Our Pipeline

We are developing potentially transformational therapies for conditions for which there are currently few or no treatment options. These include lead programs in neurology for Huntington’s disease, amyotrophic lateral sclerosis and frontotemporal dementia.

  • Huntington’s disease

    Huntington’s disease (HD) is a devastating autosomal dominant disorder that deeply impacts both patients and their loved ones.

    Causing nerve cells in the brain to deteriorate over time, HD is characterized by cognitive decline, psychiatric illness and chorea. It is ultimately fatal and currently has no cure.

    Huntington’s disease (HD) is a devastating autosomal dominant disorder that deeply impacts both patients and their loved ones.

    Causing nerve cells in the brain to deteriorate over time, HD is characterized by cognitive decline, psychiatric illness and chorea. It is ultimately fatal and currently has no cure.

    ~30K
    people in the US are estimated to be positive for HD and exhibiting symptoms
    ~200K
    people in the US
    are estimated to be at risk
    of developing the condition

    The cause of HD

    HD is a genetic disease caused by a mutation in the huntingtin (HTT) gene, which is believed to be critical for neuronal development. Specifically, an expanded section within the gene (CAG triplet repeat) results in production of an expanded huntingtin protein (mHTT). Accumulation of mHTT causes progressive loss of neurons in the brain, and can lead to neuronal cell death, causing motor, cognitive and psychiatric disability.

    People with HD still possess wild-type (healthy) HTT protein, the suppression of which may have detrimental long-term consequences. Absence of healthy huntingtin protein has been shown to be embryonic lethal.

    Our approach

    Our programs target two disease-associated single nucleotide polymorphisms (“SNPs”) within the huntingtin gene: rs362307 (“mHTT SNP-1”) and rs362331 (“mHTT SNP-2”). SNPs are naturally occurring variations within a given genetic sequence. In certain instances, SNPs can be used to distinguish between two related copies of a gene, where only one is responsible for causing production of a defective protein that causes disease. It has been shown that by targeting mHTT SNP-1 and mHTT SNP-2, the production of disease-causing proteins associated with HD can be reduced. This has the potential to provide treatment for up to 70% of people with HD.

  • Amyotrophic lateral sclerosis

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which the progressive degeneration of motor neurons in the brain and spinal cord leads to the inability to initiate or control muscle movement.

    People with ALS may lose the ability to speak, eat, move and breathe. It is ultimately fatal.

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which the progressive degeneration of motor neurons in the brain and spinal cord leads to the inability to initiate or control muscle movement.

    People with ALS may lose the ability to speak, eat, move and breathe. It is ultimately fatal.

    ~20K
    people in the US
    have ALS
    2.5yr
    median survival rate

    The cause of ALS

    ALS can be caused by mutations in the C9orf72 gene, which provides instructions for making protein found in various tissues, including nerve cells in the cerebral cortex and motor neurons. C9orf72 genetic mutations serve as the strongest genetic risk factor found to date for non-inherited (sporadic) forms of ALS and is the most common genetic mutation identified with familial ALS.

    The genetic mutation contains hundreds to thousands of hexanucleotide repeats, compared to 2-23 in wild-type transcripts, causing the formation of mutant proteins that accumulate in brain tissue.

    Our approach

    Our stereopure antisense oligonucleotides aim to selectively silence the repeat-containing transcripts in C9orf72. By doing so, we strive to suppress the production of harmful proteins.

  • Frontotemporal dementia

    Frontotemporal dementia (FTD) is a neurodegenerative disease in which progressive nerve cell loss in the brain's frontal lobes and temporal lobes leads to personality and behavioral changes, as well as the gradual impairment of language skills.

    Frontotemporal dementia (FTD) is a neurodegenerative disease in which progressive nerve cell loss in the brain's frontal lobes and temporal lobes leads to personality and behavioral changes, as well as the gradual impairment of language skills.

    ~55K
    people in the US
    have FTD
    2nd
    most common form of
    early onset dementia after
    Alzheimer’s disease in people
    under the age of 65

    The cause of FTD

    FTD is often caused by mutations in the C9orf72 gene, which provides instructions for making protein found in various tissues, including nerve cells in the cerebral cortex and motor neurons. C9orf72 genetic mutations serve as the strongest genetic risk factor found to date for non-inherited (sporadic) forms of FTD and is the most common genetic mutation identified with familial FTD.

    The genetic mutation contains hundreds to thousands of hexanucleotide repeats, compared to 2-23 in wild-type transcripts, causing the formation and accumulation of mutant proteins that accumulate in brain tissue.

    Our approach

    Our stereopure antisense oligonucleotides aim to selectively silence the repeat-containing transcripts in C9orf72. By doing so, we strive to suppress the production of harmful proteins.