Q4 2020 Voyager Therapeutics Inc Earnings Call
[music].
Good afternoon, and welcome to the Voyager Therapeutics, what corner and force.
Operator: Good afternoon, and welcome to the Voyager Therapeutics fourth quarter and four year 2020 financial results conference call. At this time, all participants are in a listen-only mode.
Financial results conference call.
At this time all participants are in a listen only mode.
Operator: This call is being webcast live on the Investor & Media section of Voyager's website at voyagertherapeutics.com. This call is the property of Voyager Therapeutics, and recording, reproduction, or transmission of this call without the express written consent of Voyager Therapeutics is strictly prohibited. Please be advised that this call is being recorded. I would now like to introduce Allison Dorval. CFO at Voyager, Good afternoon and thank you for joining us. With me on the call today are Andre Tarrant, our President and Chief Executive Officer, and Omar Khawaja, Chief Medical Officer and Head of R&D.
This call is being webcast live on the Investor and media section of Voyager's website at Voyager Therapeutics Dotcom.
This call is this property of Voyager therapeutics, and recording reproduction or transmission of this call without the expressed written consent of Voyager therapeutics is strictly prohibited.
Please be advised that this call is being recorded.
I'd now like to introduce Allison Dorval C.
CFO at Voyager.
Good afternoon, and thank you for joining us with me on the call today are Andre Turenne, our President and Chief Executive Officer, and Omar Khwaja, Chief Medical Officer and head of R&D.
Operator: This afternoon, after the market closed, we issued a press release which outlines the financial results and corporate highlights for the fourth quarter and full year 2020. 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, February 25, 2021. Voyager disclaims any obligation to update these statements to reflect future events or circumstances, except as required
Afternoon after market close we issued a press release, which outlines the financial results and corporate highlights for the fourth quarter and full year 2020. The release is available at Voyager Therapeutics Dot com.
Before we begin just a reminder that the forward looking statements included in this call represent the company's view as of today February 25th 2021.
Wage or disclaims any obligation to update these statements to reflect future events or circumstances, except as required by law.
Operator: Please refer to today's press release, as well as Voyager's filing to the DSCC for information concerning risk factors that could cause actual results to differ materially from those expressed or implied by such. With that, I'll turn the call over to Andre.
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 turn the call over to Andre.
Andre Tarrant: Right. Thank you, Allison. And good afternoon, everyone.
Alright, Thank you Alison and good afternoon, everyone welcome to our Q4 earnings and corporate update call.
Andre Tarrant: Welcome to our Q4 earnings and corporate update call. I'll begin by walking through highlights from 2020 and expectations for 2021. Omar will discuss our pipeline programs and plans, and Allison will close with our financial results and guidance.
I'll begin by walking through the highlights from 2020 and expectations for 2021.
Omar will discuss our pipeline programs and plans and Allison will close with our financial results and guidance.
Andre Tarrant: Once we've concluded our remarks, we'll take questions in the Q&A session. In 2020, we remain focused on moving our pipeline and our key platform activities forward. Among the key highlights: We made significant progress in readying our Huntington's disease program for clinical trial. Based on our preclinical data, we believe that VY-HTT01 has the potential to be a best-in-class therapy for this devastating disease. We achieved highly promising results using our tracer platform to identify capsids with a much better ability to cross the blood-brain barrier than current serotypes.
Once we've concluded our remarks, we'll take questions in a Q&A session.
In 2020, we remain focused on moving our pipeline and our key platform activities forward.
Among the key highlights.
We made significant progress in readying, our Huntington's disease program for clinical trial.
Based on our preclinical data, we believe that <unk> has the potential to be a best in class therapy for this devastating.
Disease.
We achieved a highly promising results using our tracer platform to identify GAAP says.
But a much better ability to cross the blood brain barrier.
Serotypes.
Andre Tarrant: The implications of these advances could be profound for both our own pipeline and for the field of gene therapy through calibration. We also advanced our overall pipeline and platform and provided updates on the progress through 18 presentations at scientific conferences and four publications in peer-reviewed journals. And finally, we made key additions to our team at the board level, at the SAB level, and also in senior management. While we made very good progress, the past year wasn't without its challenges.
The implication of these advances could be profound for both our own pipeline and for the field of gene therapy through collaborations.
We also advanced our overall pipeline and platform and provided updates on our progress through 18 presentations at scientific conferences and for publications in peer reviewed journals.
And finally, we made key additions to our team at the board level at the <unk> level and also at the senior management level.
Well, we made very good progress the past year wasn't without its challenges.
Andre Tarrant: Our Huntington's IMD was placed on clinical hold pending resolution of additional device and CMC-related requests from the FDA. The Parkinson's IND was also placed on clinical hold, in that case, pending follow-up imaging and clinical assessments requested by the DSMB and a risk-benefit assessment requested by the FDA. NERCRIN recently notified us of its intent to terminate the portion of our collaboration related to the VYADC program.
Our Huntington's IND was placed on clinical hold pending resolution of additional device and CMC related requests from the FDA.
The Parkinson's R&D was also placed on clinical hold in that case pending follow up imaging and clinical assessments requested by the SMB and a risk benefit assessment requested by the FDA.
And <unk> recently notified us of its intent to terminate the portion of our collaboration related to the <unk> ADC program.
Andre Tarrant: The work we do is challenging, but the potential rewards for patients and their families are enormous. Voyager was founded on a commitment to applying gene therapy to some of the most life-limiting and disabling disorders in medicine, and our resolve is unwavering. We've built a world-class team of experts at the intersection of gene therapy and neuroscience. On the back of the pioneering work we've done to date and our most recent advances, we're now poised to enter a new phase in our mission to deliver transformative therapies for people suffering from severe neurological diseases.
The work, we do is challenging but the potential rewards for patients and their families are enormous.
Voyager was founded on the commitment to applying gene therapy with some of the most life limiting and disabling disorders in medicine.
Our resolve is unwavering.
We've built a world class team of experts at the intersection of gene therapy and neuroscience.
On the back of the pioneering work we've done to date and our most recent advances.
We're now poised to enter a new phase in our mission to deliver transformative therapies for people suffering from severe neurological diseases.
Andre Tarrant: Before I turn it over to Omar, I'd like to point out some of our upcoming highlights for 2021. For the Huntington's Program, we expect to provide our response to the FDA on our IMD in the first half of the year and initiate our first in-human trial on IMD-X. For the novel capsids, we plan to present non-human primate data on our lead capsids at a scientific conference in the first half of 2021. For the Parkinson's program, we expect to provide an update on the potential path forward based on the additional information being collected by NERCRIM.
Before I turn it over to Omar I would like to point out some of our upcoming highlights for 2021.
For the Huntington's program, we expect to provide a response to the FDA on our RMB in the first half of the year.
And to initiate our first in human trial upon R&D acceptance.
For the novel Capsid, we plan to present non human primate data on our lead GAAP sits at a scientific conference in the <unk>.
First half of 2021.
For the Parkinsons program, we expect to provide an update from the potential path forward.
From the additional information being collected by Neurocrine in response to the assembly requests.
Andre Tarrant: And lastly, for the preclinical pipeline, including our innovative vectorized antibodies, we expect to announce new programs and provide updates at the scientific meeting and other presentations in the first half.
And lastly for the preclinical pipeline.
Including our innovative <unk> antibodies, we expect to announce new programs and provide updates at scientific meeting and other presentations in the first half of the year.
Omar Khawaja: With that, I'll turn the call over to Omar.
With that I'll turn the call over to Omar.
Omar Khawaja: Thanks, Andre. I'll walk through our program updates in more detail. Today we'll start with BYHTT01, our wholly owned program for Huntington's disease. Huntington's disease affects approximately 40,000 people in the United States, and it's the most common monogenic neurological disorder in the developed world. It's a relentlessly progressive and ultimately fatal disorder that strikes people in the prime of life. It's a disease characterized by a toxic gain-of-function mutation in the Huntington gene. This leads to abnormal Huntington protein aggregates that cause neuronal cell death. For patients, their families, and care partners, it's a devastating disease that results in a progressive decline of motor skills and cognitive functions.
Thanks, Andre I'll walk through our program updates in more detail per day will start with B Y Hpt's, one a wholly owned program for Huntington's disease.
Huntington's disease affects approximately 40000 people in the United States and it's the best comment monogenic neurological disorder in the developed world.
It is a relentlessly progressive and ultimately fatal disorder that strike people in the prime of life, It's a day.
<unk> characterized by a toxic gain of function mutation in the Huntington Jane.
Leads to abnormal Huntington protein I forget that caused no retinal cell path.
Our families and cash partners Inc.
A devastating disease that results in a progressive decline of medical skills and culture to function.
Omar Khawaja: Our therapeutic candidate, BY-HDP01, is an AV1 gene therapy encoding a novel mRNA designed to potentially reduce human HDP messenger RNA. We've developed our candidates and the route of administration to safely deliver the highly potent gene silencing microRNA where it can impact the neuropathology of the disease in the core structures of the striatum and cortex. The canonical RNA interference pathway used in VYHCT01 is a well-characterized and highly precise mechanism that's been validated in the clinic. Since the core data is significantly atrophied, and striatal to cortical connections are compromised in early unsignificant disease.
Our therapeutic candidate B Y Hcp's day, right. One is an AAV gene therapy encoding a novel.
Designed to potentially reduce human HBK messenger RNA.
I'll, let Paul candidates and range of administration to safely deliver highly potent gene silencing micro RNA.
Alright can impact from no rest of apology.
The disease and the cost structures of the striatum and cortex.
The economical RNA interference pathway used in DIY Tuesday, right, one is well characterized and highly precise mechanism that's been validated in the clinic.
And since the core day to significantly atrophied and strength of cortical connections are compromised and early Huntington's disease.
Omar Khawaja: We plan to deliver VYHCT01 directly to the detainment in the thalamus, targeting the primary site of disease pathology and leveraging the thalamus' extensive neuronal projections to the cortex. We've previously presented data demonstrating that delivery of VYHCT01 into the putamen and thalamus of non-human primates was well tolerated. The investigational gene therapy results in a widespread distribution of VYHTP01 vector genomes across the striatum and cortex, leading to robust reductions of HTT messenger RNA and protein in these key brain structures.
We plan to deliver B Y Hcp's, Gary one directly to the putamen and Palomar targeting the primary sites of disease pathology and leveraging the soundness has extensive new rental projections to the cortex.
We've previously presented data demonstrating that delivery of vivo piece.
Thanks, everyone.
The putamen, an element of non human primates was well tolerated.
Our investigational gene therapy results in a widespread distribution of <unk>, one casinos across the striatum and cortex.
This leads to robust reductions of HCP messenger RNA and protein in these key brain structures.
Omar Khawaja: These reductions stabilised between 6 and 12 months following a single injection of the gene therapy. VY-HTT01 treatment also demonstrated potent reductions of HTT mRNA and protein in the YAK-128 and BAK-HD transgenic mouse models of Huntington's disease, with significant improvements in motor function, allowing us to select doses that we predict to be clinically efficacious.
These reductions stabilized between six and 12 months following a single injection of the gene therapy.
<unk> one treatment also demonstrated potent reduction thats HCP mrna and protein.
<unk>, one times EBITDA back HD transgenic mouse models of Huntington's disease with significant improvements in motor function.
Following us to select doses that we predicted to be clinically efficacious.
Omar Khawaja: We're very pleased with these results, and as Andre mentioned, we plan to present preclinical data from the IND-enabling studies later this year. We submitted our IND application for VYHCT01 in September and were placed on clinical hold by the FDA pending resolution of questions on CMC-related items. These include drug device compatibility and drug substance and product characterization. Our team is working hard to complete the information request and expects to provide a complete response to the agency in the first half of 2021.
We're very pleased with these results and zone.
As I mentioned, we plan to present preclinical data from the IND, enabling studies later this year.
We submitted the IND applications as we see by HPT, Sir and one in September.
Were placed on clinical hold by the FDA pending resolution of questions on CMC related items. These include drug device compatibility.
And drug substance and product characterization.
Our payments working hard to complete the information requests and expect to provide a complete response to the agency in the first half of 2021.
Omar Khawaja: While we work to gain IND acceptance, our clinical team has been actively engaging with investigators, trial sites, as well as patient and clinician communities to ensure a smooth transition to our first in-human trial. We're focused on having our trial active and positioned to enroll patients quickly upon IND acceptance. There is currently no available disease-modifying treatment for people with Huntington's disease, and we believe BYHCP01 has the potential to change that. Andre also mentioned our vectorized anti-cow program. Tauopathies are progressive neurodegenerative disorders defined by toxic aggregates of tau protein in the brain. These are in conditions such as Alzheimer's disease, frontotemporal dementia, and progressive supranuclear palsy.
While we worked to gain acceptance.
Clinical team has been actively engaging with investigators trial sites as well as the patient and clinician communities to ensure a smooth transition to our first in human trial.
We're focused on having all trial active position to enroll patients quickly upon the IMT acceptance.
This is currently net available disease modifying treatments people with Huntington's disease.
And we believe py acte's, neither one has the potential to change that.
Triangles I mentioned thoughts that tries to anti Tau program.
The pace of our progressive Neurodegenerative disorder defined by toxic I forget how pricing in the Bryan baseline condition, such as Alzheimers disease, Frontotemporal dementia and progressive Supranuclear palsy.
Omar Khawaja: Current treatments address symptoms only. We had originally started this program in collaboration with ADVI, where we not only developed our process for vectorizing antibodies but also worked on antibody discovery. When Avri terminated the collaboration last summer, we retained the rights to the vectorization technology and certain novel vectorized antibodies that had been developed. The Virtualized Anti-Cow Program is now included in our wholly owned site.
Current treatments address symptoms directly.
We had originally started this program I'm sure our collaboration with Abbvie, where we've not only developed a process of <unk> antibodies, but also from the antibody discovery.
When abbvie terminated the collaboration last summer, we retained the right to the visualization technology and sudden double vectren antibodies that have been developed.
Does that flow detailed program is now included in our wholly owned pipeline.
Omar Khawaja: We believe that the delivery of vectorized antibodies can overcome many of the limitations of passive immunization, including the amount of antibody reaching the brain. The advances we've made to date validate our belief that we have a better method for delivering antibodies to the brain. We will continue to drive these efforts forward.
We believe that the deliberate choice antibodies can overcome many of the limitations of passive immunization, including the amounts of time for the leaching the Brian.
The advances with Mesa day validate our belief that we have assessed a method for delivering antibodies it's Brian.
We continue to drive these efforts forward.
Omar Khawaja: In 2021, we plan to select our development candidates and begin dose range finding and biodistribution studies on this program. We're also advancing our work in vectorizing novel payloads, including innovative antibody and other biotherapeutic formats. I'd like to spend the next few minutes discussing our progress on novel capsid discoveries.
'twenty, one we plan to collect sales development candidate and again dose range, finding and bio distribution studies on this product line.
We're also advancing <unk> novel payloads, including if its advance Buddy in the other biotherapeutic format.
I'd like to spend the next few minutes discussing our progress on novel Capsid discovery.
Omar Khawaja: An area of Voyager is conducting groundbreaking work and is a leader in the field of gene therapy. We're using our tracer functional screening technology, a directed evolution approach in non-human primates, to find novel capsids with improved abilities to cross the blood-brain barrier. Without better capsids, the field will remain limited to relying upon either direct delivery to the brain or systemic dosing with high doses that carry immune and safety risks. Capsules with better bio-distribution allow not just an improved route of administration for patients but significantly open up the number and types of neurological disorders that could be realistically addressed by AAV gene therapy.
Voyager is conducting groundbreaking work and it's a leader in the sales of gene therapy.
Using all trace of functional screening technology.
The evolution approach in non human primates.
Novel Capsid with improved stability to cross the blood brain barrier.
Without debt to cap, that's the sales will remain limited to relying upon either direct delivery to get that Brian well systemic dosing with high doses that carry immune and safety risks.
Catches the specified distribution allow not just an interest rate of administration for patients that's significantly open up the number and types of neurological disorders that could be realistically addressed by AAV gene therapy.
Omar Khawaja: We believe our novel capsid discoveries have the potential to support a significant number of programs, including current programs and those yet to be named. We recently had a publication in Molecular Therapy Methods and Clinical Development entitled Rapid Evolution of Blood-Brain Barrier Penetrating AAV Captors by RNA-Driven Biopanning, which describes the foundational rodent proof-of-concept experiment for the TRAITOR platform. This platform has allowed us to advance our efforts working directly with non-human primates. The data we're seeing from the experiments using non-human primates suggests these novel capsids could have significant potential for blood-brain barrier penetration and that these capsids could be effective for a number of neurological diseases where optimal treatment would be IV delivery for AAV gene therapy.
We believe our novel capsid discoveries have the potential to support a significant number of programs, including current private brands and those yet to be named.
We recently had the publication in molecular therapy methods and clinical development and cycle rapid evolution of blood brain barrier penetrating AAV capsid by RNA driven by timing.
Which describes the foundational proof of concept experiment.
Tried to platform.
This platform has allowed us to advance our assets working directly with non human primates.
The data we're seeing from the experiments using non human Primate suggests these novel capsid could have.
At significant potential.
The blood brain barrier penetration and that these captures could be affected for a number of neurological diseases, where optimal treatment with the IV delivery.
Gene therapy.
Omar Khawaja: Treatment of diseases such as Friedrich's ataxia, Alzheimer's disease, and certain childhood disorders could benefit from these efforts. We've characterized captives from our first proprietary library with notable results so far, and we continue to work on several others.
<unk> diseases, such as free next day taxpayer Alzheimers disease, and certain childhood disorders could benefit from these efforts.
With characterize cap because from our first proprietary library with notable results say Paul.
We need to work on several others, we had to share and HP data from these novel capsid that debt.
Omar Khawaja: We hope to share our NHP data from these novel captive efforts at a scientific conference in the first half of this year. Lastly, let's move to the VYADC program for Parkinson's disease with Neurocrine. As Andre mentioned, the RestoreOne trial was placed on clinical hold by the FDA in December 2020. This followed Neurocrin, the study sponsor and IND holder, filing a safety report regarding the observation of MRI abnormalities in some study participants.
The conference in the first half of this year.
Okay.
Lastly, let's move to the <unk> ADC program for Parkinson's disease with Neurocrine.
As Andre mentioned the restore one trial was placed on clinical hold by the FDA in December 2020.
Felt like Neurocrine the study sponsor IND filing.
Finding a safety report regarding the observation of MRI abnormalities in some study participants.
Omar Khawaja: The DSMB met most recently in January and requested additional clinical and imaging data. Neurocrin has committed to provide these data to the DSMB. We intend to support Neurocrin on ongoing matters related to the completion of imaging and clinical assessments as requested by the DSMB, as well as the provision of other information requested by the FDA. The clinical significance of these radiological findings remains unknown and is being evaluated. We will work to determine the potential path forward for the VYA-ADC program based on the additional information being collected by NeuroCrim in response to the DSMB request. We plan to continue to provide updates across all our pipeline initiatives in 2021. I'll now pass the call on to Alison.
But the SMB, Matt Nice recently in January and requested additional clinic clinical and imaging data.
<unk> is committed to provide these bankruptcies that day SMB.
We intend to support Neurocrine on ongoing matters related to the completion of imaging and clinical assessments as requested by the day S&P as well as the profession. This other information requested by the FDA.
The clinical implications of things radiological findings remains.
And is being evaluated.
Well what to determine the potential path forward for the day why ADC program based on the additional information being collected by Neurocrine in response to the day S&P request.
We plan to continue to provide updates across all our pipeline initiatives.
Paul.
I'll now pass the call loans to Allison.
Thanks Omar.
Allison Dorval: I'll review the highlights of our financial results and guidance. We ended 2020 with $174.8 million in cash, cash equivalents, and marketable debt securities compared to $281.5 million at the end of 2019. We've worked collaboration revenues of $6.5 million in Q4 2020 and $171.1 million for the year, compared to $32.7 million and $104.4 million for the same period of 2019. The quarter-over-quarter decrease reflects the reduction of revenue related to research services and cost reimbursements from the collaborations with Neurocrin and AbbVie.
Ill review the highlights of our financial results and guidance.
We ended 2020 with $174 8 million in cash cash equivalents and marketable debt securities compared to $281 5 million at the end of 2019.
Good luck to collaboration revenues of $6 5 million in Q4, 2020, and $171 1 million for the year compared to $32 7 million and 104 4 million from the same periods of 2019.
Quarter over quarter decrease reflects the reduction of revenue related to research services and cost reimbursements from the collaborations with Neurocrine and Abbvie flow.
Full year 2020 revenue includes $105 2 million related to the recognition of the remaining deferred revenue for abbvie upon the collaboration termination from the summer.
All research services related to the Abbvie collaborations were completed prior to the fourth quarter of 2020.
Allison Dorval: Full year 2020 revenue includes $105.2 million related to the recognition of the remaining deferred revenue for AbbVie upon the collaboration termination in the summer. All research services related to the ADVI collaborations were completed prior to the fourth quarter of the year.
Net loss was $15 9 million for Q4, 2020, and net income was $36 7 million for the full year compared to net losses of $12 6 million and $43 6 million from the same period of 2019.
R&D expenses were 22.0 million for Q4 of 2020 and $108 8 million for the full year.
Allison Dorval: The net loss was $15.9 million for Q4 2020, and net income was $36.7 million for the full year, compared to net losses of $12.6 million and $43.6 million for the same period of 2019. R&D expenses were $22.0 million for Q4 2020 and $108.8 million for the full year, compared to $36.6 million and $119.7 million for the same period of 2019. The decrease in R&D expenses was primarily related to lower external costs for services supporting our clinical and preclinical pipeline programs.
Net to $36 6 million and $119 7 million for the same periods of 2019.
Decrease in R&D expenses was primarily related to lower external cost for services supporting our clinical and preclinical pipeline programs.
G&A expenses were $8 3 million for Q4 of 2020, and 35.0 million for the full year compared to $9 9 million from $36 3 million for the same periods of 2019.
The decrease in G&A expenses was primarily related to legal and professional fees.
Turning now to our financial guidance.
Excluding any potential financing or business development activities in 2021, we expect to end the year with cash cash equivalents and marketable debt securities between 50 and $60 million.
Based on our current operating plan, we expect this cash balance along with the amounts that we expect to receive for reimbursement of development costs from the Neurocrine collaboration will continue to be sufficient to meet our needs for projected operating expenses and capital expenditures into mid 2022.
Allison Dorval: G&A expenses were $8.3 million for Q4 2020 and $35.0 million for the full year, compared to $9.9 million and $36.3 million for the same period of 2019. The decrease in GNA expenses was primarily related to legal and professional. Turning now to our financial guidance.
We've consistently demonstrated a disciplined financial approach and strategic partnering strategy and we will continue to evaluate opportunities to thoughtfully fund our business.
We look forward to continuing our progress through multiple milestone events across our programs in 2021 and with that we'd like to now open the call up for questions operator.
Allison Dorval: Excluding any potential financing or business development activities in 2021, we expect to end the year with cash equivalents and marketable debt securities between $50 and $60 million. Based on our current operating plan, we expect this cash balance, along with the amounts that we expect to receive for reimbursement of development costs from the Neurocrin collaboration, will continue to be sufficient to meet our needs for projected operating expenses and capital expenditures into mid-2022. We've consistently demonstrated a disciplined financial approach and strategic partnering strategy and will continue to evaluate opportunities to thoughtfully fund our business.
Ladies and gentlemen, if you have a question at this time. Please press Star then one on your Touchtone telephone. If your question has been answered or you wish to remove yourself from the queue. Please press the pound key.
And any background noise, we ask that you. Please place your line on mute. Once your question has been stated.
Our first question comes from the line of Joe <unk> with Cowen. Your line is open. Please go ahead.
Good afternoon, Thanks for taking my question.
Just two questions from US first on the http clinical hold.
Are you able to give us any more information about what it is you have to accomplish and whats going to be in your complete response was submitted to the FDA in the first half of the year.
Yes, Thanks, Phil for the question Omar.
Thank you for this.
Okay.
Yes, Thanks Bill so.
The Fda's concerns are limited to CMC issues and.
Just to emphasize that that's been a concern with the preclinical safety or toxicity.
Operator: We look forward to continuing our progress through multiple milestone events across our programs in 2021. And with that, we'd like to now open the call to questions. Operator? Ladies and gentlemen, if you have a question at this time, please press star then 1 on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. To prevent any background noise, we ask that you please place your line on mute once your question has been stated.
The request from the FDA.
Like to sort of two pieces of data one is information regarding.
Devices, and we're seeing that from the third parties that have been the bulk of the manufacturer of licensing of those devices.
I mean, that's almost a pure information request and then the second as relates to the biocompatibility of the gene therapy product not just with the cannula that he used to infuse the.
The gene therapy, but also the entire fluid pathway. So the tubing and switches, which are used as well and so we're generating about biocompatibility data and that will be.
The other significant piece of the information that we will submit to the FDA.
Operator: Our first question comes from the line of Phil Nadeau with Cowan. Your line is open, please go ahead. Good afternoon. Thanks for taking my question. First, on the HTT clinical hold, are you able to give us any more information about what it is you have to accomplish and what your complete response will be that's submitted to the FDA in the first half of the year?
In response to the clinical hold.
That's very helpful. And then second on the restore trial what.
Do you hope to learn over the next few months it could better elucidate either causes or consequences of the MRI abnormalities are you watching the patients to see if those abnormalities cure.
True themselves or is there other information, that's particularly important because you'd like to submit to the FDA.
Operator: Yeah, thanks, Phil, for the question. Omar, I'll turn it to you for this.
Yeah. So thanks, Phil So there are some imaging.
Omar Khawaja: just to emphasize that there have been no concerns with preclinical safety or toxicity. Really, the request from the FDA relates to sort of two pieces of data. One is information regarding devices, and we're seeking that from third parties that have been involved in the manufacture or licensing of those devices. I mean, that's almost a pure information request. And then the second relates to the biocompatibility of the gene therapy product, not just with the cannula that's used to infuse the gene therapy but also the entire fluid pathway, so the tubing and syringes which are used as well. And so we're generating that biocompatibility data, and that will be the other significant piece of the information that we'll submit to the FDA in response to the clinical hold
Data that we're going to get from.
At a later time points for the patients that were enrolled in the.
Phase one and further restore study there are.
A couple of additional clinical assessments that theyre going to be.
Got it.
For those patients as well.
Additional pet scan for debt.
Patients before in the restore one.
These are the.
That's information that.
Marathon is.
Is working and we're supporting them too.
Correct.
Over the coming months.
That's very helpful. Thanks for taking my questions.
Thanks Bill.
Thank you and our next question comes from the line of Laura Chico with Wedbush Securities. Your line is open. Please go ahead.
Hey, guys, it's Ken Shields on for Laura Chico, Thanks for taking our questions.
So the first thing.
How are you guys prioritizing the pipeline respect to cash position.
We still plan to develop free why ABC independently at this point.
Omar Khawaja: That's very helpful. And then second, in the RESTORE trial, what do you hope to learn over the next few months that could better elucidate either the causes or consequences of the MRI abnormalities? Are you watching the patients to see if those abnormalities cure themselves, or is there other information that's particularly important that you'd like to submit to the FDA?
Yeah. So.
We have.
The number of programs that we've been advancing and as we've said we'll look to.
Announced some of these programs.
For scientific meetings.
Throughout our presentations in the first half of the year.
At this point on the <unk> program.
Omar Khawaja: Yeah, so thanks, Phil. So there are some imaging data that we're going to get from at a later time point for the patients that were enrolled in phase one. And for the restore study, there are a couple of additional clinical assessments that are going to be gotten on for those patients, as well as additional PET scans for the patients that were in the restore one. So this is the information that NeuroCrim is working on and we're supporting them to... Collect them all over the coming months.
We're focused on is getting the additional information that the SMB as requested.
Based on that we're going to be able to make an informed portfolio decision.
As to the best path forward.
The program, but at the moment.
The key priority for us portfolio wise.
On the Huntington's program.
Submit the complete response, and then advancing some of the earlier stage program, including some day novel payloads and from the programs that are enabled by novel Capsid, that's where we've been.
Operator: That's very helpful. Thanks for taking my questions.
Working on.
We will look forward for unfortunately in the <unk>.
Operator: Thanks, Phil.
First after year.
Operator: Thank you. And our next question comes from the line of Laura Chico with Woodbush Securities. Your line is open. Please go ahead. Hey guys, it's Ken Shields on behalf of Laura Chico.
To provide updates on our full portfolio.
Okay. Thanks, and then I guess, just one more I mean, you mentioned the novel Capsid program.
And it looks like you guys have been exploring them in non human primates.
Operator: Thanks for taking our questions. So the first is, how are you guys prioritizing the pipeline with respect to cash? Will you guys still plan to develop BYADC independently at this point?
Going to be sharing data later this year, but maybe could you provide an update on maybe what the next steps or the overall strategy will be there going forward. Thank you.
Sure Omar.
Our non address this.
Yes of course so.
In terms of the next steps from the.
Andre Tarrant: Yeah, so we have a number of programs that we've been advancing, and as we've said, we'll look to announce some of these programs at scientific meetings and other presentations in the first half of the year. At this point, on the BYDC program, what we're focused on is getting the additional information that the DSMV has requested, and based on that, we're going to be able to make an informed portfolio decision.
Theories of cabinets that we're getting from.
The first lightly.
Yeah.
Does that imply.
So does.
Those cuts just that.
Very promising in terms of absolute performance characteristics.
This is 89 for example, those cuts are done now in advanced stages approach validation, including.
Andre Tarrant: as to the best path forward for the program. But at the moment, the key priority for us, portfolio-wise, is on the Huntington's program to submit the complete response and then advancing some of the earlier stage programs, including some of the novel payloads and some of the programs that are enabled by the novel capsids that we've been working on. So we'll look forward to an opportunity in the first half of the year to provide updates on the full portfolio.
Understanding the manufacture ability of the captives as well.
The.
Identifying potentially the receptors that are involved in that.
Improvements in transaction that was saying that these capsid.
So that's the sort of detailed characterization from the first tranche of absolute debt I imagine from the library.
Then have at it.
Significant number of <unk> from a number just from parental capsid serotypes.
Operator: Okay, thanks. And then I guess just one more.
Operator: I mean, you mentioned the novel captive programs. And it looks like you guys have been exploring them in non-human primates, and you're going to be sharing data later this year. But maybe could you provide an update on maybe what the next steps or the overall strategy will be there going forward?
I'll now getting through the choices you know somewhere in late stages of screening others are in earlier stages and we'll we plan to advance that is true the choice of process and then begin to characterize the constant absent that much from those as well.
The second part of the strategy will relate to deploying the choice of platform. So.
Omar Khawaja: Sure. Omar, do you want to address this?
Omar Khawaja: Yeah, of course. So, in terms of the next steps from the first series of capsids that we're getting from the first library that we touched on, we're getting some human primates. So those capsids that, you know, look very promising in terms of their performance characteristics versus AAV9, for example, those capsids are now in advanced stages of characterization, including understanding the manufacturability of the capsids, as well as identifying potentially the receptors that are involved in the, you know, parent improvements in transduction that we've seen with these capsids.
Captured characteristics that will be beneficial.
No.
Gene therapy, including sales specific 12% school, so different cell types in the net system as well as potential other other tissue systems as well.
Okay. Thanks, so much guidance.
Thank you and our next question comes from the line of Jay Olson with Oppenheimer. Your line is open. Please go ahead.
Hi, This is Matt on for Jay.
We were wondering I guess generally how is the how is your view for gene therapy in Parkinson's if that's changed at all as a result of the clinical hold.
Omar Khawaja: So there's a sort of detailed characterization of the first tranche of capsids that are emerging from the libraries. We then have a significant number of libraries from a number of different parental capsid serotypes that are now going through the tracers. You know, some are in the late stages of the tracer screening process, while others are in earlier stages. And we plan to advance those through the tracer process and then begin to characterize the promising capsids that emerge from those as well.
<unk> see.
So in general maybe just given recent setbacks for others.
Who have gene therapies, including Bluebird and unique share obviously different but what would you say to investors, who may know perceive gene therapy, generally and kind of a negative light definitely appreciate the color. Thank you.
Omar Khawaja: The second part of the strategy will relate to deploying the TRACER platform for other captured characteristics that would be beneficial for neuro AAV gene therapy, including cell-specific tropisms for different cell types in the nervous system, as well as potential other tissue systems as well.
Yes, Thanks, Matt Hello Omar.
If you want to start.
I may add to your comments.
Yes, I mean I think.
Obviously the.
Patient safety is our top priority and so in terms of the <unk> ADC program.
Our goal is to really determine whether they radiological findings that we have.
Operator: Okay, thanks so much, guys. Thank you, and our next question comes from the line of Jay Olson with Oppenheimer. Your line is open. Please go ahead. Hi, this is Matt on behalf of Jay. We were wondering, I guess, generally, how your view is for gene therapy in Parkinson's, if that's changed at all as a result of the clinical hold on BYADC? And also, in general, maybe just given recent setbacks for others who have gene therapies, including Bluebird and Unicare, obviously different, but what would you just say to investors who may now perceive gene therapy generally in kind of a negative light? Definitely appreciate the color. Thank you.
Being reported.
Has any clinical significance and say that the immediate focus and understanding that and then as we get that information then 10 per pack.
Those requests per day, F&B and and also respond to the Fda's request for more detailed assessment of the risks.
With benefits of the product will in parallel this hub and the next steps for that the way to see program.
I think in terms of the field of gene therapy, I think one of the things T.
That's probably important to differentiate.
Is the absolute price of viral vector that's used in.
So in AAV is generally a non integrating virus.
And.
That's somewhat different to til amplifiers switches are integrating box and say.
Operator: Yeah, thanks, Matt. Omar, if you want to start, I may add to your comments.
The safety liabilities from may be quite different from 95 per se.
Omar Khawaja: Yeah, I mean, obviously, patient safety is a top priority. And so, in terms of the VYADC program, our goal is to really determine whether the radiological findings that we've been reporting have any clinical significance. And so that's the immediate focus on understanding that. And then as we get that information and can prepare those requests to the DSMB and also respond to the FDA's requests for more detailed assessments of the risk benefits of the product, we'll, in parallel, determine the next steps for the VYADC program.
We anticipate limited way true from the challenges that may be for example, I believe the Bluebird day.
Akshay do you want to add anything to that.
Oh, let me add that part of our endeavor with novel capsid is to be able to lower the dose is too when we deliver systemically.
And then.
Maybe like.
Most other therapeutics.
Where there.
There could be from liabilities.
The surfacing with higher doses.
That's part of the.
The benefit of getting.
Omar Khawaja: You know, I think, in terms of the field of gene therapy, I think one of the things that's probably important to differentiate between is the actual type of viral vector that's used. So in AAV, it's generally a non-integrating virus, and that's somewhat different to lentivirus, which is an integrating virus, and so the safety liabilities of AAV are quite different from those of lentivirus. So, you know, we anticipate limited read-throughs on the challenges that may be, for example, blue dots and blue vertices. Andre, do you want to add anything to that?
Improved GAAP since with better properties.
It may allow for lower doses to be administered with.
The benefit.
Both the safety and the efficacy from.
Got it that's helpful. Thank you and looking forward to the novel Capsid data I appreciate the time thanks.
Thank you.
Thank you and again, ladies and gentlemen, if you have a question at this time. Please press Star then one our next question comes from the line of Jeff Hung with Morgan Stanley. Your line is open. Please go ahead.
Hi, guys. This is hannah on for Jeff.
Just two quick questions. So for Parkinson's, what kind of protocol amendments or you're thinking might be necessary is it more from modeling or are there other ways to change the administration to reduce the risk of the MRI abnormalities and then just second any read through to the Huntington's program. Since the drug candidate is also injected directly into the brain.
Andre Tarrant: I'll only add that part of our endeavor with novel capsids is to be able to lower the doses when we deliver them systemically, and that may be like most other therapeutics where there could be some liabilities that start coming out with higher doses, so that's part of the benefit of getting improved capsids with better properties. It may allow for lower doses to be administered with the benefit.
You.
Yes, thanks for your questions Donna Omar.
Yeah in terms of the protocol Amendment.
Operator: Got it. That's helpful. Thank you. And I'm looking forward to the novel captured data. Appreciate the time. Thanks.
The most.
You had nice immediate protocol amendments are really focused on adding the additional imaging as well as clinical assessment that.
Operator: Thank you.
Operator: Thank you. And again, ladies and gentlemen, if you have a question at this time, please press star then 1. Our next question comes from the line of Jeff Hung with Morgan Stanley. Your line is open. Please go ahead. Hi, guys. This is Hannah. I'm on behalf of Jeff.
But the SMB if requested.
We're not anticipating otherwise any significant change in the route of administration or the infusion procedure, but really the protocols are being amended right now too.
Operator: So just two quick questions. For Parkinson's, what kind of protocol amendments are you thinking might be necessary? Is it more for monitoring? Or are there other ways to change the administration to reduce the risk of the MRI abnormalities? And then, second, any read through to the Huntington's program since the drug candidate is also injected directly into the brain? Thank you. Yeah.
<unk>.
The additional assessments that are being requested.
So MRI and <unk>.
And clinical assessments.
In terms of potential breakthrough I mean, I think it's important to understand that the two programs are quite different and so I think both utilize enterprise Paul administration highlight that the.
The debt because the difference between the.
Operator: Thanks for your questions, Anna. Omar?
Omar Khawaja: In terms of the protocol amendments, the most immediate protocol amendments are really focused on adding the additional imaging as well as clinical assessments that the DSMB requested. So we're not anticipating otherwise any significant change in the route of administration or the infusion procedure, but really, the protocols are being amended right now to implement the additional assessments that have been requested, so MRI and clinical assessments. In terms of potential breakthrough, I mean, I think it's important to understand that the two programs are quite different, and so they both utilize intraparenchymal administration. However, the vectors are different between the two programs.
Between the two programs and the like because I'm at the ADT, whereas in the Huntington's program and we're using a one also.
The Parkinson's program mid day is.
Is it pricing that's an enzyme that's being replaced that's quite different to the Huntington's, where we're delivering a micro RNA knockdown.
Not down.
Dump down the toxic.
That's all right.
Huntington Specie.
The third thing is that the doses are quite different between the two programs because of the.
Clara Nate that we're using in Huntington's is an extremely potent and said we're using significantly lower doses.
The four things that we've got a very extensive non human primate.
Omar Khawaja: So in the VY-ADC program, it's AD2, whereas in Huntington's program, we're using AD1. Also, the Parkinson's program is a protein, it's an enzyme that's being replaced. That's quite different to Huntington's where we're delivering a microRNA to knock down the toxic, the toxic species, Huntington's disease. And the third thing is that the doses are quite different between the two programs because of the microRNA that we're using in Huntington's. And the fourth thing is that we've got a very extensive non-human primate safety package with data up to one year after dosing in non-human primates at a range of doses.
Safety package.
<unk> data up to one year after dosing in non human primates that range.
Doses and so we believe that <unk> guidance, the importance and understanding the safety profile of <unk>. One program. So we're looking forward to submitting our response to the FDA and anticipating moving forward.
With the clinical trial once that dose can assist us.
Great. Thank you.
Thank you and our next question comes from the line of Brian Smith from.
Murky share with Baird. Your line is open.
Jack dialing in for Brian. Thank you so much for taking our questions. The first one is a bit more of a housekeeping question. I was wondering if you could provide some comments about the financial implications of the Neurocrine.
Omar Khawaja: And so we believe that's also going to be important in understanding the safety profile of the VYHT-T01 program. So we're looking forward to submitting our response to the FDA and anticipateing moving forward with the clinical trial once the dosing is listed.
The solution of the partnership.
Then the second question is more a quite early but the novel catches are very interesting and you do.
Did mentioned from potential indications, but we were wondering if you could provide some more color as to what areas you would be looking to move these assets can do thank you so much.
Operator: Great, thank you. Thank you. And our next question comes from the line of Brian Snorky. You're with Baird. Your line is open. Back dialing in for Brian.
Yes, thanks for your questions Alison on the financials.
Sure.
On the financial side, Yeah, we've we've projected that we'll end 2021 with $50 million to $60 million of cash and cash equivalents on hand and.
Operator: Thank you so much for taking our questions. The first one is a bit more of a housekeeping question. We were wondering if you could provide some comments about the financial implications of the Neurocrin dissolution of the partnership. And then the second question is more quite early, but the novel capses are very interesting. And you did mention some potential indications, but we're wondering if you could provide some more color as to what areas you'd be looking to move these assets into. Thank you so much.
And that we continue to have cash on hand to reach me.
Mid 2022, which is consistent with what we've said in the past we continue to execute on our strategy with.
Financial discipline and evaluating strategic alternatives for them.
Additional financing to run our business.
You know at this point I think no no real impact from.
The debt termination and then American program.
Operator: Yeah, thanks for your questions. Allison on the financials.
Thanks, Jonathan and our newest fragrance.
Second question around the targets for novel Capsid. So this.
Allison Dorval: Sure. So on the financial side, you know, we've projected that we'll end 2021 with 50 to $60 million of cash and cash equivalents on hand and that we will continue to have cash on hand to reach the mid-2022, which is consistent with what we've said in the past. We continue to execute on a strategy with Financial Discipline and evaluating strategic alternatives for additional financing to run our business. You know, at this point, I think there will be no real impact from The Determination of an American Program.
The early campaigns that are that have read through and that are in various stages of <unk>.
Characterization.
These are for IV delivery.
To enable a good transaction.
Target cells different regions of the brain.
So we have an opportunity with the different captured that have different distribution.
To be able to marry the neuro pathology with the distribution of a given Jeff said.
So that's the.
That's the process that.
We.
I've gone through and we will continue to go through as we read through additional GAAP suits.
Allison Dorval: Thanks, Alfred. And on your second question about the targets for novel capsids, so this
And Thats the type of information that we'll look to provide an update on in the first half per year.
Awesome. Thank you so much very exciting.
Andre Tarrant: The early campaigns that are...
Andre Tarrant: that I've read through and that are in various stages of characterization. These are for IV delivery to enable good transduction of target cells into different regions of the brain. So we have an opportunity with different capsids that have different distributions to be able to marry the neuropathology with the distribution of a given capsid. So that's the process that we have gone through, and we'll continue to go through as we read through additional capsules. And that's the type of information that we'll look to provide an update on in the first half of the year.
Thank you.
Thank you and our next question comes from the line of eight and has enough with benchmark. Your line is open. Please go ahead.
Hi, Thank you for taking my questions first.
First question is.
About Parkinson's program.
So you have 23 patients that were treated in phase one studies so far.
Did you see any MRI abnormalities in those 23 patients ended the SMB request the MRI images from the phase one trials as well.
Yeah. Thanks Steven.
Omar.
Yes.
Couple of things.
Just.
The F&B, how quick plus debt.
Operator: Awesome. Thank you so much. Very exciting.
MRI scans to.
To be reviewed from the from the phase one.
Operator: Thank you.
Be patient.
Operator: Thank you. And our next question comes from the line of Aiden Hausenhoff with Benchmark. Your line is open. Please go ahead.
One of the differences between the.
Imaging that was collected in the phase one studies and in restore one is the timing of the imaging so in restore one.
Operator: Thank you for taking my questions.
Operator: My first question is about Parkinson's program. So you have 23 patients that were treated in phase one studies so far. Did you see any MRI abnormalities in those 23 patients? And did DSMB request the MRI images from the phase one trials as well? Yeah, thanks, Leighton. Omar?
Imaging out to one year, whereas in the phase one studies.
Imaging went out six months so.
One of the things that the person be able requesting us to get longer term emerging from the phase one patients as well as a review of the imaging already collected to date.
Omar Khawaja: Uh, yeah, so a couple of things to note. I mean, just the DSMB has requested MRI scans to be reviewed from the Phase I B patients. One of the differences between the imaging that was collected in the Phase I studies and in Restore 1 is the timing of the imaging. So in Restore 1, there was imaging out to one year, whereas in the Phase I studies, the imaging went out to six months.
So it's not really possible because there's not it's not an apples to apples comparison on the imaging from Es until we've had longer term imaging data from the phase one patients.
Okay. Thank you Jeff.
And.
Yes.
That's helpful.
And Paul for Huntington and I have another question. So you mentioned that this is this could be a potential best in class therapy could you.
Omar Khawaja: So one of the things that the DSMB is requesting is for longer-term imaging from those Phase I patients, as well as a review of the imaging already collected to date. It's not really possible because it's not an apples-to-apples comparison on the imaging front until we've had longer-term imaging data from the Phase I patients. Okay, thank you for that. And, Yeah, that's helpful.
Give us some more color why do you think it could be the best in class and do you have any specifics from the preclinical data other than safety.
Thank you.
Okay.
Yeah no. Thanks.
Thanks for that so.
What.
What we know from our preclinical work is that we have a very.
Potent construct.
We now.
Also that the true.
Work, we've done to optimize the delivery.
Operator: And for Huntington, I have another question. So you mentioned that this could be a potential best in class therapy.
We get from.
Good.
Transport of the day.
Operator: Todd Carter, Yanan Zhu, Jay Olson, Divya Rao, Todd Carter, Joon Lee, Ingrid Ibarra, Ross
Vector genomes true.
Richard and then third rate.
Travel.
Operator: Thank you.
Andre Tarrant: Yeah, thanks for that. So what we know from our preclinical work is that we have a very potent construct. We know also that through the work we've done to optimize delivery, that we get some good transport of the vector genomes through retrograde and intergrade travel. So the route of administration that we've chosen to target the cutamen and the thalamus from the preclinical work suggests that we should be able to get a broad distribution of HTT knockdown. Um, and we, uh, uh, we have.
So where the route of administration that we've chosen to target.
Damon Palmas.
From the preclinical work.
Jeff that we should be able to get it broadened distribution of <unk> knockdown.
And we.
We have.
The results as Omar mentioned from.
Our transgenic rodent models showing that we get.
From.
Strong phenotypic.
Andre Tarrant: Transgenic Rodent Models
Rescue.
Jeff.
Andre Tarrant: strong and phenotypic rescue. In these HD disease models, transgenic models, so it's the totality of the evidence that we've developed to date that gives us some confidence about the profile of the program. And we'll look to present additional preclinical results later this year on the program so that we can show the longer-term results that we've had in non-human primates where we've studied the knockdown for up to 12 months. We will be able to provide updates on these longer-term NHP experiments.
In these in these HD disease models transgenic models. So it's the totality of the evidence.
Net evidenced that we build up to date.
Give us.
Some.
Our confidence about the profile of the program.
And.
We will look to true.
Additional preclinical results.
Later this year.
On the program so that we can.
So the longer term results.
We've had in non human primates, where we've been.
We've studied the knockdown.
Up to 12 months, we'll be able to provide.
From these longer term and HP experiments.
Operator: All right. Thank you very much. This is helpful. Thank you, and I'm not showing any further questions at this time, and I would like to turn the conference back over to Andre Turin for any further remarks.
Alright. Thank you very much it's helpful. Thank you.
Thank you and I'm showing no further questions at this time I would like to turn the conference back over to Andre Turenne for any further remarks.
Andre Tarrant: Okay, well, thanks everyone for joining us today, and we look forward to keeping you updated on our progress through the rest of the year. Thanks very much.
Okay, well, thanks, everyone for joining us today, and we look forward to keeping you updated on our progress.
Through the rest of the year, thanks very much.
Operator: Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program, and you may all disconnect. Everyone, have a great day! BF-WATCH TV 2021
Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program and you may all disconnect everyone have a great day.
Okay.
[music] volume.
Yes.
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Non-GAAP.
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