Open Broad Agency Announcement Awardees

The ARPA-H Open Broad Agency Announcement (BAA) provides 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 and will be funded on a rolling basis through March 14, 2024.

Awards made from the Open BAA will generally be in the form of contracts. Exact award amounts are dependent upon meeting milestones, typical of the ARPA-H process.

ARPA-H is pleased to announce the following Open BAA awardees:

MATRIX: ML/AI-Aided Therapeutic Repurposing In eXtended uses

Millions of individuals worldwide suffer from diseases for which there are no available treatments. While the Food & Drug Administration (FDA) has approved roughly 3,000 drugs to address a corresponding number of diseases, there remain an additional 9,000 diseases without a single approved therapy. Given that numerous diseases share common underlying mechanisms of action, and individual drugs can target multiple mechanisms, the existing pool of 3,000 FDA-approved drugs holds the promise of addressing the 9,000 diseases that currently lack therapeutic options. 

MATRIX (Machine Learning/Artificial Intelligence-Enabled Therapeutic Repurposing in eXtended uses) aims to develop computational methodologies for identifying the FDA-approved drugs most likely to treat diseases with inadequate treatment options, and to identify and validate top candidates for drug repurposing using these methodologies. 

This program aims to develop the first comprehensive scoring system that queries the world’s biomedical knowledge of “all drugs vs all diseases” to predict the efficacy for every drug to treat every human disease. The resulting information on the pharmaco-phenome will be made available open-source, allowing researchers to view the probability of efficacy across the entire landscape of FDA-approved drugs and human diseases.  

  • Date Awarded
  • Amount Awarded up to $48 million
  • Prime Awardee Institution Every Cure 
  • Principal Investigator Grant Mitchell, M.D.
  • Location Philadelphia, PA

PIC-OCT: Enabling Technologies for Photonic Chips-based Optical Coherence Tomography

As the US population ages, and with the increasing prevalence of obesity and related chronic health problems that affect the eye, debilitating eye disease poses a substantial medical and cost concern. With early diagnosis and appropriate management, > 90% of severe vision loss may be prevented. Imaging modalities that excel at screening, early diagnosis, staging, and tracking treatment response, and can do so safely, quickly, and inexpensively are highly valued by ophthalmologists. Optical Coherence Tomography (OCT)-based technologies have revolutionized eye disease diagnosis, along with demonstrating clinical potential across a myriad of other areas – including cardiology, urology, dentistry, and more. However, high cost and complex assembly of current systems limit their widespread adoption and hamper their broad implementation. This project will develop next-generation OCT systems based on photonic integrated circuits (PICs) and custom-designed electronic integrated circuits (ICs). By leveraging the latest advances in the nanofabrication of photonic and electronic ICs, acquisition speeds 50 times faster than the current standard will be achieved alongside immense decreases in the OCT system footprint (i.e., readily employable at walk-in clinics) and unprecedented reductions in manufacturing cost that will facilitate community-wide accessibility. Pediatric patients will especially benefit from the shorter scan times. Altogether, by enhancing patient treatment and adherence to repetitive testing, PIC-OCT will substantially reduce vision loss and its medical and societal costs. 

  • Date Awarded
  • Amount Awarded Up to $20M
  • Prime Awardee Institution Washington University in St. Louis
  • Principal Investigator Chao Zhou, Ph.D.
  • Location St. Louis, MO

REO: REvolutionizing the Oral route: delivery of electroceuticals and mRNA therapeutics for transforming health

Metabolic diseases are on the rise, with roughly 40% of Americans being obese and 10% diabetic. Treating these chronic diseases currently requires daily injections, surgery, or expensive drugs. Recent innovations, such as continuous glucose monitoring and insulin pumps, have greatly lowered the burden on patients but can still be painful to use and can limit activity.  

The MIT team aims to revolutionize these treatments by developing two orally delivered pill-sized devices. The first device will sense its location in the gastrointestinal tract and then inject mRNA into the tract lining that provides long term treatment for diabetes or obesity. The second device will temporarily reside in the GI tract, electrically stimulating it to release hormones associated with hunger and satiety. The devices will be remotely controlled and wirelessly powered for enhanced efficacy and safety.  

Although the proof-of-concept effort focuses on metabolic diseases, the designs could be applied to deliver therapies for many clinical conditions. Critically, this innovative delivery of therapies could provide treatment access to socioeconomically disadvantaged classes, who are most affected by metabolic diseases. The self-administration of capsule-sized devices could also reduce healthcare worker involvement, the need for hospitalizations, and healthcare costs associated with the need to store, stabilize, and medications. 

 

  • Date Awarded
  • Amount Awarded Up to $65.6M
  • Prime Awardee Institution Massachusetts Institute of Technology
  • Principal Investigator C. Giovanni Traverso, M.D., Ph.D., MBBCH. 
  • Location Cambridge, MA

DARTS: Defeating Antibiotic Resistance through Transformative Solutions

Bacterial infections remain a leading cause of death worldwide and will likely become an even greater health care challenge. The number of antibiotic-resistant pathogens grows daily while the discovery of new antibiotics lags dangerously. When a patient arrives at a hospital with a bloodstream infection, every minute matters but choosing the correct antibiotic is also crucial to success. Current methods of bacterial identification and antibiotic susceptibility are not up to the challenge. Testing can take hours, if not days, resulting in longer hospital stays, major complications, and higher mortality rates. Defeating Antibiotic Resistance through Transformative Solutions (DARTS) aims to address these challenges by advancing an ultra-high throughput imaging and culturing platform that can continuously track and test billions of bacteria one by one. If successful, the system will serve as a rapid platform for the discovery and development of new antibiotics. It will also be adapted for patient use as a microbial diagnostic that can rapidly identify the pathogen and the appropriate antibiotic to prescribe, enhancing the stewardship of antibiotics that remain effective. Such a rapid microbial diagnostic would enhance health outcomes, not just for the tested patient, but for everyone, as the diagnostic would greatly reduce the misuse of the antibiotics that remain effective.

  • Date Awarded
  • Amount Awarded Up to $104M
  • Prime Awardee Institution Harvard Medical School
  • Principal Investigator Johan Paulsson, Ph.D.
  • Location Boston, MA

CDTR: Stem Cell-Derived Thymus Rejuvenation

Thymmune Therapeutics’ Stem Cell-Derived Thymus Rejuvenation (CDTR) project aims to restore immune and endocrine function in patients lacking a functional thymus by using engineered stem cell-derived treatment. The thymus is an organ responsible for supporting normal immune cell development. The project is divided into two phases. The goal of the first phase is to use a combination of chemical and genetic factors to make best-in-class human induced pluripotent stem thymic epithelial cells (iPS-TECs) with capacity for supporting T lymphocytes (white blood cells) development in vitro. In the second phase, Thymmune plans to develop protocols for transplantation and long-term engraftment of iPS-TEC in animal models to achieve effective immune function, demonstrating a path towards using iPS-TEC to ultimately treat patients lacking functional thymus. Overall, Thymmune’s disease-agnostic approach to combat thymus dysfunction by bolstering immune responses against pathogens, cancer, and vaccines presents a potentially revolutionary means to reboot immunity. Thymmune has the potential to both rescue patients lacking a functional thymus from morbidity and mortality and addresses a crucial unmet need to rejuvenate immunity in the aging population.

  • Date Awarded
  • Amount Awarded Up to $37M
  • Prime Awardee Institution Thymmune Therapeutics
  • Principal Investigator Bing Lim, M.D., Ph.D. and Stan Wang, M.D., Ph.D.
  • Location Cambridge, MA

CODA: Mapping the Cancer and Organ Degradome Atlas to Unlock Synthetic Biomarkers for Multi-Cancer Early Detection

For most tumor types, there are currently no effective diagnostic tests for detecting most cancers at the earliest stages, when tumors are still localized and most responsive to treatment. Ongoing efforts that focus on native tumor-shed biomarkers face significant challenges, as these markers are often found in vanishingly small quantities in blood or other fluids. The CODA (Cancer and Organ Degradome Atlas) platform uses cutting-edge synthetic biology and cell engineering technologies to catalog cellular profiles unique to diseased cancer cells and leverages them to build bioengineered sensors that can be deployed inside the body to hunt for malignant cells. These biosensors use unique metabolic changes in tumor cells to drive the release of synthetic biomarkers that can reach high enough levels in biofluids to enable earlier cancer detection. This technology has the potential to produce a highly precise, accurate, and cost-effective test for multi-cancer early detection (MCED) that can identify common cancers earlier, when treatment can be most effective, and streamline clinical intervention when tumors are still small.

  • Date Awarded
  • Amount Awarded $49.5M
  • Prime Awardee Institution Georgia Institute of Technology
  • Principal Investigator Gabe A. Kwong, Ph.D.
  • Location Atlanta, GA

HEART: Health Enabling Advancements through Regenerative Tissue Printing

Over 3 million patients in the United States need tissue transplants, with more than 100,000 patients on the national transplant waiting list. Unfortunately, many of these people die while waiting for a donated organ. The Health Enabling Advancements through Regenerative Tissue Printing (HEART) project proposes to advance multiple technologies, including the optimization of purity and scalability of human cells, improved 3D printing technology and speed, advances in computational modeling, and novel approaches to organ maturation and implantation. The end result is the 3D printing of a human heart in one hour. This ambitious project has the potential to revolutionize the fields of human tissue and organ printing through large advances across multiple technologies. HEART could create a world where a doctor could 3D print an organ for their patient instead of waiting for a donor, effectively ending waitlists for transplants. This advance would improve the lifespan and quality of life for many Americans and provide broader patient access across all communities.

  • Date Awarded
  • Amount Awarded Up to $26M
  • Prime Awardee Institution Stanford University
  • Principal Investigator Mark Skylar-Scott, Ph.D.
  • Location Palo Alto, CA

SPIKEs: Programmable Scalable Therapeutics for Immune-directed Cancer-killing

Cancer immunotherapy, which harnesses the body’s own immune system to attack tumor cells, holds great potential. However, this therapy is currently hampered by very high costs, long and involved preparation processes, and frequent inefficacy against solid tumors. The University of Missouri’s Synthetic Programmable bacteria for Immune-directed Killing in tumor Environments (SPIKEs) project aims to develop a new class of living cancer immunotherapy that that can effectively address these limitations. The SPIKEs platform utilizes genetically programmable bacteria designed to sense tumor-associated metabolites as an exquisitely precise homing mechanism and then deliver therapeutic payloads that activate immune-directed killing of solid tumor cells without the need for the long and costly processes currently used. Bacterial therapeutics carrying programmable genetic circuitry that allows safe tissue targeting, on-demand activation and clearance, and multiple therapeutic functions – including immune cell recruitment, activation, and targeting – represent an innovative, scalable, cost-effective, and accessible treatment modality for cancer.

  • Date Awarded
  • Amount Awarded Up to $19.9M
  • Prime Awardee Institution University of Missouri
  • Principal Investigator Paul de Figueiredo, Ph.D.
  • Location Columbia, MO

THOR: Targeted Hybrid Oncotherapeutic Regulation

Peritoneal cancers, such as ovarian and primary colorectal cancers, cause more than one third of all cancer deaths in the United States. An effective treatment could save 187,000 American lives each year, yet unfortunately many solid tumors, such as those found in peritoneal cancers, often do not respond effectively to current immunotherapies. A revolutionary approach in the fight against peritoneal cancers has emerged, thanks to the convergence of several technological and medical innovations. This new effort, called Targeted Hybrid Oncotherapeutic Regulation (THOR), will create a compact device designed to trigger the immune system against tumors. The device will be implanted in proximity of the tumor and will house specialized cells responsible for producing and delivering therapeutic molecules. These molecules will activate the immune system both locally around the tumor site and throughout the body. Additionally, the device will incorporate advanced sensors to detect and monitor biomarkers of cancer. The integration of these two components in a single device will enable precise delivery of therapeutic doses tailored to each patient’s needs.

  • Date Awarded
  • Amount Awarded Up to $45M
  • Prime Awardee Institution Rice University
  • Principal Investigator Omid Veiseh, Ph.D.
  • Location Houston, TX

CUREIT: Curing the Uncurable via RNA-Encoded Immunogene Tuning

More than 25 million Americans currently live with autoimmune disease, and almost two million are projected to be diagnosed with cancer in 2023. Immune dysregulation is an underlying component of not only cancer and autoimmune diseases, but also infectious diseases, transplant rejection, and other common medical conditions. Current methods of immune modulation used to treat and mitigate these conditions are often expensive or not completely effective. Curing the Uncurable via RNA-Encoded Immunogene Tuning (CUREIT) aims to address immune dysregulation by directly programming immune cell function. Advances in gene-encoded technology will be leveraged to develop a platform capability able to both enhance protective immune responses as well as modulate insufficient or ineffective immune profiles. CUREIT seeks to develop a disease-agnostic toolbox of methods and technologies, including the in vivo delivery of mRNA-based drugs, cell targeting lipid nanoparticles, and ex vivo modulation of immune cells. This technology has the potential to make significant advancements towards managing or eliminating many diseases and conditions affecting all ages and demographics, including diseases that are currently untreatable.

  • Date Awarded
  • Amount Awarded Up to $24M
  • Prime Awardee Institution Emory University
  • Principal Investigator Philip J. Santangelo, Ph.D.
  • Location Atlanta, GA