ARO-ALK7 / Arrowhead Regional Medical Center - LARVOL DELTA

A First-In-Human Study of ARO-ALK7 in Adults With Obesity With and Without Type 2 Diabetes Mellitus (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: Arrowhead Pharmaceuticals | Trial completion date: Oct 2026 ➔ Feb 2027 | Trial primary completion date: Oct 2026 ➔ Feb 2027

First-in-human • Trial completion date • Trial primary completion date • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Versatile siRNA Delivery Platform Enabling Dual-Targeting and Multitissue Gene Silencing for Treatment of Metabolic Disorders (ADA 2026) - "The first adipose-targeted siRNA, ARO-ALK7, has entered clinical development... These results establish a versatile siRNA delivery platform that enables selective, durable, and tunable gene silencing in adipose tissue, with the added capability of dual-target and multi-tissue targeting. It provides a foundation for next-generation RNAi therapeutics addressing the multifactorial nature of obesity and metabolic disease."

Metabolic Disorders • Obesity

A First-In-Human Study of ARO-ALK7 in Adults With Obesity With and Without Type 2 Diabetes Mellitus (clinicaltrials.gov) - P1/2 | N=138 | Recruiting | Sponsor: Arrowhead Pharmaceuticals | Trial completion date: Jul 2026 ➔ Oct 2026 | Trial primary completion date: Jul 2026 ➔ Oct 2026

First-in-human • Trial completion date • Trial primary completion date • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

The Phase 1/2a studies of ARO-INHBE and ARO-ALK7 are ongoing... (Businesswire) - "...Company expects to report and present additional results in 2026....Company hosting a virtual KOL webinar today, January 6, 2026, at 11:30 am EST to discuss results."

P1/2 data • Obesity • Type 2 Diabetes Mellitus

Select ARO-ALK7 Phase 1/2a Results (Businesswire) - "ARO-ALK7 achieved dose dependent reductions in adipose ALK7 mRNA with a mean reduction of -88% at the 200 mg dose at week 8 with a maximum reduction of -94% (n = 4)...In addition, a single dose of ARO-ALK7 led to rapid dose dependent reductions in mean visceral fat with a -14.1% reduction, adjusted for placebo, already observed at Week 8...ARO-ALK7 has been generally well tolerated to date as monotherapy in participants with obesity....No TEAEs led to study or study drug discontinuation. No SAEs were reported."

P1/2 data • Obesity

Study of ARO-ALK7 in Adult Volunteers With Obesity With and Without Type 2 Diabetes Mellitus (clinicaltrials.gov) - P1/2 | N=126 | Recruiting | Sponsor: Arrowhead Pharmaceuticals | Trial completion date: Dec 2026 ➔ Jul 2026 | Trial primary completion date: Dec 2026 ➔ Jul 2026

Trial completion date • Trial primary completion date • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Arrowhead Pharmaceuticals Reports Fiscal 2025 Third Quarter Results (Businesswire) - "Selected Recent Events:...Dosed the first subjects in a Phase 1/2a clinical trial of ARO-ALK7, the company’s investigational RNAi therapeutic being developed as a potential treatment for obesity. ARO-ALK7 is designed to intervene in a known pathway that signals the body to store fat in adipose tissue with a novel mechanism of action that may better preserve lean muscle mass compared to currently approved obesity therapies. The study initiates in otherwise healthy obese subjects using single and multiple escalating doses of ARO-ALK7 monotherapy and is expected to progress rapidly to investigate combinations of ARO-ALK7 with tirzepatide in obese patients with and without type 2 diabetes."

Trial status • Obesity

Study of ARO-ALK7 in Adult Volunteers With Obesity With and Without Type 2 Diabetes Mellitus (clinicaltrials.gov) - P1/2 | N=126 | Recruiting | Sponsor: Arrowhead Pharmaceuticals | Not yet recruiting ➔ Recruiting | N=90 ➔ 126 | Trial completion date: Aug 2027 ➔ Dec 2026 | Trial primary completion date: Aug 2027 ➔ Dec 2026

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

ARO-ALK7, a RNAi Therapeutic Targeting Adipose ALK7 Expression for Obesity (ECO 2025) - "Combination therapy of ALK7 RNAi conjugate with tirzepatide in DIO mice resulted in an additive effect on body weight reduction compared to tirzepatide monotherapy, and allowed for the use of lower dose levels of tirzepatide to achieve similar therapeutic effects as a high dose of tirzepatide monotherapy. ARO-ALK7 represents a RNAi therapeutic which could alter body composition through a novel mechanism. We have demonstrated in animal models that ARO-ALK7 is potent and well tolerated, supporting clinical development."

Cardiovascular • Diabetes • Genetic Disorders • Obesity • Type 2 Diabetes Mellitus

Study of ARO-ALK7 in Adult Volunteers With Obesity With and Without Type 2 Diabetes Mellitus (clinicaltrials.gov) - P1/2 | N=90 | Not yet recruiting | Sponsor: Arrowhead Pharmaceuticals

New P1/2 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Select ARO-ALK7 Preclinical Results (Businesswire) - "DIO mice treated with an ALK7 siRNA exhibit a 39% suppression in body weight gain relative to controls. Adipose ALK7 silencing reduced fat mass by 50% while preserving lean mass. Similar to INHBE silencing in hepatocytes, ALK7 silencing in adipocytes enhanced catecholamine sensitivity, increasing lipid mobilization and oxidation, which was not associated with liver steatosis. In fact, treated animals showed less liver fat accumulation relative to saline controls. In combination studies with tirzepatide, ALK7 siRNA enhanced the therapeutic benefits versus tirzepatide monotherapy, with additive effects on body weight and fat mass reduction while ameliorating the significant loss of lean mass associated with tirzepatide monotherapy...The company anticipates dosing in the ARO-ALK7 study will begin in the second quarter of 2025 with initial data from the single-ascending dose portion of the study possible by year end 2025."

Clinical data • New trial • Preclinical • Metabolic Disorders • Obesity

Arrowhead Pharmaceuticals Presents Preclinical Data on ARO-ALK7 for Treatment of Obesity (Businesswire) - "The results were presented in a poster at the Keystone Symposia on Obesity and Adipose Tissue held February 23–26, 2025....Single subcutaneous doses of ARO-ALK7 led to dose-dependent and durable reductions in ALK7 mRNA in abdominal fat: Approximately 80% knockdown achieved at 0.3 mg/kg; Approximately 91% knockdown achieved at 1.5 mg/kg with 75% knockdown still observed after 12 weeks....ALK7 silencing in adipose tissue suppressed body weight gain and improved body composition: Body weight gain was suppressed by 40% relative to control; Approximately 50% reduction in fat mass with preservation of lean mass by DEXA imaging was observed in treated animals....Arrowhead received regulatory clearance to initiate a Phase 1/2a clinical trial of ARO-ALK7 in New Zealand, which the company anticipates will begin dosing in the second quarter of 2025."

New P1/2 trial • Preclinical • Obesity