ALN-PNP / Alnylam, Regeneron - LARVOL DELTA

PNPLA3 MRNA SILENCING WITH ALN-PNP REDUCES LIVER FAT IN PATIENTS WITH MASLD HOMOZYGOUS FOR PNPLA3 P.I148M (AASLD 2025) - "In this single-dose study, ALN-PNP was well tolerated at all dose levels tested and reduced liver fat in PNPLA3 p.I148M homozygotes with MASLD by up to 48%."

Clinical • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • PNPLA3

A Trial to Learn if Receiving ALN-PNP siRNA is Safe and Well Tolerated, and How it Works in Adult Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a Genetic Risk Factor (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: Regeneron Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • APOB • PNPLA3

A Trial to Learn if ALN-PNP is Safe and Well Tolerated in Healthy Adults and Adult Participants With Non-Alcoholic Fatty Liver Disease (NAFLD) (clinicaltrials.gov) - P1 | N=23 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=96 ➔ 23

Enrollment change • Enrollment closed • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease

A Trial to Learn if Receiving ALN-PNP siRNA is Safe and Well Tolerated, and How it Works in Adult Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a Genetic Risk Factor (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=104 ➔ 9

Enrollment change • Enrollment closed • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • PNPLA3

A Trial to Learn if Receiving ALN-PNP siRNA is Safe and Well Tolerated, and How it Works in Adult Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a Genetic Risk Factor (clinicaltrials.gov) - P1 | N=104 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2026 ➔ Sep 2025 | Trial primary completion date: May 2026 ➔ Sep 2025

Enrollment open • Trial completion date • Trial primary completion date • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • PNPLA3

A Trial to Learn if ALN-PNP is Safe and Well Tolerated in Healthy Adults and Adult Participants With Non-Alcoholic Fatty Liver Disease (NAFLD) (clinicaltrials.gov) - P1 | N=96 | Recruiting | Sponsor: Regeneron Pharmaceuticals | N=64 ➔ 96 | Trial completion date: Dec 2023 ➔ Sep 2025 | Trial primary completion date: Dec 2023 ➔ Sep 2025

Enrollment change • Trial completion date • Trial primary completion date • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease

A Trial to Learn if Receiving ALN-PNP siRNA is Safe and Well Tolerated, and How it Works in Adult Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a Genetic Risk Factor (clinicaltrials.gov) - P1 | N=104 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Jan 2026 ➔ Dec 2026 | Initiation date: Nov 2023 ➔ Apr 2024 | Trial primary completion date: Jan 2026 ➔ May 2026

Trial completion date • Trial initiation date • Trial primary completion date • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • PNPLA3

A Trial to Learn if Having ALN-PNP siRNA is Safe and Well Tolerated, and How it Works in Adult Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a Genetic Risk Factor (clinicaltrials.gov) - P1 | N=96 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P1 trial • Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • APOA1 • APOB • PNPLA3

A Trial to Learn if ALN-PNP is Safe and Well Tolerated in Adult Healthy Participants (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • APOB

A Trial to Learn if ALN-PNP is Safe and Well Tolerated in Adult Healthy Participants (clinicaltrials.gov) - P1 | N=64 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P1 trial • APOB