Dicerna Presents Data From Phase 1 Trial of Belcesiran at American Association for the Study of Liver Diseases (AASLD) The Liver Meeting® 2021

Dicerna Pharmaceuticals, Inc. (Nasdaq: DRNA), a leading developer of investigational ribonucleic acid interference (RNAi) therapeutics, today presented results from its Phase 1 double-blind, placebo-controlled, randomized trial of belcesiran, an investigational GalXC™ RNAi therapeutic in development for the treatment of alpha-1 antitrypsin (AAT) deficiency-associated liver disease (AATLD). These data expand upon interim results announced in July 2021, demonstrating the safety and tolerability of single ascending doses of belcesiran in healthy volunteers (up to and including the final 12 mg/kg dose cohort) and further reaffirming the dosing regimen established for the ESTRELLA Phase 2 study of belcesiran. In addition, the data demonstrated robust, dose-dependent reductions in serum AAT through the 6 mg/kg dose level, with a maximum individual reduction of 91%. The data were presented in a poster at The Liver Meeting^® 2021, the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

“In people with AATLD, misfolded AAT aggregates in the liver and causes liver injury that may progress to liver fibrosis, cirrhosis and hepatocellular carcinoma. Liver transplantation is currently the only option for individuals with this rare condition who progress to liver failure, underscoring the need for a safe and effective therapeutic approach that can reduce the production and aggregation of toxic protein in the liver,” said Shreeram Aradhye, M.D., Executive Vice President and Chief Medical Officer at Dicerna. “Belcesiran is designed to reduce the production of abnormal AAT. We are pleased by the results from the first clinical trial of belcesiran, which achieved our goals of demonstrating safety and establishing a dosing regimen for our ESTRELLA Phase 2 study of belcesiran, which is underway. We are confident in the dosing regimen that was selected for ESTRELLA and the profile that we expect it to generate.”

“The results from this first-in-human trial showed clear reduction in serum AAT with belcesiran administration,” said Edward Gane, M.D., MBChB, FRACP, MNZ, Auckland City Hospital and University of Auckland, Auckland, New Zealand, and investigator in the Phase 1 trial. “The results from this trial support further evaluation of belcesiran as a potential therapy for AATLD.”

“Enrollment in the ESTRELLA trial continues to progress as we bring more clinical trial sites online in multiple countries,” Dr. Aradhye continued. “We also look forward to expanding our inclusion criteria for ESTRELLA in the near-term to include patients on augmentation therapy – a key area of interest to us as patients with the liver manifestation can also present with AAT deficiency-associated lung disease.”

The Phase 1 trial was designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of a single subcutaneous dose of belcesiran 0.1, 1.0, 3.0, 6.0 or 12.0 mg/kg compared to placebo (n=6, 2:1 randomization per cohort) in 30 adult healthy volunteers. A validated, standard-of-care quantitative nephelometry assay was used to measure serum AAT levels. Repeat measurements of spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO) were performed to monitor pulmonary function. All participants completed their treatment periods (through Day 57). All participants receiving belcesiran and who met certain criteria entered conditional follow-up post Day 57.