Del-zota (Exon 44 Skipping Therapy) Demonstrated Reversal of Disease Progression Across Key Functional Endpoints in Phase 1/2 Trial

Avidity Biosciences announced positive new data from participants treated continuously with del-zota for one year in the EXPLORE44 and EXPLORE44-OLE trials. These data demonstrated reversal of disease progression and unprecedented improvement compared to baseline and natural history across multiple functional measures. Additional data from the EXPLORE44 program will be presented at upcoming scientific congresses. – Read More: Breakthrough Therapy: Exon 44 Skipping –

Del-zota: Exon 44 Skipping Therapy

DMD is a rare genetic condition characterized by progressive muscle damage and weakness beginning at a very young age due to the absence of dystrophin protein from birth. Del-zota is designed to deliver phosphorodiamidate morpholino oligomers (PMOs) to skeletal muscle and heart tissue to specifically skip exon 44 of the dystrophin mRNA and enable production of functional, near-full length dystrophin. Near-full length dystrophin retains key functional domains and may offer improved muscle protection for people living with DMD44.

Del-zota: Phase 1/2 Clinical Trial

• Unprecedented improvement compared to baseline and natural history in multiple functional measures including Time to Rise from Floor (TTR), 4-Stair Climb (4SC), Performance of Upper Limb (PUL) and 10-Meter Walk/Run Test (10mWRT) at approximately one year

• Unprecedented rapid reduction in creatine kinase (CK) to near normal levels maintained over 16 months of follow-up and 25% increase of normal in dystrophin production, reflecting sustained muscle fiber protection

• Avidity remains on track to submit Biologics License Application (BLA) at year end 2025 for accelerated approval

Biologics License Application (BLA) to FDA

“For the first time, we have data showing that sustained muscle protection leads to meaningful improvements across multiple key functional measures in DMD,” said Sarah Boyce, President and Chief Executive Officer of Avidity. “These unprecedented data underscore the impact of our revolutionary targeted approach to deliver RNA directly to muscle. We are acting with urgency to rapidly advance the del-zota development program and remain on track to submit a Biologics License Application (BLA) to FDA at year end 2025 for accelerated approval. We extend our deepest appreciation for the continued dedication of the investigators and their teams and, most importantly, the participants in our clinical trials and their families as we pursue a new treatment option for this relentless and devastating disease.”

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EXPLORE44: Exon 44 Skipping Program

Trial participants treated with del-zota demonstrated statistically significant increases of approximately 25 percent of normal in dystrophin production and restored total dystrophin up to 58 percent of normal. Creatine kinase (CK) levels rapidly reduced by greater than 80 percent compared to baseline and were sustained at near normal levels throughout the duration of evaluation with participants followed for up to 16 months. Additionally, 50 percent of participants had CK levels within the normal range at one year of treatment. – What is Creatine Kinase (CK) –

A total of 17 participants (12 ambulatory and 5 non-ambulatory) who began on the del-zota treated arm of EXPLORE44® and continued into the EXPLORE44-OLE™ have been followed for approximately one year. Given the study design, some participants received 5 mg/kg once every six weeks (Q6W) and some received 10 mg/kg once every eight weeks during EXPLORE44. All participants were transitioned to the 5 mg/kg (Q6W) dosing schedule during EXPLORE44-OLE. Not all participants could complete all assessments. Functional datai from these pooled dosing cohorts for del-zota treated participants, compared to DMD44 natural history (PRO-DMD-01), demonstrated improvement:

• 4-Stair Climb (4SC): Improved from baseline by 2.1 seconds. In contrast, the natural history group declined from baseline by 2.7 seconds (DMD44 Nat Hx N=22; del-zota N=10).
• 10-Meter Walk/Run Test (10mWRT): Improved from baseline by 0.7 seconds. In contrast, the natural history group declined from baseline by 1.5 seconds (DMD44 Nat Hx N=22; del-zota N=10).
• Time to Rise from Floor (TTR): Improved from baseline by 3.2 seconds. In contrast, the natural history group declined from baseline by 1.6 seconds (DMD Nat Hx N=19; del-zota N=6).
• North Star Ambulatory Assessment (NSAA): Remained stable. In contrast, the natural history group declined from baseline by 2.4 points (DMD44 Nat Hx N=20; del-zota N=10).
• Performance of Upper Limb (PUL2): Improved from baseline by 1.5 points. In contrast, the natural history group declined from baseline by 0.7 points.ii Similar PUL improvements were seen in both ambulatory and non-ambulatory participants (DMD44 Nat Hx N=27; del-zota N=17).

Safety was assessed in all participants in the EXPLORE44-OLE trial, and del-zota continued to demonstrate a favorable long-term safety and tolerability profile. Most treatment emergent adverse events (TEAEs) were mild or moderate with the most common TEAEs (occurring in greater than 3 participants) being upper respiratory tract symptoms, diarrhea, fall, backpain and headache. One participant discontinued from EXPLORE44-OLE following an event of hypersensitivity.

Avidity remains on track to submit a BLA to the U.S. Food and Drug Administration (FDA) at year end 2025. This will be the Company’s first of three planned BLA submissions over a 12-month period. Avidity continues to prepare for a confirmatory study to support full global approval.

Read More: Upcoming Exon 44 Skipping Therapies for the Treatment of Duchenne Muscular Dystrophy

Learn More: Mutations and Deletions Amenable to Exon 44 Skipping Therapies for Duchenne Muscular Dystrophy

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