Arrowhead Initiates YOSEMITE Trial for Zodasiran Treatment

Arrowhead Pharmaceuticals has dosed the first patient in its YOSEMITE Phase 3 clinical trial for zodasiran, an RNA interference therapeutic being developed for homozygous familial hypercholesterolemia. Zodasiran is the fourth investigational RNAi-based candidate developed by Arrowhead to reach late-stage pivotal studies.

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) has dosed the first patient in its Phase 3 YOSEMITE clinical trial of zodasiran, an investigational RNA interference (RNAi) therapeutic being developed for homozygous familial hypercholesterolemia (HoFH). Zodasiran is the fourth investigational RNAi-based candidate from Arrowhead to reach late-stage pivotal studies, following plozasiran, fazirsiran (licensed to Takeda), and olpasiran (licensed to Amgen).

The YOSEMITE Phase 3 study is a multicenter, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of zodasiran in adolescent and adult patients with genetically or clinically diagnosed HoFH who are on maximally tolerated lipid-lowering therapy. Approximately 60 subjects over the age of 12 will be randomized (2:1) to receive four doses of 200 mg zodasiran or placebo, with the primary endpoint being the percent change from baseline to month 12 in fasting LDL-C. Participants will have the opportunity to continue in an optional open-label extension after month 12.

Zodasiran targets ANGPLT3, an emerging therapeutic target for treating HoFH and other dyslipidemias. The drug aims to reduce the production of angiopoietin-like protein (ANGPTL3), a hepatocyte-expressed regulator of lipid and lipoprotein metabolism. Prior clinical studies have shown that zodasiran can reduce triglycerides, triglyceride-rich lipoprotein remnants, and total atherogenic lipoproteins, including LDL-C, in patients with HoFH and heterozygous familial hypercholesterolemia (HeFH) and mixed hyperlipidemia.

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. The company's RNAi-based therapeutics leverage the natural pathway of gene silencing to induce rapid, deep, and durable knockdown of target genes. The YOSEMITE study further enhances Arrowhead’s late-stage pipeline of RNAi-based cardiometabolic candidates.

For more information, please visit [Arrowhead Pharmaceuticals' website](http://www.arrowheadpharma.com).

References:
[1] https://www.morningstar.com/news/business-wire/20250708786914/arrowhead-pharmaceuticals-initiates-phase-3-yosemite-study-of-investigational-zodasiran-for-the-treatment-of-homozygous-familial-hypercholesterolemia
[2] https://ir.arrowheadpharma.com/news-releases/news-release-details/arrowhead-pharmaceuticals-initiates-phase-3-yosemite-study