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Multiple Ascending Dose clinical trial of PTI-125, a novel AD therapeutic candidate

Award Number: R44AG060878
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2018
PERIOD OF PERFORMANCE END DATE: 11/30/2020

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Multiple Ascending Dose clinical trial of PTI-125, a novel AD therapeutic candidate - Project Summary/Abstract PTI-125 is a novel small molecule Alzheimer’s disease (AD) therapeutic candidate with a novel target and mechanism of action. PTI-125 binds and reverses an altered conformation of the scaffolding protein filamin A (FLNA) to prevent Aβ42’s tight binding to and toxic signaling via the α7-nicotinic acetylcholine receptor (α7nAChR) as well as Aβ42’s aberrant activation of toll-like receptor 4 (TLR4). Hence, by restoring FLNA’s native shape and blocking these two toxic cascades, PTI-125 reduces both tau hyperphosphorylation and neuroinflammation. Downstream effects include reduced neurofibrillary lesions and amyloid deposits, suggesting disease modification, and improved synaptic plasticity and function of α7nAChR, NMDAR and insulin receptors, suggesting symptomatic improvement. We will pursue a label claim of symptomatic improvement instead of the more difficult claim of disease modification and will therefore conduct clinical studies in mild-to-moderate AD. Under a US IND, the first-in-human clinical trial showed no drug- related adverse effects (AEs) and dose proportional pharmacokinetics (PK). Our first-in- patient clinical trial in mild-to-moderate AD patients demonstrated 20-34% reductions in CSF P-tau, T-tau, neurogranin and neurofilament light chain, as well as 5-15% reductions neuroinflammatory markers. We have just initiated a 1-month blinded clinical trial to replicate these striking biomarker effects with two doses and correlate them with exploratory cognitive measures. This clinical trial has increased from 36 to 60 patients, and the current proposal requests funds associated with this increased trial size. With biomarker data replicated and potentially an effect size in cognitive measures, PTI-125 will be well positioned both for Phase 3 clinical trials and partnering efforts.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	CASSAVA SCIENCES, INC.	7801 N CAPITAL OF TEXAS HWY STE 260	AUSTIN	TX	78731	TRAVIS	USA	Aging Research	000	2	8/5/2021	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $374,500 )
2020	2020	CASSAVA SCIENCES, INC.	7801 N CAPITAL OF TEXAS HWY STE 260	AUSTIN	TX	78731	TRAVIS	USA	Aging Research	000	2	3/6/2020	SUPPLEMENT FOR EXPANSION	$374,500
														Subtotal = $374,500

Issue Date FY: 2019 ( Subtotal = $2,896,561 )
2019	2019	PAIN THERAPEUTICS, INC.	7801 N CAPITAL OF TEXAS HWY STE 260	AUSTIN	TX	78731	TRAVIS	USA	Aging Research	000	2	12/12/2018	EXTENSION WITH OR WITHOUT FUNDS	$2,896,561
2019	2019	CASSAVA SCIENCES, INC.	7801 N CAPITAL OF TEXAS HWY STE 260	AUSTIN	TX	78731	TRAVIS	USA	Aging Research	002	2	4/10/2019	EXTENSION WITH OR WITHOUT FUNDS	$235,267
2019	2018	CASSAVA SCIENCES, INC.	7801 N CAPITAL OF TEXAS HWY STE 260	AUSTIN	TX	78731	TRAVIS	USA	Aging Research	001	1	4/10/2019	SUPPLEMENT FOR EXPANSION	-$235,267
														Subtotal = $2,896,561

Issue Date FY: 2018 ( Subtotal = $635,085 )
2018	2018	PAIN THERAPEUTICS, INC.	7801 N CAPITAL OF TEXAS HWY STE 260	AUSTIN	TX	78731	TRAVIS	USA	Aging Research	001	1	9/20/2018	SUPPLEMENT FOR EXPANSION	$374,500
2018	2018	PAIN THERAPEUTICS, INC.	7801 N CAPITAL OF TEXAS HWY STE 260	AUSTIN	TX	78731	TRAVIS	USA	Aging Research	000	1	8/13/2018	NEW	$260,585
														Subtotal = $635,085

Grand Total All Awards = $3,906,146

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Multiple Ascending Dose clinical trial of PTI-125, a novel AD therapeutic candidate

Award Number: R44AG060878

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2018

PERIOD OF PERFORMANCE END DATE: 11/30/2020

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