ESCAPE Bio Announces Excellent Safety and Tolerability in Phase 1 Study of Oral S1P5 Receptor Agonist ESB1609

Multiple Ascending Dose (MAD) study to be initiated in Q1 2020

SAN FRANCISCO — ESCAPE Bio, Inc., a clinical stage company developing precisely targeted therapeutics for genetically defined neurodegenerative diseases, today announced that ESB1609 demonstrated durable CSF pharmacokinetics and excellent safety & tolerability in a single ascending dose Phase 1 Study. ESB1609 is a novel, orally administered, brain-penetrant and highly-selective sphingosine 1-phosphate 5 (S1P5) receptor agonist.

The study is a Phase 1, randomized, double-blind, placebo-controlled, safety, tolerability and pharmacokinetic single ascending dose study of ESB1609 in healthy volunteers with an open label component which collected continuous cerebral spinal fluid over 24 hours for pharmacokinetic analysis. Based on review of data to date, the drug was considered safe and well tolerated as a single, oral, once-daily dose at all doses tested without any serious or severe adverse events. ESB1609, administered once daily, demonstrated sustained exposure in continuously collected cerebral spinal fluid (CSF) samples, which the company believes is a reflection of free brain exposure and potentially sufficient to achieve efficacy based on preclinical studies.

“Results from this study provide the first clinical data in support of ESB1609 and enables its evaluation as a first-in-class oral S1P5 pathway-based therapeutic for treatment of neurodegenerative diseases, including Niemann-Pick C and GBA-Parkinson’s, our initial indications of focus,” commented Dr. Carrolee Barlow, M.D., Ph.D., ESCAPE Bio’s Chief Medical Officer. “This initial clinical data suggests ESB1609 has durable CNS drug exposure with a single oral dose with excellent safety and tolerability. No cardiac adverse events related to bradycardia or atrioventricular slowing were found, consistent with the high selectivity of our compound for S1P5. The data are consistent with a once daily administration therapy. We look forward to working towards a U.S. IND filing in the coming months.”

“S1P5 agonism provides a powerful upstream target for rectifying lysosomal deficits for neurodegenerative diseases,” said Julie Anne Smith, ESCAPE Bio President and Chief Executive Officer. “A once daily oral drug targeting the S1P5 pathway would be a novel addition to the neurodegenerative disease treatment landscape.”

Full results will be presented at an upcoming scientific conference.

About ESB1609

ESB1609 is a novel, orally-administered, brain-penetrant and highly-selective sphingosine 1-phosphate 5 (S1P5) receptor agonist. S1P5 receptors are preferentially expressed within the CNS. Agonizing S1P5 receptors upregulates CNS lipid transporters and is a powerful upstream target rectifying lysosomal deficits. Results from preclinical studies have demonstrated the potential of ESB1609 to restore dysfunctional CNS lipid homeostasis and reduce downstream markers of neurodegeneration in animal models of neurodegeneration.

About Niemann-Pick C (NPC)

NPC is a rare neurodegenerative lipid storage disorder ranging from a rapidly fatal neonatal disease to an adult-onset chronic neurodegenerative disease. Almost all patients that survive the neonatal period develop progressive neurodegeneration leading to motor dysfunction, difficulties swallowing and speaking, and cognitive deterioration. These symptoms ultimately lead to premature death. NPC patients have a defect in the gene encoding the NPC1 transporter. It is hypothesized that NPC1 is a critical sphingolipid and cholesterol transporter since mutations in NPC1 cause lysosomal storage of sphingolipids and cholesterol, along with a lipid maldistribution within cells. The resulting effect within the CNS is a chronic loss of neurons, especially Purkinje cells.

About ESCAPE Bio

ESCAPE Bio is a clinical stage, privately held biopharmaceutical company developing novel precisely targeted therapeutics for genetically defined neurodegenerative diseases. ESB1609 is in a Phase 1\1b randomized, double-blind, placebo-controlled, safety, tolerability, pharmacokinetic and biomarker study of escalating multiple doses in healthy volunteers and subjects with Niemann-Pick Disease Type C. ESCAPE’s pipeline includes small molecules targeting known genetic drivers of CNS disorders including ESB1609 for the treatment of CNS lysosomal storage disorders, a small molecule kinase inhibitor for the treatment of LRRK2 Parkinson’s Disease and an Alzheimer’s disease program targeting ApoE4. For additional information, please visit