Abstract Details

Title Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of AOC 1020 Administered Intravenously to Adult Patients with Facioscapulohumeral Muscular Dystrophy (FORTITUDE) Trial Design

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 10-007

Objective To evaluate the safety and tolerability of single and multiple ascending doses of AOC 1020 in participants with FSHD.

Background FSHD is a rare, slowly progressive, often asymmetric, genetic skeletal muscle disease caused by aberrant expression of the transcription factor DUX4 in skeletal muscle, leading to a series of downstream events that result in skeletal muscle degeneration and wasting. Strategies targeting DUX4 expression in skeletal muscle of individuals with FSHD via oligonucleotides are promising therapeutic approaches.

AOC 1020 is an antibody-oligonucleotide conjugate (AOC^TM) comprised of a DUX4-targeting siRNA conjugated to a humanized antibody targeting transferrin receptor 1 (TfR1) to facilitate delivery to muscle.

Design/Methods This phase 1/2 study is a randomized, placebo-controlled, double-blind trial conducted in three parts. The study will enroll 72 adults aged 18 to 65 years with a genetic diagnosis of FSHD1 or FSHD2. All participants will receive 5 doses of study medication administered quarterly with 1 booster at 6 weeks. Part A (N=12; 3:1 AOC 1020:placebo) utilizes a dose-titration design to evaluate the safety of AOC 1020 at two low doses. Part B (N=24; 2:1 AOC 1020:placebo) is a nested single-ascending dose/multiple-ascending dose design evaluating two presumed efficacious doses. Staggered cohorts will be initiated based on a safety data review of the preceding cohort(s). Part C (N=36; 1:1:1 AOC 1020 dose 1:AOC 1020 dose 2:placebo) is a parallel, multiple-dose design to be conducted with two presumed efficacious doses to evaluate clinical outcomes. After their final dose, participants enter a 3-month follow-up period. The total duration is 12 months. Eligible participants will have the option to enroll in an open-label extension study.

The primary objective is safety and tolerability. Secondary objectives include pharmacokinetic measurements of AOC 1020. Exploratory measures of efficacy include pharmacodynamics, PROs, and measures of muscle function, strength, and composition by MRI.

Results N/A

Conclusions N/A

Authors/Disclosures
Han Cho, PharmD (Avidity Biosciences) PRESENTER	No disclosure on file
	No disclosure on file
Elizabeth J. Ackermann, PhD (Avidity Biosciences)	Dr. Ackermann has received personal compensation for serving as an employee of Avidity Biosciences.
Teresa Brandt	Teresa Brandt has received personal compensation for serving as an employee of Avidity Biosciences. Teresa Brandt has received personal compensation for serving as an employee of Acadia Pharmaceuticals. Teresa Brandt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia Pharmaceuticals. Teresa Brandt has stock in Avidity Biosciences.
	No disclosure on file
Mark C. Stahl, MD, PhD (Insmed Gene Therapies)	Dr. Stahl has received personal compensation for serving as an employee of Avidity Biosciences. Dr. Stahl has stock in Avidity Biosciences.
Kelly Ditrapani (Avidity Biosciences)	Kelly Ditrapani has received personal compensation for serving as an employee of Avidity Biosciences. Kelly Ditrapani has received personal compensation for serving as an employee of Iovance Biotherapeutics. An immediate family member of Kelly Ditrapani has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Kelly Ditrapani has stock in Iovance Biotherapeutics. Kelly Ditrapani has stock in Avidity Biosciences. Kelly Ditrapani has stock in Aravive Inc.. An immediate family member of Kelly Ditrapani has stock in Jazz Pharmaceuticals. Kelly Ditrapani has stock in Abbvie.
	No disclosure on file
Alrabi Tawil, MD, FAAN (University of Rochester Medical Center)	Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kate Therapeutics. Dr. Tawil has received personal compensation in the range of $500-$4,999 for serving as a Consultant for meRicule. The institution of Dr. Tawil has received research support from Friends of FSH Research. The institution of Dr. Tawil has received research support from FSH Society. The institution of Dr. Tawil has received research support from NIH. The institution of Dr. Tawil has received research support from Fulcrum. Dr. Tawil has received intellectual property interests from a discovery or technology relating to health care.
Jeffrey Statland, MD (University of Kansas Medical Center)	Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arrowhead. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ML Bio. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epic Bio. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Armatus . Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kate Therapeutics. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vita Therapeutics. Dr. Statland has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne Therapeutics. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity . Dr. Statland has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fulcrum Therapeutics. Dr. Statland has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Statland has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex . The institution of Dr. Statland has received research support from NIH. The institution of Dr. Statland has received research support from FSHD Society. The institution of Dr. Statland has received research support from Friends of FSH Research. The institution of Dr. Statland has received research support from FSHD Canada. The institution of Dr. Statland has received research support from MDA.

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