With a $17 million series A fundraiser completed, Pinteon Therapeutics Inc., of Cambridge, Mass., is keeping its eyes on the phase I trial it started in September testing PNT-001, a tau antibody that targets cis-pT231 tau, a toxic epitope that drives neurodegenerative disease.

The study of healthy volunteers is designed to evaluate five single escalating dose levels. Once that's done and evaluated, Martin Jefson, Pinteon's CEO, plans on being back in the clinic for a study with patients next year.

"We'll move into a patient population where we expect there to be a much greater abundance of the drug's target," Jefson told BioWorld. "The second study should measure target engagement."

Preclinical studies show that cis-pT231 tau is behind several neurodegenerative diseases. Lawrence Golbe, a member of Pinteon's scientific advisory board, said he believes the mechanism may be relevant for treating mild traumatic brain injury, progressive supranuclear palsy and Alzheimer's disease. The aggregation of cis-pT231 tau is believed to cause neuronal death and impair learning and memory.

"We believe that PNT-001 can intervene at a critical point in disease progression to interrupt the transmission of pathological tau through neural circuits," Jefson said. "By halting the spread of pathologic tau, we hope to protect and preserve brain function in patients living with tauopathies."

The phase I now underway is a multicenter, randomized, double-blind, placebo-controlled single ascending-dose study to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of intravenous PNT-001 in healthy adults. Patients receive single escalating doses administered as a 30-minute infusion at doses of 33 mg, 100 mg, 300 mg, 900 mg and 2,700 mg.

Others researching tau include Arvinas Inc., which reported to the Alzheimer's Association's international conference in July that preclinical data on its tau-targeted Protac protein degrader programmer showed that after parenteral administration of the drug, more than 95% of pathologic tau protein was eliminated in the brain of a mouse tauopathy model. And a research team at the University of New Mexico, Albuquerque, is moving forward with the development of a vaccine against tauopathies, which includes Alzheimer's disease. Its studies conducted in mice showed positive results for the development of a virus-like particle (VLP)-based vaccine that could target hyperphosphorylated tau, potentially preventing diseases like Alzheimer's and frontotemporal dementia. (See BioWorld, July 1, 2019.)

Oligomerix Inc., of New York, said it completed phase I of the scope of work under its Small Business Innovation Research phase I/II fast track grant to scale up and synthesize a tau oligomer inhibitor to initiate IND-enabling studies in Alzheimer's disease and related dementias.

Jefson said Pinteon's series A financing gets the company through all its preclinical work, and he is in the process of speaking to investors to finance a series B in 2020 to underwrite the full completion of the phase I studies.

The management team is composed of many faces from the 27 years Jefson spent at Pfizer Inc. leading CNS research as well as the four venture-backed neuroscience startups he's been involved with the past 10 years. He was the founding chief scientific officer at Rodin Therapeutics Inc. and Ataxion Inc.

"These are folks I had personal experience working with," Jefson said. "They had the right skill sets and I had the good luck they were available."

The roster includes Michael Ahlijanian, who, in addition to being a Pfizer vet, was director of genetically defined disease biology and head of clinical biomarkers at Bristol-Myers Squibb Co., and Larry Altstiel, the chief medical officer, who directed neuroscience clinical research at Pfizer and was a group leader for neurodegenerative diseases at Eli Lilly and Co.

The series A fundraising comes solely from Morningside Ventures.

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