- Interim data from Phase 1/2a study demonstrate near complete inhibition in hemolytic activity and functional activity of alternative complement pathway

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced interim results from a Phase 1/2a clinical study of ARO-CFB, the company’s investigational RNA interference (RNAi) therapeutic targeting complement factor B being developed as a potential treatment for complement mediated diseases. The data were presented today, December 11, 2024, at the 8th Complement-Based Drug Development Summit being held in Boston.

“Dysregulated activation of the complement system can lead to progression of certain renal diseases, either by playing a directly pathogenic role, or by amplifying or exacerbating the inflammatory and damaging impact of non-complement disease triggers. In a Phase 1/2a clinical study, ARO-CFB treatment in healthy volunteers achieved deep and durable reductions in the liver production of complement factor B (CFB), which is involved in alternative complement pathway activation and associated with pathogenesis of diseases involving complement activation. Circulating levels of CFB protein were reduced by a mean of up to 90% to date, with additional data from higher doses levels pending, and a duration of response greater than 3 months,” said James Hamilton, M.D., MBA, Chief of Discovery and Translational Medicine at Arrowhead. “ARO-CFB also demonstrated dramatic reductions in measures of alternative complement pathway activation, with mean reductions at or approaching 100% in AH50 and Wieslab AP at multiple dose levels. These interim results in healthy volunteers give us confidence in the potential of ARO-CFB as we seek to complete Part 1 of the study over the coming months, and subsequently look ahead to Part 2 of the study in patients with immunoglobulin A nephropathy, which is the most common glomerular disease worldwide.”

Select ARO-CFB Results

In the ongoing AROCFB-1001 study, ARO-CFB achieved the following key results in normal healthy volunteers as of the interim data cutoff - 15 November 2024:

• ARO-CFB led to dose dependent reductions in circulating CFB protein by up to 90% with greater than 3 months duration
  • 90% mean reduction achieved after a single dose of 400 mg
  • 90% mean reduction achieved after two doses of 100 mg
• Single and multiple doses of ARO-CFB led to near complete inhibition of alternative pathway activity based on Wieslab AP
  • 100% mean reduction achieved by week 4 after a single dose at both 200 mg and 400 mg doses
  • 92% and 100% mean reductions were achieved after two doses at 100 mg and 200 mg, respectively
• Single and multiple doses of ARO-CFB led to near complete inhibition of alternative pathway hemolytic activity, measured by AH50

Safety and Tolerability Results

ARO-CFB has been generally well-tolerated to date with safety data supportive of further clinical development. There have been no treatment emergent adverse events (TEAE) leading to study or study drug discontinuation with most TEAEs being mild in severity.

About ARO-CFB

ARO-CFB is designed to reduce hepatic expression of complement factor B (CFB), which plays an important regulatory role in amplifying complement alternative pathway activation and has been identified as a promising therapeutic target. ARO-CFB is being developed as a potential treatment for complement mediated kidney diseases such as immunoglobulin A nephropathy (IgAN), which is the most common glomerular disease worldwide and carries a high lifetime risk of progression to end-stage renal disease. Additionally, ARO-CFB may have clinical applications in non-renal diseases involving complement activation.

About the AROCFB-1001 Phase 1/2 Study

AROCFB-1001 (NCT06209177) is an ongoing Phase 1/2a dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARO-CFB in up to 66 normal healthy volunteers (NHV) and patients with complement mediated kidney disease. In Part 1 of the study, NHVs will receive either one or two doses of ARO-CFB or placebo. In Part 2 of the study, adult patients with IgAN will receive 3 open-label doses of ARO-CFB. The study is designed to assess safety and tolerability and key pharmacodynamic parameters, including the change and percent change from baseline over time in serum CFB, and alternative complement pathway activity via AH50 and Wieslab AP.

About Arrowhead Pharmaceuticals

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.

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Source: Arrowhead Pharmaceuticals, Inc.

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