«ALS is one of the most devastating human diseases and new therapies are urgently needed that can affect its underlying biology.»

Severe and Rare Diseases

Rare diseases collectively affect millions of patients of all ages, but only few drugs have been developed to prevent or treat these conditions. There are more than 6000 rare diseases the majority of which are of genetic origin with often chronic and life-threatening disease courses. Neurimmune is developing antibody-based therapies for several severe rare diseases including amyotrophic lateral sclerosis, transthyretin amyloidosis related cardiomyopathy and polyneuropathy and Huntington’s disease.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease marked by the degeneration of motor neurons in the spinal cord and brain resulting in progressing paralysis and death. There is no known cure for the disease, which affects about 15,000 individuals in Europe and the US every year. In absence of effective treatment, patients survive on average only two to five years following their diagnosis. The worldwide population of ALS patients is estimated at 450,000.
For the treatment of ALS, Neurimmune scientists generated a new class of recombinant human monoclonal antibodies targeting specific misfolded forms of superoxide dismutase 1 (SOD1). Misfolded SOD1 accumulates in both familial and sporadic ALS, suggesting a generalized role as a drug target for ALS. Neurimmune’s lead candidate is highly effective at therapeutic doses in independent transgenic models of ALS. Chronic antibody treatment significantly reduces SOD1 pathology and rescues spinal cord motor neurons resulting in less muscle atrophy, improved motor functions and increased survival times. In 2013 Neurimmune entered into a collaboration with ALS Therapy Development Institute, Cambridge, MA (www.als.net) to advance the program towards clinical development.

Transthyretin (TTR) amyloid diseases comprise a broad spectrum of acquired and hereditary diseases including Senile Systemic Amyloidosis (SSA), Familial Amyloid Cardiomyopathy (FAC), and Familial Amyloid Polyneuropathy (FAP). These diseases share a common underlying pathophysiological mechanism that is driven by the dissociation of physiological TTR tetramers and their subsequent pathological misfolding and extracellular deposition as toxic TTR aggregates in various organs. There is a large unmet medical need for patients suffering from these diseases since current treatment options are limited to mainly symptomatic agents. FAP presents as a fatal progressive neuropathy with mid-life onset, initially affecting small diameter, unmyelinated nerve fibers leading to sensorimotor and autonomic dysfunction, pain, muscular weakness and wasting. Approximately 10’000 patients are affected by the disease worldwide. FAC is an infiltrative cardiomyopathy leading to diastolic dysfunction and ultimately heart failure 5-6 years after symptom onset. Estimated 40’000 patients are affected by this largely underdiagnosed disease worldwide. SSA is a common age-related amyloidosis that involves accumulation of wild-type TTR amyloid deposits that are found at autopsy in 25% of individuals over 80 years of age, predominantly in cardiac tissues.
Neurimmune has generated recombinant human antibodies that are specifically targeting TTR aggregates but not the physiological TTR tetramer. These novel antibodies promote the removal of toxic TTR aggregates and are developed as a therapy to halt and revert disease progression in TTR amyloidosis patients.

Huntington’s disease (HD) is a rare, heritable neurodegenerative disorder that is caused by an abnormally expanded polyglutamine (polyQ) tract in the huntingtin protein. HD affects 5-10 individuals per 100,000. There are approximately 500 patients in Switzerland, 500 in Austria and 8000 in Germany. In the US 30,000 patients are affected by the disease and at least 150,000 others have a 50 percent risk of developing the disease. Worldwide there are currently about 70,000 HD patients. Although the prevalence of HD is much lower than for Alzheimer’s or Parkinson’s disease, the complete penetrance of the HD mutations makes it one of the most common inherited neurodegenerative disorders. The only treatment currently approved for the disease is a symptomatic treatment targeting involuntary muscle movements associated with the loss of motor neurons which does not significantly influence time of onset or progression of disease.
Neurimmune is developing recombinant RTMTM antibodies that prevent the spreading and promote the degradation of pathogenic HTT aggregates as novel therapeutics for HD.

Neurimmune's antibody program targeting TDP-43 proteinopathies such as frontotemporal lobar degeneration and ALS was partnered with Biogen 2010.

Biogen Idec and Neurimmune announce agreement on three neurodegenerative disease programs
ALS Therapy Development Institute and Neurimmune Partner to Advance Treatments for ALS
The ALS Therapy Development Institute