Therapy Type: Immunotherapy (passive) (timeline)
Target Type: Tau (timeline)
Condition(s): Alzheimer's Disease, Traumatic Brain Injury
U.S. FDA Status: Alzheimer's Disease (Phase 1), Traumatic Brain Injury (Phase 1)
Company: Pinteon Therapeutics
PNT001 is a monoclonal antibody to the cis isomer of tau phosphorylated at threonine 231, a form of pathological tau suspected to play a role in traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer’s disease.
Phosphorylated T231 tau exists in cis and trans conformations, as modulated by the peptidyl-prolyl cis/trans isomerase Pin1 (Galas et al., 2006; Hamdane et al, 2006). Cis pT231 has been detected in brain tissue from people with AD and CTE and increases acutely after traumatic brain injury in humans and rodent models. Cis pT231 is resistant to dephosphorylation and degradation, and promotes aggregation (Nakamura et al., 2012; reviewed in Lu et al., 2016).
In preclinical models of brain injury, a mouse monoclonal antibody to cis pT231 prevented axonal pathology, astrogliosis, tau oligomerization and tangle formation, brain atrophy, and behavioral and other deficits (Kondo et al., 2015; Albayram et al., 2017; Albayram et al., 2019).
In September 2019, Pinteon began a Phase 1 safety and tolerability study of PNT001 in healthy adults. In the trial, 48 people will receive single doses of 33, 100, 300, 900, or 2,700 mg antibody or placebo, infused over 30 minutes. Primary outcomes are adverse events and abnormalities on clinical and laboratory measures after 16 weeks. Other outcomes include antibody concentration in serum and CSF, measures of total tau, cis pT231 tau, pT231 tau, and NfL in CSF, as well as serum NfL and antidrug antibodies. The trial will run through November 2020.
For details on the trial, see clinicaltrials.gov.
Last Updated: 25 Jun 2020
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