Monday, October 13, 2025 10/13/2025

Multidimensional antibody engineering to enhance the potency and breadth of a betacoronavirus medical countermeasure

Award Number: R44AI177179
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: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Multidimensional antibody engineering to enhance the potency and breadth of a betacoronavirus medical countermeasure - The magnitude and duration of the ongoing COVID-19 pandemic have underscored the need to have a well-equipped—and ideally prepositioned—arsenal of antiviral weapons to mount an adequate public health response. A key lesson is that multiple medical countermeasures (MCMs) are needed to maintain potency and efficacy in the face of a rapidly evolving virus. Several approved SARS-CoV-2 vaccines have been paramount to gaining control over the pandemic, reducing both the number of infections and severity of disease for much of the global population. Unfortunately, these vaccines provide little to no protection to immunocompromised individuals who are unable to mount an effective immune response. Half-life extended monoclonal antibodies (mAbs) offer an attractive alternative, as their long half-life and high potency offer instantaneous immunity and vaccine-like protection without requiring the generation of a robust immune response. While >10,000 mAbs and multiple mAb cocktails have been explored over the course of the pandemic and several advanced as therapeutic candidates, they have largely failed to maintain potent activity in the face of prevalent antigenic drift within the SARS-CoV-2 spike protein. Moreover, currently approved vaccines and immunotherapeutics offer no protection from a related b-CoV, Middle East respiratory syndrome (MERS) virus. While small molecule inhibitors such as Paxlovid have shown broad in vitro activity against SARS and MERS, significant issues with COVID-19 rebound following treatment suggest it may not remain efficacious against the more lethal MERS virus. A recently identified antibody, 1249A8 (renamed AR-703), that recognizes a unique and highly conserved epitope in the S2 domain of the coronavirus spike protein offers a potential solution, being refractory to antigenic drift and having broad activity b- CoV activity, inclusive of SARS and MERS. The goal of the proposal is to maximize the clinical utility of AR-703 through multidimensional structure-based approach to increase neutralization potency and expand breadth of AR-703. In parallel, bispecific antibody engineering utilizing a novel bovine ultra-long CDR3 (UL-CDR3) based bispecific platform technology will be explored to introduce synergistic neutralization and resist viral escape. The structures of bovine UL-CDR3s have a demonstrated ability to independently target cryptic highly conserved epitopes, vital to maintaining efficacy to novel viral variants. Combining AR-703 and pan-b-CoV UL-CDR3 into a single bispecific would enable dual engagement of highly conserved neutralizing epitopes offering a potent solution to SARS2 antigenic drift for the immunocompromised while also guarding against related lethal b-CoVs should they emerge in the future.


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: 2025 ( Subtotal = $1,000,000 )
2025	2025	EITR BIOLOGICS, INC.	7090 MIRATECH DR STE 130	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	2	9/25/2025	EXTENSION WITH OR WITHOUT FUNDS	$1,000,000
2025	2023	EITR BIOLOGICS, INC.	7090 MIRATECH DR STE 130	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	5/1/2025	NEW	$0
														Subtotal = $1,000,000

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	EITR BIOLOGICS, INC.	7090 MIRATECH DR STE 130	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	2/29/2024	NEW	$0
2024	2023	EITR BIOLOGICS, INC.	7090 MIRATECH DR STE 130	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	1	4/3/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $283,552 )
2023	2023	EITR BIOLOGICS, INC.	6555 NANCY RIDGE DR STE 300	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	6/26/2023	NEW	$283,552
														Subtotal = $283,552

Grand Total All Awards = $1,283,552

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Multidimensional antibody engineering to enhance the potency and breadth of a betacoronavirus medical countermeasure

Award Number: R44AI177179

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: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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