Our current internal pipeline focus is to develop gene therapies that treat nervous system diseases, including cancers affecting the brain. Our initial programs are for metachromatic leukodystrophy (MLD) and brain metastases secondary to HER2 positive breast cancer. We hope to add a new program most years.
Additionally, we plan to benefit patients through strategic partnerships. For example, through a collaboration with Vertex Pharmaceuticals, Affinia Therapeutics is combining our capsid design expertise with Vertex’s scientific, clinical, and regulatory capabilities to accelerate the development of genetic medicines for people affected by Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1), and cystic fibrosis (CF).
Diseases that affect the nervous system, and especially the central nervous system (CNS), are among the most difficult to treat because the blood-brain barrier (BBB) limits what can get into the brain from the bloodstream, including therapeutics.1 With our ART platform, we’re developing the next generation of capsids and promoters that more effectively and specifically target cells in the brain to transform the lives of people living with nervous system diseases.
Metachromatic leukodystrophy (MLD)
MLD is a rare genetic disease caused by a mutation in the ARSA gene. The ARSA gene makes the arylsulfatase A (ARSA) enzyme (protein), which is needed to break down fats that contain molecules called sulfatides. Without the ARSA enzyme, sulfatides accumulate and damage myelin, the protective fatty cover that surrounds nerves. The symptoms of MLD, which can include weakness, loss of motor function, blindness, and seizures, can appear at different times in a person’s life and are typically more severe in people with earlier onset. In childhood-onset disease, quality of life and life expectancy can be significantly reduced.2
Affinia Therapeutics is developing a next-generation gene therapy to treat MLD. It uses our proprietary rationally designed capsid, Anc80L65, which has been shown to penetrate the brain more efficiently than AAV9 in non-human primates,3 to deliver a purpose-built transgene designed to target cells in the nervous system and replace the ARSA gene. The potential gene therapy is designed to be given using a one-time lumbar puncture route of administration.
Brain metastases secondary to HER2+ breast cancer
An estimated 282,000 women are diagnosed with breast cancer in the United States alone each year and 44,000 die from the disease. The disease biology is well understood. Approximately 15% of breast cancers overexpress human epidermal growth factor receptor 2, or HER2, and are considered to be more aggressive.4 Brain metastases occur in up to 50% of patients with metastatic HER2+ breast cancer and are a major limitation of life expectancy and quality of life.5
There is a systemic therapy called trastuzumab that is currently used in a large number of patients with HER2+ breast cancer and that has made a remarkable difference in patient outcomes. However, trastuzumab, an anti-HER2 antibody, has not historically been utilized in treating brain metastases because, like many antibodies, it does not effectively cross the blood-brain barrier to where the tumor has metastasized in the brain.5
Affinia Therapeutics is developing Anc80L65-trastuzumab, a gene therapy product candidate rationally designed to deliver a gene that programs the cells to produce trastuzumab, the antibody that has been shown to be effective against this cancer. Our proprietary Anc80L65 capsid has shown rapid and broad gene expression in the brain in preclinical models.5 We intend to administer Anc80L65-trastuzumab using a one-time lumbar puncture route of administration.