Kate Therapeutics’ CSO and scientific co-founder, Sharif Tabebordbar, PhD, will present detailed preclinical efficacy and safety results in nonhuman primates (NHPs) on its product pipeline and platform at the ASGCT 2024 Annual Meeting in Baltimore.
KateTx debuted less than a year ago with a $51 million Series A round co-led by Westlake Village BioPartners and Versant Ventures, and an exclusive license of KT430 to Astellas Pharmaceuticals for the treatment of X-linked myotubular myopathy. Since that time, the company has used its DELIVER platform to identify a proprietary class of muscle- and heart-targeted, liver de-targeted “MyoAAV-LD” capsids with improved potency and selectivity in NHPs and selected KT809 as a development candidate to treat DMD.
“KateTx has made significant advances over the past 12 months,” said Kevin Forrest, PhD, co-founder, president, and CEO of KateTx. “These ASGCT presentations are a meaningful milestone for the company and demonstrate the potential of our medicines to be the preferred therapies in both DMD and FSHD. We look forward to advancing these differentiated products to patients as quickly as possible.”
Advances in next-generation DMD gene therapy
KateTx will present data on its DMD development candidate showing markedly higher and more uniform expression at lower doses than competing gene therapies in NHPs, noted Tabebordbar.
“First-generation gene therapies for DMD use high doses of naturally occurring capsids that primarily target the liver, and promoters that are more active in skeletal muscle than heart in primates,” said Tabebordbar. “By leveraging our novel capsid and gene regulation technologies, we have developed a DMD gene therapy candidate that potently, uniformly, and selectively expresses high levels of microdystrophin in both skeletal muscle and heart, which are the major affected organs in the disease, while avoiding off-target tissues like the liver.”
KateTx’s DMD development candidate also resulted in 27 times lower vector genomes per nucleus in the liver compared with animals injected with the surrogate. Collectively, these findings support the potential for superior improvements in skeletal muscle strength, cardiac function (largely responsible for mortality in DMD), and safety, according to Tabebordbar.
Preclinical data for the FSHD program
KateTx will also present new preclinical data from its program in FSHD, which is a common muscular dystrophy that results from toxic expression in skeletal muscle of a protein called DUX4. The company says its results show the potential to give a one-time gene therapy that potently suppresses DUX4 whenever it is expressed in skeletal muscles.
In vitro, KateTx’s MyoAAV-LD mediated RNAi gene therapy candidate showed potent knockdown of DUX4 in FSHD patient myotubes with no off-target effects. In mice, the therapy reduced DUX4 target gene expression and led to dose-dependent improvements in muscle function and ultimately protected animals from severe impairment in treadmill time to exhaustion at a low dose.
“Both DMD and FSHD are challenging diseases; they require delivery of therapeutic cargoes to a substantial tissue mass, and expression of significant amounts of protein uniformly and durably across skeletal muscle fibers and cardiomyocytes in the case of DMD, and effective inhibition of toxic DUX4 expression in skeletal muscle in the case of FSHD,” said Katherine A. High, MD, visiting professor at Rockefeller University, professor emerita of pediatrics at the Perelman School of Medicine at the University of Pennsylvania, and member of the KateTx Scientific Advisory Board.
“The clinical evaluation of these novel bioengineered capsids is in my judgment one of the most exciting near-term developments in our field and I look forward to these programs moving into clinical development.”