Pangea is developing OT-003, a proprietary small molecule with potential disease-modifying characteristics for the treatment of Alzheimer’s Disease (AD). To expand on recent promising preclinical data in AD models and to accelerate OT-003’s path to patients, Pangea is applying for support to enable:

1.  Production of sufficient quantities of OT-003 for preclinical safety pharmacology and toxicology studies and Phase 1 human clinical trials.

2.  Complete all components of the Phase-1 enabling toxicology and safety pharmacology package to support approval by a regulatory body

3.  Regulatory approval to initiate Phase 1 trials in Q4 2024 following completion of the work.

Background: OT-003 targets the Tropomyosin receptor kinase B (TrkB) for which brain-derived neurotrophic factor (BDNF) is the endogenous ligand. BDNF/TrkB signaling is crucial for neuronal development, survival, and plasticity, and reduced BDNF/TrkB signaling is a hallmark of many neurodegenerative diseases. These include AD, where BDNF levels are decreased in post-mortem brain tissue.1-3 

Compelling efficacy data: OT-003 activates TrkB and downstream signaling pathways, both in rat brain cells and in the hippocampus, the brain region for learning and memory, in two AD mouse models. This leads to neuronal survival, synaptic plasticity, reduction of pathological protein aggregates and normalization of aberrantly reduced BDNF levels.4-5

The promising efficacy data is supported by extensive understanding of OT-003’s pharmacokinetics, which underpin the confidence in OT-003’s potential to be disease-modifying.6

Impact: Pangea aims to initiate Phase 1 clinical trials in Q4 2024 following the completion of the proposed work. The potential impact of OT-003 on AD patients and their carers is substantial, as it holds the possibility to alleviate symptoms, modify disease progression and improve patients’ quality of life. Successful completion of this work stands to bring us closer to a cure for AD, effectively addressing the urgent need for disease-modifying therapies.