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Investigation of a nanoparticle albumin-bound mTOR inhibitor, nab-rapamycin for t

Award Number: R42CA171552
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/26/2012
PERIOD OF PERFORMANCE END DATE: 08/31/2019

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Investigation of a nanoparticle albumin-bound mTOR inhibitor, nab-rapamycin for t - DESCRIPTION (provided by applicant): In 2011, it is estimated that there will be 69,250 new bladder cancer cases in the United States, resulting in 14,990 deaths. Most cases (70-80%) present with nonmuscle-invasive bladder cancer (NMIBC) [1, 2]. Intravesical bacillus Calmette-Guerin (BCG), which elicits a nonspecific local immune response, is considered the standard first-line treatment. However, over 50% of NMIBC will recur. Several chemotherapeutics have been explored in the second-line setting with only limited efficacy, forcing many patients into a radical cystectomy. Because of high disease recurrence and morbidity, the cost per bladder cancer patient is among the highest of all cancers. Thus, the development of an effective molecularly targeted intravesical therapy is highly desirable. Inhibition of the mTOR signaling pathway is a promising therapy for bladder cancer [3]. In a genetically engineered mouse bladder cancer model that recapitulates the human disease (developed by our collaborators at Columbia University), mTOR expression increased with disease progression, and the mTOR inhibitor rapamycin effectively prevented tumor progression when administered intravesically [4]. Furthermore, rapamycin was found to potentiate the induction of a BCG-mediated immune response in mice [5]. Thus, we believe that intravesical therapy with rapamycin may have significant therapeutic value in the treatment of NMIBC as a rational molecularly targeted therapy. A novel injectable nanoparticle albumin-bound rapamycin was developed (nab-rapamycin) and in various xenograft tumor models, nab-rapamycin decreased downstream signaling and showed excellent efficacy [6-8]. In a phase 1 clinical study, intravenous nab-rapamycin was safe with evidence of responses and stable disease in a variety of solid tumors [internal data]. nab-rapamycin is in the process of being licensed to AADi, LLC, a start-up company, which is the applicant for this grant. We propose to conduct a combined phase 1/2 clinical trial to assess safety, toxicity, and efficacy of local intravesical administration of nab rapamycin in patients with NMIBC that have failed BCG treatment. Our specific aims are: Phase I portion - (1) in a clinical phase 1 study, establish safety and maximum tolerated dose of intravesical nab-rapamycin, (2) in a genetically engineered mouse bladder cancer model, evaluate efficacy of the combination of intravesical nab-rapamycin and BCG; Phase II portion - (3) in patients, evaluate blood and bladder tissue levels of nab-rapamycin, (4) evaluate potential predictive clinical biomarkers, (5) evaluate efficacy/safety in a clinical phase 2 study of single agent nab-rapamycin, and (6) evaluate efficacy/safety in a phase 2 combination with BCG. This proposal will present a unique opportunity to develop the first targeted molecular therapy with nab- rapamycin for intravesical treatment of bladder cancer. Our ultimate goal is to seek FDA approval.


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: 2020 ( Subtotal = -$414,166 )
2020	2015	AADI BIOSCIENCE INC	17383 W SUNSET BLVD STE A250	PACIFIC PALISADES	CA	90272	LOS ANGELES	USA	Cancer Treatment Research	000	2	3/13/2020	EXTENSION WITH OR WITHOUT FUNDS	-$414,166
														Subtotal = -$414,166

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2015	AADI, LLC	1343 LUNA VISTA DR	PACIFIC PALISADES	CA	90272	LOS ANGELES	USA	Cancer Treatment Research	000	2	9/12/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $168,928 )
2017	2015	AADI, LLC	1343 LUNA VISTA DR	PACIFIC PALISADES	CA	90272	LOS ANGELES	USA	Cancer Treatment Research	002	2	8/11/2017	EXTENSION WITH OR WITHOUT FUNDS	$143,780
2017	2015	AADI, LLC	1343 LUNA VISTA DR	PACIFIC PALISADES	CA	90272	LOS ANGELES	USA	Cancer Treatment Research	004	2	8/16/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
2017	2015	AADI, LLC	16730 CALLE DE CATALINA	PACIFIC PALISADES	CA	90272	LOS ANGELES	USA	Cancer Treatment Research	000	2	7/31/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
2017	2013	AADI, LLC	1343 LUNA VISTA DR	PACIFIC PALISADES	CA	90272	LOS ANGELES	USA	Cancer Treatment Research	001	1	8/11/2017	SUPPLEMENT FOR EXPANSION	$25,148
2017	2013	AADI, LLC	1343 LUNA VISTA DR	PACIFIC PALISADES	CA	90272	LOS ANGELES	USA	Cancer Treatment Research	003	1	8/14/2017	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $168,928

Issue Date FY: 2015 ( Subtotal = $924,745 )
2015	2015	AADI LLC	16730 CALLE DE CATALINA	PACIFIC PALISADES	CA	90272	LOS ANGELES	USA	Cancer Treatment Research	000	2	8/21/2015	EXTENSION WITH OR WITHOUT FUNDS	$924,745
														Subtotal = $924,745

Issue Date FY: 2014 ( Subtotal = $0 )
2014	2013	AADI LLC	16730 CALLE DE CATALINA	PACIFIC PALISADES	CA	90272	LOS ANGELES	USA	Cancer Treatment Research	000	1	7/22/2014	SUPPLEMENT FOR EXPANSION	$0
2014	2012	AADI LLC	16730 CALLE DE CATALINA	PACIFIC PALISADES	CA	90272	LOS ANGELES	USA	Cancer Treatment Research	001	1	7/22/2014	NEW	$0
														Subtotal = $0

Issue Date FY: 2013 ( Subtotal = $168,928 )
2013	2013	AADI LLC	16730 CALLE DE CATALINA	PACIFIC PALISADES	CA	90272	LOS ANGELES	USA	Cancer Treatment Research	001	1	8/6/2013	SUPPLEMENT FOR EXPANSION	$168,928
2013	2012	AADI LLC	16730 CALLE DE CATALINA	PACIFIC PALISADES	CA	90272	LOS ANGELES	USA	Cancer Treatment Research	000	1	8/1/2013	NEW	$0
														Subtotal = $168,928

Issue Date FY: 2012 ( Subtotal = $472,301 )
2012	2012	AADI LLC	16730 CALLE DE CATALINA	PACIFIC PALISADES	CA	90272	LOS ANGELES	USA	Cancer Treatment Research	000	1	9/26/2012	NEW	$472,301
														Subtotal = $472,301

Grand Total All Awards = $1,320,736

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Investigation of a nanoparticle albumin-bound mTOR inhibitor, nab-rapamycin for t

Award Number: R42CA171552

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/26/2012

PERIOD OF PERFORMANCE END DATE: 08/31/2019

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