Beta amyloid grabs most of the headlines and research dollars for Alzheimer’s disease, but efforts to develop drugs targeting that brain protein have largely come up short. Pinteon Therapeutics is trying for a better outcome with drugs that block tau, a different protein that, despite also being associated with Alzheimer’s, has garnered much less attention.
Pinteon has spent the past two years quietly developing a tau-targeting drug. On Thursday, the Cambridge, MA-based company announced a $17 million investment and a plan to advance its lead compound through early-stage tests in humans. Morningside Ventures provided the financing for the Series A funding round.
Tau is abundantly found in healthy brains, where it helps transport cellular cargo, says Michael Ahlijanian, Pinteon’s chief scientific officer. But this protein can also take on a more dangerous form, called cis-pT231. In this form, tau misfolds and aggregates, forming tangles in the brain. As these clusters of misfolded tau spread, the resulting tangles begin to disrupt the ability of neurons to communicate and impair learning and memory.
One of the ways that this pathological tau is believed to spread is by traveling between cells, traversing the space from an affected neuron to an unaffected one, Ahlijanian says. Pinteon aims to block tau from making that jump. The company’s lead drug candidate, PNT001, binds to the pathological tau and clears it away. By stopping the problem tau from spreading, the goal is to slow the progression of disease. Ahlijanian says the antibody drug is selective, binding only to a site present on “cis tau,” leaving healthy tau alone.
“That’s what we believe is particularly attractive to this asset,” he says. “Cis tau doesn’t seem to be present in normal brains.”
The science underpinning Pinteon’s approach is based on research from Kun Ping Lu and his team at the Beth Israel Deaconess Medical Center. Their research focused on Pin1, a family of enzymes that interacts with proteins, including tau, says Pinteon CEO Martin Jefson. Pin1 dysfunction is associated with the formation of pathological tau.
Morningside Ventures licensed Beth Israel’s Pin1 science in 2013 and continued to fund the research, says Jefson, a former Pfizer (NYSE: PFE) neuroscience executive. In 2017, Pinteon, whose name is derived from Pin1, narrowed its focus to the compound that is now its lead drug candidate. The drug is given intravenously. Despite being a large molecule drug, Jefson says PNT001 can cross the blood-brain barrier, the protective membrane that is difficult for some drugs to cross. Pinteon is currently enrolling healthy volunteers in a Phase 1 study.
There aren’t many other companies developing tau-blocking drugs. In the wake of the 2016 Phase 3 failure of its amyloid-targeting Alzheimer’s drug, Eli Lilly (NYSE: LLY) began scouting around for an alternative approach to the disease. Last year, it found one through a partnership with AC Immune (NASDAQ: ACIU), a Swiss company that is developing a small molecule drug meant to block tau from forming into clumps. A Phase 1 study testing the AC immune drug, ACI-3024, kicked off in July.
Earlier this year, the door appeared to have finally swing shut on the amyloid hypothesis when Biogen (NYSE: BIIB) ended a pair of late-stage trials testing aducanumab, a drug targeting that brain protein. But last week, in a surprising move, the company said it would ask the FDA to approve it anyway. (More on that here.)
Jefson says Pinteon will use the new capital used to continue its Phase 1 clinical trial. The company will need to raise more to complete the study, and to prepare for mid-stage testing. In addition to Alzheimer’s, Pinteon envisions the drug as a potential treatment for other neurodegenerative disorders associated with tau formation, including traumatic brain injury, progressive supranuclear palsy, and chronic traumatic encephalopathy.