Dear A-T families,

Today, Quince Therapeutics reported topline results from their Phase 3 “NEAT” trial in A-T. The study enrolled 105 children and evaluated eDSP, a unique approach that packages dexamethasone inside a kid’s own red blood cells, given as six infusions over about six months, with the primary outcome being change in RmICARS, a standard measure of ataxia severity.

The trial did not meet its primary or key secondary endpoints, and Quince has decided to stop development of the program. While the treated group showed a numerical trend toward benefit, the results did not reach statistical significance.

As an A-T dad, this is always hard news to absorb. Families follow every serious clinical program closely, not because we expect miracles, but because each one represents real effort, real science, and real hope.

It’s important to acknowledge what this trial did show. eDSP appeared to be generally well tolerated, and the study was executed rigorously across many international academic centers. The patients, families, investigators, and company team all did exactly what clinical research is supposed to do: test a plausible idea honestly and generate clear data.

As a community, we need to express our genuine appreciation to the Quince team for the dedication, care, and scientific rigor they brought to this program over several years. In many ways, they acted as pioneers, helping establish best practices for running large-scale clinical trials in A-T, and working closely with clinical sites that are now far better prepared to evaluate future therapies for this disease.

This particular approach didn’t cross the bar. That’s disappointing, but it’s also how progress happens in rare disease drug development. Negative trials still teach us what doesn’t work, help refine our biological models, and inform the next generation of strategies.

Importantly, I want to emphasize that the broader A-T research landscape continues to evolve. Multiple therapeutic directions are being actively explored, including antisense oligonucleotides (ASOs) designed to rescue specific ATM mutations, gene editing and gene replacement approaches aimed at restoring ATM function, and interventions targeting downstream biology such as chronic neuroinflammation and mitochondrial dysfunction.

At the same time, exciting new drug targets are emerging from basic research, involving DNA damage signaling, innate immune pathways, cellular stress responses, and metabolic regulation. These are reshaping how scientists think about A-T and helping guide where future therapies may come from.

To the families who participated in NEAT: I know your contribution often came at great personal cost and required tremendous effort (missing work, traveling, finding backup help). Please know it really mattered. Even when a trial is negative, the data you helped generate becomes part of the foundation for whatever comes next. And many more approaches to A-T are on the horizon.

With appreciation and hope,

-Brad

Brad Margus, Founder, Volunteer Board Chair and A-T Dad

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