ARPA-H Project Awardees
The ARPA-H Mission Office Innovative Solutions Openings (ISOs) and Open Broad Agency Announcement (BAA) provide funding for research that aims to improve health outcomes across a wide range of patient populations, communities, diseases, and conditions. These projects focus on transformative ideas for health research breakthroughs or technological advancements.
Awards made from the ISOs and Open BAA are generally in the form of contractual agreements. Exact award amounts are dependent upon meeting milestones typical of the ARPA-H process. As of March 2024, ARPA-H is no longer accepting submissions for the Open BAA solicitation, but ARPA-H will continue to review and consider solution summaries and proposals submitted under the Open BAA before it closed. Currently, ARPA-H will primarily use Program-Specific and Mission Office ISOs to advertise and accept submissions for its programs and projects.
ARPA-H is pleased to announce the following awardees:
Nutrition Based Satiety Modulation
Obesity and diet-related diseases have a significant negative impact on individual and public health outcomes, health care costs, and productivity. This effort ensures that Americans will have access to safe, affordable, and effective satiety modulators to control obesity. The Nutrition Based Satiety Modulation project aims to identify, characterize, and develop precision delivery nutrition platforms, beginning with testing generally recognized as safe (GRAS) compounds that confer satiety modulation/potentiation. Unlike recently developed pharmaceuticals such as GGLT2 inhibitors and GLP-1R agonists, VitaKey products will leverage natural mechanisms to modulate the body’s natural satiety responses to food intake. The goal is to formulate compounds that can be safely added to foods for broad distribution. The development and evaluation of natural, health-focused, nutrition-based satiety modulators could be scaled to provide an affordable and accessible solution for obesity treatment. If successful, this initiative has the potential to achieve GLP-1/GIP agonist effectiveness comparable to current pharmaceutical weight-loss treatments, without the associated side effects, and at significantly reduced cost. By developing these interventions, VitaKey will dramatically reduce many chronic diseases such as diabetes, cardiovascular disease, and cancer.
WHEAT: Wheat-Based High-efficiency Enzyme and API Technology
This project aims to develop a new way to make active pharmaceutical ingredients (API) in a cell-free manner using wheat germ extract (WGE), a key ingredient derived from agricultural wheat. To date, cell-free production has been plagued by low yield and inability to synthesize APIs with the required quality attributes. This project proposes using an abundant and cost-effective reagent in cell-free manufacturing. WGE is a significantly cheaper cell free production system than the competing front-runner biomass of E. coli and has the potential to be cost competitive with traditional chemical synthesis approaches. If successful, the team will have demonstrated a paradigm shift in domestic API manufacturing.
AI-Enabled Generation of Antigen-Specific Antibodies
Antibodies are effective as preventive and therapeutic measures against cancers, autoimmune disorders, and other diseases. This project aims to develop novel Artificial Intelligence (AI)-based algorithms and technologies to create novel monoclonal antibody candidates for further translational efforts and clinical validation against multiple diseases. The efforts are supported by LIBRA-seq, a single-cell technology developed by the team that enables high-throughput mapping of antibody sequence to antigen specificity for a large number of antigens and B cells at a time. Initial focus is on several priority targets to include cancer and autoimmune disease therapeutic development. For each target, lead AI-generated antibody candidates will be validated in vitro and in vivo, and one antibody candidate among all targets will be selected to perform IND-enabling studies. The results will serve as proof-of-concept for the ability of AI-based approaches to design efficacious monoclonal antibodies, will confirm the generalizability of the proposed strategies, and will showcase their broad potential impact to virtually any area where monoclonal antibodies can play an important role.
γδ CAR T-Cellular Vaccine for Solid Cancers
The treatment of solid tumors including colorectal cancer, non-small cell lung cancer, prostate cancer, and breast cancer, remains a challenge. Although chimeric antigen receptor (CAR) T-cell therapies have achieved success in treating hematologic cancers, these therapies show limited effectiveness against solid tumors. This project seeks to develop a novel approach targeting solid cancers using a Dual-action Antigen-presenting CAR γδ T-cell (DACART) therapy that combines the strengths of current advances in cancer vaccination. The team aims to leverage the advancement of four key technologies: CAR T-cell therapies, including successful therapies for blood cancers and novel strategies for solid tumors; dendritic cell (DC)-based cancer vaccines; techniques for engineering and expanding γδ T cells pioneered at Luminary Therapeutics; and efficient transposon-based cell engineering systems. The project aims to deliver a single, off-the-shelf, cost-effective cell therapy that effectively kills solid tumors while stimulating an endogenous antitumor immune response with low rate of relapse.
AdVAntage: Adenovirus Vectors Assembly for synthetic manufacturing advantage
The current production of adeno-associated virus-based gene therapy products heavily relies on cell-based manufacturing, which is inherently restrictive and inefficient. To address this issue, the project aims to establish a platform for producing cell-free gene therapy viral vectors using micro-fluidic flow chemistry. This approach will offer a more precise, scalable, and cost-effective process of gene therapy manufacturing. In addition, it will ensure a safer and more predictable product for usage in human subjects by eliminating contaminants derived from the cell-based origin. The strategy of the project involves producing viral components using cell-free systems, which will then be combined in a microfluidic flow cell to facilitate the autoassembly of viral particles. This flow cell will precisely regulate the crucial factors necessary for viral assembly in a system that reduces product manipulation for operators and manufacturing cost.
Engineered monomeric IgA neutrophil-engagers for cancer and engineered dimeric IgA for infectious disease
Various immune cell types, such as T cells, NK cells, and macrophages, have been utilized for anti-cancer therapies, resulting in successful outcomes for some cancer patients. Neutrophils are the most abundant immune cells in human circulation. Despite possessing all the characteristics of an ideal anti-cancer effector cell, neutrophils have not been utilized in cancer therapies because IgG-based therapeutic antibodies (Ab) are not able to activate neutrophils efficiently. IgA is superior to IgG in engaging neutrophils through stronger receptor binding and signaling. The project will develop a novel engineered IgA therapeutic platform for oncology and infectious disease indications, leveraging the neutrophil-engaging characteristics of IgA. In proof-of-concept studies for cancer therapeutics, the project aims to target EGFR using the platform, while transcytosis efficiency of the platform will be improved through dimeric IgA (dIgA) engineering for infectious disease applications.
STHM: Sonodynamic Therapy for Hematologic Malignancies
The standard of care for hematologic malignancies (including acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphoblastic leukemia, chronic myeloid leukemia, multiple myeloma, and myelodysplastic syndrome) includes radiation and chemotherapy followed by bone marrow transplantation. This project aims to instead treat hematologic malignancies by using in-vivo or extracorporeal sonodynamic therapy (SDT) following the administration of the company’s proprietary compound. SDT is currently showing promise in clinical trials for treatment of solid tumors. The STHM project aims to expand the use of SDT in hematologic malignancies through multiple novel approaches, including in circulating blood or via catheterization into a custom milli-fluidics device. If successful, the resulting treatment would be minimally- or non-invasive and would increase treatment efficacy, increase patient comfort, and decrease costs.
PATH: Personalized Analytics for Transforming Health
Primary approaches to disease treatment are reactive, with patients diagnosed and treated only after symptoms develop. This project aims to improve chronic disease prediction by identifying early risk factors, piloting the technology on Type 2 Diabetes (T2DM). The results of this work should enable insight into the multimodal causes of disease, identify biomarkers to predict and diagnose disease, and ensure that we move towards a model where preventative care and early intervention reduce the burden of disease and improve the health span of all individuals. The Buck Institute, in partnership with 4YouandMe and Phenome Health, aims to generate in-depth data which will be analyzed using AI/ML techniques to develop noninvasive metrics to increase health personalization and help shift health care to the home. The performers will interrogate the genomic, proteomic, metabolomic, environmental, and social factors that precede disease onset, enabling elucidation of more comprehensive risk factors, determinants of disease and disease pathways, and novel biomarkers for early detection. PATH aims to focus on data-driven health care to provide actionable, personalized information to the individual for democratization of health care.
PROTECT – Pro/Prebiotic Regulation for Optimized Treatment and Eradication of Clinical Threats
PROTECT is a platform technology that combines a precision blend of native microbiome-enhancing probiotics and prebiotics, working synergistically as a synbiotic to prevent infection and restore healthy microbiota. Probiotics consist of beneficial bacteria while prebiotics consist of nutrients that selectively enable growth of these beneficial bacteria. PROTECT is predicated on the concept of niche exclusion, allowing beneficial bacteria to outcompete the pathogens (such as Staphylococcus aureus and Pseudomonas aeruginosa (PA)) and preventing them from taking hold, spreading, or developing antibiotic resistance. The proposal is focused on systematically defining the appropriate bacteria and growth conditions for rational development of a synbiotic treatment to prevent PA infection in individuals with cystic fibrosis and other lung infections. Findings from this work could create a generalizable platform for producing protective agents against chronic and acute infections. The project intends to generate an integrated resource (the “Airway Systematic Microbial Atlas,” or ASMA). ASMA will store and present all data and analyses and link to the reagents developed (including a strain bank), providing the broader scientific and medical communities with unique data and material resources to extend analysis for novel applications.
RADIANT: Real-time Analysis and Discovery in Integrated And Networked Technologies
The proposed Real-time Analysis and Discovery in Integrated And Networked Technologies (RADIANT) toolkit seeks to develop an extensible, federated framework for rapid exchange of multimodal clinical and research data on behalf of accelerated discovery and patient impact. The development activities pair software-enabled national infrastructure for data integration and interoperability with leading-edge portals and cloud platform deployments. Together, the RADIANT toolkit seeks to revolutionize current practices by enabling a new research care framework for real-time discovery and translational impact with children diagnosed with brain tumors as a driver use case. Coordination and implementation of initial RADIANT deployments will leverage a network of more than 35 partnered health care systems and participating patient families within the Children’s Brain Tumor Network (CBTN) and the Pediatric Neuro-Oncology Consortium (PNOC).