LBX-100 is derived from natural ingredient and an FDA-approved food additive which is generally regarded as a safe substance. It is
cleaved by lipases to produce certain metabolites in the body, rendering in herapeutically beneficial slowrelease and high-exposure
drug delivery. While this metabolite, when taken directly, is rapidly excreted through urine and therefore high doses are often required
to be efficacious, a steady and amplified level of the metabolite in the blood with a lower dose significantly minimizes side effects
associated with high doses of the metabolite. Based on recent pre-IND discussions with the US FDA, it has been confirmed that
OSP-100 will be treated as a new chemical entity (NCE) under 505(b)(1) and a prodrug given its affinity to metabolize into known
compounds once administered.
LBX-100 has shown very promising efficacies to treat a number of neurodegenerative disorders, including Parkinson’s disease,
Huntington’s disease and nonkitonic hyperglycinemia (NKH), also known as glycine encephalopathy. The compound is believed to have
a number of mechanism of action which may also have therapeutic effects on other rare indications, such as urea cycle disorders
(UCD) and other metabolic rare disorders.
LBX-200 is an organic compound found in many plants and is previously shown in both Parkinson’s disease (PD) and
Alzheimer’s disease (AD) animal models to exert therapeutic effects through the activation of peroxisome proliferator-activated
receptor alpha (PPARа) agonist.
LBX-200 has also shown highly successful efficacies in a murine model for non-ketonic hyperglycinemia (NHK).
PPARa agonist which activates PPARa that binds to specific DNA sequences called peroxisome proliferator response elements(PPREs)
located in the promoter region of the target gene, thereby upregulating Transcription Factor EB (TFEB) expression.
LBX-200 has shown strong mechanism of action to increase lysosomal biogenesis to clear lipids and other deposits at intracellular
levels. Based on disease-induced murine proof of concept studies, LBX-300 has successfully demonstrated disease-modifying results
for a number rare indications in lysosomal storage and metabolic disorders. In addition, LBX-300 has also shown to lower the amyloid
plaque burden in the hippocampus and cortex of the 5XFAD murine model of Alzheimer’s disease (AD). LBX-300 is shown to reduce
microgliosis and astrogliosis associated with plaque in these mice. The administration of the drug also improves spatial learning and
memory of the 5XFAD mice.
In addition, it is understood that hexadecanamide (Hex) is present in vivo in hippocampal nuclei of normal mice as an indogenous ligand
of PPARa. LBX-300, through PPARa activation, induces Hex which upregulates brain-drived neurotrophic factors (BDNF), protecting
hippocampal neurons, resulting in therapeutic effects for AD.
Based on these multiple mechanism of actions, we believe LBX-300 may provide substantial treatment benefits to our target
indications, possibly as a combo drug along with LBX-100.