Date: 2016-11-14
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the American Heart Association's Scientific Sessions 2016 in New Orleans
Company: Arrowhead Pharmaceuticals (USA - CA)
Product: ARC-F12
Action
mechanism: RNAi. ARC-F12 is an RNAi therapeutic that inhibits the production of Factor XII. Factor XII is a key component of the contact activation pathway involved in thrombosis and the kinin-kallekrein system involved in angioedema. It is predominantly produced in the liver and circulates in plasma, so Arrowhead believes that it is a uniquely suited target for an RNAi-therapeutic delivered with the proprietary Dynamic PolyconjugateTM (DPCTM) delivery system.
Disease: hereditary angioedema, thrombosis
Therapeutic area: Rare diseases - Genetic diseases - Hematological diseases
Country:
Trial details:
Latest
news: * On November 14, 2016, Arrowhead Pharmaceuticals delivered oral presentations on ARC-F12, its preclinical development program targeting factor XII (F12) for the prophylactic treatment of thromboembolism and hereditary angioedema, at the American Heart Association's Scientific Sessions 2016 in New Orleans . The oral poster titled, "Targeting factor XII (F12) with a novel RNAi delivery platform as a prophylactic treatment for thromboembolism", describes advancements in the preclinical development of ARC-F12. Key details of the presentation include that F12 is an attractive target for an RNAi therapeutic. F12 is also a key component at the top of the contact coagulation cascade and is predominantly expressed in the liver and circulates in blood.
Inhibition is genetically validated and deficiency protects from thromboembolic disease but is not associated with either bleeding or thrombotic disorders.
Arrowhead developed RNAi triggers that gave greater than 95% reductions of serum F12 levels after a single subcutaneous injection. Dose dependent reductions in serum F12 levels were observed with single injections of ARC-F12 of 1 mg/kg and 3 mg/kg leading to mean reductions of 86% and 96% respectively. A statistically significant reduction (p=0.002) in thrombus weight was observed at greater than 95% F12 knockdown in a rat arterio-venous shunt model
There was no increased bleeding risk in ARC-F12 treated mice, even with greater than 99% knockdown of F12 levels.
