September 29, 2026

Dear Myotonic Dystrophy Community,

As we shared last week, we, at Dyne are fully committed to the myotonic dystrophy type 1 (DM1) community, to advancing zeleciment basivarsen (z-basivarsen, also known as DYNE-101) and to learning from the work being done across the entire field of DM1 research. In that spirit, we’re pleased to announce new one-year efficacy data from a group of participants from the ongoing Phase 1/2 ACHIEVE clinical trial of z-basivarsen in people living with DM1.

These data come from up to 26 participants in the ACHIEVE trial who received z-basivarsen for one year. While most of these participants received dose levels lower than the dose selected for potential regulatory submission, this approach helps us understand whether a larger group showed the same positive trends previously observed in a smaller set of participants receiving the higher, registrational dose.

So, what did we see?

After one year, participants in this mixed dose group showed improvements from where they started across multiple measures assessing function, strength and disease-related symptoms reported by participants themselves (press release here).

In addition, for the first time, we compared these results to a separate group of untreated people with DM1 who are not in our trial (a “natural history” cohort), matched to look similar to the treated trial participants. That comparison matters because it helps us understand whether people receiving the therapy are doing better than the naturally expected DM1 disease trajectory. And although this was not a randomized comparison, participants receiving z-basivarsen demonstrated better outcomes than the matched natural history cohort after one year.

We also provided a safety and tolerability data update from participants enrolled in this first portion of the ACHIEVE trial. Z-basivarsen continued to demonstrate a favorable safety profile, and no serious related treatment emergent adverse events were identified as of the data cutoff of April 20, 2026.

These findings are encouraging because they suggest that z-basivarsen may have the potential to positively impact multiple aspects of DM1, including symptoms as reported by patients, myotonia, function and strength. These one-year results provide further evidence of the potential of z-basivarsen, supporting the continued development of the program.

It is also important to note that z-basivarsen remains investigational, and there is still more to learn and do. We expect to build on these findings through our ongoing global clinical trials, including the registrational expansion cohort of the ACHIEVE trial, from which we expect data in Q1 2027, and the Phase 3 HARMONIA study, which is currently recruiting participants at over 35 active sites across the globe.

We look forward to discussing these data with physicians, researchers and other members of the neuromuscular community this week at the International Congress of the World Muscle Society (WMS) and the Annual Meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), where we will be presenting these most recent results.

What is z-basivarsen?

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 (FDA) 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 allowing normal mRNA processing.

In simple terms, z-basivarsen is designed to reach muscles and the brain, reduce the toxic RNA that drives DM1, and help cells function more normally.

What comes next?

Moving forward, there are two important parts of the z-basivarsen clinical program:

The ACHIEVE registrational expansion cohort is fully enrolled with 71 participants, and topline results are expected in Q1 2027
- These results are expected to be a key component of our potential regulatory submission to the FDA for Accelerated Approval in the United States
The Phase 3 HARMONIA study is currently enrolling participants globally

Thank you

None of this research and encouraging results would be possible without the individuals and families who choose to participate in clinical trials. We are deeply grateful for the time, effort and trust that participants and their families contribute to advancing DM1 research.

We also recognize that this is a challenging and emotional time for the DM1 community. Scientific progress is rarely a straight line, and every study contributes to what we collectively understand about this complex disease. We remain committed to approaching our work with scientific rigor, transparency and urgency, while listening to the people and families whose lives are affected by DM1 every day.

We look forward to continuing to share what we learn as the z-basivarsen program moves forward.

With gratitude,

The Dyne 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.