September 21, 2026

A Message from Dyne to the Global Myotonic Dystrophy Community

The recent news that the Phase 3 HARBOR study of del-desiran did not meet its primary endpoint has been disappointing for the entire myotonic dystrophy type 1 (DM1) community.

Most importantly, our thoughts are with the individuals and families who participated in the study. Clinical research is only possible because patients choose to participate, bringing their courage, energy, and hope for a better future. Every participant’s contributions result in valuable knowledge that helps move the field forward.

As our community processes this news, it is critical to remember that one clinical trial result does not define the future of myotonic dystrophy research – and potential treatments.

As we’ve always known, DM1 is a complex multi-systemic disease. Progress and options for our patient community will come from exploring multiple scientific approaches, learning from every study, and continuing to invest in innovation.

Every DM1 Investigational Therapy Is Different

While many investigational therapies share the goal of addressing the underlying cause of DM1, they can differ significantly in their design, mechanism of action, delivery approach, and the biological pathways they target.

Because of these differences, the outcome of one clinical program should not be assumed to predict the outcome of another. Each investigational therapy will be evaluated based on its own science, clinical data, safety profile, and potential benefit for people living with DM1.

How Zeleciment Basivarsen (z-basivarsen, also known as DYNE-101) Is Different

Dyne remains committed to advancing z-basivarsen, which is currently being evaluated for use in DM1 in two ongoing global clinical trials. Although both z-basivarsen and del-desiran are being investigated for DM1, they are distinct molecules with different structures, mechanisms of action, and development programs.

Z-basivarsen is our investigational therapeutic being evaluated in the fully enrolled global Phase 1/2 ACHIEVE clinical trial and the currently recruiting global confirmatory Phase 3 HARMONIA clinical trial. We intend to use data from the ACHIEVE trial to support potential regulatory submission to the U.S. Food and Drug Administration for Accelerated Approval in the United States.

Unlike other therapies in clinical development for DM1, z-basivarsen consists of an antisense oligonucleotide (ASO) conjugated to an antigen-binding fragment (Fab) that targets the transferrin receptor 1 (TfR1) to enable broad delivery to muscle and the central nervous system. We chose to utilize an ASO because ASOs are known to get to the nucleus of cells, which is where the core pathology of DM1 occurs. This approach is designed to address the underlying genetic mechanism believed to drive DM1, by reducing toxic nuclear DMPK RNA and allow normal mRNA processing.

In simple terms, z-basivarsen is designed to reach muscles and the brain, address the underlying cause of DM1, and help cells function more normally.

Clinical results of z-basivarsen from the ACHIEVE trial have been shared previously, and we plan to share new, additional one year data at upcoming medical meetings (press release here).

Why Multiple Approaches Matter

History has shown that meaningful advances in medicine often come from pursuing several approaches simultaneously.

Different therapies may:

• Reach different tissues or cell types and access different parts of the cell, e.g. the nucleus

• Affect disease biology through different mechanisms

• Produce different types of clinical benefit and different safety considerations

• Benefit different patient populations

• Generate important scientific insights that advance the field

For a disease as complex as DM1, a diverse set of approaches increases the likelihood that people living with the disease will ultimately benefit from effective treatment options.

Continuing to Move Forward

The DM1 community has waited far too long for disease-modifying therapies. While setbacks are painful, they are also a reality of drug development.

What matters most is that research continues.

We support efforts to fully understand and learn from the data generated through every clinical study. Each participant helps move the field forward. And each scientific approach brings us closer to the shared goal of delivering meaningful treatments to people living with DM1.

At Dyne, we remain fully committed to the DM1 community, to advancing z-basivarsen and to learning from the work being done across the entire field of DM1 research. Scientific progress rarely follows a straight path, and important advances are often built on lessons learned from both successes and setbacks.

The path forward may not always be linear, but progress is built one study, one discovery, and one patient at a time.

For patients and families, the message remains clear: the fight against myotonic dystrophy is far from over. Multiple promising approaches continue to be pursued, and the commitment of researchers, clinicians, advocates, industry partners, and patients and families remains stronger than ever.

With gratitude,

The Dyne Therapeutics Team

* Z-basivarsen is an investigational therapeutic and has not been approved by the Food and Drug Administration (FDA), the European Medicines Agency (EMA), or any other regulatory authority, and the safety and efficacy of z-basivarsen have not been established.