Based on current methods and procedures, the treatment effect of DT-216 on FXN protein was inconclusive due to high intra-individual variability, consistent with what was seen in the observational study.
There was a transient increase of FXN mRNA in peripheral blood mononuclear cells (PBMCs) 24 hours after dose, which is consistent with and confirms the results from the Phase 1 single ascending dose study. As of this data cutoff, PBMC FXN protein results are not available.
DT-216 Program Next Steps
The initial results from Design’s Phase 1 multiple ascending dose trial underscore the promise of DT-216 as a potential disease-modifying treatment for FA.
The favorable systemic safety profile and FXN response support continued development of DT-216. However, the company has elected to complete dose escalation in this Phase 1 study at the 300mg cohort due to concern for potential worsening of injection site thrombophlebitis at higher doses with multiple administration. Design has shifted focus to developing DT-216 with an improved formulation to enable higher exposures and chronic intravenous administration for treatment of FA. Nonclinical studies showed that the injection site reactions were attributable to the excipients in the current DT-216 formulation, and that improving the formulation composition could enable higher doses and chronic administration. Design has since shown that an improved formulation had favorable injection site tolerability following multiple intravenous administrations and enabled dosing to increase tissue exposure.
The company is now conducting bridging nonclinical studies to resume clinical development and expects to begin a multiple-dose Phase 1 clinical trial to assess safety, pharmacokinetics and pharmacodynamics of an improved DT-216 formulation in the second half of 2024, with initial clinical data expected in the first half of 2025.
“Data from the Phase 1 program showed that the therapeutic hypothesis of DT-216 is playing out in FA patients —restoring endogenous transcription of FXN into therapeutically relevant levels,” said João Siffert, M.D., president and chief executive officer of Design Therapeutics. “The totality of the data from our Phase 1 program supports the continued development of DT-216 for FA, and we believe leveraging an improved formulation will enable us to explore the full DT-216 therapeutic potential for treatment of people with FA, which is our ultimate goal. Our team will continue to work tirelessly such that clinical development with DT-216 can be resumed and we can report data from a multiple dose Phase 1 clinical trial in the first half of 2025. I am proud of the Design team for its incredible efforts, and we extend our sincerest gratitude to the patients and caregivers participating in our clinical trials.”
Webcast and Conference Call Information
Design will host a live webcast and conference call today at 4:30 pm ET to discuss these updates. The event is accessible through the "Events" section of the Investors page of www.designtx.com. A replay of the webcast will be archived on the Design website for 30 days.
Dial-in information for conference participants may be obtained by registering for the event here.
https://finance.yahoo.com/news/design-therapeutics-reports-initial-results-200100604.html
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