#Sava yahoo finance trial#

#Sava yahoo finance trial#

The randomized period of this trial was followed by an open-label extension for participants who completed previous Phase 2 trials, plus new enrollees to bring its participant number up to 100. The primary endpoint was change in CSF phosphorylated tau, neurofilament light chain, neurogranin, total tau, YKL-40, and Aβ42 secondary outcomes include cognition and plasma biomarkers. It compared 100 or 50 mg PTI-125 with placebo, dosed twice daily for 28 days, in 64 participants with a clinical diagnosis of mild to moderate AD, confirmed by CSF biomarkers. The data were published after peer review ( Wang et al., 2020).įrom September 2019 to March 2020, the company ran an NIH-funded Phase 2b study at 10 sites across the U.S. Multiple forms of modified tau declined in plasma, including p-tauT181, p-tauT202, and p-tauT231, as did a nitrated form of tau, n-tauY29 ( Dec 2019 conference news). At CTAD, the company presented data showing reduction in plasma levels of neurogranin, total tau, neurofilament light, and YLK-40 after treatment. The ratio of phosphorylated tau to Aβ42 apparently improved. Every participant showed changes on most markers with treatment. P-tauT181 and neurogranin fell by about a third with treatment, while the inflammatory markers decreased from 5 to 14 percent. In a September 2019 press release, Cassava claimed that drug treatment significantly decreased CSF total and phosphorylated tauT181, neurofilament light, neurogranin, YKL-40, Il-6, Il-1β, and TNFα, consistent with drug effects countering neurodegeneration and -inflammation. The study measured levels of PTI-125DX, an experimental diagnostic biomarker to indicate altered filamin in blood. Primary outcomes were pharmacokinetic measures secondary ones were CSF biomarkers of Alzheimer’s pathology, neurodegeneration, and neuroinflammation. They took 100 mg PTI-125 capsules twice daily for 28 days. This open-label, multicenter safety, pharmacokinetics, and biomarker study enrolled 13 participants with MMSE scores between 16 and 24 and a CSF total tau/Aβ42 ratio of 0.30 or higher. In early 2019, the company ran an NIH-funded Phase 2a trial in people with mild to moderate AD. In 2017, Cassava Sciences started with a Phase 1 safety study of 50, 100, or 200 mg of PTI-125 in 24 healthy adults. Most research on filamin, Aβ42 and Alzheimer's comes from the same laboratory. PTI-125 was said to preferentially bind altered filamin and normalize its conformation ( Wang et al., 2017). The study claimed that Aβ42 induces a conformational change in filamin, which would promote its association with the α7 and toll-like receptors, enabling Aβ42 toxicity and inflammation. Two months of oral PTI-125 in 3xTg AD mice reportedly reduced tau hyperphosphorylation, amyloid and tau deposition, and neuroinflammation, and restored synaptic function, nesting behavior, and spatial and working memory relative to untreated mice. When applied to human AD postmortem brain tissue, PTI-125 was reported to cause filamin and Aβ42 to dissociate from the α7 receptor ( Jul 2012 news). PTI-125 reportedly tamped down Aβ-induced inflammatory cytokine release by blocking filamin recruitment to toll-like receptor 4.

Concomitant intraperitoneal PTI-125 injections prevented this association, reduced tau phosphorylation and amyloid deposition, and normalized signaling through the α7, NDMA, and insulin receptors. In one, daily infusions of human synthetic Aβ42 into mouse cerebral ventricles resulted in association of Aβ42 and filamin with α7 receptors in the hippocampus and prefrontal cortex.

Preclinical studies suggest that PTI-125 prevents and reverses the binding of Aβ42 to α7nAChR. Filamin has been reported to stabilize the high-affinity interaction of soluble Aβ42 and the α7 nicotinic acetylcholine receptor (α7nAChR), which has been reported to trigger tau phosphorylation and synaptic dysfunction in some experimental systems ( Wang et al., 2000 Wang et al., 2003 Snyder et al., 2005). Simufilam binds to filamin, a ubiquitous scaffolding protein and regulator of the actin cytoskeleton. FDA Status: Alzheimer's Disease (Phase 3) Company: Cassava Sciences Background Name: Simufilam Synonyms: PTI-125, sumifilam Chemical Name: 4-benzyl-8-methyl-1,4,8-triazaspirodecan-3-one Therapy Type: Small Molecule (timeline) Target Type: Amyloid-Related (timeline) Condition(s): Alzheimer's Disease U.S. How would you like to share? Facebook Twitter LinkedIn