Q2 2022 Voyager Therapeutics Inc Earnings Call

Operator: A good day and welcome to Voyager Therapeutics' second quarter 2022 conference call.

Gabor, Good day and welcome to Voyager Therapeutics second quarter 2022 conference call. All participants are now in listen only mode. There will be a question and answer session. At the end of this call, which will be recorded if you require operator assistance. Please.

Operator: All participants are now in listen-only mode.

Operator: There will be a question and answer session at the end of this call, which will be recorded.

Operator: If you require operator assistance, please press star then zero on your telephone keypad.

Operator: I would now like to turn the call over to Julie Burek, Vice President of Finance at Voyager.

Julie Burek: Thank you, operator.

Please press Star then zero on your telephone keypad I would now like to turn the call over to Julie Burak, Vice President of finance at Voyager.

Julie Burek: Good afternoon, everyone, and welcome to this conference call to discuss our second quarter 2022 results and prioritized pipeline.

Operator: Goodbye.

Thank you operator.

Good afternoon, everyone and welcome to this conference call to discuss our second quarter 2022 results and prioritize pipeline a replay of today's call, including the Q&A will be available on the investors section of our website approximately two hours after completion of this call.

Our prepared remarks, we will open the call for Q&A.

As a reminder, various remarks that we make during this call about the company's future expectations plans and prospects constitute forward looking statements for purposes of the safe Harbor provision under the private Securities Litigation Reform Act of 1995 actual results may differ materially from those indicated by these forward looking.

Statements as a result of various important factors, including those discussed in the risk factors section of our most recent annual report on Form 10-K, which is on file with the SEC and as updated by our subsequent filings. In addition, any forward looking statements represent our views only as of today and should not be.

Relied upon as representing our views as of any subsequent date.

Sept as required by law, we specifically disclaim any obligation to update or revise any forward looking statements. Even if our views change I'm joined today by our Chief Executive Officer Doctor Al Sandrock for the Q&A portion of the call. We will be joined by our senior Vice President of research Dr. Todd Carter now.

Julie Burek: A replay of today's call, including the Q&A, will be available on the investor's section of our website approximately two hours after completion of this call.

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I will turn the call over to al.

Thanks, Julie and good afternoon, everyone.

I'm extremely pleased to discuss some exciting new developments at Voyager.

<unk> mission is to pioneer the discovery of transformational AAV capsid.

We hope will enable the development of life changing gene therapies.

We believe that the novel capsid derived from our proprietary tracer platform represents a breakthrough innovation that will address certain fundamental limitations. They currently have for gene therapy.

We and our partners plan to leverage these assets to advance the field of gene therapy for the central nervous system as well as other organs.

Julie Burek: After our prepared remarks, we will open the call for Q&A.

We believe that our ongoing collaborations involving the tracer cap.

Including those recently signed with Pfizer and Novartis are progressing well.

Both have option exercise milestones coming up in the next several quarters.

Julie Burek: As a reminder, various remarks that we make during this call about the company's future expectations, plans, and prospects will be recorded on the Q&A's website.

Soon after joining the company as CEO earlier this year I led a comprehensive process to evaluate voyagers R&D programs and determine where to focus with the goal of creating important new therapies for patients and growing shareholder value, while maintaining our cash.

Runway into 2024.

Julie Burek: In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date.

Julie Burek: Except as required by law, we specifically disclaim any obligation to update or revise any forward-looking statements, even if our views change.

Today, we are excited to announce our prioritize development pipeline, which builds on advances we've made with our tracer capsid.

Julie Burek: I'm joined today by our Chief Executive Officer, Dr. Al Sandrock.

Julie Burek: For the Q&A portion of the call, we will be joined by our Senior Vice President of Research, Dr. Todd Carter.

Gene therapy has the potential to transform the treatment of many serious CNS diseases.

Julie Burek: Now, I will turn the call over to Al.

A clear example of this is the transformational impact that <unk> had.

Alfred Sandrock: We believe that our ongoing collaborations involving the tracer capsids, including those recently signed with Pfizer and Novartis, are progressing well. Both have option exercise milestones coming up in the next several quarters.

<unk> for the treatment of infants with spinal muscular atrophy.

Alfred Sandrock: Soon after joining the company as CEO earlier this year, I led a comprehensive process to evaluate Voyager's R&D programs and determine where to focus, with the goal of creating important new therapies for patients and growing shareholder value while maintaining our cash runway into 2024. Today, we are excited to announce our prioritized development pipeline that builds on advances, we've made with our tracer capsids.

However, the FDA label limits the use of the old Gen.

Two up to age two.

Alfred Sandrock: Gene therapy has the potential to transform the treatment of many serious CNS diseases. A clear example of this is the transformational impact that Zolgensma has had for the treatment, of infants with spinal muscular atrophy.

The blood brain barrier appears to preclude the use of intravenous gene therapy in older children and adults.

Alfred Sandrock: However, the FDA label limits the use of Zolgensma to up to age two.

Consequently delivery methods, such as the direct injection of gene therapy into the cerebrospinal fluid or CSF space or into the brain parenchyma.

Alfred Sandrock: The blood-brain barrier appears to preclude the use of intravenous gene therapy in older children and adults. Consequently, delivery methods such as the direct injection of gene therapy into the cerebral spinal fluid or CSF space, or into the brain parenchyma have been and are being attempted. On slide five, we show examples from the published literature of what happens when these delivery methods are used, in non-human primate experiments.

Ben and are being attempted.

On slide five we show examples from the published literature, what happens when these delivery methods that are used in nonhuman primate experiments.

Alfred Sandrock: We believe the situation is analogous when similar methods are employed in humans. The example on the left panel on this slide comes from a published study in Cynomolgus monkeys, in which AAV9 expressing green fluorescent protein or GFP is injected intrathecally into the CSF space at multiple spinal levels.

We believe the situation is analogous when similar methods are employed in humans.

For example on the left panel on this slide comes from a published study and Cinemark is monkeys in which AAV nine expressing green fluorescent protein or GSP is injected interests equally into the CSF space at multiple spinal levels.

Alfred Sandrock: As you can see by the number of green stained cells, there's a clear drop-off in the number of transduced cells, as you go from the lumbar spinal cord to more rostral levels and even less in the brain where there are a few weakly stained cells in patchy areas of the cerebral cortex and other regions.

As you can see by the number of Green space. So there is a clear drop off in the number of transduce cells. As you go from this lumbar spinal cord to more rostral levels and even less in the brain, where there are a few weekly, Spain, so and patchy areas of the cerebral cortex and other regions.

Alfred Sandrock: Injections into other CSF spaces such as the cisterna magna are not likely to be much better.

Injections into other CSF spaces, such as the cisterna magna are not likely to be much better.

Alfred Sandrock: Clearly, for most CNS disease applications, this pattern of distribution and low transduction efficiency, is a major limitation and likely precludes significant clinical benefits. The panel on the right comes from a published study in which AAV5 expressing GFP was injected directly into the brain parenchyma, in this case the putamen, by means of a surgical procedure. GFP expression, as seen here by the brown staining, is highly localized to the site of injection. Interparenchymal injections, even with convection-enhanced delivery, result in highly localized distribution.

Clearly for most of the MS disease applications. This pattern of distribution and low trust transduction efficiency is a major limitation and likely preclude significant clinical benefit.

The panel on the right comes from a published study and which AAV five expressing GFE was injected directly into the brain per acre in this case, the putamen by means of a surgical procedure.

DSP expression has seen here by the Brown staining is highly localized to the site of injection.

Venture parenchymal injection, even with convection enhanced delivery result in highly localized distribution.

Alfred Sandrock: Moreover, although some CNS diseases may begin in the deep gray structures of the brain, most eventually involve the entire brain.

Our over although some CNS diseases may begin in the deep great structures of the brain most.

Most eventually involve the entire brain.

Alfred Sandrock: So the limited distribution of gene therapy that is likely to result from such localized delivery methods, imposes severe benefit-risk limitations for therapeutic utility.

So the limited distribution of gene therapy that is likely to result from such localized delivery methods and poses severe benefit risk limitations for therapeutic utility.

Alfred Sandrock: As these limitations became increasingly clear over the past several years, Voyager scientists believed that we could do better.

As these limitations became increasingly clear over the past several years.

Boyd's your scientists believe that we could do better.

Alfred Sandrock: We set out to discover novel capsids with improved trophism, as a potential solution to the delivery and distribution challenges. We invented an approach, now known as TRACER, which has resulted in capsids that in non-human primates have been shown to far more efficiently transduce CNS tissue after IV delivery than any conventional AAV capsid in use today. At the core of TRACER is our proprietary expression-driven in vivo screening platform. This platform has enabled our scientists to identify novel capsids that preferentially target the CNS and other tissues of interest.

We set out to discover novel capsid with improved tropism as a potential solution the delivery and distribution challenges.

We invented and approach now known as tracer, which has resulted in capsid and a nonhuman primates have been shown.

So far more efficiently transduce CNS tissue after IV delivery in any conventional AAV capsid in use today.

At the core of tracer is our proprietary expression driven in vivo screening platform.

This platform has enabled our science is doing to identify novel capsid that preferentially targets, the CNS and other tissues of interest.

Alfred Sandrock: TRACER has allowed our team to evaluate more than 20 million variants of AAV5 and AAV9 capsids and select only those capsids that display increased transduction in the target organ. This approach has two distinct advantages.

Fraser has allowed our team to evaluate more than $20 million variance of AAV, five and AAV nine capsid and select only those captive display increased transduction in the target Oregon.

This approach as two distinct advantages.

Alfred Sandrock: First, we perform the initial screening along with a series of subsequent screens in non-human primates so that we're selecting for capsids that show improved trophism in species very closely related to humans, not capsids that may only show activity in mice, which past experience has taught us may not translate well to other species, let alone human beings.

First we performed the initial screening along with a series of subsequent screen in nonhuman primates. So that we're selecting for capsid.

That show improved tropism, and specie is very closely related to humans not capsid that may only work that may only show activity in mice, which past experience has taught us may not translate well to other species, let alone human beings.

Alfred Sandrock: Second, we measure the performance of our capsids at each step of the screening process by evaluating gene expression, that is, at the level of messenger RNA. When we measure production of the desired mRNA in the target tissue, we have confidence that we're selecting capsids that not only get across the blood-brain barrier, but that also enter into cells and deliver and express their payload productively.

Second we measure the performance of our caps at each step of the screening process by evaluating gene expression that is at the level of messenger RNA.

When we measure production of the desired mrna in the target tissue, we have confidence that we're selecting capsid, but not only get to cross the blood brain barrier, but that also enter into sell and deliver and express their payload productively.

Alfred Sandrock: The results from TRACER have been remarkable. Our capsids have displayed more than 100-fold higher transgene expression in the brain as compared to the conventional AAV capsids in non-human primates. Slide 7 highlights some of what we have observed thus far with the novel capsids derived from TRACER.

The results from trades, there have been remarkable.

<unk> have displayed more than 100 fold higher transient expression in the brain as compared to the conventional AAV capsid in nonhuman primates.

Slide seven highlights some of what we have observed thus far with the novel capsid derived from tracer.

Alfred Sandrock: We have found that our novel capsids can efficiently target numerous therapeutically relevant regions of the brain, including the cerebral cortex, hippocampus, and spinal cord, after IV delivery. At the cellular level, our capsids can efficiently transduce neurons, glia, or both cell types. Remarkably, while our capsids increase targeting of neurons and glia in the CNS, at the same time, they can also de-target cells that may result in toxicity, such as liver cells and dorsal root ganglion neurons.

We have found that our novel capsid can efficiently target numerous therapeutically relevant regions of the brain, including the cerebral cortex, if a campus and spinal cord after IV delivery.

At the cellular level, our cabinets can efficiently transduce neurons glia.

Both cell types.

Remarkably while our capsid increased started getting those neurons English in the CNS at the same time. They can also D. Toric itself that May result in toxicity, such as liver cells and dorsal root ganglion neurons.

Alfred Sandrock: Finally, we've also found that our capsids have improved CNS tropism across species, such as the macaque, the marmoset, and the mouse, which we believe improve the likelihood of translation into humans. In summary, we believe our data demonstrate that we can identify truly unique AAV capsids with the potential to enable promising therapeutic candidates for many CNS diseases that could not be adequately addressed using the currently available conventional AAV capsids.

Finally, we've also found that our cap rates have improved.

Tropism across species.

As the macaque, the marmosets and the mouth, which we believe improves the likelihood of translation into humans.

In summary, we believe our data demonstrate that we can identify truly unique AAV capsid with the potential to enable promising therapeutic candidates for many CNS diseases that could not be adequately addressed using the currently available conventional AAV capsid.

Alfred Sandrock: We are also very pleased to announce today that we have recently identified a receptor, for one of our most promising tracer capsids. We plan to provide further details on this finding at an upcoming scientific conference. What I can tell you today is that we have strong data supporting the identification, of a binding receptor for one of our capsids, including data that show that our capsid binds to the human isoform of the receptor, which is expressed in brain endothelial cells and other CNS cell types. We believe that the characterization, of this receptor capsid interaction further increases the probability that this capsid will cross the blood-brain barrier in humans.

We're also very pleased to announce today that we have recently identified a receptor for one of our most promising tracer capsid.

We plan to provide further details on this finding in an upcoming scientific conference.

But I can tell you today is that we have strong data supporting the identification of a binding receptor for one of our cast at <unk>.

<unk> data that show that our caps it binds to the human isoform of the receptor, which is expressed in brain endothelial cells and other CNS cell types.

We believe that the characterization of this receptor captive interaction further increases the probability that this capsid will cross the blood brain barrier in humans.

Alfred Sandrock: Importantly, this discovery may provide a path for the rational design, of IV-delivered BBB penetrant capsids.

Importantly, this discovery may provide a path for the rational design of IV deliberate EBV penetrated cabinets.

Alfred Sandrock: Moreover, experiments are now underway to explore the possibility, that this receptor may enable the CNS delivery of other therapeutic modalities, such as proteins, antibodies, and oligonucleotides.

Moreover, experiments are now underway.

Florida the possibility that this receptor may enable the CNS delivery of other therapeutic modalities, such as proteins antibodies and all the good nucleotide.

Alfred Sandrock: I've discussed how our tracer platform has resulted in the generation of capsids, that we believe can overcome some of the most pressing hurdles facing CNS gene therapy, and have tremendous potential to treat human and CNS diseases.

I have discussed how our trade show platform has resulted in the generation of capsid that we believe can overcome some of the most pressing hurdles facing CNS gene therapy and have tremendous potential to treat human CNS diseases.

Alfred Sandrock: We are now combining these unique tracer capsids with our team's deep knowledge, of CNS disease biology and drug development, with the aim of developing therapies against well-validated targets with potentially transformative clinical impact.

We are now combining these unique tracer capsid with our teams deep knowledge of CNS disease biology, and drug development with the aim of developing therapies against well validated targets with potentially transformative clinical impact.

Alfred Sandrock: I will now discuss our pipeline.

I will now discuss our pipeline.

Alfred Sandrock: Before doing so, I'd like to tell you how we prioritize the pipeline. First, we chose diseases with high unmet medical needs, serious life-threatening diseases, where patients have few, if any, treatment options.

Before doing so I'd like to tell you how we prioritize the pipeline.

First we chose diseases with high unmet medical needs serious life, threatening diseases, where patients have few if any treatment options.

Alfred Sandrock: Second, we chose well-validated targets for these diseases, those validated by human genetics, and human clinical pathologic data that indicate that we are dealing with targets in disease-causing biological pathways.

Second we chose well validated targets for these diseases.

Validated by human genetics, and human clinical pathologic data that indicate that we are dealing with targets and disease, causing biological pathways.

Alfred Sandrock: Third, we selected programs where it would be possible to rapidly, and efficiently establish proof of concept, or at least proof of biology in early phase clinical trials. Fourth, we chose programs where we had evidence of robust preclinical pharmacology.

Third we selected programs, where it would be possible to rapidly and efficiently establish proof of concept or at least proof of biology in early phase clinical trials.

Fourth we chose programs, where we had evidence of robust preclinical pharmacology and.

Alfred Sandrock: And finally, we focused on programs, that should provide meaningful commercial opportunities.

And finally, we focused on programs that should provide meaningful commercial opportunities.

Alfred Sandrock: Based on these criteria, three programs are now our top priorities. BbA1 gene replacement for Parkinson's disease, SOD1 gene silencing for SOD1-mediated ALS, and antithelpassive immunotherapy for Alzheimer's disease. We will focus today's pipeline discussion on our prioritized internal programs, and our plans to advance each toward clinical development.

Based on these criteria three programs are now our top priorities.

DBA, one gene replacement for Parkinson's disease.

So the one gene silencing for <unk> mediated ALS.

An anti Tau passive immunotherapy for Alzheimers disease.

We will focus today's pipeline discussion on our prioritized internal programs.

Our plans to advance each toward clinical development.

Alfred Sandrock: We note that in addition to these prioritized programs, we will also continue, to conduct early research on gene therapy for Huntington's disease and vectorized HER2 antibodies. We hope to be able to advance these programs into later stages of research one day in the future.

We note that in addition to these prioritized programs. We will also continue to conduct early research on gene therapy for Huntington's disease and <unk> two antibodies.

We hope to be able to advance these programs into later stages stages of research one day in the future.

Alfred Sandrock: Let's now review each of our prioritized internal development programs in more detail.

Let's now review each of our prioritized internal development programs in more detail.

Alfred Sandrock: I'll start with the GBA-1 Parkinson's disease program.

I'll start with the GBA Parkinson's disease program.

Alfred Sandrock: Parkinson's disease is the second most common neurodegenerative disease, impacting about 1 million people in the U.S. alone. Up to 10% of Parkinson's disease patients have a mutation in GBA-1, the most common genetic risk factor, increasing the risk of the disease approximately 20-fold. GBA-1 encodes the lysosomal enzyme glucocerebrosidase, or GKs, which degrades glycosphingolipid substrates. Homozygous loss-of-function GBA-1 mutations result in Gaucher's disease, a lysosomal storage disease, and heterozygous loss-of-function GBA-1 mutations result in an increased risk of Parkinson's disease. Loss-of-function in GKs leads to the accumulation of glycosphingolipid substrates and alpha-synuclein aggregates, which are thought to be toxic to neurons.

Parkinson's disease, the second most common neuro degenerative disease impacting about 1 million people in the U S alone.

Up to 10% of Parkinson's disease patients have a mutation in GBA want the most common genetic risk factor decreasing the risk of the disease approximately twentyfold.

DBA wanting codes, the lysosomal enzymes glucose rebirth sideways or G case, which degrades glycosphingolipid substrates.

Homozygous loss of function GBA. One mutations result, these mutations result in gosh as disease, a lysosomal storage disease and heterozygous loss of function GPA. When mutations resulted in an increased risk of Parkinson's disease.

Loss of function in Gk's leads to the accumulation of Glycosphingolipid substrates, and Alpha nucleon aggregates, which are thought to be toxic to neurons.

Alfred Sandrock: We hypothesize that the restoration of GKs in patients with Parkinson's disease with GBA mutations will have therapeutic benefits.

We are involved the size that the restoration of PK in patients with Parkinson's disease with GBA mutations.

We'll have therapeutic benefit.

Alfred Sandrock: The restoration of GKs may also benefit patients with idiopathic PD, where there is evidence of loss of GKs in the substantia nigra even in the absence of GBA-1 mutations.

The restoration of Gk's may also benefit patients with idiopathic PD, where there is evidence of loss of gk's into substantial Niagara even in the absence of DVA one mutations.

Alfred Sandrock: Moreover, there is growing evidence of lysosomal dysfunction in general in idiopathic Parkinson's disease. As shown on slide 13 on the left panel, sorry, as shown on slide 15 on the left panel, because of loss-of-function mutations in the GBA-1 gene, there is reduced GKs activity in the relevant brain regions of patients who had Parkinson's disease or dementia with Lewy bodies who were GBA carriers.

Moreover, there is growing evidence of lysosomal dysfunction in general in idiopathic Parkinson's disease.

As shown on slide 13 on the left panel sorry as shown on slide 15 on the left panel because of loss of function mutations in the GBA. One gene there is reduced gk's activity and the relevant brain regions of patients, who has parkinson's disease or dementia with lewy bodies.

Who in GBA carriers.

Alfred Sandrock: Interestingly, as alluded to earlier, there's evidence of reduced GKs activity in the substantia nigra even in PD patients who did not have GBA-1 mutations relative to control patients.

Interestingly as alluded to earlier, there's evidence of reduced gk's activity into substantial Niagara even in PD patients, who did not have GBA mutation relative to control patients.

Alfred Sandrock: Consequently, as shown on the right panel, substrates for the GKs enzymes, such as glucothelium ceramide, are elevated in the cerebral spinal fluid in PD patients who harbor the GBA-1 mutation.

Consequently, as shown on the right panel substrates for the Gk's enzymes, such as glucose steel ceramide are elevated industry, both spinal fluid in PD patients who harbor the GBA one mutation.

Alfred Sandrock: This provides an opportunity to demonstrate proof of biology in an early phase clinical trial.

This provides an opportunity to demonstrate proof of biology and in early phase clinical trials.

Alfred Sandrock: If our gene therapy restores GKs enzyme expression in the brain, substrate levels in the CSF should fall to normal, providing a potential path to early clinical development de-risking. In a preclinical study presented at the ASGCT meeting this year, Voyager scientists showed that an IV-delivered gene replacement therapy in rodents increases GKs protein and enzyme activity in the brain, and thus lowers the level of both glucothelium ceramide and glucothelium sphingosine in the brain in a dose-dependent manner.

Our gene therapy restores gk's enzyme expression in the brain.

Straight levels in the CSF should fall to normal providing a potential path to early clinical development derisking.

In a preclinical study presented at the <unk> meeting this year Voyager Sciences showed that an IV delivered gene replacement therapy in rodents increases gk's protein and enzyme activity in the brain and thus lowers the level of both Lucas steel ceramide exit goods sales figures seen in the brain.

In a dose dependent manner.

Alfred Sandrock: This is shown on slide 16.

This is shown on slide 16.

Alfred Sandrock: We hope to achieve similar results in the clinic with one of our tracer-derived capsids, and we are moving this program forward, as shown on slide 17. We are evaluating tracer capsids in anticipation of selecting an IV-delivered capsid for this program by year-end.

We hope to achieve similar results in the clinic with one of our tracer drive capsid and we are moving this program forward as shown on slide 17.

We are evaluating tracer cap sits in anticipation of selecting an IV delivered cap just for this program by year end.

Alfred Sandrock: In the first half of 2023, we expect to finalize selection of a development candidate.

In the first half of 2023, we expect to finalize selection of a development candidate following that in the second half of 2023, we expect to initiate a dose range finding study in nonhuman primates, and we anticipate initiating GOP toxicology studies in 2020 for this <unk>.

Alfred Sandrock: Following that, in the second half of 2023, we expect to initiate a dose-range finding study in non-human primates, and we anticipate initiating GLP toxicology studies in 2024. This timeline puts us on track for an IND in 2025, but we are actively reviewing options to accelerate the program.

<unk> puts us on track for an IND in 2025, but we are actively reviewing options to accelerate the program.

Alfred Sandrock: Moving now to SOD1-ALS. Amyotrophic lateral sclerosis is a rapidly-progressing neurodegenerative disease that typically leads to death approximately three years after diagnosis. Current treatments are minimally effective, and there is a great need for improved therapies. Autosomal-dominant superoxide dismutase I mutations are thought to cause a toxic gain of function that leads to the degeneration of motor neurons along the entire length of the spinal cord, the brainstem, as well as the upper motor neurons in the cerebral cortex.

Moving now to <unk>.

Yes.

Am I supposed to be collateral sclerosis is a rapidly progressing neuro degenerative disease that typically leads to death approximately three years. After diagnosis current treatments are minimally effective and theres a great need for improved therapies.

Autosomal dominant superoxide dismutase, one mutations are thought to cause a toxic gain of function that leads to the degeneration of motor neurons motor neurons, along the entire length of the spinal cord the brain stem as well as the upper motor neurons in the cerebral cortex.

Alfred Sandrock: We believe that by reducing the expression of SOD1 in the central nervous system, we can provide therapeutic benefit to ALS patients with SOD1 mutations.

We believe that by reducing the expression of <unk> in the central nervous system, we can provide therapeutic benefit to patients with <unk> mutations.

Alfred Sandrock: From a clinical development standpoint, the ability to demonstrate reduced levels of SOD1 in CSF as a target engagement biomarker, as well as the ability to measure plasma neurofilament light chain as a surrogate biomarker of clinical efficacy, greatly facilitate clinical development.

From a clinical development standpoint, the ability to demonstrate reduced levels of the vessels do you want <unk> in CSF.

Target engagement biomarker.

As well as the ability to measure plasma neuro filament light chain as a surrogate biomarker clinical efficacy greatly facilitate clinical development.

Alfred Sandrock: Our therapeutic approach for SOD1-ALS combines a potent siRNA construct with a CNS-trophic BDD penetrant capsid.

Our therapeutic approach for <unk> combines a potent sorry, RNA construct with a CNS trophic BBB penetrate capsid.

Alfred Sandrock: Because of the potential for broad CNS targeting, we hope to address all of the major disease manifestations involving the entire neuroaxis, namely the brain, brainstem, and spinal cord with an IV-delivered tracer-derived capsid.

Because of the potential for broad CNS targeting we hope to address all of the major disease manifestation involving the entire near axis, namely the brain brainstem and final court with an IV delivered tracer derive capsid.

Alfred Sandrock: Preclinical data that were presented at the ASGCT conference earlier this year, shown on slide 20, demonstrate that IV delivery of siRNA gene therapy leads to robust SOD1 knockdown in all regions of the spinal cord and significant improvements in motor performance, body weight, and survival in the G93a SOD mouse model. We believe these data provide preclinical pharmacologic support for our approach, and we're eager to advance toward the clinic.

Preclinical data that were presented at the <unk> Conference earlier. This year shown on slide 20 demonstrates that IV delivery of SA RNA gene therapy leads to robust <unk> knockdown in all regions of the spinal cord and significant improvements in motor performance body weight.

And survival in the gene Ninety-three, a S O D mouse model.

We believe these data provide preclinical pharmacologic support for our approach and we're eager to advance towards the clinic.

Alfred Sandrock: Slide 21 shows the anticipated milestones for this program, which are as follows. Our NHP capsid evaluation study is underway, and we expect to select a final candidate by the end of this year. We plan to obtain a non-human primate dose range finding study readout in 2023, and we anticipate initiation of GLP toxicology studies in the first half of 2024. If we achieve these milestones in a timely manner, an IND filing in the second half of 2024 is anticipated.

Slide 21 shows the anticipated milestones for this program, which are as follows.

<unk> capsid evaluation study is underway and we expect to select the final candidate by the end of this year.

We plan to obtain in nonhuman primate dose ranging.

The dose.

Dose range finding study readout in 2023, and we anticipate initiation of GOP toxicology study in the first half of 2024.

If we achieved these milestones in a timely manner, an IND filing in the second half of 2024 as anticipated.

Alfred Sandrock: I'll now transition to our passive immunotherapy program, Targeting Tau.

I'll now transition to our passive immunotherapy program targeting Tau.

Alfred Sandrock: This program is based on research conducted by our team since the earliest days of the founding of our company. Our Tau antibody discovery work for vectorization led to the discovery of novel antibodies selectively targeting pathological Tau. These antibodies have a number of favorable characteristics supporting continued development. These include high affinity for pathological forms of Tau, a protein that has been linked to a number of neurodegenerative diseases, including Alzheimer's disease.

This program is based on research conducted by our team since the earliest days of the founding of our company.

Our Tau antibody discovery work for back to origination led to the discovery of novel antibodies selectively targeting pathological Tao.

<unk> antibodies have a number of favorable characteristics supporting continued development.

These include high affinity for pathological forms of Tau protein that has been linked to a number of neuro degenerative diseases, including Alzheimer's disease.

Alfred Sandrock: Robust efficacy in animal models of Tau spreading, and clear differentiation from other anti-Tau antibodies, including those that have been shown to be clinically ineffective.

Robust efficacy in animal models of Tau spreading.

Clear and clear differentiation from other anti Tau antibodies, including those that have been shown to be clinically ineffective.

Alfred Sandrock: We plan to first leverage an anti-Tau antibody as an IV immunotherapy. This approach has the potential to lead to high value clinical candidates for the treatment of Alzheimer's disease and other Tauopathies with tremendous unmet need.

We plan to first leverage an anti tau antibody as an IV immunotherapy.

This approach has the potential to lead to high value clinical candidates for the treatment of Alzheimer's disease, and other tau apathy with tremendous unmet need they.

Alfred Sandrock: It may also lead the way for eventual vectorization of these antibodies as gene therapy candidates.

It may also lead the way for an eventual Beck <unk> of these antibodies as gene therapy candidates.

Alfred Sandrock: Some important advantages of this approach from a drug development standpoint are that immunotherapies with IV administration have already been shown to produce important effects in the brain and neurodegenerative diseases such as Alzheimer's disease.

Some important advantages of this approach from a drug development standpoint, or that Immunotherapies with IV administration have already been shown to produce important effects in the brain and neuro degenerative diseases, such as all farmers disease Mauro.

Alfred Sandrock: Moreover, we plan to use Tau PET imaging, which should allow for the rapid and efficient demonstration of proof of biology in an early phase clinical trial.

Moreover, we plan to use Tau pet imaging, which should allow for the rapid and efficient demonstration of proof of biology and in early phase clinical trial.

Alfred Sandrock: We've known for some time now that Tau pathology propagates across certain brain regions in a stereotype fashion in Alzheimer's disease, as shown on slide 24, and as demonstrated by the seminal work of Brock and Brock. Some investigators have pointed out that the accumulation of Tau pathology correlates better with dementia than any other biomarkers. Modern PET imaging studies, for example, as shown on the left panel of slide 24, have also shown that the spread of Tau, have also shown the spread of Tau pathology correlating with increased impairment and advancing broad stage.

We've known for some time now this tau pathology propagate across certain brain regions, and a stereotype fashion and Alzheimers disease.

On slide 24, and as demonstrated by the seminal work that brought in broth.

Some investigators that pointed out that the accumulation of Tau pathology correlate better with dementia than any other biomarker.

Modern pet imaging studies for example, as shown on the left panel of Slide 24.

I have also shown that the spread of clouds have also shown the spread of Tau pathology correlating with increased impairment and advancing broad stage.

Alfred Sandrock: In recent years, several controlled trials of amyloid directed therapies have demonstrated the feasibility of evaluating the spread of Tau pathology and longitudinal assessments of Tau PET images in patients with mild cognitive impairment due to Alzheimer's disease over the course of 12 to 18 month trials. Our therapeutic hypothesis is that an antibody targeting Tau may block the neuron-to-neuron spread of Tau at several plausible extracellular sites, as shown on the right side of this slide, and that this may attenuate the progression of diseases such as Alzheimer's disease.

In recent years several controlled trials of amyloid directed therapies have demonstrated the feasibility of evaluating the spread of Tau pathology and longitudinal assessments of Tau pet images in patients with mild cognitive impairment due to Alzheimer's disease over the course of 12 to eight.

18 months trials.

Our therapeutic hypothesis is that an antibody targeting Tau may block the neuron to neurons spread of Tau at several plausible extra cellular sites as shown on the right side of this slide and that this may attenuate the progression of diseases, such as Alzheimer's disease.

Alfred Sandrock: Tau has been the target of several monoclonal antibodies, including those that have not demonstrated clinical efficacy.

Bob has been the target of several monoclonal antibodies, including those that have not demonstrated clinical efficacy.

Alfred Sandrock: We are well aware of these studies, and we're careful to differentiate from these antibodies by targeting a different epitope.

We are well aware of these studies and we are careful to differentiate from these antibodies by targeting a different epitope.

Alfred Sandrock: The Voyager antibody targets the C-terminal, which to our knowledge has not been tested in a well-controlled efficacy trial of tau immunotherapy.

The Voyager antibody targets, the <unk> terminal, which to our knowledge has not been tested in a well controlled efficacy trial of Tau immunotherapy.

Alfred Sandrock: Slide 26 shows that our antibody in a rodent pathological tau spreading model is also differentiated in terms of biological activity from an N-terminal antibody that is equivalent to one that has failed to show efficacy in a Phase II clinical trial.

Slide 26 shows that our antibody and erosion pathological Tau spreading model is also differentiated in terms of biological activity from an N terminal antibody that is equivalent to one that has failed to show efficacy in a phase II clinical trial with.

Alfred Sandrock: We just presented this data on the panel on the right side of this slide at the AAIC meeting in San Diego.

We just presented this data on the right side of this on the panel on the right side of this slide at the AIC meeting in San Diego.

Alfred Sandrock: In this animal model, pathological tau called paired helicofilamentous tau is extracted and enriched from brain tissue from Alzheimer's disease patients. This material called ePHF can be injected into the hippocampus of the P301S mouse, a mouse strain that expresses a mutant human form of tau, where it induces substantial formation of pathological tau. This pathological tau also spreads to and accumulates in the contralateral hippocampus.

In this animal model pathological Tao cord called paired helical filamentous Tau is extracted and enriched from brain tissue from all timers disease patients.

This material called E. THF can be injected into the hippocampus of the P. 301, as smiles are miles strain that express is amusing human pharma Tau, whereas where it induces substantial formation of pathological Tao.

This pathological Tau also spreads to an accumulation accumulate in the contralateral hippocampus.

Alfred Sandrock: In our studies, we began dosing seven-week-old mice with antibodies for one week, injected ePHF, continued antibody dosing afterward, and sacrificed the animal six weeks later. Levels of pathological tau accumulation were then measured in the ipsilateral and contralateral hippocampus.

In our studies, we began dosing seven week old mice with antibodies for one week injected EPA, Jeff continued antibody dosing afterward, and sacrifice the animals six weeks later.

Levels of pathological Tau accumulation, where then measured in the ipsilateral contralateral if a campus.

Alfred Sandrock: There was significant reduction of tau pathology in both the ipsilateral and contralateral hippocampus.

There was a significant reduction of Tau pathology, and both ipsilateral contralateral hippocampus.

Alfred Sandrock: In contrast, as published in 2019 and shown in the figure on the left panel on this slide, the N-terminal antibody IPN002 has been shown to be ineffective in a very similar mouse seeding experiment.

In contrast, as published in 2019 and shown in the figure on the left panel on this slide the end terminal antibody IP and 002 has been shown to be ineffective in a very similar mouse seeding experiment.

Alfred Sandrock: Of note, the IPN002 antibody had been immunized and when tested in the clinic, sorry, had been humanized, and when tested in the clinic, failed to show efficacy in a phase two clinical trial.

Of note the IP and 002 antibody has been immunized and when tested in the clinic, sorry had been humanized and when tested in the clinic failed to show efficacy in a phase II clinical trial.

Alfred Sandrock: As a result of experiments such as these, we believe that the Voyager antibody, by targeting the C-terminal, may have an advantage over N-terminal targeting antibodies in blocking the spread of pathological tau in the brain.

As a result of experiments such as these we believe that the Voyager antibody by targeting the C terminal may have an advantage over and terminal targeting antibody and blocking the spread of pathological tau in the brain.

Alfred Sandrock: We are advancing our anti-tau immunotherapy program toward the clinic, and humanization of our murine antibody is already underway.

We are advancing our anti Tau immunotherapy program toward the clinic and Humanization of our murine antibody is already underway.

Alfred Sandrock: Looking ahead, we anticipate selection of a development candidate in the first half of 2023, followed by initiation of GLP toxicology studies later that year. If we achieve these milestones in a timely manner, we would target IND filing in 2024.

Looking ahead, we anticipate selection of a development candidate in the first half of 2023, followed by initiation of GOP Toxicology studies later that year.

If we achieve these milestones in a timely manner, we would target IND filing in 2024.

Julie Burek: I'll now pass the call to Julie to review our financial results.

I'll now pass the call to Julie to review our financial results.

Julie Burek: Thank you, Al.

Thank you al.

Julie Burek: As we've previously announced, we have executed two important deals with Pfizer and Novartis, two global leaders in gene therapy, for the application of our capsids for certain specific diseases. These deals have provided Voyager with meaningful, non-dilutive capital and have the potential to result in substantial additional milestone and royalty-based revenue.

As we've previously announced we have executed two important deals with Pfizer and Novartis two global leaders in gene therapy for the application of our caps in certain specific diseases.

Let's have provided Voyager with meaningful non dilutive capital and have the potential to result in substantial additional milestone and royalty based revenue. We believe both the Pfizer and Novartis collaboration have been progressing well with our teams collaborating closely looking ahead, we anticipate either option exercise.

Julie Burek: We believe both the Pfizer and Novartis collaborations have been progressing well, with our teams collaborating closely. Looking ahead, we anticipate the Pfizer option exercise decision by October 2022 and the Novartis option exercise decision by March 2023.

Decision by October 2022, and the Novartis option exercise decision by March 2023.

Julie Burek: I'd also note that Voyager has ongoing partnership with Neurocrine Biosciences on a preclinical, Friedrichs ataxia program and two undisclosed discovery programs.

I'd also note dental ager has ongoing partnership with Neurocrine Biosciences on a preclinical friedrichs ataxia program and two undisclosed discovery programs. We are optimistic about the potential to enter into additional tracer caps in collaboration with the goal of further leveraging our tracer technology in partnership.

Julie Burek: We are optimistic about the potential to enter into additional tracer-capsin collaborations, with the goal of further leveraging our tracer technology in partnership with other pharma companies and in doing so potentially helping to bring important new medicines forward.

Like other pharma company and in doing so potentially helping to bring important new medicines forward.

Julie Burek: I'll now turn to our financial results.

I'll now turn to our financial results in the interest of time I'll focus on a few key metrics.

Julie Burek: In the interest of time, I'll focus on a few key metrics.

Julie Burek: Voyager is in a strong position as we advance our platform and portfolio forward.

And here is in a strong position as we advance our platform and portfolio of flooring.

Julie Burek: We reported cash equivalents in marketable securities of $148.1 million as of June 30, 2022. Based upon our current operating plan, we expect that existing cash equivalents in marketable, securities will be sufficient to meet planned operating expenses and capital expenditures into 2024.

We reported cash cash equivalence and marketable securities of $148 $1 million.

June 32022.

Based upon our current operating plan, we expect that existing cash cash equivalents in marketable securities will be sufficient to meet planned operating expenses and capital expenditures into 2024.

Julie Burek: Please see our press release and SEC filings for further details on our financial results.

Please see our press release and SEC filings for further details on our financial results.

Julie Burek: I'll now pass the call to Al for concluding remarks.

I'll now pass the call to al for concluding remarks.

Alfred Sandrock: Thank you, Julie.

Thank you Julie.

Alfred Sandrock: Before I get to my concluding remarks, I'd like to welcome Catherine Mackey to our board, at this pivotal time in Voyager's evolution. Catherine's outstanding track record of R&D success coupled with her vast expertise, in strategic collaborations with industry partners will be invaluable to Voyager as we advance our pipeline and maximize our tracer capsid discovery platform.

Before I get to my concluding remarks, I would like to welcome Kathryn Mackie to our board at this pivotal time in Voyager's evolution.

Catherine outstanding track record of RMB success.

With her vast expertise and strategic collaborations with industry partners will be invaluable to Voyager as we advance our pipeline and maximize our tracer capsid discovery platform.

Alfred Sandrock: I joined Voyager because I'm optimistic about our ability to make a meaningful impact, on the lives of patients. I believe that the potential of gene therapy is enormous, but the challenge of delivering, these therapies safely and effectively to the central nervous system, as well as other organ systems, has limited its utility to date.

I joined Voyager, because im optimistic about our ability to make a meaningful impact on the lives of patients.

I believe that the potential of gene therapy is enormous.

But the challenge of delivering these therapy safely and effectively to the central nervous system as well as other Oregon system at.

As limited its utility to date.

Alfred Sandrock: We believe, I believe, our novel tracer capsids can address some of these limitations and, provide an opportunity for us and our partners to advance differentiated programs toward the clinic. The demonstration that our tracer capsids have improved target organ tropism across, species, combined with the very recent identification of the receptor for one of our promising capsids and its human homolog, gives us additional optimism that our capsids will offer the potential for improved tropism in humans.

We believe I believe our novel Tracer capsid can address some of these limitations and provides an opportunity for us and our partners to advance differentiated programs towards the clinic.

The demonstration that our tracer capsid have improved target, Oregon tropism across species combined with the very recent identification of the receptor for one of our promising capsid and its human homolog gives us additional opposite optimism that arc, our capsid will offer the potential for improved <unk>.

There is some inhuman.

Alfred Sandrock: Our ongoing collaborations are going well, and there are upcoming license option exercise, dates, including with Pfizer in October of this year. We're also optimistic about other potential collaborations in the future, given the promise, offered by the novel capsids derived from tracer across multiple disease areas.

Our ongoing collaborations are going well.

And there are upcoming license option exercise dates, including with Pfizer in October of this year.

We're also optimistic about other potential collaborations in the future given the promise offered by the novel capsid derived from tracer across multiple disease areas.

Alfred Sandrock: Our prioritized pipeline includes differentiated programs against validated targets for diseases, of high unmet need, featuring strong preclinical pharmacology, as well as clinical development plans with efficient paths to human proof of biology.

Our prioritized pipeline includes differentiated programs against validated targets for diseases of high unmet need featuring strong preclinical pharmacology as well as clinical development plans with efficient path to human proof of biology.

Alfred Sandrock: We look forward to updating you about the progress on our science, our pipeline, and, our partnerships in the coming months.

We look forward to updating you about the progress on our science, our pipeline and our partnerships in the coming months.

Alfred Sandrock: Thank you for listening.

Thank you for listening we will now open it up for questions.

Operator: We will now open it up for questions.

Operator: We will now begin the question and answer session.

We will now begin the question and answer session.

Operator: To ask a question, you may press star then 1 on your telephone keypad.

To ask a question you May press Star then one on your telephone keypad.

Operator: If you are using a speakerphone, please pick up your handset before pressing the keys.

If youre using a speakerphone please pick up your handset before pressing the keys.

Operator: If at any time your question has been addressed and you would like to withdraw your question, please press star then 2.

If at any time your question has been addressed and you'd like to withdraw. Your question. Please press Star then two.

Operator: At this time, we will momentarily pause to assemble our roster.

At this time, we will momentarily paused to assemble our roster.

Operator: The first question comes from Jack Allen with Baird.

The first question comes from Jack Allen with Baird.

Jack Allen: Please go ahead.

Please go ahead.

Jack Allen: Hi.

Alright. Thank you so much for taking the questions and congratulations on all the progress and the prioritization of the pipeline maybe first.

Jack Allen: Thank you so much for taking the questions and congratulations on all the progress and, the prioritization of the pipeline.

Jack Allen: Maybe first, at a very high level, I was hoping you could provide some more context around, the three assets that you plan to move forward and maybe characterize the de-risk nature of each of the assets and maybe the riskiness, to put it another way, of each of the assets.

At a very high level I was hoping you could provide some more context around the three assets that you plan to move forward maybe characterize the.

Jack Allen: Then I have a follow-up as well.

Derisk nature of each of the assets and maybe the riskiness or put another way of each of the assets and I have a follow up as well.

Alfred Sandrock: Hi, Jack.

Alfred Sandrock: This is Al.

Alfred Sandrock: Thanks for the question.

Hi, Jackie this is al thanks for the question.

Alfred Sandrock: I'm not sure I heard the first, something that nature, I know I heard the risky nature, but what was the first part of that?

Sure I heard the first something that nature I know if I heard the risky nature, but it was the first part of that.

Jack Allen: Just to put it another way, how de-risky maybe do you each of these candidates, if you could, think about the overall risk profile of each of the assets, would be great.

So said another way how derisked do you each of these candidates, yes, if you can think about.

The overall risk profile of each of the assets would be great.

Jack Allen: Yeah.

Alfred Sandrock: No, thanks.

No. Thanks, Yes, no look.

Alfred Sandrock: Yeah.

Alfred Sandrock: No, it's, look, these are high risk, high reward, right? I mean, because they're, we tackle diseases with high unmet need, but we feel we can manage, the risk because we chose programs deliberately where we could de-risk early in clinical development and efficiently. So, for example, in the case of the Tau program, we feel we can use Tau PET imaging to see, whether or not we can block the spread of Tau in a very efficient manner in an early phase clinical trial, perhaps even in a phase 1b trial in a matter of, say, 12 months.

These are high risk high reward right I mean, because there we tackle diseases with high unmet need, but we feel we can manage the risks because we chose programs deliberately where we could derisk early in clinical development and efficiently. So for example in.

The case of the Tau program, we feel we can use tau pet imaging to see whether or not we can block the spread of tau and a very efficient manner.

And in early phase clinical trials, perhaps even in a phase one b trial.

In a matter of say 12 months.

Alfred Sandrock: And in the case of SOD1 ALS, for example, we can measure CSF SOD1 levels to make sure, we're silencing or reducing the expression of SOD1.

And in the case of.

<unk> for example, we can measure CSF <unk>, one levels to make sure we're silencing or reducing the expression of SMB, one and we can also look at plasma neuro filament as a way of assessing whether or not we're decreasing the degeneration of.

Alfred Sandrock: And we can also look at plasma neurofilament as a way of assessing whether or not we're, decreasing the degeneration of spinal cord motor neurons as well as brain stem motor neurons.

Spinal cord motor neurons as well as bringing some motor neurons. So so I think.

Alfred Sandrock: So, I think, you know, it's important to realize that one of the key criteria we used in selecting, these programs is that we can efficiently de-risk, if you will, and gain proof of biology and proof of concept.

It's important to realize that one of the key criteria. We used in selecting these programs that we can efficiently.

De risk, if you will and gain proof of biology and proof of concept.

Jack Allen: Great.

Okay, Great and then just a follow up I know that the Shaoguan AOS program does have.

Jack Allen: And then just to follow up, I know that the SOD1 ALS program does have an asset under, regulatory review to first in from BioGED.

And asset under.

Regulatory review to first thing about from Biogen.

Jack Allen: I was wondering if you could just speak to the results you've seen from that asset to, date and any confidence that gives as you move towards the clinic with your asset and how it could impact the treatment landscape moving forward as well.

I was wondering if you could just speak to the results you've seen from that asset to date in any conference decades as you move towards the.

The clinic with your asset and how it could impact the treatment landscape moving forward as well.

Alfred Sandrock: Well, everything I've seen is based on public information, and from what I see, if we use, baseline neurofilament as a covariate, as presented at the recent NCALS meetings, that there's efficacy on several important clinical outcome measures, including the functional rating scale.

Well everything I have seen has.

Based on public information and.

And from what I see.

We use baseline neuro filament as a covariate as presented at the recent <unk> meeting.

Meeting.

That there is efficacy.

On several important clinical outcome measures, including the functional rating scale.

Alfred Sandrock: So I think that, and then there are, you know, I mean, there are certainly reports of patients, who are, have very long extensions of survival.

So I think that.

And then there are.

I mean, there are certainly reports of patients who are.

Very long.

Extensions of survival.

Alfred Sandrock: So you know, those are more in the anecdotal reports, but I remember seeing a report on, CBS Morning News of a patient who's still playing golf after several years.

So.

Those are more on the anecdotal.

Reports, but.

I remember seeing report on CBS morning news of the patients who still playing golf after several years.

Alfred Sandrock: And so, which I think is pretty remarkable.

So, which I think is pretty remarkable so anyway. So look I think a lot more I look forward to seeing more data, particularly as the file I guess they have now filed it.

Alfred Sandrock: So anyway, so I look, I think a lot more, I look forward to seeing more data, particularly, as the file, I guess they've now filed it, they're going to file for approval, and the, FDUFA data, I believe, is next January.

They are going to file for approval and the <unk> data I believe is next January so.

Alfred Sandrock: So I expect to see much more data.

To see much more data and of course by the time, we get into the clinic, we'll see a lot more data from the FDA briefing documents and other documents in the public domain. So we'll learn a lot from that and we'll leverage whatever information we get.

Alfred Sandrock: And of course, by the time we get into the clinic, we'll see a lot more data from the, FDA briefing documents and other documents in the public domain.

Alfred Sandrock: So we'll learn a lot from that, and we'll leverage whatever information we get and incorporate, into our clinical development plan.

Incorporated into our clinical development plan.

Jack Allen: Great.

Jack Allen: Thanks so much.

Great. Thanks, so much congrats on the progress.

Jack Allen: Congrats on the progress.

Alfred Sandrock: Thank you.

Thank you.

Operator: The next question comes from Divya Rao with Cowen and Company.

The next question comes from Dave <unk> with Cowen and company. Please go ahead.

Divya Rao: Please go ahead.

Divya Rao: Hi, this is Divya on for Phil.

Hi, This is <unk> on for Phil Thanks for taking our questions and congrats on the quarter and the exciting pipeline update.

Divya Rao: Thanks for taking our questions, and congrats on the quarter and the exciting pipeline update.

Divya Rao: Just two questions from us.

Just two questions from US one based on just flavors previous clinical data, especially in Parkinson's disease do you see any overlap in the current pipeline programs obviously.

Divya Rao: One, based on just Voyager's previous clinical data, especially in, you know, Parkinson's, disease, do you see any overlap in the current pipeline programs?

Divya Rao: Obviously, others, like, in terms of the actual candidate that you're selecting, that would, potentially enable rapid entry and progression through the clinic.

In terms of the actual candidate that you're selecting that would potentially enable rob.

Rapid entry.

And progression through the clinic and then just like a more I guess specific question what are the limitations with <unk>, especially when delivered systemically increased liver accumulation.

Divya Rao: And then, just like a more, I guess, specific question, one of the limitations with AAVs, especially when delivered systemically, is the increased liver accumulation.

Divya Rao: I was wondering if you had any comments on what you're seeing in terms of liver accumulation, with these capsids, either in rodents or the non-human primates.

Wondering if you had any comments on.

What youre seeing in terms of avera accumulation with these captains either in rodents or Don.

Divya Rao: Thank you.

Thank you.

Alfred Sandrock: Thanks, Divya.

Alfred Sandrock: Those are great questions.

Thanks, Steve Yeah. Those are great questions first of all in terms of overlap.

Alfred Sandrock: First of all, in terms of overlap, you know, the previous Parkinson's program, which was, actually terminated last year, and it was a partnership with Neurocrin, was a different payload. It was actually delivering ADC, L-aromatic amino acid decarboxylase, and it was actually, using intraparenchymal, convection-enhanced intraparenchymal delivery.

Previous Parkinson's program, which was actually terminated last year and it was a partnership with Neurocrine was a different payload.

Chile.

Delivering ADC.

Aromatic amino acid decarboxylase.

And it was actually using intra parenchymal convection enhanced intra earn income on delivery.

Alfred Sandrock: And so, our program is very different.

And so our program is very different we plan to go over the IV delivered tracer capsid, so different capsid different route of administration different payload here, we're going to be paid.

Alfred Sandrock: We plan to go with IV-delivered tracer capsids, so different capsids, different route of administration, different payload.

Alfred Sandrock: Here, we're going to be, the payload is GKase, the enzyme that is encoded by the gene GBA.

Payload is gk's the enzyme.

Of that.

Is encoded by the gene DBA and ours is more of a disease modifying approach if you will.

Alfred Sandrock: And ours is more of a disease-modifying approach, if you will.

Alfred Sandrock: And so, not too much overlap, I would say, with the last, with the program that was terminated, last year.

And so.

<unk>.

Not too much overlap I haven't saved with the last with the program that was terminated last year I don't know if Tom has anything to add before I before I jump to the next.

Alfred Sandrock: I don't know if Todd has anything to add before I, before I jump to the next part of the question, on liver.

Part of the question on member non thank you Catherine I think importantly.

Todd Carter: No, I think you captured it.

Todd Carter: I think, importantly, the goal of doing something that could be disease-modifying is truly important.

The goal of doing something that could be disease modifying in distribution.

Todd Carter: Yeah, yeah.

Alfred Sandrock: And then, in terms of the liver, that's a great question. I think that, you know, one of the reasons why we're excited about the tracer capsids, is that not only do they increase tropism into the desired organs, like the CNS, but many of them show, at the same time, de-targeting organs like the liver, where we get toxicity.

Yes.

And then in terms of the labor Thats a great question I think that one of the reasons why we're excited about the trade Street capsid.

Is that not only do they increase.

Tropism into the desired Oregon's like the CNS, but many of them show at the same time D targeting.

Oregon's like deliver where we get toxicity.

Alfred Sandrock: So that's very promising.

So that's very promising and then the second thing is that since they are so potent at getting into the brain with IV delivery, we hope to be able to use lower doses and in fact, we're going to be showing data and Todd Im sure note much much more about this.

Alfred Sandrock: And then the second thing is that since they're so potent at getting into the brain with IV delivery, we hope to be able to use lower doses.

We're we're doing dose range finding studies.

To show that we can go to lower doses.

Which should also help with the with the liver toxicity issues.

Alfred Sandrock: And in fact, we're going to be showing data, and Todd, I'm sure, knows much more about this.

Yes, so how do you capture that.

And it's a great question I think the whole field is seeing toxicity.

And the <unk> and in <unk> and what we're seeing with our cash as Alan pointed out is we identify those captured that deliver into the brain, while targeting the liver and DRG and potentially other regions as well. So it's one of the things that we are.

Todd Carter: We're doing dose range finding studies with, you know, to show that we can go to lower doses, which should also help with the liver toxicity issues.

Todd Carter: Todd?

Find most compelling about taxes.

And again to that enhanced DVD penetration and would allow a lower dose.

That's really helpful. Thank you so much.

Todd Carter: Yeah.

Again, if you have a question. Please press Star then one.

The next question comes from June Zhang with BTG. Please go ahead.

Todd Carter: So, Al, you captured it.

Hi, Thank you very much for taking the questions. So the first one on the technology platform.

Do you have a sense.

Your expectation the dose level that you will be able to achieve sufficient maybe exposure in the brain.

And sorry have you looked at Immunogenicity, because oftentimes when with novel capsid.

I believe we have seen a lot of unwanted immune response.

Thank you I'm going to ask Todd to answer these questions. Thanks for the great questions and excellent questions. Thank you with the dose levels, what we're seeing as we reported this is priority <unk>.

Gene therapy conferences that we are able to get substantially better delivery. So 100, plus so they're delivering into the brain versus what is currently the standard of the earned 89.

So what were anticipating is intensely with better improvement or lowering of the dose.

We hope to achieve that we are seeing evidence that we can.

So we're anticipating some additional.

Reports on this upcoming Keith.

Gene therapy conferences that al referenced earlier.

On the Immunogenicity side, so by and large we're making specific tweaks to these gas since we're targeting particular loops that we've identified that we can modify an ounce.

Causing problems with the capsid and by and large those do not impact the initiative that you've seen so preexisting immunity. So far is there a similar.

To the parents of casting.

We have not identified any increase.

Immunogenicity up to now.

Okay. So if I can ask a question about indication.

How was your experience was Alzheimer's and with companies experienced with Parkinson's.

It is reasonable, but given the complexity of the pathophysiology behind those diseases, what's your comfort level that you'll be able to use a gene therapy approach target those very complicated neuro degenerative diseases and.

I think yes.

That's the question. Thank you very much.

Yes, well, let me start and.

Todd.

Also answer.

I believe that.

By targeting but we chose targets that are highly validated.

And in the case of PD for example, we're going to start with the subset of patients.

That have GBA GBA carriers.

It's still up but it's a pretty large subset as we set up to 10% some pay per say, 5%, some say, 10%, but it's up to 10% of Parkinson's patients have GBA mutation. The most common genetic risk factor. So so I think it is a complex disease.

But I think if we by targeting net debt fairly large subset of patients who are who are GBA carriers.

I think that we will be.

The complexity. If you will we also can measure whether or not we would replace the enzyme.

Again, another derisking maneuver that we can do early in clinical development, we can see whether or not we replace the enzyme.

And gotten normal expression or at least getting toward normal expression of the enzyme by looking at three books spinal fluid levels.

And so and then also in the case of all famous disease.

That was the other part of your question.

Again, I think tile is a pretty darn well validated target.

As I mentioned earlier in some ways.

The progression of Tau.

Is better correlated with dementia than any other biomarker.

And again, the ability to image Tau I think greatly.

Also a measure of phosphorylated Tau, where pathologic forms of Tau in the CSF and blood really help us.

Derisked the program so.

So I'm pretty optimistic.

Not only about our ability to do therapeutics in these diseases, but I think the whole field.

Has learned a lot and we're going after well validated targets using modern measurement tools.

So I'm actually very optimistic.

Okay, great. Thank you very much.

Todd Carter: It is a great question.

Todd Carter: I think the whole field has seen toxicities in the DRGs and in the liver.

Todd Carter: And what we're seeing with our capsids, as Al pointed out, is we identify those capsids that deliver into the brain while de-targeting the liver and DRG, and potentially other regions as well.

This concludes our question and answer session and Voyager Therapeutics second quarter 2022 conference call. Thank you for attending today's presentation. You may now disconnect.

Todd Carter: So it's one of the things that we find most compelling about the capsids, in addition to that enhanced BBB penetration that would allow a lower dose.

Goodbye.

Okay.

[music].

Okay.

[music].

Yeah.

Yeah.

[music].

Divya Rao: That's really helpful.

Divya Rao: Thank you so much.

Operator: Again, if you have a question, please press star, then 1.

[music].

[music].

Operator: The next question comes from Yoon Jong with BTIG.

Operator: Please go ahead.

Yoon Jong: Hi.

Yoon Jong: Thank you very much for taking the question.

Yoon Jong: So the first one on the technology platform, do you have a sense of your expectation, the dose level, that you will be able to achieve sufficient, maybe, exposure in the brain?

Yoon Jong: Sorry.

Yoon Jong: Have you looked at immunogenicity?

Yoon Jong: Because oftentimes, with novel capsids, I believe we have seen a lot of unwanted immune response.

Yoon Jong: I'm going to ask Todd to answer these questions.

Todd Carter: Thanks for the great questions.

Todd Carter: Excellent questions.

Todd Carter: Thank you.

Todd Carter: With the dose levels, what we're seeing, we reported this at prior ASGCT, the teen therapy conferences, that we're able to get substantially better delivery.

Todd Carter: So 100-plus fold better delivery into the brain versus what's currently the state-of-the-art A89.

Todd Carter: So what we're anticipating is a 10-fold better improvement or lowering of the dose that we hope to achieve, and that we're seeing evidence that we can.

Todd Carter: And we're anticipating some additional reports on this at upcoming teen therapy conferences that Al referenced earlier.

Todd Carter: On the immunogenicity side, so by and large, we're making specific tweaks to these capsids. We're targeting particular loops that we've identified that we can modify without causing problems with the capsid.

Todd Carter: And by and large, those do not impact the immunogenicity that we've seen.

Todd Carter: So pre-existing immunity so far is very similar to the parental capsid.

Todd Carter: We have not identified any increased immunogenicity up to now.

Yoon Jong: Okay, so if I can ask a question about indication.

Yoon Jong: I know, Al, with your experience with Alzheimer's and with companies' experience with Parkinson's, it's reasonable.

Yoon Jong: But given the complexity of the pathophysiology behind those diseases, what's your comfort level that you will be able to use a gene therapy approach to target those very complicated neurodegenerative diseases?

Yoon Jong: And I think, yeah, that's the question.

Yoon Jong: Thank you very much.

Yoon Jong: Yes, well, let me start and Todd can also answer.

Alfred Sandrock: I believe that, you know, by targeting, we chose targets that are highly validated.

Alfred Sandrock: And in the case of PD, for example, we're going to start with the subset of patients that have GBA, that are GBA carriers. It's still, it's a pretty large subset, as we said, up to 10%. You know, some papers say 5%, some say 10%. But up to 10% of Parkinson's patients have GBA1 mutations, the most common genetic risk factor.

Alfred Sandrock: So, so I think it is a complex disease.

Alfred Sandrock: But I think if we by targeting that, that very large subset of patients who are who are GBA carriers, I think that we, we reduce the complexity, if you will.

Alfred Sandrock: And we also can measure whether or not we've replaced the enzyme by, again, another de-risking maneuver that we can do early in clinical development, we can see whether or not we've replaced the enzyme and gotten a normal expression or at least getting toward normal expression of the enzyme by looking at cerebral spinal fluid levels.

Alfred Sandrock: And so, and then also in the case of Alzheimer's disease, you know, that was the other part of your question.

Alfred Sandrock: You know, again, I think tau is a pretty darn well validated target. As I mentioned earlier, in some ways, the progression of tau is better correlated with dementia than any other biomarker.

Alfred Sandrock: And, again, the ability to image tau, I think greatly, and also measure phosphorylated tau or pathologic forms of tau in the CSF and blood really help us de-risk the program.

Alfred Sandrock: So I'm pretty optimistic, not only about our ability to do therapeutics in these diseases, but I think the whole field has learned a lot.

Alfred Sandrock: And we're going after well-validated targets using modern measurement tools.

Alfred Sandrock: So I'm actually very optimistic.

Yoon Jong: Okay, great.

Yoon Jong: Thank you very much.

Operator: This concludes our question and answer session and Voyager Therapeutics' second quarter 2022 conference call.

Operator: Thank you for attending today's presentation.

Operator: You may now disconnect.