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Neuroscience biotech led by former Pfizer crew wins $17M to target toxic tau

With big pharma players marching out of the disaster-prone field of neurosciences one-by-one, small biotechs are picking up the tab.

Cambridge, Massachusetts-based Pinteon Therapeutics is the latest initiative. The company, founded in 2014, is developing a tau antibody to address an array of neurodegenerative disorders. On Thursday, it unveiled $17 million in series A funding from Morningside Ventures.

Its experimental drug PNT001 targets a toxic conformation of tau, called cis-pT231 tau, which encourages the abnormal aggregation of tau proteins in neurons. The accumulated tau creates neurofibrillary tangles, which cause neuronal death, thwart communication and impair memory and learning. 

The biotech is hoping the drug could potentially tackle tau-driven diseases, such as chronic traumatic encephalopathy, traumatic brain injury, progressive supranuclear palsy and maybe even Alzheimer’s.

The quest for treatments to prevent and treat Alzheimer’s, the most common form of dementia, is littered with failure. For long, researchers were partial to the amyloid hypothesis, which suggests that targeting beta-amyloid plaques that collect between neurons and disrupt cell function could make a material impact on the progression of the disease.

However, setback after setback seemingly put the nail in the amyloid coffin earlier this year after Biogen, one of the last flag bearers of the theory acknowledged their failure. But in a dramatic twist last week, Biogen indicated it had resurrected its faith in the amyloid theory, at least in a subset of patients, following a protracted period of data mining.

Meanwhile, researchers are also looking at tau. Initially, anti-tau therapies were focused on inhibiting kinases or tau aggregation, or on stabilizing microtubules (which help guide nutrients and molecules from the cell body to the axon and dendrites) — but most of these approaches have been abandoned due to toxicity or a lack of efficacy, or both. Scientists are now looking at developing tau-targeting immunotherapies.

Larry Altstiel

“If we talk about the development of Alzheimer’s disease, obviously this is a challenge. To call it a challenge is an understatement, to be sure,” said Pinteon’s chief medical officer Larry Altstiel, who has formerly worked in the neurosciences divisions at Pfizer and Eli Lilly.

“One of the reasons that we’re interested in tau is that we know that the cognitive decline in Alzheimer’s disease is directly related to the extent of tau deposition.”

Pinteon has only just kicked off its phase I study in healthy volunteers, which is designed to test the safety, tolerability, and pharmacokinetics of PNT001. There will be another set of early-stage ascending dose studies in one or more patient populations to determine a dose where the cerebral spinal fluid concentration (CSF) of the drug could be considered potentially effective.

“When we get the appropriate CSF concentration from our phase one studies we’ll move into a (tau-driven) disease population and the choice of that population is really going to be data-driven,” Altstiel said.

Martin Jefson

The proceeds from the series A have largely been utilized in preclinical development of the compound, Pinteon chief Martin Jefson, who led CNS research at Pfizer, noted in an interview with Endpoints News.

“We’re going to need additional funds and we’re beginning to now approach both Morningside as well as additional investors to put together a follow on round to support the completion of phase I studies and preparation for phase II.”

Three months after Amgen folded up a late-stage Alzheimer’s study of their failed Novartis-partnered BACE inhibitor, the large drugmaker on Wednesday announced its exit from neurosciences. Pfizer deserted the field early last year, spinning out a startup, Cerevel, which Bain elected to fund.

Written by: Natalie Grover

Published on: October 31, 2019 06:05 AM EDTUpdated 07:31 AM

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