The agreement gives Takeda the option of co-developing and co-commercializing Huntington’s therapies and of licensing Alzheimer’s and Parkinson’s treatments. The deal also allows Wave to continue working on neuromuscular disease treatments.
“This partnership provides additional resources to advance our clinical programs through multiple data readouts while continuing to expand our pipeline in neurology and other therapeutic areas. We look forward to working with Takeda and leveraging our expertise in oligonucleotides and clinical capabilities to grow our company and continue to make scientific and medical advances on behalf of patients,” Paul Bolno, the president and chief executive officer of Wave Life Sciences, said in a press release.
Particularly relevant for Huntington’s patients is the first component of the agreement. It grants Takeda the option to co-develop and co-commercialize WVE-120101 and WVE-120102, which target the mutant allele of the huntingtin (HTT) gene.
Huntington’s is caused by a defect in this gene, which contains the instructions for cells to produce the Huntingtin protein. Researchers are not sure of the protein’s normal role in the body, but it is thought to be important to the proper functioning of nerve cells.
Accumulation of mutant HTT protein causes progressive loss of nerve cells in the brain. Healthy HTT protein is fundamental to neuron function, and research suggests that its long-term suppression can have detrimental consequences.
WVE-120101 and WVE-120102 are designed to prevent the production of mutant HTT protein. They do this by inhibiting the protein’s corresponding messenger RNA (mRNA), molecules that are read by the cell’s protein-making machinery.
Both compounds belong to a new class of medication called antisense oligonucleotides (ASO) that are designed to target mRNA. They hone in on the mRNA produced from the mutant HTT gene, but not the mRNA from the normal HTT gene.
Roughly two-thirds of people with Huntington’s disease carry one of two markers that identify the mutant HTT gene. These are called single nucleotide polymorphisms (SNPs).
WVE-120101 is designed to treat people who carry SNP1, and WVE- 120102 people who carry SNP2.
The first component of the agreement depends on Wave demonstrating in two ongoing Phase 1/2 clinical trials that its therapies address the Huntington’s mechanism they are supposed to address. The trials are PRECISION-HD1 (NCT03225833) and PRECISION-HD2 (NCT03225846).
Both trials continue to recruit patients. The multicenter, randomized, double-blind, placebo-controlled studies are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of WVE-120101 or WVE-120102. The participants are adults with early Huntington’s disease who carry either SNP1 or SNP2.