As Scholar Rock shakes up its C-suite, their loss has been startup Triplet Therapeutics’ gain as it nabs chief scientific officer Alan Buckler, Ph.D.
Scholar Rock, which is testing drugs in spinal muscular atrophy and its cancer immunotherapy, loses its CSO Buckler who had helped lead these programs, and comes after Scholar also saw its founding CEO Nagesh Mahanthappa, Ph.D., who becomes its scientific adviser.
Buckler now moves over to Triplet, picking up the CSO role there, and comes off a distinguished career that has seen him serve as vice president, cell and protein sciences at Biogen, and a nine-year stint as leading drug discovery programs at Novartis Institutes of Biomedical Research.
His new home launched late last year with $59 million and a mission to develop drugs for repeat expansion disorders such as Huntington disease and fragile X syndrome.
The company is taking aim at disorders caused by too many repeats of certain DNA sequences. These include triplet repeat disorders, or repeat expansion disorders (RED), so called because they result from repeats of three nucleotide bases, or letters.
The biotech says it’s able to think more holistically about this group of diseases, which number about 40, because of a new understanding of how they develop.
Thanks to new genetic data—most of which weren’t even available when Triplet was founded in 2018—the company identified one central pathway that drives repeat expansion disorders: the DNA damage response (DDR) pathway.
One kink can make the DNA more likely to develop more kinks, growing longer and longer, like a snowball rolling down a hill. Eventually, it reaches a point where it becomes toxic to the cell, he said.
Current treatments for Huntington disease (HD) and other repeat expansion disorders focus on improving symptoms and do not change the course of the disease. Development efforts by companies like Roche and Wave Life Sciences target RNA, which stops toxic proteins from being made, but they do not address the underlying mutation.
What the biotech aims to is to work on drugs against very specific members of the DDR pathway to stop that expansion from taking place.
The company is working on antisense oligonucleotides and small interfering RNA medicines, with its leading clinical candidate, TTX-3360, focused on HD, with the biotech also eyeing up the med for spinocerebellar ataxias, fragile X syndrome, and familial amyotrophic lateral sclerosis (ALS).
Targeting the DDR pathway means Triplet will develop drugs not on a disease-by-disease basis, but on a tissue-by-tissue basis. That means it could potentially target several diseases with one drug.
“We are delighted to welcome Alan to Triplet,” said Nessan Bermingham, Ph.D., founder, president and CEO of Triplet. “His foundational understanding of the genetic basis for REDs and his extensive experience in R&D complements our existing management team, our deep understanding of a novel pathway in REDs, and the R&D strategy for our thRED Engine, from which our recently announced clinical candidate TTX-3360 was identified.
“We are rapidly advancing therapies that could be transformative for patients with REDs and expect to file an IND in the second half of 2021.”
“Grounded in human genetics, Triplet’s approach is uniquely designed to target a fundamental driver of repeat expansion disorders,” added Buckler. “I am excited to join this first-class team as we work to advance innovative therapies for patients living with these devastating diseases.”