Gilead had tested a humanized antibody called andecaliximab, or GS-5745, in close to 1,000 patients before giving up on it a few years ago. The company had multiple mid- and late-stage attempts in various cancers, autoimmune disorders and cystic fibrosis.
Now, a nimble Brisbane, CA biotech named āshibio is emerging with $40 million in seed and Series A funds to salvage the MMP-9 inhibitor and take it into a different indication: the ultra-rare bone disorder known as fibrodysplasia ossificans progressiva (FOP).
The genetic disease, which usually begins in childhood, leads to abnormal bone formation across muscles, tendons, ligaments and other soft tissues. FOP impacts an estimated 4,000 people globally, according to the National Organization for Rare Disorders.
Steering the biotech is a former Gilead oncology leader, Pankaj Bhargava, who is also a partner at Series A lead investor MPM BioImpact. Other financial backers include Agent Capital, YK Bioventures and Mirae Asset Venture Investment.
“There’s not a whole lot happening in the bone space,” Bhargava said in an interview with Endpoints News. “The bone space has been devoid of any large approvals for a while.”
The biotech is also in the process of licensing another molecule for a different bone disease, Bhargava said.
Āshibio won’t be the first in FOP, though. After years of trying, Ipsen secured the first FOP treatment approval from the FDA last year for Sohonos.
Meanwhile, Regeneron is in Phase 3 with its candidate, the activin A inhibitor garetosmab, which it said last November could be filed for FDA approval in 2025 or later. At the time of a Phase 2 data drop in early 2020, the New York drugmaker said it would discuss submission with regulators, but later that year it ran into safety issues. The Phase 3 is slated to collect final primary data next April, according to the US clinical trials database.
While Ipsen’s Sohonos goes after the gamma subtype of retinoic-acid receptors and Regeneron’s experimental medicine is an activin inhibitor, āshibio is creating an antibody that inhibits matrix metalloproteinase-9, or MMP-9. A paper in the Journal of Bone and Mineral Research earlier this year outlined how the enzyme could become a new target for FOP based on a case study of a 35-year-old.
“This guy has a one-in-a-million FOP mutation and then he has an overlying MMP-9 mutation that’s protecting him from the disease,” Bhargava said. “This gave us very strong conviction for going forth in FOP.”
Āshibio plans to start a Phase 2/3 study before the end of this year and has already received IND clearance from the FDA. The trial will be in two parts: first, a lead-in study and then a randomized, placebo-controlled trial, Bhargava said. The combined Phase 2/3 is expected to serve as a registrational trial, the CEO added. The US regulator and the European Medicines Agency have both given the candidate orphan drug status.