GHP June 2017

GHP / June 2017 27 Company: Polaryx Therapeutics, Inc Name: Hahn-Jun Lee, M.Sc., Ph.D. Email: [email protected] Web Address: Address: 140 E. Ridgewood Avenue, NJ 07652 USA Telephone: +1 201 940 7236 Small Molecule Based Non-Invasive Therapy for Late Infantile Neuronal Ceroid Lipofuscinosis g enzymes (CLN1/PPT1, CLN2/ TPP1, CLN10/CTSD, CLN13/ CTSF) and a soluble lysosomal protein. CLN11 is present in the secretory pathway. In addition, there are transmembrane proteins (CLN3, CLN6, CLN7/ MFSD8, CLN8, CLN12/ ATP132A) and two cytoplasmic proteins that associate peripherally with membranes (CLN4, CLN14). CLN6 and CLN8 localize in the endoplasmic reticulum while CLN4/DNAJC5 and CLN14/KCTD7 are cytoplasmic and associate with cell membranes. However, most of the physiological substrates of the lysosomal enzymes and functions of the transmembrane proteins are largely unknown. Such multiple responsible genes and various gene mutations make therapeutic interventions very challenging. The standard of care is to minimize symptoms, especially relief from seizures.” “The core technology of Polaryx has defined mechanisms of action. PLX-200 binds to the retinoid X receptor-α (RXRα), which binds to PPARα thereby up-regulating the expression of TPP1 mRNA in brain cells via the PPARα/RXRα heterodimer. PLX-200 also activates PPARα, which enhances production of transcription factor EB (TFEB) in brain cells. TFEB then binds to the promoter of genes involved in lysosome biogenesis and activates their production. TFEB can regulate lysosomes due to its effects on the expression of lysosomal genes. This is very important mechanism of action of our drug candidate.” Dr. Jay Vijayan stated that one of the strengths of the company is their broad intellectual property portfolio, and also their non- invasive therapeutic intervention will be helpful to patients in the future. This patient-friendly treatment compares very favourably to the other invasive technologies currently under development or in use. Dr. Hahn-Jun Lee explained more about the current treatment available, the company’s non- invasive oral treatments, and why the company was set up. “Moreover, because the disease progression is rapid and often misdiagnosed, the disease has generally significantly progressed at the time of diagnosis and initiation of treatment. The current invasive method of administration, such as enzyme replacement therapy and the proposed viral gene delivery to young paediatric patients, reduces the interest of patient families in trying such aggressive treatments. “Our patient-friendly technology includes oral small-molecule therapeutics which have shown efficacy in an animal CLN disease model. The mice live longer after treatment and have a delayed decline in motor function. Polaryx’s treatment may provide patients with a non-invasive treatment option that can be taken either alone or in combination with other treatments. Furthermore, because we are using a drug repurposing strategy capable of saving development time and also providing a safety history, we will be able to bring safe our therapeutic interventions to patients quickly. Although various types of studies, including gene therapy, stem cell therapy, enzyme replacement therapy, and chaperone small molecules, have been extensively investigated, the complicated genetics of the disease, lack of efficacy of drug candidates, and regulatory hurdles limit their applications to patients. The company was set up to develop therapeutic interventions for patients suffering from this devastating disorder, which leads to premature death of affected patients.” Dr. Hahn-Jun Lee then told us more about PLX-200 and the relevant clinical trials. “PLX-200 is a repurposed drug that has been safely used in both adults and children. It has a therapeutic and/or prophylactic potential for Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2). Its mechanism of action is unique and involves upregulation of TPP1 mRNA expression and an increase in lysosome biogenesis. It also has neuroprotective and anti- inflammatory effects that prolong the life span of CLN2 deficient animals.” Looking to the future, Dr. Hahn- Jun Lee emphasized that the company is working very hard and making progress with a meeting scheduled with the U.S Food and Drug Administration (FDA) to clinically develop this drug in 2017. “We plan to perform a clinical trial as soon as possible and are currently preparing our critical trial course. We hope that our treatment will be very helpful for the patients with Batten disease and can increase the patients’ and families’ quality of life with our approach.”