Work completed to date

Simply put, we have spent the last 15 years developing this potential drug. All of our work has been peer reviewed and funded by government grants and foundations. We are now ready to take this drug into humans for testing.
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We generated and characterized a monoclonal humanized version of a select mouse antibody targeting a non-phospho-epitope located in the N-terminal region of Tau spanning aa 2–18 (Tau2-18, known as PAD, phosphatase activation domain). This part of the protein is normally hidden in a paperclip-like conformation in native (normal) protein, but becomes exposed in aggregated (bad) pathological Tau. It has been shown that exposed PAD plays an important role in the inhibition of anterograde fast axonal transport as well as in polymerization of Tau. In other words, if Tau breaks then your brain can't process information and memory.

Studies of human postmortem tissues from Alzheimer's Disease brain extracts with antibodies that only recognize the bad Tau, demonstrated that exposure of the N-terminal region of Tau is an early event in Alzheimer's Disease that becomes more and more exposed as Alzheimer's Disease progresses.

Based on the above, we expected, and found, that our antibodies generated against Tau2–18 epitope recognize pathological (bad), but not normal Tau and prevent/decrease the polymerization of this molecule.

We hired GenScript to humanize and characterize our anti-Tau antibody. GenScript has also developed a CHO cell line of our anti-tau antibody producing >1.5 g/l of this therapeutically potent Mab. Moving from laboratory to production scale is very important. Not everybody can make such transfer without losing quality and efficacy.

The humanized antibody was termed Armanezumab according to "Programme on International Nonproprietary Names (INN), Quality Assurance and Safety: Medicines, Essential Medicines and Pharmaceutical Policies (EMP)" of WHO (World Health Organization).

Accumulation of pathological Tau in the brains correlates with dementia in Alzheimer's Disease patients. Thus, by the time clinical symptoms appear, there is already substantial Tau pathology in the brains. Therefore, we expect that anti-Tau therapy may be most effective when disease progression is more advanced.

Currently, the majority of neuroscientists agree that one of the main targets for Alzheimer's Disease is pathological forms of Tau protein. The majority of scientific data support the hypothesis that "bad" (pathological) Tau aggregation is the main significant event in Alzheimer's Disease pathogenesis and which leads to obvious cognitive changes in people's behavior.
The more "bad" Tau the higher progression of dementia in Alzheimer's Disease patients.
It is important to note that "normal" Tau protein plays a very important role in the brain. The functions of folding and unfolding are typical for a healthy person. But when the transforming function of Tau (from folding to unfolding and back) is broken then the person faces major neurological problems. The Tau aggregates into plaques and tangles blocking normal functioning of the brain. The brain starts dying and shrinking. That is why it is very important to selectively bind "bad" Tau and not touch normal Tau. Our product binds "bad" Tau and stops aggregation and spreading (propogation) of this pathological molecules from "bad" neurons to healthy neurons and transforming it to "bad" neurons. "Bad" Tau just can't mass into tangles because its sites for connection/aggregation are already busy with our product. No sites for connection available - no aggregation and tangles - no progression of disease.

Our data have been published in many scientific journals (references are available at the end of this whitepaper) and presented at many Alzheimer's Disease conferences. However, it is useful to show some key experiments which demonstrate that our drug stops the progression of Alzheimer's Disease in animal models and that the brains of these treated animals resemble those of normal mice.
Our drug has been named
Armanezumab
Selected Data:

Our drug binds pathological Tau in fixed brain sections from Alzheimer's Disease cases but not in normal brains. (The brown staining represents bad Tau):
Armanezumab (our drug) Prevents Tau Toxicity – the higher the bars the healthier the cells. The black bars are normal cells, the light grey bars are cells treated with Tau, the dark grey bars are cells treated with Tau but also our antibody and the white bars are cells treated with Tau and a random antibody. As you can see below from the dark grey bars, our drug protected the cells from Tau.

To demonstrate the therapeutic activity in vivo, Armanezumab was injected into one side of the brains of aged mice with Alzheimer's Disease. Changes in Tau on the 5th day after antibody injection. There was a substantial decrease of total Tau (HT7) and different phosphorylated Taus in the side of the brains injected with Armanezumab versus the opposite half of the brains injected with a random antibody. These data demostrate that Armanezumab is able to significantly reduce pathological (bad) Tau in the brains of mice with Alzheimer's Disease after injection into the brain.

Importantly, therapeutics aimed at eliminating pathological tau may also be beneficial for treatment of a group of neurodegenerative disorders other than Alzheimer's Disease, categorized as tauopathies. These diseases include ALS, FTD with parkinsonism linked to chromosome 17, Pick's Disease, PSP, Creutzfeldt-Jakob Disease, Dementia Pugilistica, Down's Syndrome and others.
To demonstrate the therapeutic activity in vivo, Armanezumab was injected into one side of the brains of aged mice with Alzheimer's Disease. Changes in Tau on the 5th day after antibody injection. There was a substantial decrease of total Tau (HT7) and different phosphorylated Taus in the side of the brains injected with Armanezumab versus the opposite half of the brains injected with a random antibody. These data demostrate that Armanezumab is able to significantly reduce pathological (bad) Tau in the brains of mice with Alzheimer's Disease after injection into the brain.

Importantly, therapeutics aimed at eliminating pathological tau may also be beneficial for treatment of a group of neurodegenerative disorders other than Alzheimer's Disease, categorized as tauopathies. These diseases include ALS, FTD with parkinsonism linked to chromosome 17, Pick's Disease, PSP, Creutzfeldt-Jakob Disease, Dementia Pugilistica, Down's Syndrome and others.

Efficacy on mice (special mice with Alzheimer's Disease):
Legend: PS19 is the experimental mouse model that has the tauopathy. PS19/1C9 is the PS19 mouse treated with the mouse form of Armanezumab, PS19/IgG is the PS19 mouse treated with a random antibody and WT is a normal mouse that is untreated.

Summary: Mice with incorporated Alz disease, which were treated by Armanezumab have totally restored their cognitive abilities (the test consists of tasks to recognize new place and new object). The mice which were cured by other/random therapeutic had not showed positive changes.