DT-216P2 Shows Dose-Dependent Frataxin Increases and Clinical Improvements After 4 Weeks of IV Dosing in Friedreich Ataxia

Design Therapeutics has reported positive 4-week biomarker and clinical data from the ongoing phase 1/2 RESTORE-FA clinical trial evaluating DT-216P2, an investigational small-molecule GeneTAC therapy designed to increase endogenous frataxin (FXN) expression by targeting the GAA trinucleotide repeat expansion in the FXN gene—the underlying genetic cause of Friedreich ataxia (FA). The data showed dose-dependent increases in FXN mRNA and protein alongside improvements across multiple clinical outcome measures in patients treated with weekly intravenous dosing over 4 weeks.

As of May 17, 2026, 16 patients had completed 4 weeks of weekly intravenous DT-216P2 across 4 dose cohorts of 0.1, 0.3, 0.6, and 1 mg/kg (n = 4 per cohort). At the highest dose cohort of 1 mg/kg, patients demonstrated mean improvements from baseline of 6.4 points on the modified Friedreich's Ataxia Rating Scale (mFARS) and 2.7 points on the Upright Stability Score. On the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale, changes exceeding 5 points were observed both at the end of the 4-week treatment period and at 2 weeks following the last dose—surpassing the 3-point threshold generally regarded as a minimally important difference for that instrument.

On the biomarker side, dose-dependent increases in endogenous FXN mRNA and protein were observed in whole blood and muscle tissue. At the 1 mg/kg dose cohort following 4 weeks of treatment, whole blood FXN mRNA levels increased by 65% from baseline (P < .001). Whole blood FXN-M and FXN-E protein levels increased by 22% to 27% from baseline at 2 weeks after the last dose (P < .001), and muscle FXN mRNA levels increased by 42% from baseline (P = .015). The company characterized the concordance of blood and muscle biomarker activity as mechanistic evidence of the clinical improvements seen.

DT-216P2 was deemed generally well-tolerated in the study, with no serious adverse events (AEs) or treatment discontinuations reported. All AEs were determined to be mild or moderate in severity. AEs that occurred in more than 1 patient and were considered to be possibly or probably related to treatment included transient, asymptomatic alanine aminotransferase (ALT) elevations observed in 3 patients, none of which were accompanied by elevations in bilirubin. The company noted that transient ALT elevations are a recognized downstream consequence of enhanced mitochondrial activity associated with FXN restoration.

Design Therapeutics indicated it intends to pursue a registrational development path for DT-216P2 based on the new data. The company also noted that it anticipates that it will provide an update on plans in the fourth quarter of this year.

“These data represent an advancement for FA treatment, demonstrating that DT-216P2 increased endogenous frataxin and translated biomarker observations into clinical improvements after only 4 weeks of treatment,” Pratik Shah, the chief executive officer of Design Therapeutics, said in a statement.¹ “To our knowledge, this is the first time increases in endogenous FXN have been observed alongside clinical improvements of this magnitude in patients with FA, overcoming the presence of the underlying GAA repeat expansion. We observed both dose-dependent increases in FXN levels and dose-dependent improvements across multiple clinical measures, including mFARS, upright stability score and patient-reported fatigue. Based on these findings, we believe DT-216P2 has the potential to be a best-in-disease treatment for patients with FA and look forward to advancing the program toward registrational development.”

In addition to DT-216P2, Design is also developing drugs for several other neurology indications, including GeneTAC small molecule DT-818, which is being evaluated for the treatment of myotonic dystrophy type-1.² According to an April 2026 business update press release, the company anticipates that its planned phase 1 trial for DT-818 will begin dosing patients before the end of the first half of 2026. Design also has several candidates in preclinical development for the potential treatment of Huntington disease.

“The first quarter was marked by continued operational execution across our portfolio as we progress our clinical programs, including our ongoing RESTORE-FA multiple ascending dose trial evaluating DT-216P2…” Shah said in the April press release.² “We believe our GeneTAC platform represents a novel way to modulate gene expression, with the potential to unlock new therapeutic opportunities across a broad range of rare genetic diseases.”

REFERENCES
1. Design Therapeutics announces four-week IV data from the RESTORE-FA trial of DT-216P2 demonstrating clinical improvements and comprehensive biomarker activity in Friedreich ataxia. News release. Design Therapeutics, Inc. May 18, 2026. Accessed May 19, 2026. https://investors.designtx.com/news-releases/news-release-details/design-therapeutics-announces-four-week-iv-data-restore-fa-trial
2. Design Therapeutics announces first quarter 2026 financial results and recent business updates. News release. Design Therapeutics, Inc. April 28, 2026. Accessed May 19, 2026. https://investors.designtx.com/news-releases/news-release-details/design-therapeutics-announces-first-quarter-2026-financial