RP-A501

CRANBURY, NJ, USA I August 20, 2025 I Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a fully integrated, late-stage biotechnology company advancing a sustainable pipeline of genetic therapies for rare disorders with high unmet need, today announced that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold on the Company’s pivotal Phase 2 trial of RP-A501 for the treatment of Danon disease. The hold was lifted in under three months, underscoring the efficiency of the FDA’s review process and Rocket’s commitment to expeditiously optimize safety and resume the trial. In its correspondence, the FDA confirmed that Rocket satisfactorily addressed issues outlined in the clinical hold. The FDA authorized the pivotal study to resume first with a recalibrated dose of 3.8 x 10¹³ GC/kg of RP-A501 in three patients, treated sequentially with a minimum four-week interval between each treatment. This adjusted dose aligns with the lower range of administered doses that were associated with efficacy across multiple biomarkers, echocardiographic and clinical endpoints in the Phase 1 study, and has been determined as most likely to confer the safety and efficacy identified in the low-dose Phase 1 cohorts. In addition, Rocket will collaborate with investigators to implement an immunomodulatory regimen more closely reflecting that administered in the Phase 1 pediatric cohort. The revised regimen discontinues prophylactic use of a C3 complement inhibitor, while maintaining sirolimus, rituximab, and steroids. Additionally, the protocol will specify a lower threshold for administering a C5 inhibitor (eculizumab) in response to impending complement activation. To date, six patients with Danon disease have been treated in the Phase 2 study with RP-A501. Further updates about the Phase 2 study can be expected following review of data from the next three patients. RP-A501 Phase 2 Pivotal Trial Overview The global, single-arm, multi-center 12-patient Phase 2 pivotal trial evaluates the efficacy and safety of RP-A501 for the treatment of Danon disease. The trial began with a pediatric safety run-in (n=2) and treated a total of six patients at a dose level of 6.7 x 10 13 GC/kg. Per alignment with the FDA upon lifting of the clinical hold, three additional patients are expected to be treated at a dose level of 3.8 x 10 13 GC/kg with a minimum four-week interval between dosing, followed by additional patients to complete the trial. Details about the Phase 2 study can be found at www.clinicaltrials.gov under NCT identifier NCT06092034. About RP-A501 RP-A501 is Rocket’s investigational gene therapy for the treatment of Danon disease and the first gene therapy for a cardiovascular condition to demonstrate safety and efficacy in clinical studies. RP-A501 has the potential to restore or stabilize cardiac function in patients with Danon disease. RP-A501 consists of a recombinant adeno-associated serotype 9 (AAV9) capsid containing a functional version of the human LAMP2B transgene (AAV9.LAMP2B) which is administered as a single intravenous (IV) infusion. In clinical studies, RP-A501 has been shown to target cardiac cells (cardiomyocytes) and deliver the functional LAMP2B gene to heart tissue, which led to improved cardiac structure and function in patients. RP-A501 holds FDA RMAT, Fast Track, Rare Pediatric, and Orphan Drug designations in the U.S. along with ATMP and PRIME designations in the EU. About Danon Disease Danon disease is a rare X-linked inherited, multi-organ lysosomal-associated disorder with a devastating clinical course. The causative mutation has been identified in the gene encoding for lysosome-associated membrane protein, otherwise known as LAMP2 , an important mediator of autophagy and primarily expressed in heart, skeletal muscle and brain tissue. This mutation results in accumulation of autophagosomes and glycogen, particularly in cardiac muscle and other tissues, which ultimately leads to heart failure, and for male patients, frequent death during adolescence or early adulthood. The only available treatment option for Danon disease is cardiac transplantation, which is associated with substantial complications and is not considered curative, representing the high unmet medical need for patients with Danon disease. It is estimated to have a prevalence of 15,000 to 30,000 patients in the U.S. and Europe. In 2023, Rocket secured an ICD-10 code from the Centers for Medicare and Medicaid Services (CMS) to document patients with LAMP2 deficiency in Danon disease. About Rocket Pharmaceuticals, Inc. Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) is a fully integrated, late-stage biotechnology company advancing a sustainable pipeline of investigational genetic therapies designed to correct the root cause of complex and rare disorders. Rocket’s innovative multi-platform approach allows us to design the optimal gene therapy for each indication, creating potentially transformative options that enable people living with devastating rare diseases to experience long and full lives. Rocket’s adeno-associated viral (AAV) vector-based cardiovascular portfolio includes a late-stage clinical program for Danon Disease, a devastating heart failure condition resulting in thickening of the heart, and an early-stage clinical program for PKP2-arrhythmogenic cardiomyopathy (ACM), a life-threatening heart failure disease causing ventricular arrhythmias and sudden cardiac death. Rocket has also received IND clearance for its AAV-based gene therapy for BAG3-associated dilated cardiomyopathy (DCM), a heart failure condition that causes enlarged ventricles. Rocket’s lentiviral (LV) vector-based hematology portfolio consists of late-stage programs for Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, Fanconi Anemia (FA), a difficult-to-treat genetic disease that leads to bone marrow failure (BMF) and potentially cancer, and Pyruvate Kinase Deficiency (PKD), a monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia. For more information about Rocket, please visit www.rocketpharma.com and follow us on LinkedIn , YouTube, and X . SOURCE: Rocket Pharmaceuticals