Design Therapeutics Announces Start of Friedreich Ataxia Patient Dosing Ex-U.S. in its RESTORE-FA Phase 1/2 Multiple-Ascending Dose Trial of DT-216P2
- Initial Phase 1 single-ascending dose trial showed favorable safety profile and improved drug exposure
- First FA patient dosed successfully with no adverse events reported
- Trial expansion to multiple countries starting with Australia
- FDA placed clinical hold on IND application for U.S. trial sites due to nonclinical deficiencies
- Data from MAD trial not expected until 2026, indicating a lengthy development timeline
Insights
Design's FA drug DT-216P2 advances with ex-US dosing but faces FDA clinical hold, creating mixed investment implications.
Design Therapeutics has reached a significant clinical milestone with their first Friedreich ataxia (FA) patient dosed in the RESTORE-FA Phase 1/2 multiple-ascending dose trial for DT-216P2. This represents progress for their lead candidate targeting this rare neurodegenerative disorder with no approved disease-modifying treatments.
The initial single-ascending dose data in healthy volunteers demonstrates a favorable safety profile with no injection site thrombophlebitis - a critical improvement over their first-generation formulation. This suggests the company has potentially overcome previous administration challenges.
However, the FDA clinical hold on the US IND application creates significant uncertainty. While the exact deficiencies remain undisclosed until the official FDA letter arrives, this regulatory hurdle will delay US site activation and potentially impact enrollment timelines. The company characterized the hold as related to "nonclinical deficiencies," which typically refers to preclinical/toxicology issues rather than clinical safety concerns.
The expected data readout in 2026 from the multiple-ascending dose trial will be pivotal, as it will measure frataxin (FXN) expression - the protein deficient in FA patients - after 12 weeks of treatment. This will provide the first efficacy signal in actual patients and determine whether DT-216P2 can deliver meaningful clinical benefit.
This announcement presents a mixed picture: clinical advancement internationally but regulatory challenges domestically. The Australian trial provides a path forward regardless of FDA timelines, but resolving the clinical hold will be crucial for accelerating enrollment and maintaining investor confidence.
Initial Data from the Ongoing, Blinded Phase 1 Single-Ascending Dose Trial Has Demonstrated Favorable Safety and Pharmacokinetics
IND Application Submitted to Expand RESTORE-FA Trial to U.S. Sites; Notice Received from FDA Placing Clinical Hold on IND Application to Open U.S. Sites
CARLSBAD, Calif., June 04, 2025 (GLOBE NEWSWIRE) -- Design Therapeutics, Inc. (Nasdaq: DSGN), a clinical-stage biotechnology company developing treatments for serious degenerative genetic diseases, today announced that the first Friedreich ataxia (FA) patient has been dosed via intravenous (IV) infusion in its RESTORE-FA (Reactivating Expression Suppressed Through Overcoming Repeat Expansion for FA) open-label Phase 1/2 multiple-ascending dose (MAD) clinical trial of DT-216P2.
The RESTORE-FA trial is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of IV and subcutaneous administration of DT-216P2 in patients with FA. DT-216P2 has been administered in one patient to date with no adverse events reported, including no injection site thrombophlebitis. The trial is currently open for enrollment in Australia. Design anticipates reporting data from the MAD trial, including levels of frataxin (FXN) expression based on 12 weeks of dosing, in 2026.
In addition, the company announced that it has submitted an investigational new drug (IND) application for DT-216P2 with the U.S. Food and Drug Administration (FDA). The company received a clinical hold notice on the IND application from FDA, noting nonclinical deficiencies. Further details will be provided in an official letter from FDA within 30 days and the company plans to address their questions, once received.
Initial data from the ongoing Phase 1 single-ascending dose (SAD) trial in healthy volunteers showed that DT-216P2 was generally well-tolerated, with no cases of injection site thrombophlebitis. The company believes the initial PK analysis is supportive of DT-216P2’s overall development profile and demonstrates improved exposure over the first-generation formulation.
“We are pleased by the initial findings from the SAD trial that demonstrated a favorable safety profile for DT-216P2 and support its advancement in the MAD FA patient trial. We are surprised by FDA’s notice and intend to work closely with them to expand development to the U.S. as expeditiously as possible,” said Pratik Shah, Ph.D., chairperson and chief executive officer of Design Therapeutics.
About DT-216P2
DT-216P2 is an improved formulation of a GeneTAC® small molecule designed to specifically target the GAA repeat expansion mutation that is the underlying cause of FA and restore the production of endogenous frataxin (FXN) proteins to therapeutic levels.
About Design Therapeutics
Design Therapeutics is a clinical-stage biotechnology company developing a new class of therapies based on its platform of GeneTAC® gene targeted chimera small molecules. The company’s GeneTAC® molecules are designed to either dial up or dial down the expression of a specific disease-causing gene to address the underlying cause of disease. In addition to its clinical-stage GeneTAC® programs, DT-216P2, in development for patients with Friedreich ataxia, and DT-168, for Fuchs endothelial corneal dystrophy, the company is advancing programs in myotonic dystrophy type-1 and Huntington’s disease. Discovery efforts are underway for multiple genomic medicines. For more information, please visit designtx.com.
Forward-Looking Statements
Statements in this press release that are not purely historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to: the anticipated reporting of clinical data and the timing thereof; the belief that the initial PK analysis is supportive of DT-216P2’s overall development profile and demonstrates improved exposure over the first-generation formulation; the expected timing for receiving an official letter from the FDA and the company’s plan to work with the FDA to expand development to the U.S.; Design's ability to advance its pipeline of GeneTAC® small molecules and create long-term value; and the capabilities and potential advantages of Design’s pipeline of GeneTAC® small molecules. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “believes,” “designed to,” “anticipates,” “capable of,” “on track to,” “plans to,” “expects,” “estimate,” “intends,” “will,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Design’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with: the FDA or comparable foreign regulatory authorities may disagree as to the design or implementation of our clinical trials, or the sufficiency of nonclinical data to initiate clinical trials; there can be no assurance that we will be able to successfully develop DT-216P2 on the timeframe we expect, or at all, or that we will be able to achieve our anticipated timeline for resumed Phase 1 clinical development in the United States and for reporting data; we do not know whether or to what extent the FDA clinical hold will potentially impact the planned clinical development of DT-216P2, including the ongoing MAD trial in Australia; conducting a clinical trial and patient enrollment, which are affected by many factors, and any difficulties or delays encountered with such clinical trial or patient enrollment may delay or otherwise adversely affect Design’s clinical development plans; the process of discovering and developing therapies that are safe and effective for use as human therapeutics and operating as a development stage company; undesirable side effects or other undesirable properties, which could cause Design or regulatory authorities to suspend or discontinue clinical trials and thereby delay or prevent Design’s product candidates’ development or regulatory approval; Design’s ability to develop, initiate or complete nonclinical studies and clinical trials for its product candidates; whether promising early research or clinical trials will demonstrate safety and/or efficacy in later nonclinical studies or clinical trials; changes in Design’s plans to develop its product candidates; reliance on third parties to successfully conduct clinical trials and nonclinical studies; competitive products, which may make any products we develop or seek to develop obsolete or noncompetitive; Design’s reliance on key third parties, including contract manufacturers and contract research organizations; Design’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; regulatory developments in the United States and foreign countries; Design’s ability to obtain and maintain intellectual property protection for its product candidates; Design’s ability to recruit and retain key scientific or management personnel; and market conditions. For a more detailed discussion of these and other factors, please refer to Design’s filings with the Securities and Exchange Commission (SEC), including under the “Risk Factors” heading of Design’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, as filed with the SEC on May 7, 2025. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Design undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof, except as required by law.
Contact:
Renee Leck
THRUST Strategic Communications
renee@thrustsc.com
FAQ
What is the current status of Design Therapeutics' RESTORE-FA trial for DT-216P2?
Why did the FDA place a clinical hold on Design Therapeutics' (DSGN) IND application?
What were the results from Design Therapeutics' Phase 1 single-ascending dose trial?
When will Design Therapeutics (DSGN) report data from the RESTORE-FA MAD trial?
What is the purpose of Design Therapeutics' RESTORE-FA trial?
