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IND FIH study and month tox for PTI a novel therapeutic for Alzheimer s disease

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R44AG056166-01
Agency Tracking Number: R44AG056166
Amount: $1,866,748.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: NIA
Solicitation Number: PA16-302
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-09-15
Award End Date (Contract End Date): 2018-08-31
Small Business Information
Austin, TX 78731-1192
United States
DUNS: 134270623
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (650) 624-8200
Business Contact
Phone: (512) 501-2484
Research Institution

PTI is a novel compound with a novel target designed to treat and slow the progression of
Alzheimer s disease AD PTI binds with femtomolar affinity to a particular site on filamin A
FLNA a scaffolding protein we recently demonstrated is critical to beta amyloid s toxicity Beta
amyloid A exerts its toxic effects by hijacking the nicotinic acetylcholine receptor
nAChR and signaling via this receptor to hyperphosphorylate tau In addition to disrupting
normal function of nAChR and tau this toxic signaling leads to the signature tangles and
plaques found in brains of AD patients We have shown that this toxic signaling of A requires
FLNA recruitment to nAChR The recruited FLNA stabilizes A nAChR complexes
promoting a femtomolar interaction to enable further A piling and the toxic signaling that leads
to eventual neurodegeneration PTI binding to FLNA prevents or reverses the FLNA
nAChR association and A s tight binding and subsequent toxic effects A also impairs the
function of two other receptors that are pivotal to neuronal survival cognition and memory the
NMDA receptor and the insulin receptor By binding to FLNA PTI restores normal function
of all three receptors PTI also disrupts a similar association of FLNA with toll like receptor
TLR a receptor responsible for releasing inflammatory cytokines Hence PTI has a
second function of blocking the inflammation noted in AD brain Preclinical efficacy was
demonstrated in an acute ICV A infusion mouse model in normal aged mice and most
importantly in human postmortem AD brain tissue The effective concentration in postmortem
human brain is as low as pM PTI has completed and cleared all IND enabling studies and
the GMP manufacture and Phase I clinical drug supply is underway The day toxicity studies
demonstrated a fold safety margin between the NOAEL no observable adverse event level
in rat and a fold safety margin in dog compared to the efficacious doses in both mouse efficacy
studies PTI is rapidly absorbed and eliminated with nearly oral bioavailability dose
proportional PK and no accumulation Metabolic profiling showed minimal metabolism across
species In Phase I of this Fast track proposal we will file an IND With a successful IND
submission we will initiate Phase II a single ascending dose SAD study in healthy volunteers
followed by month toxicity studies in two species Further work outside this proposal included a
SAD clinical study in AD patients which will determine the dosing frequency for a multi dose PK
and safety study in AD patients The month toxicity studies will support clinical trials of month
duration but are also needed to determine doses for the chronic toxicity studies needed to support
clinical trials of any duration as well as an NDA There is currently no approved therapeutic for Alzheimer s disease AD that can slow or halt the
course of the disease PTI is a novel compound has been shown to alleviate multiple
pathological features of AD in mouse models and in postmortem brain tissue from AD patients
including receptor dysfunctions inflammation a marker for synaptic plasticity and the hallmark
plaques and tangles IND enabling studies are complete and the GMP manufacture of the clinical
lot ongoing With a successful IND submission that is Phase I of this proposal we will advance to
Phase II conduct a single ascending dose Phase I clinical trial followed by month toxicity studies
in two species

* Information listed above is at the time of submission. *

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