Study Rationale: Parkinson’s disease (PD) poses a huge disease burden to patients and their families. Current approved therapies are largely focused on symptom relief and have little impact on the detrimental progressive loss of dopaminergic neurons, the key brain cells affected in PD. Pangea is developing OT-1xx2, as a novel, oral treatment for PD that prevents the loss of these neurons. OT-1xx2 has shown initial promise for PD by protecting dopaminergic neurons from degeneration and reducing toxic alpha-synuclein (asyn) aggregates in cell assays. To advance OT-1xx2’s development, we propose i) to conduct cellular and animal PD models to determine OT-1xx2’s potential therapeutic efficacy, and ii) to conduct critical drug development activities to enable rapid progression towards an estimated Phase 1 clinical study in Q4 2027.
Hypothesis: In PD the BDNF/TrkB signaling pathway is impaired leading to neuronal cell death and asyn aggregation. OT-1xx2 activates TrkB and restores normal function, thus promoting neuronal survival and reduction of toxic asyn aggregates, ultimately improving motor function.
Study Design: The project will involve stepwise in vitro and in vivo pharmacology studies to determine OT-1xx2’s potential for reducing dopaminergic cell death, asyn accumulation, and motor dysfunction, as well as assessing potential biomarkers for target engagement. In parallel, compound characterization and chemical synthesis route development will enable subsequent activities to support regulatory approval to start human clinical trials..
Impact on Diagnosis/Treatment of Parkinson’s disease: Today’s PD treatment is largely focused on symptomatic relief of motor symptoms with no impact on the progressive loss of dopaminergic neurons. OT-1xx2 has the potential to prevent disease progression and provide a novel, transformative medicine for PD patients to live longer and healthier lives.
Next Steps for Development: At the end of the proposed project, Pangea will have generated a strong pre-clinical data package for OT-1xx2 enabling progression to clinical trial enabling studies with an estimated human Phase I clinical trial start in Q4 2027.