Orpheris' clinical focus will be to advance OP-101 to proof-of-concept in in its first indication, childhood cerebral adrenoleukodystrophy (ccALD). We will assess the ability of OP-101 to restore microglia to a normal state, using neural imaging techniques. We intend to employ both radioligands for activated microglia using positron emission tomography (PET), and gadolinium enhancement using magnetic resonance imaging (MRI). Orpheris has discussed the phase 1/2/3 clinical study protocol with FDA and expects to begin that study upon completion of the ongoing Phase 1 study in healthy normal volunteers.
In parallel to our clinical efforts with OP-101 in ccALD, we are also conducting additional preclinical studies to investigate the potential of OP-101 in other neurological diseases. We have already demonstrated a significant reduction in activated microglia by OP-101 in an established animal model of Parkinson's disease. We intend to further explore the effectiveness of OP-101 in Parkinson's disease and ALS animal models to enable a rapid transition upon completion of the Phase 1/2 stage ccALD study proof of concept.
We are also exploring the potential to link other disease modifying agents to our platform hydroxyl dendrimer technology. We have several research studies ongoing with our founding scientists at the Johns Hopkins University.
Adrenoleukodystrophy, or ALD, is a deadly genetic disease that affects 1 in 18,000 people. It most severely affects boys and men. The cerebral form of the disease, ccALD, appears in childhood, generally between the ages of four and ten years old. This is the most common form of ALD, representing about 45% of all ALD cases. It is characterized by a severe loss in brain function and eventual death in most cases. Currently, the standard of care for preadolescent patients in the early stages of ccALD pathology is hematopoietic stem cell transplantation (HSCT). Orpheris believes that OP-101 will be effective in increasing survival and reducing the loss of neurological function in ccALD patients not eligible for bone marrow transplant. OP-101 entered a Phase 1, healthy subject study in the Spring of 2018.
Parkinson's disease is the second most common age-associated neurodegenerative disorder (after Alzheimer's) that generally presents as tremors, slow movement, muscle stiffness, and impaired balance. The Parkinson's Foundation Prevalence Project estimates that 930,000 people in the United States will be living with PD by the year 2020. This number is predicted to rise to 1.2 million by 2030. Parkinson's disease is caused by a loss of dopaminergic neurons in the area of the brain known as the substantia nigra. Post mortem brains from PD patients indicate that misfolded alpha synuclein accumulates extracellularly and aggregates to form Lewy bodies. The aggregated alpha synuclein may activated microglia leading to chronic inflammation observed in post mortem brains from PD patients. Positron emission tomography (PET) ligands for activated microglia administered to PD patients has revealed a substantial increase in activated microglia in the substania nigra. Our lead product, OP-101, significantly reduces activated microglia in animal model of PD as measured by PET imaging. We believe that addressing the inflammatory process of the microglia in PD patients may slow disease progression. We are planning additional studies of OP-101 in PD animal models to optimize the dose and regimen alone and in combination with other agents.
Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder effecting the neurons responsible for voluntary muscle movement. ALS is a rapidly progressive with most patients suffering respiratory failure within 3-5 years of diagnosis. It is estimated that approximately more than 20,000 patients in the US are living with ALS with 6,000 patients diagnosed annually. A genetic cause of ALS is associated with the mutant form of a protein expressed in the motor cortex, superoxide dismutase-1 (SOD1). SOD1 protein aggregates have been found in post mortem samples of ALS patients. Positron emission tomography (PET) ligands for activated microglia administered to ALS patients has revealed a substantial increase in activated microglia in the motor cortex. The neurotoxic properties of the activated microglia facilitate neuronal death and a chronic inflammatory state. Studies of ALS patient post mortem samples have demonstrated that the rate of ALS progress is significantly correlated with the amount of activated microglia in the brain. ALS progression was significantly faster in ALS patients with a great extent of activated microglia. We believe that treating ALS patients with OP-101 may reduce the rate of disease progression. We are currently planning experiments with OP-101 in SOD1 mutant animal models to optimize the dose and regimen prior to clinical studies.