R43AI183983
Project Grant
Overview
Grant Description
Peptide-HLA-DQ8 biologics for antigen-specific therapy in type 1 diabetes - Project summary/abstract
Antiger Therapeutics Inc is a startup biotech company specializing in engineering recombinant human leukocyte antigens (HLA) and membrane proteins.
In this SBIR Phase I application, we leverage this expertise to develop targeted immunotherapies for type 1 diabetes (T1D), a global health challenge affecting around 8.4 million individuals.
As a chronic autoimmune disease, T1D leads to severe complications like cardiovascular and kidney injuries, substantially reducing life expectancy by an average of 13 years.
Current immunotherapies suppress the immune system in a nonselective manner, and the associated toxicity precludes their long-term use for T1D control.
The sole FDA-approved immunotherapy for T1D, Teplizumab, only delays the disease onset for approximately two years.
Antiger Therapeutics Inc aims to address this problem by selectively targeting the aberrant immune response in T1D.
One pivotal immunogenetic factor in T1D development is the HLA-DQ8 membrane protein, which presents autoantigens such as insulin peptides to activate pathogenic T cells and disrupt immune tolerance.
Our primary objective is to specifically block the pathogenic T cells that recognize the insulin peptide-DQ8 (PDQ8) complex, thereby safely preventing or reversing T1D.
Antiger's proposed product is an innovative biologic comprised of functional multimers of PDQ8.
However, assembling the PDQ8 complex poses technical challenges due to inefficient pairing between DQA and DQB chains.
To overcome this problem, the company employs novel solutions involving disulfide bond engineering and the production of full-length membrane proteins.
Antiger's recent work has demonstrated the effectiveness of disulfide engineering in producing functional, dimeric PDQ7-FC at increased yields.
Through structural modeling, conserved regions in DQ7 and DQ8 were identified with the potential for disulfide bond engineering to improve complex assembly and production yield.
In Specific Aim 1, we will generate dimeric PDQ8-FC fusion proteins.
The PDQ8 complex will be stabilized by inter-chain disulfide bond introduced by site-directed mutagenesis to enhance the production yield; the FC portion enables dimerization of the PDQ8 complex in an antibody-like structure.
In Specific Aim 2, we will generate PDQ8-transmembrane proteins on detergent micelles.
The transmembrane domains of full-length α and β chains of DQ8 protein will promote the assembly of PDQ8 complex to be solubilized on micelles.
In both aims, we will assess the yield and purity of multimeric PDQ8 proteins and measure their inhibitory effect on PDQ8-specific T cell hybridomas.
By the end of this Phase I SBIR, we expect to generate one or more candidate proteins that meet pre-specified acceptance criteria on production yield, purity, and function.
Phase II plans encompass testing the biologic in humanized murine T1D models, assessing immunogenicity and optimization, ultimately preparing for IND submission.
Commercially, Antiger intends to collaborate with or license the product to a pharmaceutical company for further development, aiming to tap into the high-demand T1D therapeutic market, projected to be worth $24 billion by 2029.
Moreover, the scalable technology holds promise for addressing other class II HLA-associated autoimmune disorders, such as celiac disease and rheumatoid arthritis.
Antiger Therapeutics Inc is a startup biotech company specializing in engineering recombinant human leukocyte antigens (HLA) and membrane proteins.
In this SBIR Phase I application, we leverage this expertise to develop targeted immunotherapies for type 1 diabetes (T1D), a global health challenge affecting around 8.4 million individuals.
As a chronic autoimmune disease, T1D leads to severe complications like cardiovascular and kidney injuries, substantially reducing life expectancy by an average of 13 years.
Current immunotherapies suppress the immune system in a nonselective manner, and the associated toxicity precludes their long-term use for T1D control.
The sole FDA-approved immunotherapy for T1D, Teplizumab, only delays the disease onset for approximately two years.
Antiger Therapeutics Inc aims to address this problem by selectively targeting the aberrant immune response in T1D.
One pivotal immunogenetic factor in T1D development is the HLA-DQ8 membrane protein, which presents autoantigens such as insulin peptides to activate pathogenic T cells and disrupt immune tolerance.
Our primary objective is to specifically block the pathogenic T cells that recognize the insulin peptide-DQ8 (PDQ8) complex, thereby safely preventing or reversing T1D.
Antiger's proposed product is an innovative biologic comprised of functional multimers of PDQ8.
However, assembling the PDQ8 complex poses technical challenges due to inefficient pairing between DQA and DQB chains.
To overcome this problem, the company employs novel solutions involving disulfide bond engineering and the production of full-length membrane proteins.
Antiger's recent work has demonstrated the effectiveness of disulfide engineering in producing functional, dimeric PDQ7-FC at increased yields.
Through structural modeling, conserved regions in DQ7 and DQ8 were identified with the potential for disulfide bond engineering to improve complex assembly and production yield.
In Specific Aim 1, we will generate dimeric PDQ8-FC fusion proteins.
The PDQ8 complex will be stabilized by inter-chain disulfide bond introduced by site-directed mutagenesis to enhance the production yield; the FC portion enables dimerization of the PDQ8 complex in an antibody-like structure.
In Specific Aim 2, we will generate PDQ8-transmembrane proteins on detergent micelles.
The transmembrane domains of full-length α and β chains of DQ8 protein will promote the assembly of PDQ8 complex to be solubilized on micelles.
In both aims, we will assess the yield and purity of multimeric PDQ8 proteins and measure their inhibitory effect on PDQ8-specific T cell hybridomas.
By the end of this Phase I SBIR, we expect to generate one or more candidate proteins that meet pre-specified acceptance criteria on production yield, purity, and function.
Phase II plans encompass testing the biologic in humanized murine T1D models, assessing immunogenicity and optimization, ultimately preparing for IND submission.
Commercially, Antiger intends to collaborate with or license the product to a pharmaceutical company for further development, aiming to tap into the high-demand T1D therapeutic market, projected to be worth $24 billion by 2029.
Moreover, the scalable technology holds promise for addressing other class II HLA-associated autoimmune disorders, such as celiac disease and rheumatoid arthritis.
Awardee
Funding Goals
TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Missouri
United States
Geographic Scope
State-Wide
Antiger Therapeutics was awarded
Project Grant R43AI183983
worth $303,274
from the National Institute of Allergy and Infectious Diseases in August 2025 with work to be completed primarily in Missouri United States.
The grant
has a duration of 5 months and
was awarded through assistance program 93.855 Allergy and Infectious Diseases Research.
The Project Grant was awarded through grant opportunity PHS 2024-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 8/20/25
Period of Performance
8/11/25
Start Date
1/31/26
End Date
Funding Split
$303.3K
Federal Obligation
$0.0
Non-Federal Obligation
$303.3K
Total Obligated
Activity Timeline
Additional Detail
Award ID FAIN
R43AI183983
SAI Number
R43AI183983-2348667659
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Small Business
Awarding Office
75NM00 NIH National Institute of Allergy and Infectious Diseases
Funding Office
75NM00 NIH National Institute of Allergy and Infectious Diseases
Awardee UEI
WSY4SWA56WQ7
Awardee CAGE
9KAS0
Performance District
MO-90
Senators
Joshua Hawley
Eric Schmitt
Eric Schmitt
Modified: 8/20/25