CAMBRIDGE, Mass.--(BUSINESS WIRE)--Triplet Therapeutics, Inc., a biotechnology company leveraging insights from the human genetics of repeat expansion disorders (REDs), announced today the selection of TTX-3360 as the first clinical candidate developed from Triplet’s proprietary thRED Engine. TTX-3360, an antisense oligonucleotide, is the first therapeutic candidate with the potential to modify the course of REDs, including Huntington’s disease, by targeting the DNA Damage Response (DDR) pathway.
“The development of TTX-3360 is an important step towards our goal of treating REDs at the genetic level by targeting the primary driver of disease,” said Nessan Bermingham, Ph.D., Triplet’s chief executive officer, president, and co-founder. “Based on our data – as well as an extensive body of evidence from patient genetics – our target in the DDR pathway has the potential for significant therapeutic impact across many of these devastating diseases.”
REDs are a group of more than 50 known genetic diseases associated with DNA nucleotide repeats, many of which have been shown to lengthen, or expand, in cells over a patient’s lifetime. A significant body of evidence, including patient genome-wide association studies across multiple indications, supports the role of the DDR pathway as the primary driver of repeat expansion and subsequent disease onset and progression.
Preclinical data, including findings presented this year by Triplet at the annual meetings of CHDI and the American Society of Gene and Cell Therapy, indicate that ~50% knockdown of a single target in the DDR pathway can slow or stop the expansion of DNA repeats in vitro in human patient-derived cell lines and in vivo in Huntington’s disease model mice.
Recent experiments by Triplet demonstrated that a single dose of TTX-3360 induced significant knockdown of the target gene mRNA at 29 days in the cortex (>75%) and caudate (>45%) in non-human primates. No adverse events were observed, and the treatment was well-tolerated, at the therapeutic dose.
Triplet plans to initiate IND-enabling studies in the second half of 2020 and to file an IND in the second half of 2021, with an initial focus on Huntington’s disease. TTX-3360 may also be expanded into other central nervous system indications including spinocerebellar ataxias, fragile X syndrome, and familial amyotrophic lateral sclerosis (ALS). To support its clinical development, Triplet recently launched an international natural history study, SHIELD HD, to assess clinical outcomes and biomarkers that will inform future clinical trials.
“Thousands of patients with REDs currently have no disease-modifying therapeutic options,” said Irina Antonijevic, M.D., Ph.D., Triplet’s chief medical officer. "We are excited to be moving quickly toward a first-in-human trial in Huntington’s disease and ultimately toward therapies with the potential to slow or prevent these devastating disorders.”
About Huntington’s disease
Huntington’s disease is a genetic disorder linked to a mutation in the HTT gene characterized by an increase in the number of CAG repeats within the gene. The presence of these repeats, beyond a certain threshold, wreaks havoc on brain function, affecting mood, cognition and motor skills, ultimately leading to death. Thanks to the contributions of thousands of patients – whose participation in genetic research has built a fundamentally new understanding of the cause of REDs – it is now known that the number of repeat sequences expands over time in patients, increasing the toxic impact on cells, particularly neurons. The DDR pathway plays a central role in driving this process.
About Triplet Therapeutics
Triplet Therapeutics is a biotechnology company developing transformational treatments for patients with repeat expansion disorders (REDs) – a group of more than 50 known genetic diseases including Huntington’s disease, myotonic dystrophy, spinocerebellar ataxias, fragile X syndrome, and familial amyotrophic lateral sclerosis (ALS) – leveraging insights from patient genetics. Triplet designs and develops potential therapeutics for REDs using its proprietary thRED Engine, which enables the Company to develop a single oligonucleotide targeting the DNA Damage Response (DDR) pathway to potentially treat multiple REDs.
Triplet is backed by investments from Atlas Venture, MPM Capital and Pfizer Ventures, along with Invus, Partners Innovation Fund and Alexandria Venture Investments. Triplet is headquartered in Cambridge, Mass. For more information, please visit https://www.triplettx.com/