• Danon disease has an estimated prevalence of about 15,000-30,000 patients in the U.S. and E.U.
• Danon disease is a devastating multisystemic disorder that typically leads to death in patients from progressive heart failure in their teens and twenties
• RP-A501 elicited phenotypic reversals at a structural and molecular level in cardiac, liver, and skeletal muscle tissue

Rocket Pharmaceuticals, Inc. (Nasdaq:RCKT) (“Rocket”) announced on 11/26/18 it is developing its first adeno-associated viral vector (AAV)-based gene therapy, RP-A501, that is designed to restore the lysosome-associated membrane glycoprotein 2 (LAMP-2) gene which is defective in patients afflicted with Danon disease. Rocket also announced animal study data which provides preclinical proof-of-concept for the RP-A501 program.

“Danon disease is a devastating multisystemic disorder that typically leads to death in patients from progressive heart failure in their teens and twenties. Along with severe cardiomyopathy, other Danon disease symptoms can include skeletal muscle weakness, liver disease, and intellectual impairment. Heart transplantation is an important treatment option but is not curative and is associated with approximately 50% ten-year survival post-transplant, considerable morbidity, and a very high cost to the medical system. Due to its nonspecific clinical presentation and the lack of standardized genetic testing, Danon disease is poorly recognized, under diagnosed, and often confused with other multisystemic disorders,” said Dr. Adler. “RP-A501 is the first investigational gene therapy for Danon disease and has the potential to prevent and treat heart failure and other sequelae for these patients. Preclinical studies show RP-A501 improves survival and corrects the disease phenotype with dose-dependent improvements in molecular, structural, and functional endpoints alongside a clean safety and tolerability profile. Rocket has exceptional core strength in clinical development, and I look forward to advancing the first gene therapy program for a monogenic heart failure syndrome to the finish line with them.”

“We have adequate vector supply for the planned clinical trials with RP-A501 and are on track to begin studies in early 2019. Finally, through an agreement with REGENXBIO we have gained rights for the AAV9 capsid as well as alternate capsids relevant for the devastating manifestations of Danon disease,” said Rocket CEO, Dr. Guarav Shah.

Summary Preclinical RP-A501 Data:
Preclinical efficacy studies were performed in LAMP-2 knockout (KO) mice. Four doses of vector were tested for optimal transduction of the heart, skeletal muscle, and liver. Toxicology studies were conducted in wild-type mice and non-human primates. The results from these studies are summarized as follows:
Increased survival rates were observed at higher doses of RP-A501 along with dose-dependent improvements and restoration of cardiac function.

• RP-A501 elicited phenotypic reversals at a structural and molecular level in cardiac, liver, and skeletal muscle tissue.
• There were no treatment-related adverse events or deaths associated with RP-A501. All doses were observed to be well-tolerated in Good Laboratory Practice (GLP) biodistribution and toxicology studies in both wildtype mice and additional studies in non-human primates.

Based on the preclinical safety and efficacy data observed in mice and non-human primate studies, Rocket plans to initiate a Phase 1 dose-escalation study of RP-A501 in patients with Danon disease in the first half of 2019.

Danon disease has an estimated prevalence of about 15,000-30,000 patients in the U.S. and E.U.