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Safe and effective anti CD154 antibodies for therapeutic intervention

Award Number: R44AI098261
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2012
PERIOD OF PERFORMANCE END DATE: 04/30/2019

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Safe and effective anti CD154 antibodies for therapeutic intervention - Abstract. CD154 (CD40L) is a key target for immunomodulation due to its central role in controlling the activation of the immune system. This well studied immune “switch” has been the focus of extensive drug development for over two decades. The validation of this drug target consists of reproducible and robust data using rodent and NHP models of chronic inflammation, autoimmune disease and organ transplant. In fact, this is one of the few undeveloped drug targets where antibodies have shown promising therapeutic efficacy in treating human autoimmune disease in several clinical trials. Therefore, the choice of CD154 as a drug target for commercial development is clear. The limitation on commercializing this clinical success was based on the thromboembolic toxicity of the drugs used in early trials and the limited knowledge on the cause of these adverse events (AEs). Consequent to these early trials the mechanism of toxicity was shown to be related to the FcR binding capacity of those former antibody drugs. Aggressive approaches to fix the AE's have proven successful in early human trials however these molecules show reduced potency in inhibiting the CD154 pathway likely owing to the use of non-conventional drug design. ImmuNext's engineering and development of a high affinity anti-CD154 antibody (INX021) shows that silencing the platelet Fc binding and ablating the complement fixation properties of the molecule eliminates the risk of thromoboembolic toxicity as demonstrated in vitro and an in vivo non-GLP NHP tox study. INX021 is a high affinity drug with a long half-life and likely low immunogenicity. Together, these features place INX021 as a best-in-class drug for several disease indications. Systemic lupus erythematosus is the first indication of choice. The mechanisms of action of CD154 also suggest that treating idiopathic thrombocytopena, IBD and TNF-resistant RA are plausible alternative indications to be considered following the completion of human safety studies. The Specific Aims of this proposal are: 1. Process Development, Formulation Development & Manufacture of GLP Tox Material. 2. Design of Phase 1A and 1B Clinical Trials and Supporting GLP Tox Study When these Aims are complete, ImmuNext can perform the IND-enabling GLP tox study that will enable partnering of this asset. Induction of tolerance - the `holy grail' of immunology - will be one step closer to commercial reality.


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: 2019 ( Subtotal = -$117,482 )
2019	2017	IMMUNEXT, INC.	1 MEDICAL CENTER DR	LEBANON	NH	03756	GRAFTON	USA	Allergy and Infectious Diseases Research	000	6	8/27/2019	NON-COMPETING CONTINUATION	-$117,482
														Subtotal = -$117,482

Issue Date FY: 2017 ( Subtotal = $912,191 )
2017	2017	IMMUNEXT, INC.	1 MEDICAL CENTER DR	LEBANON	NH	03756	GRAFTON	USA	Allergy and Infectious Diseases Research	001	6	4/27/2017	NON-COMPETING CONTINUATION	$912,191
2017	2015	IMMUNEXT, INC.	1 MEDICAL CENTER DR	LEBANON	NH	03756	GRAFTON	USA	Allergy and Infectious Diseases Research	000	4	4/18/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $912,191

Issue Date FY: 2016 ( Subtotal = $912,191 )
2016	2016	IMMUNEXT INC	16 CAVENDISH COURT	LEBANON	NH	03766	GRAFTON	USA	Allergy and Infectious Diseases Research	000	5	5/9/2016	COMPETING CONTINUATION	$912,191
														Subtotal = $912,191

Issue Date FY: 2015 ( Subtotal = $1,000,000 )
2015	2015	IMMUNEXT INC	16 CAVENDISH COURT	LEBANON	NH	03766	GRAFTON	USA	Allergy and Infectious Diseases Research	000	4	2/27/2015	NON-COMPETING CONTINUATION	$1,000,000
														Subtotal = $1,000,000

Issue Date FY: 2014 ( Subtotal = $962,696 )
2014	2014	IMMUNEXT INC	16 CAVENDISH COURT	LEBANON	NH	03766	GRAFTON	USA	Allergy and Infectious Diseases Research	000	3	2/28/2014	NON-COMPETING CONTINUATION	$962,696
														Subtotal = $962,696

Issue Date FY: 2013 ( Subtotal = $998,002 )
2013	2013	IMMUNEXT INC	16 CAVENDISH COURT	LEBANON	NH	03766	GRAFTON	USA	Allergy and Infectious Diseases Research	000	2	1/30/2013	COMPETING CONTINUATION	$998,002
														Subtotal = $998,002

Grand Total All Awards = $4,667,598

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Safe and effective anti CD154 antibodies for therapeutic intervention

Award Number: R44AI098261

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2012

PERIOD OF PERFORMANCE END DATE: 04/30/2019

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