SBIR-STTR Award

Direct to Phase II

Infective Endocarditis (IE) occurs when bacteria or fungi adhere to the endocardial surface forming small lesions. This invasive disease is characterized by a mortality rate exceeding 25%, is associated with extended hospitalization, and often impairs the quality of life for those who survive. Early microbial diagnosis and antimicrobial intervention are crucial to improved patient outcomes and reduced hospitalization time. However, currently accepted diagnostic approaches still rely on primary blood culture, which exhibits long and variable turnaround times and can provide false-negative results. There is therefore a significant need for new diagnostic approaches that do not require culture and provide faster, more accurate results. To address this unmet need, HelixBind developed RaPID/IE, a fully automated sample-to-answer test which identifies and characterizes these infections directly from blood in ~3 hours, without cultures. Implemented on the RaPID (Resistance and Pathogen IDentification) platform and appropriate for placement throughout the hospital, RaPID/IE incorporates a broad test menu including both bacterial and fungal pathogens, as well as a marker of antimicrobial resistance. Crucially, the test is not compromised by prior antimicrobial treatment and provides species level detail with single CFUs/ml sensitivity, enabling selection of appropriate antimicrobials. Commercialization of RaPID/IE will provide timely identification and characterization of the invasive agent and thus enable intervention with targeted antimicrobial treatment. This is expected to result in improved patient outcomes and a reduction in the use of unnecessary antimicrobials, slowing the rise of antimicrobial resistance. HelixBind has met and exceeded all the Specific Aims defined in the Phase II SBIR. This included menu expansion to cover antibiotic resistance as well as pathogens associated with IE which cannot be recovered by clinical cultures, automation of the assay onto single-use disposables operated by a benchtop instrument, and testing of clinical specimens. Clinical results demonstrate a sensitivity and specificity of 92.7% and 98.8%, respectively. In addition, based on feedback from potential customers, the test menu was expanded further to include coverage of pathogens associated with conditions sharing symptoms with IE. The disposable and instrument were transitioned to manufacturing and extensive analytical testing was performed to ensure the assay meets specifications associated with regulatory and market requirements. In this CRP program, HelixBind will build on our success in Phase II to prepare for regulatory clearance and market launch. This includes (1) development of analytical methods, based on FDA feedback, required to successfully complete analytical and clinical validation studies; and (2) development of scalable manufacturing processes for certain reagent sets to ensure 12-month, room temperature stability, of tests cassettes, and (3) completion of an on-site analytical evaluation and blinded, clinical assessment study. Upon completion of this project, we will be well placed to initiate formal analytical and clinical studies for FDA clearance of RaPID/IE.

Public Health Relevance Statement:
NARRATIVE Infective Endocarditis is a life-threatening disease and a significant economic burden due to prolonged intensive treatment. Early identification of the microbial infection is crucial to improving outcomes, but current standards relying on blood cultures are slow and often yield false-negative results. This prevents the administration of evidence-based antimicrobials precisely when they are maximally beneficial. The efforts described in this Commercialization Readiness Pilot program proposal will advance the maturity of a novel, fully automated test capable of identifying and characterizing these infections directly from patient blood in only a few hours. Success in this effort will result in a critically needed diagnostic, ready for manufacturing scale up as required for FDA trials and market launch. Terms: