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Efficacy and resistance mechanisms of LD-aminopterin in psoriasis

Award Number: U44AI114473
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2014
PERIOD OF PERFORMANCE END DATE: 01/31/2021

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Efficacy and resistance mechanisms of LD-aminopterin in psoriasis - DESCRIPTION (provided by applicant): Psoriasis is a chronic, genetically influenced, remitting and relapsing scaly and inflammatory skin disorder that affects 1-3% of the world's population, resulting in total annual costs of $5.2 billion in the United States in 2012. Approximately 20% of patients with moderate-to-severe chronic plaque psoriasis require phototherapy and/or a variety of systemic treatments, where methotrexate (MTX) is the mostly widely used oral systemic agent. Despite the relative effectiveness of MTX, as a monotherapy, it does not achieve greater than a 75% reduction in the baseline psoriasis area-and-severity index (PASI 75) in 40% of patients, and fails to achieve remission (i.e. > PASI 90) in 60% of patients. Furthermore, up to 30% of patients with moderate-to-severe plaque psoriasis discontinue oral MTX primarily because of intolerance to the drug. While much effort has been directed to identifying the mechanism behind poor and/or toxic responses to MTX based on genetic factor and quantitation of its active metabolites, the majority of MTX failures remain unexplained. Given the efficacy and safety limitations of MTX and the cost of biologics compared to MTX (~$20,000 vs. $300 per year), there is a clear market opportunity for an improved antifolate with better efficacy and/or safety than MTX, but that is priced between MTX and biologics. LD-Aminopterin (LD-AMT) is a patented composition developed by Syntrix Biosystems that studies indicate has greater cellular uptake (i.e. polyglutamylation to the active metabolites) than MTX, and less liver and CNS toxicity, properties that may translate into better efficacy and/or safety. In addition to identifying LD-AMT as a potential improvement on MTX, gaining a mechanistic understanding of antifolate resistance in general has important clinical implications for treating inflammation with LD-AMT or MTX, by possibly identifying clinical biomarkers to predict optimal response or risk of toxicity in advance of initiating treatment. This U44 Fast-Track proposal aims to advance LD-AMT to the clinic by testing LD-AMT for efficacy in a placebo-controlled phase 2 trial and advancing a novel hypothesis-driven mechanistic explanation for antifolate resistance.


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: 2022 ( Subtotal = -$6,220 )
2022	2018	SYNTRIX BIOSYSTEMS, INC.	215 CLAY ST NW STE B-5	AUBURN	WA	98001	KING	USA	Allergy and Infectious Diseases Research	000	4	3/24/2022	NON-COMPETING CONTINUATION	-$6,220
														Subtotal = -$6,220

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	SYNTRIX BIOSYSTEMS, INC.	215 CLAY ST NW STE B-5	AUBURN	WA	98001	KING	USA	Allergy and Infectious Diseases Research	000	4	3/26/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $304,057 )
2018	2018	SYNTRIX BIOSYSTEMS, INC.	215 CLAY ST NW STE B-5	AUBURN	WA	98001	KING	USA	Allergy and Infectious Diseases Research	000	4	2/3/2018	NON-COMPETING CONTINUATION	$304,057
														Subtotal = $304,057

Issue Date FY: 2017 ( Subtotal = $649,697 )
2017	2017	SYNTRIX BIOSYSTEMS, INC.	215 CLAY ST NW STE B-5	AUBURN	WA	98001	KING	USA	Allergy and Infectious Diseases Research	000	3	1/23/2017	NON-COMPETING CONTINUATION	$649,697
														Subtotal = $649,697

Issue Date FY: 2016 ( Subtotal = $490,033 )
2016	2016	SYNTRIX BIOSYSTEMS INC	215 CLAY STREET NW	AUBURN	WA	98001	KING	USA	Allergy and Infectious Diseases Research	001	2	2/19/2016	EXTENSION WITH OR WITHOUT FUNDS	$490,033
2016	2014	SYNTRIX BIOSYSTEMS INC	215 CLAY STREET NORTHWEST	AUBURN	WA	98001	KING	USA	Allergy and Infectious Diseases Research	000	1	2/14/2016	NEW	$0
														Subtotal = $490,033

Issue Date FY: 2014 ( Subtotal = $225,000 )
2014	2014	SYNTRIX BIOSYSTEMS INC	215 CLAY STREET NW	AUBURN	WA	98001	KING	USA	Allergy and Infectious Diseases Research	000	1	7/31/2014	NEW	$225,000
														Subtotal = $225,000

Grand Total All Awards = $1,662,567

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Efficacy and resistance mechanisms of LD-aminopterin in psoriasis

Award Number: U44AI114473

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 08/01/2014

PERIOD OF PERFORMANCE END DATE: 01/31/2021

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