This $700,000 Project Grant award from the National Institute of General Medical Sciences (NIGMS) Biomedical Research and Research Training Program (CFDA 93.859) supports the clinical validation of Prenosis, Inc.'s IMMUNIX platform, a precision medicine endotyping solution for sepsis. The project aims to: 1) validate the IMMUNOSCAN multiplex rapid test and mapping functions to Luminex immunoassays; 2) validate a parsimonious model for point-of-care endotyping; and 3) demonstrate the ability to...
This $305,000 project grant awarded by the National Institute of General Medical Sciences (NIGMS), under the Biomedical Research and Research Training program (CFDA 93.859), supports the development of a clinical decision support system (CDSS) called Sepsis FLO. The CDSS is designed to precisely guide blood volume diagnosis and treatment for sepsis patients. Key activities include: 1) Developing an alpha prototype of the CDSS through user-centered design; 2) Validating three functional...
The National Institute of Allergy and Infectious Diseases (NIAID) awarded a $473,937 Project Grant under the Allergy and Infectious Diseases Research Program (CFDA 93.855) to The General Hospital Corporation, doing business as Massachusetts General Hospital (MGH), to develop a novel point-of-care liquid biopsy for early detection of sepsis-associated organ damage. The project aims to optimize a microfluidic enrichment and digital PCR assay to detect tissue-derived circulating rare cells...
This National Science Foundation (NSF) Technology, Innovation, and Partnerships (CFDA 47.084) Project Grant award supports the development of a novel device that can rapidly and automatically extract pathogen DNA from whole blood samples to enable faster diagnosis of sepsis. The $274,858 award to New England Hemolytics, Inc., with a project period from September 1, 2024 to February 28, 2025, will fund the testing and optimization of this technology across common sepsis-causing pathogens. The...
This Project Grant award of $412,250 from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) will fund the development of a continuous, real-time, automated smart catheter analyzer to enable early identification of sepsis through urine biomarkers. The primary goal is to create a device that can quickly diagnose sepsis, a life-threatening condition, without requiring invasive blood tests. The 2-year R61 (Phase I) project will...
This Project Grant award of $455,000 from the National Institute of General Medical Sciences (NIGMS) Biomedical Research and Research Training Program (CFDA 93.859) aims to decrease sepsis mortality in the pediatric population. The key products and services to be delivered include: Developing an AI-guided early sepsis identification tool to enable timely diagnosis and treatment. Performing sepsis phenotyping and creating digital twin patient models to predict personalized treatment responses....
This $294,244 Project Grant award, funded by the Department of Health and Human Services (DHHS) Agency for Healthcare Research and Quality (AHRQ) under the Research on Healthcare Costs, Quality and Outcomes (CFDA 93.226) program, supports research to identify sepsis phenotypes associated with antibiotic-resistant pathogens. The project aims to leverage machine learning techniques, including large language models applied to clinical notes, to augment electronic health record (EHR) data and define...
This Project Grant awarded by the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $197,640 to The General Hospital Corporation (doing business as Massachusetts General Hospital) to investigate the role of a novel monocyte transcriptional state, termed "monocyte substate 1" (MS1), in the immunopathogenesis and patient heterogeneity of sepsis. The 5-year project will apply single-cell RNA...
This Project Grant award of $186,221 from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 - Allergy and Infectious Diseases Research) supports research to develop personalized sepsis therapeutics for pediatric patients. The key objectives are to: 1) Augment sepsis phenotypes using high-frequency physiologic data to identify additional subtypes and predict disease progression; 2) Retrospectively identify signs of bloodstream infection prior to traditional diagnostic signs...
The University of California, San Diego (UCSD) received a $312,974 Project Grant award from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859) to develop accurate, efficient, and interpretable multi-modal foundation models for the early detection of sepsis. Over the 5-year project period from February 1, 2025 to January 31, 2030, UCSD will focus on several key objectives: curating large-scale electronic health...
VALIDATION AND EARLY DEVELOPMENT OF A BLOOD-BASED RAPID DIAGNOSTIC TEST FOR SEPSIS ENDOTYPES - ABSTRACT SEPSIS, A SYSTEMIC INFLAMMATORY CONDITION, OCCURS AS A COMPLICATION OF INFECTION AND IN SEVERE CASES MAY BE ASSOCIATED WITH ACUTE AND LIFE-THREATENING ORGAN DYSFUNCTION. IN THE US ALONE, SEPSIS CLAIMS ~270,000 LIVES EACH YEAR AMONG ~1.7 MILLION PATIENTS DIAGNOSED ANNUALLY, AND GLOBALLY, SEPSIS-RELATED MORTALITY IS ESTIMATED TO ACCOUNT FOR 20% OF TOTAL DEATHS. ALTHOUGH IMPROVEMENTS IN THE TREATMENT PROTOCOL FOR SEPSIS AND TIMELY ADMINISTRATION OF ANTIBIOTICS HAVE REDUCED MORTALITY RATES, NOT A SINGLE DRUG FOR SEPSIS HAS EVER BEEN SUCCESSFULLY BROUGHT TO MARKET, DESPITE OVER 100 INTERVENTIONAL TRIALS, AND IT IS TREATED TODAY AS 60 YEARS AGO: ANTIBIOTICS AND SUPPORTIVE CARE. SEPSIS IS UNUSUAL IN THAT A GREAT DEAL OF THE IMMUNE RESPONSE IS ACTUALLY ADAPTIVE (BENEFICIAL) VS. DISEASE-CAUSING (MALADAPTIVE), SO REVERSING THE INFLAMMATORY RESPONSE CAN CAUSE THE INFECTION TO GO UNCHECKED. WE BELIEVE THAT A TREATMENT SHOULD REVERSE THE MALADAPTIVE (ORGAN-DAMAGING) COMPONENTS OF THE IMMUNE RESPONSE, WHILE KEEPING THE ADAPTIVE (PATHOGEN-FIGHTING) COMPONENTS INTACT. WE BELIEVE THAT TO ACHIEVE IMPACTFUL PROGRESS, NEW APPROACHES ARE REQUIRED THAT HARNESS IMMUNE SUB-GROUPS. IN THIS PROJECT, WE PROPOSE A PRECISION MEDICINE APPROACH TO SUBDIVIDE SEPSIS PATIENTS INTO TREATABLE SUBCLASSES OR "ENDOTYPES" USING A COMPANION DIAGNOSTIC TEST, HOSTDX-ENDOTYPES. WE ANTICIPATE THAT CLASSIFYING SEPSIS PATIENTS INTO SUCH ENDOTYPES MAY ALLOW US TO IDENTIFY IMPROVED TREATMENT REGIMENS, LEADING TO THE DISCOVERY OF NEW TARGETS OR PATHWAYS FOR ENDOTYPE-SPECIFIC THERAPIES AND/OR REPURPOSING OF AVAILABLE DRUGS. IN PHASE 1 WORK WE ALREADY DEMONSTRATED PROOF-OF-CONCEPT BY IDENTIFYING 3 SEPSIS ENDOTYPES (INFLAMMOPATHIC, ADAPTIVE, AND COAGULOPATHIC) AND VALIDATED ACROSS MULTIPLE EXTERNAL DATA SETS. WE HAVE SHOWN THAT OUR HOSTDX ENDOTYPES CAN STRATIFY PATIENTS INTO NOVEL, POTENTIALLY TREATABLE SUBGROUPS ACROSS 3 PUBLICATIONS USING SEVERAL RETROSPECTIVE COHORTS, AND TWO PROSPECTIVE COHORTS. WE HAVE ALSO DEMONSTRATED THE CLINICAL UTILITY OF THIS PARADIGM WITH INSEPTM, OUR ROBUST CLASSIFIER FOR ACUTE INFECTIOUS DISEASE, BASED ON OUR HOSTDX POINT OF CARE TEST SYSTEM PLATFORM. TO BRIDGE OUR PROOF-OF-CONCEPT WORK TO PRODUCT DEVELOPMENT FOR HOSTDX-ENDOTYPES, WE WILL (AIM 1) EMPLOY RIGOROUS MACHINE LEARNING ALGORITHMS AND PROCESSES TO FINALIZE AND LOCK AN OPTIMAL CLASSIFIER; (AIM 2) APPLY AN INNOVATIVE APPROACH OF DRUG REPURPOSING TO IDENTIFY AND RANK-ORDER ENDOTYPE-SPECIFIC DRUG CANDIDATES FOR CLINICAL STUDIES ON SEPSIS TREATMENT, AND (AIM 3) TRANSLATE THE FINAL MRNA PANEL TO INFLAMMATIX'S QLAMP CARTRIDGE AND PLATFORM. AT PHASE II COMPLETION WE WILL HAVE PRODUCED THE HOSTDX ENDOTYPES RESEARCH-READY CARTRIDGE, TOGETHER WITH A LIST OF REPURPOSED DRUGS FOR INTENDED CLINICAL TRIALS, AND WILL BE READY TO ENTER THE FORMAL PRODUCT DEVELOPMENT PHASE; WE WILL HAVE INITIATED THE FDA PRE-SUBMISSION. ULTIMATELY, THE GOAL OF THIS PRODUCT WILL BE TO DEFINITIVELY LINK A PATIENT SEPSIS ENDOTYPE WITH A THERAPEUTIC INTERVENTION, TO ENABLE BETTER THERAPY SELECTION AND RESOURCE ALLOCATION.