat with the onset Pete.
Especially in of the funds James.
<unk> at 26 weeks.
Just the by analytics, we had we done yet I'm confident that we can say that the truancy next question has.
That being knocked down.
Phyllis: Operating expenses are anticipated to be $150 million to $155 million, exceeding our previously forecasted range of $140 million to $150 million, largely as a result of higher-than-planned non-cash expenses. Nevertheless, we continue to project year-end cash, cash equivalents, and marketable debt securities to be in the previously forecasted range of $280 million to $290 million. Based on our current operating plans, we expect these amounts to be sufficient to meet our operating needs and capital expenditure requirements into mid-2022. With that, we would like to now open the call to questions. Operator?
Impact it's also fit.
Hey, as well so that's why that's the reason that we decided to no submit within trims 26, we take that continue to studies 53 week.
I've met with the full dataset.
That's helpful in I guess.
When you say hasn't plateaued is the level of knockdown continuing to increase or is it decreasing towards the plateau.
And what are the implications for the human data when what time point do you think human proof of concept data. Therefore will be available is that there's going to take 52 weeks a follow up for that as well.
Yeah. That's a great question I mean, I think it's not say much that.
And then knockdown of 18 level haven't outside but we really need another data point to ensure that that is a true plots had rather than a you know that's just to time points that was saying that we've got caught not found in its stable I think they need to have.
Operator: Ladies and gentlemen, to ask a question, you will need to press star 1 on your telephone. To scroll through your question, press the pound.
I had one to the south into that.
Operator: In the interest of time, we ask that you please limit yourself to one question and one follow-up. If you have any additional questions, you may rejoin the queue. Please stand by while we compile the Q&A roster. And our first question comes from Phil Nadeau with Cowan & Company. Your line is now open. Good morning.
I think we'll probably have to directly.
Extrapolate that two to the human situation until we actually conduct the human study actually difficult snipe, how that extrapolate, but it's definitely employ a based on what we hope that they thought that.
On the on that probably fall that we see so far it means that it's likely that it's going to be at least three months and they can then that we would see the maximum expression of the funds Jane.
Philip M. Nadeau: Thanks for taking my question. My question is on Huntington's program. You mentioned in your prepared remarks that you think one-year data is necessary for the IND, given the difference in kinetics in the knockdown between rodents and non-human primates. Can you talk a little bit more about the difference, what exactly you're seeing, and why is one-year data more informative than six-month data?
Just to answer the clarification the fail what we're seeing is a continued reduction in or increase in a knock down overtime.
So that's the direction. So if that that's going to be a positive clinically that the you have a the peach lowering that's is higher than the what we've observed at the five weeks in the earlier studies, what as Omar said, what we're looking to have is just a comfort that.
Andrei Teren: Yeah, thanks, Phil, for the question. I'll ask Omar to address it.
Omar Khawaja: Yeah, so back in 2017, Voyager had a pre-IND meeting with the FDA, and in the discussions around the definitive toxicology and biodistribution study that was planned, the feedback from the FDA was that the selected time points for the assessment of toxicology should match the kinetics of transgene expression, and the specific request was that the time points would coincide with the onset, peak, and plateaued expression of the transgene. At 26 weeks, in terms of the bioanalytics we have, we don't yet, and aren't yet confident that we can say that the transgene expression has plateaued and that the knockdown impact is also at its plateau as well. So that's why, that's the reason that we decided to not submit with interim 26 week data but to continue to study to 53 weeks and submit with a full data set.
We have an understanding of how low it goes and at what point to that that has achieved.
That's very helpful. Thanks for taking my question.
Thank you.
Thank you and our next question comes from Charles Duncan with Cantor Fitzgerald. Your line is no.
Hi, guys. Thanks for taking the question condolences to Alison and question on the PD program and then a follow up on H.T. program regarding the P.D. program I'm wondering if you said that you have agreed to the stat plan with Neurocrine.
For restore and I'm just kind of wondering if you can provide additional color now that you're thinking about what to do there in terms of the patient population.
Are you seeing and timing for restore one can you provide any additional color on that.
Yeah. Thanks transferred a question. So at this stage, we're not ready yet to give a the further guidance as to the exact size of this study we anticipate as we've said previously that it will be in the range that we've guided.
Omar Khawaja: That's helpful. And I guess...
Omar Khawaja: When you say it hasn't plateaued, is the level of knockdown continuing to increase, or is it decreasing towards a plateau? And what are the implications for the human data? At what time point do you think human proof-of-concept data will be available? Is it going to take 52 weeks of follow-up for that as well?
75 to 100 patients.
And the work that we've done there's just to determine.
I would argue partner.
What are the precise targets is going to be what it does range and then to get that same alignment with the agency. So.
Why do we have that.
Omar Khawaja: Yeah, that's a great question. I mean, I think it's not so much that the knockdown and protein levels haven't plateaued, but we really need another data time point to ensure that that is a true plateau rather than, you know, that's just two time points that we're saying that we've got knocked down and it's stable. I think we need to have a third one to be certain of that. I think we'll probably have to directly extrapolate that to the human situation until we actually conduct the human study. It's going to be difficult to know how that's extrapolated, but it certainly implies, based on what we've observed so far, that on the profile that we see so far, it means that it's likely that it's going to be at least three months in the human before we would see the maximum expression of the transgen
In alignment with the agency, we're going to be able to provide.
That update along with an update on that given the number of patients and where we're at and the enrollment.
Some on your targets for one we expect to.
I'll be able to complete enrollment to the full enrollment this study.
Okay. That's it sounds consistent with your previous thinking and then if I can ask a follow up on that there are other E. D. C gene therapy programs for neuro indications and Omar did a great job in terms of talking about your different.
Okay, some with regard to wear.
Hi, there the drug is it's really administered but I guess, if you look across a DC programs. How do you see you being differentiated from others in terms of say vector user basic construct.
Omar Khawaja: Just to add to the clarification, Phil, what we're seeing is a continued reduction or increase in the knockdown over time. So that's the direction. And if that could be positive clinically, that you have the peak lowering that is higher than what we've observed at five weeks in the earlier studies.
Yeah. Thanks for that question and Omar can add to it but I think in his prepared remark you touched on a key differentiation, which is this a activity or to modulate that their response, a with the control of the Zogenix 11 dopa.
Omar Khawaja: That's very helpful. Thanks for taking my question. Thank you. Thank you. And our next question comes from Charles Duncan with Cantor Fitzgerald. Your line is now open. Hi guys.
So that I think is a in contrast to with the Oh alternative approach that's in development, which.
Provides a more direct production up dope I mean.
Our approach as one again as highlighted that allows for the dialing of the amount of domain to be produced I'm like that are delivering our delivery in the putamen.
Charles Duncan: Thanks for taking the question, and condolences to Allison. I had a question on the PD program, and then a follow-up on the HD program. Regarding the PD program, I'm wondering. You said that you have agreed to the stat plan with Neurocrin for Restore. And I'm just kind of wondering if you can provide additional color now that you're thinking about what to do there. In terms of the patient population sizing and timing for Restore 1, can you provide any additional color on that?
Isn't that comment and that's a good targets to have a stable reservoir of that enzyme as it's a structure that is not the two impact and in Parkinson's disease, and and we've been able to observe in our.
Experience to date, a in a in our preclinical experience that the.
Very durable expression of the enzyme production.
Andrei Teren: Yeah, thanks, Chas, for the question. So at this stage, we're not ready yet to give further guidance as to the exact size of this study. We anticipate, as we've said previously, that it will be in the range that we've guided, 75 to 100 patients, and the work that we've done is just to determine with our new partner what the precise target is going to be within that range, and then to get that same alignment with the agency. So when we have that in alignment with the agency, we're going to be able to provide that update, along with an update on, given the number Okay.
In the after administration and if you Damon.
It also marianna highlight any additional points, yeah, I think the anything to add to that in handsets that differentiation.
That's the lighting Avi too because we want to restrict.
Distribution at the back to two.
And I think one of the things that we plan on.
<unk>.
That it's not just the actual concentration if they didn't deliver but ill say the coverage.
And I think a important.
Use of Entropic Tomorrow, I I'd be administration of gene therapy, together with a contrast.
And add to ensure that we already restricting.
The placement.
Two other REIT structure that will say with that right degree distribution is challenging with and within that structure as well.
Andrei Teren: Okay, that sounds consistent with your previous thinking, and then if I can ask a follow-up question on that. You know, there are other AADC gene therapy programs for neuroindications, and Omar did a great job in terms of talking about your differentiation with regard to where the drug is really administered, but I guess if you look across AADC programs, how do you see you being differentiated from others in terms of, say, vector use or basic constructs?
Got it that's helpful last question on the Huntingtons with regard to the patient population.
What are you thinking about in terms of what would be the best tied to patient to evaluate initial activity and thanks for taking all the questions.
Yeah that said that's been an important consideration for us I mean that he two factors one it's ultimately obviously that.
Omar Khawaja: Yeah, no, thanks for that question, and Omar can add to it. But I think in his prepared remark, he touched on a key differentiation, which is this activity to modulate the response through the control of the exogenous levodopa. So that, I think, is in contrast with an alternative approach that's in development, which provides a more direct production of dopamine. Our approach is one, again, as highlighted, that allows for the dialing of the amount of dopamine to be produced. Like that. Our delivery in the Putamen is common, and that's a good target to have a stable reservoir of that enzyme as it's a structure that is not too impacted in Parkinson's disease, and we've been able to observe in our experience today, in our preclinical experience, that very durable expression of the enzyme production after administration and imputament. I don't know.
And.
Gene therapy in.
It's going to be.
Oh, I should let jean than Ive been any nerds degenerative condition that B.L. yeah.
Given the better in early clinical development goals that we call it.
Take patients who are.
Let's say the ice and snow, but at what we really want to do is kick off our development pipeline in a population that as closely as.
Well support eventual.
Of the gene therapy.
In the broader safely.
Ed.
The second thing is actually just the.
Selection of the patients that have the.
Yeah.
Intact, so that structures that the gene therapy is going to be type and I'd say again add just based on 87, a seven subjects.
And our I study.
General we really on.
And then eventually Haven.
Very significantly the generated.
Omar Khawaja: Yeah, I think the only thing to add to that in terms of differentiation with the approach is that our approach is purposely selecting AV2 because we want to restrict the distribution of the vector to the putamen. And I think one of the things that we've learned through the Phase 1B programs is that it's not just the actual concentration of the vector that's being delivered but also the coverage of the putamen. And I think an important part of our program is the use of intraoperative MRI and the administration of gene therapy together with a contrast agent to ensure that we are really restricting the placement of the vector into the right structure.
Page one.
So we.
Okay.
Early stages.
That's helpful. Mark Thank you.
Thank you. Our next question comes from Dane Leone with Raymond James Your line is now open.
Hi, Thank you for the update.
This one one specific question regarding the Huntingtons program since its interoperate Pericom all.
Are you going to be able to use nfls a biomarker for these patients potentially versus what we've seen with interest equal approaches for the arent aaas stuff with like Ioannis and Roche.
And then the second question is when will we have a little bit more clarity would you expect in terms of enrollment updates and timeline for a that the pivotal Parkinsons program.
Omar Khawaja: Got it. That's helpful. Last question on Huntington's. With regard to the patient population, what are you thinking about in terms of what would be the best type of patient to evaluate initial activity? And thanks for taking all the questions.
Yeah. Thanks, Dane first a question. So yes, we do plan on that capturing a fit on it never felt like chain as one of our fluid biomarkers into Huntingtons program. We will have a other biomarkers fluid biomarkers, we will have some color metric.
Omar Khawaja: Yeah, that's been an important consideration for us. I mean, there are two factors. One is that ultimately, obviously, the potential for gene therapy in Huntington's is going to be for all patients who are gene positive, and as in any neurodegenerative condition, the earlier it's given, the better. In early clinical development, of course, we can't take patients who are completely asymptomatic. But, you know, what we really want to do is kick off our development program in a population that closely matches or will support the eventual use and uptake of the gene therapy in the broader safety population that could benefit. The second thing is actually just the selection of the patient that has the intactness of the structures that the gene therapy is going to be placed into. And so, again, just based on our 87-subject MRI study that was conducted with Mass General, we really understand that both CORT8 and then eventually the containment become very significantly degenerated as you move past stage one. And so we are going to target patients in the earliest stages.
Biomarkers as well so that say.
That's a part of the plan to capture a lot of these data points in the early clinical experience.
As for to be the program and providing guidance or where we have to do this now jointly with our partner with a nonrecurring and as stated previously we are waiting to have the in but how many patients were going to target to recruit and the full.
Study.
To align them with our enrollment rate to be able to provide an update on the.
Enrollment so target for completing the study.
We also plan.
To be able to.
Share an update on the activities towards the second pivotal which we're planning a so.
Again, we're looking to get a regulatory guidance before the end of this year on the program. So as soon as we have that we should be able to jointly with our partner provide buddies updates.
Gives a further clarity as to timing.
Omar Khawaja: That's helpful, Mark. Thank you. Thank you. Our next question comes from Dane Leone with Raymond James. Your line is now open.
Timing for this one and a subsequent a trial that we we continue to plan to do and staggered a parallel fashion.
Ahead of the completion of the restore one study.
Dane Leone: Thank you for the update. I had, uh, one specific question regarding the Huntington's program since it's intraparachymal. Are you going to be able to use NFL as a biomarker for these patients, potentially, versus what we've seen with the intrathecal approaches for the RNAi stuff with like Ionis and Roche? And then the second question is, when will we have a little bit more clarity, would you expect, in terms of enrollment updates and timeline for the Pivotal Parkinson's program?
Okay and the last one for me I guess since its November maybe it's fair to ask.
Is there any update in terms of what your team hopes against the clinic next year.
With either a wholly owned programs are partnered programs.
<unk>.
Yeah. So the for it to get Intrexon Act as a second program for US a into the clinic.
We're looking at our Huntingtons program as guided.
Omar Khawaja: Yeah, thanks, Dane, for the question. So yes, we do plan on capturing neurofilament light chain as one of our fluid biomarkers in the Huntington's program. We will have other biomarkers, fluid biomarkers. We will have some polymetric biomarkers as well.
And Ah we we our plan is as expressed that we'll look to have the first a patient both screen and treated.
During the year next year.
We continue to looked at all the Unfortunately is also externally that may.
Omar Khawaja: So that's part of the plan to capture a lot of these data points in the early clinical experience. As for the PD program and providing guidance, we have to do this now jointly with our partner, Neurocrin. And as stated previously, we are waiting to have the input of how many patients we're going to target to recruit in the full study to align then with our enrollment rate to be able to provide an update on the enrollment target for completing the study. We also plan to be able to share an update on the activities towards the second pivotal study which we're planning. So again, we're looking to get regulatory guidance before the end of this year on the program, and as soon as we have that, we should be able, jointly with our partner, to provide these updates to give further clarity as to timing for this one and the subsequent trial that we continue to plan to do in a staggered, parallel fashion ahead of the completion of the Restore One study.
Accelerates our pipeline and that's a benefit a again of our focus on the easy for neurological diseases that we have the ability to have a.
An opinion on every.
A program that's out there and a if there is.
In the future, a enabling technology or an early stage program that we think and compelling a compelling away.
Add to our portfolio accelerator effort, we will rollout will be a good position to.
Make an assessment of that so at this time its really about the the Huntingtons program, becoming another clinical program and following a behind that is off predicts attacks. Yeah for the also in a co development way with NERC rent.
And then a right behind our a lot of these oh earlier stage program and that we are advancing in parallel.
And again that the discovery platform that have not yet been disclosed we are expecting next year decided a fortunately to provide a.
An update as to the progress we're making against these new targets.
Andrei Teren: Okay, and the last one for me, I guess since it's November, maybe it's fair to ask, is there any update in terms of what your team hopes to get into the clinic next year with either wholly owned programs or partnered programs? Thank you.
Thank you.
Welcome.
Thank you. Our next question comes from Jim Birchenough with Wells Fargo. Your line is no.
Hi, guys. Thanks for the update and the opportunity to follow up so just a couple of questions on the Parkinson's disease program. As we look ahead to 11, a one in 11 nocita longer term call what could you maybe speak to the expected natural history of those patients over a two to three year period, given their stage disease.
Andrei Teren: Yeah, so the for it to get into the clinic as a second program for us to get into the clinic, we're looking at our Huntington's program as guided. And we, our plan is, as expressed, that we'll look to have the first patient both screen and treated during the year next year.
And what we should look for over the longer term with the gene therapy.
Yeah. Thanks, Jim first question Oscar Omar to start with the answer yes. Thanks, Jim the one of the actions that we've taken that as one of the exploratory endpoints and 11 I wanted to mentioned this disease stage and keep the modified Hudson yards.
Andrei Teren: We continue to look at all the opportunities also externally that may accelerate our pipeline, and it's a benefit again of our focus on AAV for neurological diseases that we have the ability to have an opinion on every program that's out there, and if there is. In the future, enabling technology or an early stage program that we think can, in a compelling way, add to our portfolio accelerator effort, we will be in a good position to make an assessment of that. So at this time, it's really about the Huntington's program becoming another clinical trial. And following behind that is our Friedrichs ataxia effort, also in a co-development way with Neurocrin. And then right behind are a lot of these earlier stage programs that we are advancing in parallel. And against that discovery platform that has not yet been disclosed, we are expecting next year to find an opportunity to provide an update as to the progress we're making against these new targets.
And that basically as a an assessment of the patients rule welcome Tony and symptoms.
As I have that disease, where assets are over several years and patients move along.
Stages at depending on the degree of involvement or whether things are just happening on one side.
And then we'll say the degree of instability, which relates to the big more well they did season concessions which is.
Our full.
And data that we presented that a month ago at that movement disorder Society and will present did not say on loans and data suggest that patient starts at prior to treatment and at fairly advanced stages. If that had any also stage three and pool and that at that time points that we bought.
Already published and then we'll we'll provide that full data that we had data from 11 I one plus two year enough and then two data that these patients actually moving back and stage. It said that would be on anticipated by natural history alone.
Andrei Teren: Our next question comes from Jim Bertroneau with Wells Fargo. Your line is now open.
Yeah, I will add that we will continue to.
Jim Bertroneau: Hi guys, thanks for the update and the opportunity to follow up. So just a couple questions on the Parkinson's disease program as we look ahead to 1101 and 1102 longer-term follow-up. Could you maybe speak to the expected natural history of those patients over a 2 to 3 year period, given their stage of disease, and what we should look for over the longer term with the gene therapy?
Look at then we'll provide updates on both the patient reported outcomes and and physician a assess the status and the last one that Omar mentioned isn't that category.
So that we get a real full picture of the amelioration the patients or are they have.
And over longer time.
Time period. So there is natural history that we will leverage the that exists for Vince BD, but we're also working what our partner to substantiate the what exists with some patient cohorts that more.
Omar Khawaja: Yeah, thanks Jim for the question. I'll ask Omar to start with the answer.
Omar Khawaja: Yeah, thanks, Jim. The, you know, one of the measures that we've taken as one of the exploratory endpoints in 11.01 and 11.02 are measures of disease staging, particularly the modified Hernan-Yarn. And that basically is an assessment of the patient's overall Parkinsonian symptoms as the disease progresses over several years. And patients move along stages, depending on the degree of involvement of whether things are just happening on one side of the body or both, and then also the degree of instability, you know, which relates to one of the big morbidities in Parkinson's, which is four. And the data that we presented a month ago at the Movement Disorders Society, and we'll present an update on long-term data, suggests that patients started prior to treatment in fairly advanced stages of the Hernan Llarso Stage 3 and 4, and that the time points that we've already published, and then we'll provide the full data, three-year data from 11-01 plus two-year 11-02 data, that these patients are actually moving back in stages, so that would be unanticipated by natural history alone.
Closely matched the ones that are enrolled in our trial so more to come on this as ball, but but clearly as the Omar shared a in his prepared remarks earlier.
It's a contrast of patient reported and finish and assess the improvements against a natural history or as we get the longer and longer data points becomes increasingly significant and likely in sharper and sharper contrast with ER.
What that normally occurs in a neuro degenerative disease.
I think and things to look out for I guess.
I think it's good.
So.
Well that say, all I, whether or not they move in the same directional say like a alone.
And then I think the second thing that will be important to look for it in terms of the patients use of that that's in the magic medications and whether this is happening on the backgrounds or reduce staple or actually patients still needing to increase the amount of exogenously.
Okay.
Yes. So these long term long term results are exciting for us I think they're gonna be are important also for the field to have these types of long term gene therapy results and one last point on this is that's it.
Andrei Teren: Yeah, I will add that we will continue to look at and will provide updates on both patient-reported outcomes and physician-assessed status, and the last one that Omar mentioned is in that category, so that we get a real full picture of the amelioration that the patients may have over a longer time period. So there is natural history that we will leverage that exists for advanced PD, but we're also working with our partner to substantiate what exists with some patient cohorts that more closely match the ones that are enrolled in our trial. So more to come on this as well, but clearly, as Omar shared in his prepared remarks earlier, this contrast of patient-reported and clinician-assessed improvements against the natural history as we get longer and longer data points becomes increasingly significant and likely in sharper and sharper contrast with what normally occurs in a neurodegenerative disease.
As Omar noted we have an extension study so projecting forward, we will have even longer data points a that beyond the three year.
A period of the 11 or 111 11 or two studies.
And then just Andre following up on your prior comments on evaluating external asset.
That leverage your capabilities could you could you maybe speak to what are the kind of things that you're looking for if you were to source an external.
I'd gene therapy opportunity and maybe contrast that with Parkinson's as an example, [noise].
Yeah, Yeah. Thanks, Jim So our focus will remain on that Uh huh.
Leveraging our internal expertise to be able as we do are doing right now to a discover in advance programs, we have a lot of.
In our expertise and we've invested in our discovery engine to be able to to have a consistent flow obi Andy opportunities or behind our lead programs at the moment. So that's the primary approach, but but again big.
Omar Khawaja: I think the things to look out for, as Andre said, I think it's going to be the confluence of these measures as well, whether or not they move in the same direction and stay like that over the long term. And then I think the second thing that will be important to look for is in terms of the patient's use of other desmenergic medications and whether this is happening on a background of reduced, stable, or actually patients are still needing to increase the amount of exogenous levodopa that they're taking.
Cause we have the benefit of that focus.
We are in a actively scanning to space in discussions actively with Ah Ah leaders in academia and certain companies that have a program, but less of a focus less of that the.
Andrei Teren: Yes, so these long-term results are exciting for us. I think they're going to be important also for the field to have these types of long-term gene therapy results.
Focus on the Avi narrower than we do.
Where we think.
Our efforts and our capabilities could that go to help accelerate efforts.
Omar Khawaja: One last point on this.
So in terms of the profile of what we look it can be enabling technologies that they complement the.
Omar Khawaja: As Omar noted, we have an extension study, so projecting forward, we will have even longer data points beyond the three-year period of the 1101 and 1102 studies.
What we have and Ah.
And what we're going to be looking for for any program. What are their denovo in house programs are external are ones, where we have a thick there genetic.
Jim Bertroneau: And then just, Andre, following up on your prior comments on evaluating external assets that leverage your capabilities, could you maybe speak to what are the kind of things that you're looking for if you were to source an external AAD gene therapy opportunity and maybe contrast that with Parkinson's as an example?
Or a biological validation of the target.
Where we can have some claire and fairly rapid and a proof of concept a attainment.
And and probably the most overarching criteria is where we think we can have the biggest impact or four patients. So where we think the clinical utility would be the highest so so these are guiding principles, but.
Andrei Teren: All right.
Andrei Teren: Thanks, Jim. So our focus will remain on leveraging our internal expertise to be able, as we are doing right now, to discover and advance programs. We have a lot
Again Betsy.
Inclination that we have to not the only rely on our internal a source of innovation, but make sure that word.
Andrei Teren: In-house expertise, and we've invested in our discovery engine to be able to have a consistent flow of IND opportunities behind our LEAD programs at the moment. So that's the primary approach, but again, because we have the benefit of that focus. We are actively scanning the space and having active discussions with leaders in academia and certain companies that have a program but less of a focus, less of that focus on the AAV now than we do, where we think our efforts and our capabilities could help accelerate efforts. So in terms of the profile of what we look for, it can be enabling technologies that complement what we have. And what we're going to be looking for, for any program, whether they're de novo, in-house programs, or external, are ones where we have a clear genetic or biological validation of the target, where we can have some clear and fairly rapid proof of concept attainment.
Very very originally connected with the external environment and that's what we've invested in doing in the past year.
Terrific. Thanks for taking the questions.
Thank you as a reminder, ladies and gentlemen that Star then once asked the question.
Your next question comes from Jeff on with Morgan Stanley . Your line is no open.
Thanks for taking the questions to clarify with over 20 active sites for restore one have you begun to enroll patients.
Yes, we have.
Yes.
As you know to a pretty much all of our sites a active and.
Enrolling so the study Oh continues to move while and Oh, we have.
Earlier this year.
All right in fact, a late last year initiate and the the study a and it continues to progress while.
Okay. Thanks, and then for sod one or two I guess can you provide an update on where you are preparing for now hi, Andy and what remains outstanding any can you remind us if you will continue preclinical studies, while looking to partner the program, where we wait for a partner to complete the studies needed for 90. Thanks.
Andrei Teren: Probably the most overarching criteria is where we think we can have the biggest impact for patients, so where we think the clinical utility would be the highest. So these are guiding principles, but again, that's an... Inclination that we have to not only rely on our internal source of innovation but make sure that we're very, very richly connected with the external environment. And that's what we've invested in doing in the past.
Yeah, Thanks, Jeff so far to sort of on the program or we are completing the work that was initiated.
As we continue to entertain discussions, but others. So we can't comment obviously on the.
Potential transactions.
Jim Bertroneau: Terrific, thanks for taking the questions. Thank you. As a reminder, ladies and gentlemen, that's star then one to ask a question.
Got it remains our intention to partner.
On the sort of on so we continue to advance our efforts there.
On Saudi one but more broadly.
In a allies.
Thanks.
Thank you. Our next question comes from Laura Chico with Wedbush Securities. Your line is no.
Jeff Hung: Our next question comes from Jeff Hung with Morgan Stanley. Your line is now open. Thanks for taking the questions. To clarify, with over 20 active sites for RestoreOne, have you begun to enroll patients?
Hi, good morning, and thanks for taking the question I guess one on the Parkinsons program you mentioned the phase three program.
If you could just step back and remind us on the dosing.
Andrei Teren: Yes, we have. We have, as you know, pretty much all of our sites active and enrolling. So the study continues to move well. And we have earlier this year, or, in fact, late last year, initiated the study, and it continues to progress well.
What gives you confidence in that the dose selected as the optimized one.
Yeah, Thanks, Laura Omar.
Yeah, Hey, Great question say, we conducted two phase one be study I'm.
Jeff Hung: Okay, thanks. And then for SOD 102, I guess, can you provide an update on where you are preparing for an IND and what remains outstanding? And can you remind us if you'll continue preclinical studies while looking to partner the program, or will you wait for a partner to complete the studies needed for an IND? Thanks.
11, I one was a single ascending doses of the fact that and that essentially that has contributed intensive I'm standing foams. Some political response to that is increasing devices and then at PD Eleveneight two was a collection of that.
At dice between the dice and two and three in 11 I won but this time, a using the pace to interject, we'd rather than in front of stack trade fuel injection into the payment and this is because the at summer logical response seems to rely not just on.
Andrei Teren: Yeah, thanks Jeff. So for the SODIWAN program, we are completing the work that was initiated as we continue to entertain discussions with others. So we can't comment obviously on potential transactions, but it remains our intention to partner on SODIWAN, so we continue to advance our efforts there on SODIWAN, but more broadly in ALS.
The actual amounts of back to that placed into the payment, but also a distribution all that bad theatrical coverage of excitement with debt and thought collection on infusion.
Laura Kathryn Chico: Thank you. Our next question comes from Laura Chico with Wedbush Securities. Your line is now open. I guess one on the Parkinson's program. You mentioned the phase three program.
The dates that we selected for the pivotal trial.
The dice that we think ultimately combined coverage as well at the absolute number genome is being placed in the retainment and that has really given that most all small responsive and that add to face won't be studies.
Laura Kathryn Chico: If you could just step back and remind us of the dosage.
Laura Kathryn Chico: What gives you confidence in the dose selected as the optimized one?
Omar Khawaja: ...
Omar Khawaja: Yeah, thanks, Laura. Omar.
Omar Khawaja: Yeah, it's a great question. So, we conducted two Phase 1b studies. So, 1101 was single ascending doses of the vector, and essentially, that has contributed in terms of understanding the pharmacological response to those increasing doses. And then, PD1102 was a selection of a dose between the doses in cohorts 2 and 3 in 1101, but this time, using the posterior trajectory rather than a frontal trajectory for injection into the putamen. And this is because the pharmacological response seems to rely not just on the actual amount of vector that's placed into the putamen but also on its distribution, the actual coverage of the putamen with the convection-enhanced infusion. So the dose that we selected for the pivotal program is the dose that we think optimally combines coverage as well as the absolute number of vector genomes being placed in the putamen. And that has really given the most optimal responses in the two-phase, one-B studies.
Thank you and just one quick follow up if I could could you talk a little bit more about your expected capacity to supply the market. I. Obviously are you starting phase three but as you're getting to a potential launch stage what would be your capacity is it's quite a market on a patient number basis.
Yeah, I'll ask a madoff morar, Chief operating officer to address your question, though.
Good morning.
We made the decision early and voyagers history to invest into Baculovirus platform and so our Parkinsons program.
Was the first program to be transition from what had previously been a triple transfection platform for prior studies.
We get the comparisons and 90 amendment with the FDA based on comparability.
So that the material that we're using in this now a plan for Registrational study as well as the second that's in the process of being planned.
Using that material.
With the productivity of that process.
Matthew Baron Hershenhorn: Thank you. And just one quick follow-up, if I could. Could you talk a little bit more about your expected capacity to supply the market? Obviously, you're just starting phase three, but as you're getting to the potential launch stage, what would your capacity be on a patient number basis?
We have effectively an unlimited.
Ability to supply the future at this product a deep you would be in single digit no batches per year or anticipated.
We could readily handle.
Your existing contract manufacturers or in the future given our process expertise in developing the platform as well as analytical capability, we could transfer it to it internal site, we decided to it at some point on the delivery side, Laura to add to what Matt as a describing on a manufacturing.
Andrei Teren: Yeah, I'll ask Matt Othmer, our Chief Operating Officer, to address your question.
Matthew Baron Hershenhorn: Good morning. We made the decision early in Voyager's history to invest in the baculovirus platform, and so our Parkinson's program was the first program to be transitioned from what had previously been a triple transfection platform for prior studies. We did the comparisons and an IND amendment with the FDA based on comparability, so that the material that we're using in this study is now planned for a registrational study, as well as the second that's in the process of being planned, using that material. With the productivity of that process, we have effectively an unlimited ability to supply the future of this product. It would be in single-digit batches per year, which we could readily handle through existing contract manufacturers, or in the future, given our process expertise in developing the platform as well as our analytical capability, we could transfer it to an internal site. We decided to do so at some point.
The plan is to have a centers of excellence that model.
And there are dozens upsides in the U.S. that have the proper.
Ability to duties Oh, stereotactic procedures on their MRI guidance.
So that's a that's the plan to be able to me so the market demand once we get there.
Is to be able to leverage sites like this that can function at the sufficiently high volume to meet the demand.
Thanks very much.
Thank you.
Thank you. Our next question comes from Sumant Kulkarni with Canaccord. Your line is now open.
Mike Thanks for taking my questions. If it did have a bigger picture one as an organization I know you've been focused on manufacturing relatively early in the company's evolution. So what are your lead talks on what cost of goods might look like given the transition from interest and do the new one oh in any updates on our latest thoughts there would be appreciated.
Andrei Teren: On the delivery side, Laura, to add to what Matt is describing about the manufacturing, the plan is to have a centers of excellence model, and there are dozens of sites in the U.S. that have the proper ability to do these stereotactic procedures under MRI guidance. So that's the plan to be able to meet market demand once we get there; to be able to leverage sites like this that can function at a sufficiently high volume to meet the demand.
Yeah, well, thanks amount for the question so for us our to lead programs or our interrupt rank them all delivery of very small volumes of the gene therapy. So to mats appoint a we're able to run a single bowel reactor that the produce.
As a hundreds of doses. So we expect that the cost of goods or is gonna be quite low and we don't have a yet they are guidance on this but again given the volumes involved for the lead programs, we expect to be the case.
Laura Kathryn Chico: Thanks very much.
Sumant Satchidanand Kulkarni: Thank you.
Andrei Teren: Thank you. Our next question comes from Sumant Kulkarni with Canaccord.
Sumant Satchidanand Kulkarni: Your line is now open. Thanks for taking my questions. This is a bit of a bigger picture one. As an organization, I know you've been focused on manufacturing relatively early in the company's evolution. So what are your latest thoughts on what the cost of goods might look like, given the transition from your old system to the new one? And any updates on our latest thoughts there would be appreciated. Thanks.
The choice of the Baculovirus assist them for a number of our programs moving forward. Once we move into programs that we intend to deliver systemically and leverage capsids ability to cross the blood brain barrier.
That we because of that choice to have a.
A a baculovirus system that is very proactive we also expect to be able to keep the cost of goods.
Andrei Teren: Yeah. Well, thanks, Sumant, for the question.
Andrei Teren: So for us, our two lead programs are intraparenchymal delivery of very small volumes of gene therapy. So to Matt's point, we're able to run a single bioreactor that produces hundreds of doses. So we expect that the cost of goods is going to be quite low, and we don't yet have guidance on this, but again, given the volumes involved for the lead programs, we expect this to be the case. The choice of the baculovirus system for a number of our programs moving forward, once we move into programs that we intend to deliver systemically and leverage CAHPSID's ability to cross the blood-brain barrier.
Relatively low so that's all that's the current plan at the moment just too in a big picture of our strategy for manufacturing we continue to execute on our stated strategy. That's what we think it's important to have in house the expertise on the process develop.
Meant Anna Nicole development fronts.
But we worked with a selected CDMO goes to produce the clinical batches for clinical program and future programs. Once we have the demand for continuous needs to produce at a higher volume.
Then we'll consider eventually at the right time internalizing fully manufacturing, but for now we continue to execute on this.
Andrei Teren: That we, because of that choice to have a baculovirus system that is very proactive, we also expect to be able to keep the cost of goods relatively low. So that's the current plan. At the moment, just in the big picture of our strategy for manufacturing, we continue to execute on our stated strategy that we think is important, to have in-house expertise on the process development and analytical development fronts. But we work with the selected CDMOs to produce the clinical batches for the clinical program and future programs. Once we have the demand for continuous,
Hybrid model, where we internalized some of the expertise and and turn to partners for some production.
Got it thank you.
Thank you think you.
Our next question comes from Debjit, Chattopadhyay, but H.C. Wainwright your line is now.
Hi, guys. Good morning, Thanks for taking the call.
Aaron unprecedented and I just had a question about the.
Disease program.
How many clinical study you could tell us anything about the design of the trial.
Going to be randomize completed indications surgery control arm and if you think that would impact enrollment and also if you have any minimum requirements on the number of CHF therapy for patients.
Andrei Teren: [inaudible]
Divya Rao: Got it, thank you. Our next question... Dubjit Chattopadhyay with H.C. Wainwright, your line is now open. Hi, guys. Good morning. Thanks for taking the call. This is Aaron on for a dead fit.
Ah yes, thanks to the question. So as we don't anticipate the phase one study to be blinded. We say, we know we do not anticipate and have a placebo along.
In in the initial politics that active development plan.
Omar Khawaja: And I just had a question about the Humane Disease Program, upcoming clinical studies. If you could tell us anything about the design of the trial, if it's going to be randomized, including imitation surgery, controlled, and if you think that would impact enrollment. And also, if you have any minimum requirements about the number of CAG repeats for patients.
Handsets base.
No we will be stratifying patients that.
At this stage wave and not ready to disclose details of how we gained like patients will face one other than that they will be patients in the early stages.
Okay, great. Thank you and could you comment also on thoughts on.
Relative a relevant metrics for the Arnie I could be a if you're going to evaluate based on the TSS considering that.
Omar Khawaja: Thanks for the question. We don't anticipate the Phase 1 study to be blinded. We do not anticipate having a placebo arm in the initial part of the development plan. In terms of the CAG repeat number, we will be stratifying patients, but at this stage, we're not ready to disclose the details of how we're going to select patients for Phase 1, other than that there will be patients in the early stages of the disease.
The.
Decrease in Huntington protein may not be reflected that.
In the CSF purses deep brain structures.
I'll now.
Yes. Good question I mean, the tough thing, it's really to measure.
My car and I am on AMC assess just in times of the absolute and how the taxable and then actually really has to extrapolate too that's on the pharmacokinetics of the drugs.
Omar Khawaja: Okay, great. Thank you. And could you also comment on thoughts on a relevant metric for the RNAi activity if you're going to evaluate it based on the CSF, considering that the decrease in the Huntington's protein may not be reflective of that in the CSF versus the deep brain structures? Any thoughts on that?
It it may ultimately be that pricing is the best.
The dynamic measures that we can really.
Hey, you know that that we can really assessing the human and but we are developing a model in tons of be pharmacokinetics inside the bank to Gina, but ill say that and my car and I and M&A and tissue NCS assets and non human primate and use that create model to a understand the PK PD relationship.
Omar Khawaja: Yeah, it's a good question. I mean, the tough thing is really measuring microRNA and mRNA and CSF just in terms of the absolute amounts that are detectable, and then actually really how to extrapolate those to the pharmacokinetics of the drug. It may ultimately be that protein is the best Pharmacodynamic measure that we can really, (inaudible).
And the human studies.
Okay, great. Thank you.
Omar Khawaja: Okay, great. Thank you. Thank you. I am not showing any further questions at this time. I would now like to turn the call back over to Andre Turen for any closing remarks.
Thank you I'm not showing any further questions at this time I would now like to turn the call back over to Andre trend for any closing remarks.
Yes. Thank you operator, and thank you everyone for joining us on the call look forward to updating it all of you soon on our progress. Thank you.
Andrei Teren: Yeah, thank you, operator. And thank you everyone for joining us on the call. I look forward to updating all of you soon on our progress. Thank you.
Ladies and gentlemen, this concludes todays conference call. Thank you for participating you may now disconnect.
Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating.