12 August 2020 - - US-based Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) has dosed the first subjects in AROENaC1001, a Phase 1/2 clinical study of ARO-ENaC, the company's investigational RNA interference therapeutic being developed as a treatment for patients with cystic fibrosis, the company said.

cystic fibrosis is a rare disease caused by genetic mutations that lead to progressive deterioration in lung function due to poor clearance of mucus and associated recurrent infections.

ARO-ENaC utilizes Arrowhead's proprietary Targeted RNAi Molecule (TRiM) platform and is the company's first inhaled RNAi candidate to target pulmonary epithelium.

ARO-ENaC is designed to reduce activity of the epithelial sodium channel alpha subunit in the airways of the lung. In patients with CF, dysfunction in the cystic fibrosis transmembrane conductance regulator causes increased ENaC activity which contributes to airway dehydration and reduced mucociliary transport.

This predisposes patients to persistent lung infections, structural damage, and progressive loss of pulmonary function. ENaC has been extensively explored as a potential therapeutic target for CF, but the development of inhaled small molecule ENaC inhibitors has been limited by on-target renal toxicity and short duration of action in the lung.

AROENaC1001 is a Phase 1/2 dose-escalating study to evaluate the safety, tolerability, and pharmacokinetic effects of ARO-ENaC in up to 24 normal healthy volunteers and to evaluate the safety, tolerability, and efficacy in up to 30 patients with CF.

Exploratory objectives in patients with CF include assessing the effects of ARO-ENaC on changes in lung clearance index and evaluating changes in forced expiratory volume.

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them.

Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes.

RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein.

Arrowhead's RNAi-based therapeutics leverage this natural pathway of gene silencing.