Early trial of experimental Huntington’s treatment expected by year’s end
ATL-101 aimed at shutting down production of harmful protein
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Before the end of the year, Arexera Therapeutics is planning to launch a Phase 1 clinical trial testing its experimental therapy ATL-101 in people with Huntington’s disease.
According to a company press release, the upcoming trial is expected to test one-time treatment with ATL-101 at various doses, with the goal of evaluating the therapy’s safety and its effect on markers of disease in the fluid around the brain. The company didn’t provide further details about the upcoming study.
“We look forward to initiating our Phase 1 study in Huntington’s disease patients and using the safety and biomarker findings to guide the program’s next steps,” said Pedro Gonzalez-Alegre, MD, PhD, chief medical officer of Arexera, formerly known as Atalanta Therapeutics.
Joanne Kotz, PhD, Arexera’s CEO, added: “As Arexera, we are now preparing to enter clinical development with our lead program with the goal of developing disease-modifying therapies for HD [Huntington’s disease] patients.”
Arexera’s platform would deliver molecules to cells deep within brain
Huntington’s is caused by mutations in the HTT gene, leading to the production of a mutated version of the huntingtin (HTT) protein. This mutated protein is thought to play a key role in driving the disease. There are currently no approved therapies that can slow Huntington’s progression.
When genes like HTT are read to make protein, the genetic code is copied from a cell’s DNA into a temporary molecule called messenger RNA (mRNA), which is then used as a template for protein production.
Small interfering RNA, or siRNA, is a type of technology that can selectively destroy mRNA molecules from a specific gene, effectively shutting down the production of the resulting protein.
Over the past year, we have refined our strategic focus, assembled an experienced leadership team and expanded the capabilities of our siRNA platforms
Arexera is developing a platform to deliver divalent siRNA (di-siRNA) molecules to cells deep within the brain. While standard siRNA is traditionally limited by poor tissue delivery and rapid clearance, di-siRNA overcomes these challenges by linking two chemically engineered siRNA molecules together.
To date, the company has raised about $150 million to support its platform and pipeline.
“Over the past year, we have refined our strategic focus, assembled an experienced leadership team and expanded the capabilities of our siRNA platforms,” Kotz said.
ATL-101 specifically targets the HTT gene
The company’s lead di-siRNA program, ATL-101, specifically targets the HTT gene, with the aim of shutting down production of mutant huntingtin protein and ultimately slowing disease progression.
“Huntington’s disease is predominantly a disease of the deep brain, has well-established genetic drivers and a profound unmet need for treatments that change its course,” Kotz said. “We believe the robust, durable deep brain activity of our siRNA platforms provides strong differentiation and rationale for HD as an initial application.”
In preclinical studies, the therapy, administered directly into the spinal canal of nonhuman primates, showed good efficacy for reducing huntingtin protein production in key brain regions that are affected by Huntington’s. No significant safety signals were observed.
“ATL-101 has demonstrated a differentiated preclinical profile characterized by best-in-class HTT suppression in deep brain regions, prolonged durability and a favorable preclinical safety profile, attributes we believe may be important for achieving meaningful disease modification,” Gonzalez-Alegre said.
Arexera is also developing a di-siRNA-based therapy targeting MSH3, another protein that’s been implicated in Huntington’s. The company is also developing a candidate that targets HTT and MSH3 simultaneously. Both of those treatments are in preclinical stages.
“By pursuing a potentially best-in-class approach to HTT lowering in ATL-101 alongside a di-siRNA targeting MSH3, we are building a Huntington’s disease franchise designed to address complementary drivers of disease onset and progression,” said Bob D. Brown, PhD, president of research and development and chief scientific officer at Arexera. “We believe the dual HTT/MSH3-targeting approaches we are pursuing for HD can create a blueprint for combination approaches to treat other severe neurological diseases.”
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