The United States Food and Drug Administration (FDA) has cleared Design therapy to begin a Phase 1 clinical trial of its small molecule GeneTAC DT-216 for the treatment of Friedreich’s Ataxia (AF).
This clearance comes after the submission of an Investigational New Drug (IND) application based on promising data in preclinical studies. Trial enrollment is expected to begin in the coming weeks, with key trial data expected in the second half of 2022, Design said.
“The IND clearance for DT-216 is an important milestone for the company, further validating the therapeutic potential of our GeneTAC platform, a new class of drugs in development for severe degenerative diseases caused by a single genetic defect,” João Siffert, MD, President and CEO of Design, said in a press release.
FA is caused by mutations in the FXN gene that causes a deficiency in the protein frataxin, which is needed for energy production. The most common disease-causing mutation consists of excessive repetitions of a series of three nucleotides – the building blocks of DNA; one guanine (G) and two adenines (A) — in one region of the gene.
While this sequence repeats many times in healthy people, around five to 33 times, FA patients often have hundreds of repeats, which disrupts frataxin production.
GeneTAC are small molecules that can target repeat nucleotide expansions and promote or prevent protein construction. DT-216 was designed to specifically target the mutated region in the FXN gene and restore its function, allowing the production of a working protein frataxin.
“GeneTAC molecules, designed on the basis of decades of pioneering research into the mechanisms of gene transcription, are able to increase or decrease the expression of pathogenic genes and therefore have the potential to attack the root cause of diseases. genetic diseases,” Siffert said. .
The upcoming Phase 1 trial is designed to assess the safety, tolerability and pharmacokinetics of DT-216 – the movement of the drug into, through and out of the body – in patients with FA. The ability of the treatment to increase frataxin levels will also be monitored.
The trial builds on previous preclinical studies, in which low doses of DT-216 restored frataxin levels in heart-derived nerve and muscle cells from patients to levels comparable to those seen in cells from people in good health. It should be noted that heart nerve and muscle cells are most affected by frataxin deficiency.
Additionally, repeated administration of DT-216 was well tolerated in rodents and non-human primates at doses greater than those required to restore frataxin production.
Overall, the data suggests that DT-216 may safely and successfully restore frataxin levels and may slow the progression of FA.
Design is also developing a second GeneTAC program for myotonic dystrophy type 1another inherited disease of repeated nucleotide expansion for which there is no approved treatment.
“DT-216 is the first in a pipeline of GeneTAC molecules, which can be engineered and selected for desirable pharmaceutical properties such as tolerance, wide tissue distribution, including CNS. [central nervous system], efficient manufacturing and convenient administration. We look forward to beginning clinical development of DT-216 for people with FA, for whom no disease-modifying therapy is available today,” said Siffert.