HOW DOES A DRUG GET DEVELOPED?

Stages of Development for DT-216 and DT-261P2

The drug development process can be thought of as a series of stages, and successful drugs must pass through each stage to become available to patients.

Link to Design Therapeutics

In 2017, Dr. Aseem Ansari reported a novel class of compounds called synthetic transcription elongation factors (Syn-TEFs). These compounds incorporate two distinct chemical moieties: (i) programmable DNA binders that target desired genomic loci and (ii) ligands that engage the transcription elongation machinery. Polyamides are used as the DNA binders, in this case selected for specificity to the GAA repeat, and they are tethered to JQ1 which regulates RNA polymerase II pausing to promote transcription elongation. In the published work, the team demonstrated that SynTEF1 could restore FXN expression in FA patient-derived cell lines to the level observed in healthy cells.

The preclinical data shows DT-216 is well tolerated and achieves concentrations needed to restore frataxin (FXN) gene expression.

Prior to beginning clinical trials, Design Therapeutics presented an Informational Webinar on DT-216 and completed IND-enabling studies with DT-216 that support initiation of clinical trials in the first half of 2022.

February 2022: The Investigational New Drug Application (IND) for DT-216 is cleared by the FDA.

March 2022: Design Therapeutics initiates a Phase 1 clinical trial of DT-216 to assess the safety, tolerability, pharmacokinetics, and frataxin levels in patients with FA in March 2022.

The company also receives scientific advice from the European Medicines Agency consistent with the favorable feedback previously received from the FDA, supporting the development plan for its DT-216.

The development of DT-216 for the treatment of patients with FA is granted Fast Track designation by the U.S. Food and Drug Administration (FDA).

December 2022: Design reports on the initial results from the single-ascending dose (SAD) Phase 1 clinical trial of DT-216 in patients with FA. The single dose study results shows that DT-216 is generally well-tolerated and able to generate a greater than two-fold increase in FXN mRNA in the cohort with the highest response.

August 2023: Design announces the initial data from the multiple ascending dose (MAD) study. Exploratory analyses demonstrate that DT-216 treatment achieved a statistically significant and dose-related increase in frataxin mRNA levels in skeletal muscle (p < 0.05). DT-216 was generally well-tolerated. However, injection site reactions, called thrombophlebitis, were associated with the formulation excipients, and observed across all dose cohorts.

This led to the decision to re-formulate DT-216. Design has chosen and tested a new formulation containing different excipients. DT-216 in this new formulation must now undergo additional preclinical testing and a new IND must be filed. The new MAD study is expected to take place in the first half of 2024, with a Phase 2 study to start in 2025.

While frataxin mRNA was increased in those receiving DT-216, muscle frataxin protein levels were variable, even within a person when measured a few days apart. Frataxin mRNA transiently increased in peripheral blood mononuclear cells (PBMCs). The data on frataxin protein changes in PBMCs has not been reported.

March 19, 2024: Design Therapeutics Outlines Progress Across GeneTAC™ Platform and Announces Fourth Quarter and Full Year 2023 Financial Results

Design Therapeutics has developed a new drug product, DT-216P2, with a favorable nonclinical pharmacokinetic and injection site safety profile. They announced an intent to complete GLP studies by year-end 2024 and to start patient trials in 2025.

 

 

News and Press Releases

News
| May 8, 2024

Design Therapeutics Announces First Quarter 2024 Financial Results and Highlights Upcoming Program Milestones

Industry News
News
| Mar 19, 2024

Design Therapeutics Outlines Progress Across GeneTAC™ Platform and Announces Fourth Quarter and Full Year 2023 Financial Results

Industry News
News
| Aug 14, 2023

Design Therapeutics Provides Pipeline Update and Reports Second Quarter 2023 Financial Results

Industry News
News
| Dec 7, 2022

Design Therapeutics Reports Positive Data from Single-Ascending Dose Trial of DT-216 for the Treatment of Friedreich Ataxia and Portfolio Progress

Industry News
News
| Mar 30, 2022

Design Therapeutics Completes Dosing in First Patient Cohort of Phase 1 Trial of DT-216 GeneTAC™ Molecule for the Treatment of Friedreich Ataxia

Industry News
News
| Feb 28, 2022

Design Therapeutics Announces FDA Clearance of Investigational New Drug Application for First GeneTAC™ Molecule for Friedreich Ataxia

Industry News
News
| Aug 9, 2021

Design Therapeutics Reports GeneTAC™ Portfolio Progress and Second Quarter 2021 Results

Industry News
News
| Mar 20, 2020

Design Therapeutics Launches with $45 Million to Develop a New Class of Disease-Modifying Therapies for Serious Degenerative Disorders

Industry News