Our Programs

About Huntington’s Disease

Huntington’s disease (HD) is a fatal, inherited neurodegenerative disease that results in the progressive decline of motor and cognitive functions and a range of behavioral and psychiatric disturbances. The disease affects approximately 30,000 individuals in the U.S.,

Huntington’s disease (HD) is a fatal, inherited neurodegenerative disease that results in the progressive decline of motor and cognitive functions and a range of behavioral and psychiatric disturbances. The disease affects approximately 30,000 individuals in the U.S., according to the Huntington’s Disease Society of America, with symptoms usually appearing between the ages of 30 to 50, and worsening over a 10 to 25-year period. HD is caused by mutations in the huntingtin, or HTT, gene. While the exact function of the HTT gene in healthy individuals is unknown, it is essential for normal development before birth and mutations in the HTT gene ultimately lead to the production of abnormal intracellular huntingtin protein aggregates that cause neuronal cell death. HD is an autosomal dominant disorder, which means that every child of a parent with Huntington’s has a 50/50 chance of inheriting the faulty HTT gene. Currently, there are no approved treatments targeting the underlying cause of the disease.

Voyager is developing proprietary next-generation AAV capsids derived from our TRACERTM technology platform. These capsids power our second-generation programs in Huntington’s disease and ALS. TRACER has generated capsids that have achieved superior transduction of targeted tissues over AAV9 in non-human primates. Our capsid technology may enable intravenous administration and achieve broad distribution to affected tissue. This new approach offers an opportunity to potentially confer greater patient benefit with a more favorable safety profile.

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About Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a rare, rapidly progressive, fatal disease characterized by the degeneration of nerve cells in the spinal cord and brain resulting in severe muscle atrophy with loss of the ability to walk and speak,

Amyotrophic Lateral Sclerosis (ALS) is a rare, rapidly progressive, fatal disease characterized by the degeneration of nerve cells in the spinal cord and brain resulting in severe muscle atrophy with loss of the ability to walk and speak, and premature death. The median survival is approximately three years, and 90 percent of people with ALS die within five years of symptom onset¹. ALS affects approximately 20,000 people in the U.S., with less than 10,000 new cases identified each year reflecting a high rate of mortality and short survival, relative to other diseases with similar incidences².

Patients with ALS typically develop weakness in one body region (upper or lower limb or bulbar) and then develop symptoms and signs of progressive dysfunction of motor neurons. The majority of ALS cases occur sporadically and with unknown cause, but in approximately 10 percent of patients, the cause is familial and can be linked to an identifiable genetic defect. An estimated 20 percent of familial cases can be attributed to mutations in superoxide dismutase 1 gene (SOD1). SOD1 is the first mutant gene discovered to cause the development of ALS, through a toxic gain of function mechanism leading to motor neuron pathogenesis³.

Voyager is generating a clinical candidate for the treatment of ALS due to mutations in SOD1. Multiple studies have demonstrated that mutant SOD1 is toxic to motor neurons, and leads to their progressive loss. The candidate will be composed of a proprietary TRACER AAV capsid and transgene with a micro RNA (miRNA) expression cassette that harnesses the RNAi pathway to selectively silence, or knockdown, the production of SOD1 messenger RNA. This candidate may have the potential to durably reduce the levels of toxic mutant SOD1 protein in the CNS to slow the progression of disease.

Voyager’s proprietary AAV capsid has been derived from our TRACERTM technology that is designed to identify novel capsids that may overcome limitations of AAV9. These capsids power our second-generation programs in Huntington’s disease and ALS. TRACER has generated capsids that have achieved superior transduction of targeted tissues over AAV9 in non-human primates. One capsid, Capsid 9P801, displayed in non-human primates more than a 1,000-fold higher transgene expression in the brain compared to AAV9delivery. Our capsid technology may enable intravenous administration and may achieve broad distribution to affected tissue. This new approach offers an opportunity to potentially confer greater patient benefit with a more favorable safety profile.

[1] Sorenson EJ, et al. (2002) Neurology 59:280-282.
[2] www.alsa.org
[3] Rosen D, et al. (1993) Nature 362:59-62.

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About Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA) is a rare, neuromuscular disease affecting voluntary muscular movement. SMA is caused by a mutation in the survival of motor neuron 1 (SMN1) gene, which encodes for the SMN protein,

Spinal Muscular Atrophy (SMA) is a rare, neuromuscular disease affecting voluntary muscular movement. SMA is caused by a mutation in the survival of motor neuron 1 (SMN1) gene, which encodes for the SMN protein, a protein responsible for regulating the health and function of motor neurons involved in crawling and walking, grasping or reaching, breathing and swallowing. Roughly 10,000 to 25,000 children and adults are living with SMA in the US. SMA is found in an estimated 1 in every 6,000 to 1 in every 10,000 people¹. There are four primary types of SMA. Type 1 is the most severe – children with this form of SMA generally do not live beyond their second birthday. SMA symptoms vary depending on the type. SMA patients typically experience a progressive loss of muscle control, movement and strength, which progressively worsens with age. The disease often most severely affects the muscles closest to the torso and neck. While some people with SMA never walk, sit or stand, others gradually lose their ability to do these actions.

No cure exists for SMA. Treatments vary based on disease type and symptoms. Those with SMA can benefit from physical and occupational therapy or assistive devices including orthopedic braces, crutches, walkers and wheelchairs. Certain disease-modifying therapies that stimulate production of the SMN protein can also be administered. Gene replacement therapy may also offer benefits to patients under two years of age.

Voyager is committed to developing a best-in-class therapeutic option for SMA utilizing a novel, proprietary AAV capsid, derived from our TRACERTM technology. TRACER is designed to identify novel capsids that may overcome limitations of AAV9 capsids. TRACER has generated capsids that have achieved superior transduction of targeted tissues over AAV9 in non-human primates. One capsid, Capsid 9P801, displayed in non-human primates more than a 1,000-fold higher transgene expression in the brain compared to AAV9 delivery.. Our capsid technology may enable intravenous administration and may achieve broad distribution to affected tissue. This new approach offers an opportunity to potentially confer greater patient benefit with a more favorable safety profile.

[1] https://my.clevelandclinic.org/health/diseases/14505-spinal-muscular-atrophy-sma

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About Friedreich’s Ataxia

Friedreich’s ataxia is a debilitating neurodegenerative disease resulting in poor coordination of the legs and arms, progressive loss of the ability to walk, generalized weakness, loss of sensation, scoliosis, diabetes and cardiomyopathy as well as impaired vision,

Friedreich’s ataxia is a debilitating neurodegenerative disease resulting in poor coordination of the legs and arms, progressive loss of the ability to walk, generalized weakness, loss of sensation, scoliosis, diabetes and cardiomyopathy as well as impaired vision, hearing and speech. The typical age of onset is 10 to 12 years, and life expectancy is severely reduced with patients generally dying of neurological and cardiac complications between the ages of 35 and 45. According to the Friedreich’s Ataxia Research Alliance, there are approximately 6,400 patients living with the disease in the United States and no FDA-approved treatments.

Friedreich’s ataxia patients have mutations of the FXN gene that reduce production of the frataxin protein, resulting in the degeneration of sensory pathways and a variety of debilitating symptoms. Friedreich’s ataxia is an autosomal recessive disorder, meaning that a person must obtain a defective copy of the FXN gene from both parents in order to develop the condition. One healthy copy of the FXN gene, or 50 percent of normal frataxin protein levels, is sufficient to prevent the disease phenotype. We therefore believe we may be able to achieve success by restoring FXN protein levels to approximately 50 percent of normal levels using AAV gene therapy.

In conjunction with Neurocrine, we are developing an AAV gene therapy approach that delivers a functional version of the FXN gene to the sensory pathways through intrathecally or intravenously. We believe this approach has the potential to improve the balance, ability to walk, sensory capability, coordination, strength and functional capacity of Friedreich’s ataxia patients. Most Friedreich’s ataxia patients produce very low levels of the frataxin protein, which, though insufficient to prevent the disease, exposes the patient’s immune system to frataxin, thus reducing the likelihood that the FXN protein expressed by AAV gene therapy would trigger a harmful immune response.

Our joint program with Neurocrine for Friedreich’s ataxia is currently in preclinical development. Once a lead candidate for this program is identified, we will assess with Neurocrine the potential for preclinical studies to evaluate the safety and efficacy of a lead candidate, including studies in a relevant animal model of Friedreich’s ataxia and IND-enabling studies.

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About Tauopathies including Alzheimer’s Disease and Other Neurodegenerative Diseases

Pathological and aggregated tau protein is believed to play a key role in severe CNS diseases. In healthy individuals, tau is an abundant soluble cytoplasmic protein that binds to microtubules to promote microtubule stability and function.

Pathological and aggregated tau protein is believed to play a key role in severe CNS diseases. In healthy individuals, tau is an abundant soluble cytoplasmic protein that binds to microtubules to promote microtubule stability and function. In Alzheimer’s disease (AD) and other tauopathies, tau aggregates and becomes hyper-phosphorylated, forming insoluble tau-containing neurofibrillary tangles (NFTs). The progressive spread of tau pathology along distinct anatomical pathways in the brain closely correlates with disease progression and severity in a number of tauopathies, including AD, frontotemporal lobar degeneration (FTD), Pick’s disease, progressive supranuclear palsy (PSP) and corticobasal degeneration. Because the extent of tau pathology in AD and other tauopathies closely correlates with the severity of neurodegeneration, synapse loss, and cognitive deficits, attempts to prevent, reduce or slow the development of tau pathology have become important therapeutic strategies for these diseases.

In previous preclinical studies, despite high, weekly or biweekly infusions of anti-tau monoclonal antibodies over three to six months, only very low levels of antibody reach the brain parenchyma from the systemic circulation resulting in modestly reduced tau pathology. This incomplete and modest reduction in tau pathology following treatment with very high and frequent systemic doses of these antibodies may pose therapeutic challenges in humans with various tauopathies.

To address these limitations, scientists at Voyager Therapeutics, working in collaboration with colleagues at Weill Cornell Medical College, carried out a study demonstrating that a single injection of an AAV vector to deliver an anti-tau antibody, PHF1, resulted in very high antibody expression in hippocampal and cortical neurons and reduced tau pathology by up to 90 percent in a robust tauopathy animal model as compared to 40-50 percent reductions in tau pathology reported by others in preclinical models using weekly, systemic infusions of anti-tau antibodies¹.

These preclinical studies provide proof of principle in a robust animal model that AAV vectors can be used to deliver monoclonal antibodies to misfolded pathological proteins like tau to increase brain antibody levels beyond what can be achieved by traditional passive immunization and to potentially enhance their therapeutic effects.

[1] Liu W, et al. (2016) Journal of Neuroscience 36 (49): 12425-12435

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