Wave Life Sciences in a Tuesday filing with the SEC said Takeda has elected to terminate its option to continue work on Wave’s WVE-003 clinical-stage Huntington’s disease program—a potential $5 billion commercial opportunity, according to the biotech.
Japanese pharma Takeda will no longer be working with Wave Life Sciences on the investigational antisense oligonucleotide WVE-003 for the treatment of Huntington’s disease, according to an SEC document filed by the Massachusetts-based biotech on Tuesday.
Wave in its filing did not detail why Takeda pulled out of its partnership, noting only that the pharma no longer intends to exercise “and therefore elected to terminate its option” to take the candidate forward. The biotech will now have full responsibility over WVE-003 and will be able to develop the investigational therapy “independently or with other partners.”
Because the Huntington’s program was the only remaining active collaboration between Takeda and Wave, the standing agreement between the two companies—which was inked in February 2018—is “expired with immediate effect,” per the SEC filing. Wave has received around $260 million from Takeda under this agreement.
Under the original 2018 agreement, Takeda made a $110 million upfront payment and a $60 million equity investment for the option to co-develop and co-commercialize various neuro programs, including Huntington’s disease, amyotrophic lateral sclerosis and frontotemporal dementia. Takeda took the first step away from Wave in 2021, when it paid $22.5 million to abandon the discovery research part of the deal and instead focus on clinical-stage candidates.
Takeda’s decision to withdraw from the Huntington’s partnership is unexpected, particularly as WVE-003 just recently cleared its Phase Ib/IIa study. Wave in June 2023 announced that the antisense oligonucleotide significantly and selectively lowered levels of the mutant huntingtin protein by 46% at 24 weeks, or around eight weeks after the final dose.
The mid-stage study found that the reduction in mutant huntingtin was also tied with slower atrophy in the caudate region of the brain, a known imaging biomarker of clinical outcomes in Huntington’s disease. WVE-003 also slowed the decline of motor function in patients, though the study was not powered to detect significant effects on clinical outcomes, Wave said at the time.
“WVE-003 alone represents a potential $5 billion commercial opportunity, with potential to expand to $10 billion with programs targeting other single nucleotide polymorphisms (SNPs), and Wave’s recently completed SELECT-HD clinical trial has generated significant interest from prospective partners,” the company said in Tuesday’s SEC filing, noting that it expects “feedback from the regulators on a potential pathway to accelerated approval for WVE-003 by the end of 2024.”
For Wave, Takeda’s decision comes as the biotech continues to gain ground in its other pipeline programs.
On Wednesday, Wave reported that it successfully delivered the “first-ever clinical demonstration of RNA editing in humans.” Proof-of-mechanism data showed that its investigational oligonucleotide WVE-006 restored expression levels of the M-AAT protein in alpha-1 antitrypsin deficiency (AATD) patients with genotypes that would have otherwise prevented them from producing this protein.
Designed to be subcutaneously administered, WVE-006 is an RNA editing oligonucleotide that works by changing the A residue on its target RNA to an I residue. It is being developed to address AATD-related lung or liver diseases, or both.
Wave last month also announced that its exon-skipping oligonucleotide WVE-N531 improved dystrophin expression in patients with Duchenne muscular dystrophy. Mizuho analyst Salim Syed at the time said that WVE-N531’s performance “exceeded the bar for efficacy” with a “clean” safety profile.
In its SEC filing on Tuesday, Wave maintained that losing Takeda as a development partner will not affect its cash runway. The biotech expects its current cash and cash equivalents to be enough to support it into 2027. Wave is scheduled to hold a virtual research day on October 30.
