Photo Courtesy: © 2020 Karius Inc.
Photo of Karius' Lab technology in Redwood City, California. Courtesy: © 2020 Karius Inc.

Karius, the world leader in non-invasive liquid biopsy for infectious diseases designed helps clinicians make rapid treatment decisions, secured US $ 165 million in new (Series B) funding.

The funding round was led by SoftBank Vision Fund 2, with additional participation from General Catalyst, HBM Healthcare Investments, and existing investors Khosla Ventures and LightSpeed Venture Partners.

Liquid biopsies are a powerful technique that has been applied to different stages of cancer screening and treatment. In the asymptomatic population, liquid biopsies have been used to identify cancer patients to improve early diagnosis,  leading to better interventions.

While liquid biopsies have been used to establish the cancer genetic status of patients based on circulating tumor DNA (ctDNA), circulating tumor cells, or other tumor-derived materials in blood plasma, Karius pioneered the development and application in infectious diseases by measuring microbial cell-free DNA (mcfDNA), enabling non-invasive detection of pathogens throughout the body with its Karius® Test, which is used in over 100 hospitals and health systems nationwide.

Photo Courtesy: © 2020 Karius Inc.

Transformative
“This transformative [funding] round will allow Karius to help more patients faster, fuel the next wave of clinical studies, and accelerate technology innovation,” said Mickey Kertesz, Ph.D., Chief Executive Officer at Karius.

Using part of the funds, Karius is expected to further expand its proprietary technology to help doctors diagnose infectious diseases, broaden clinical development, and accelerate technology innovation.

“We are humbled to be part of the team that delivered the first clinical applications of microbial cell-free DNA and we’re excited about what’s ahead for Karius,” Kertesz added.

A novel approach
Microbes infecting different parts of the human body leave traces of their DNA in blood, known as microbial cell-free DNA.

Karius’ test uses next-generation sequencing, based on novel genomics and Artificial Intelligence (AI), to identify, measure and quantify microbial cell-free DNA (mcfDNA) from more than 1,250 clinically relevant bacteria, DNA viruses, fungi and eukaryotic parasites from a single blood draw.  The results help inform doctors about the likely types and quantities of infectious microorganisms affecting their patients.

The company’s test delivers results typically the day after the company’s laboratory receives the blood sample, allowing doctors to better diagnose and treat their patients.

“Infections are a leading cause of death for patients with leukemia in the United States,” Said Karius Senior Medical Director, Asim Ahmed, MD.

“Because our Karius Test® can not only rapidly detect infectious pathogens, but can also measure their quantity, [we] can help doctors quickly target and track treatment for patients,” Ahmed added.

Cause of death
“Infectious diseases are the second leading cause of deaths worldwide. Karius’ innovative mcfDNA technology accurately diagnoses infections that cannot be determined by other existing technologies,” said Deep Nishar, Senior Managing Partner at SoftBank Investment Advisers.

“We are excited to support Karius and their mission to use genomic insights to fight infectious diseases and save lives,” Nishar noted.

“Next-generation sequencing (NGS) has already transformed diagnostics through non-invasive prenatal testing and liquid biopsies for oncology,” said Chandra P. Leo, Investment Advisor at HBM Partners.

“Karius is now applying the power of NGS of microbial cell-free DNA to the field of infectious disease diagnostics, helping physicians to non-invasively identify a broad range of pathogens in severely ill patients,” Leo observed.

Clinical validation
In 2018 researchers at St. Jude Children’s Research Hospital confirmed that the initial phase of a study of high-risk pediatric leukemia patients vulnerable to serious, life-threatening infections, demonstrated positive results. [1]

The majority of children and adolescents diagnosed with cancer will experience one or more episodes of fever or infection during their course of therapy. The most common microbiologically documented infection is bloodstream infection (BSI), which can be associated with severe sepsis or death.

Current methods of diagnosis require a significant load of live bacteria in the blood making early very detection difficult. Delayed diagnosis and delayed optimal therapy of BSIs are associated with increased morbidity and mortality.

The objective of the study (PREDSEQ; NCT03226158) was to estimate the sensitivity and specificity of next-generation sequencing (NGS) of pathogens for the prediction of bloodstream infection in children with cancer at high risk of infection.

As part of this study, researchers at St. Jude enrolled 31 pediatric patients receiving treatment for relapsed or refractory malignancy at high risk of serious infection in an institutional review board (IRB-) approved prospective cohort study and sent blood samples to the Karius laboratory.

Episodes of febrile neutropenia, diagnosed as the development of fever, often with other signs of infection, in a patient with neutropenia, an abnormally low number of neutrophil granulocytes (a type of white blood cell) in the blood, or documented infection were collected prospectively from medical records. Bloodstream infection was defined according to the criteria of the CDC’s National Healthcare Safety Network (NHSN).[1]

In this study, control samples were defined as samples collected ≥7 days before or after any fever or documented infection. After filtering human sequences, reads were aligned to a curated pathogen database, and organisms above a statistically significant threshold were reported by Karius.

As part of this study, a total of 11 BSI episodes occurred in 9 participants during the study period. Predictive sensitivity of NGS in the 2 days before onset of infection (n = 9) was 78% (95% CI 40 – 99.7%), and diagnostic sensitivity on the day of infection (n = 11) was 82% (48 – 98%).[1]

The specificity of NGS for the development of fever or infection within 7 days (n = 10) was 80% (95% CI 44 – 98%). NGS was positive up to 6 days prior to the onset of BSI. In samples collected before or during documented infections, NGS also identified multiple additional uncultured bacteria and fungi.

These results were the first step to determining whether the detection of pathogen DNA in blood could be used as a monitoring tool to enable pre-emptive antimicrobial treatment of bloodstream infections in high-risk pediatric cancer patients. If successful, the scientist determined, this approach could reduce the serious consequences of bloodstream infections in these patients while also limiting their use of prophylactic antibiotics.

Based on the test results, researchers at St. Jude Children’s Research Hospital are confinced that this test demonstrates Karius’ ability identify bloodstream infections prior to clinical symptoms.

“Our leukemia treatment protocols are now curing a high percentage of children, making addressing the infectious complications of their treatment even more important as we aim to further increase survival rates,” noted Charles Gawad, MD, Ph.D., a leukemia specialist and assistant faculty member at the Departments of Oncology and Computational Biology at St. Jude Children’s Research Hospital.

“This study shows that it may be possible to reduce these complications with the purposeful application of this exciting new technology,” Gawad concluded.

Other results
Last year, the journal Nature Microbiology published the analytical and clinical validation of Karius’ test demonstrating a 93.7% agreement with blood culture in a cohort of 350 patients with a sepsis alert and identified the likely pathogens in an independently adjudicated cause of the sepsis alert more often than all of the microbiological (standard) testing combined. [2]

Other published studies have also presented real-world clinical utility of the Karius Test in various populations with serious illnesses.

For example, immunocompromised patients are vulnerable to a wide variety of severe infections and frequently require invasive procedures to identify the pathogen. In a recent study of immunocompromised pediatric patients, Karius non-invasively identified the pathogen causing infection more frequently than invasive procedures, and even more frequently than all microbiological tests combined. Nearly two-thirds of the invasive diagnostic procedures performed in these pediatric patients might have been avoided based on Karius’ test results.

Additional publications support the use of Karius® Test in other applications including complex pneumonia, invasive fungal infections, and endocarditis.

These studies demonstrate the value of mcfDNA to help clinicians rapidly make critical treatment decisions.

Clinical trial
Next Generation Pathogen Sequencing for Prediction of Adverse Events (NCT03226158)

Reference
[2] Goggin K, Inaba Y, Gonzalez-Pena V, Allison KJ, Lok Chan K, Hollemon D, Ahmed A, Hong D, M Prediction of Bloodstream Infection Prior to Onset of Symptoms by Plasma Metagenomic Sequencing in Pediatric Patients With Relapsed or Refractory Malignancy (PREDSEQ), Open Forum Infectious Diseases, Volume 5, Issue suppl_1, November 2018, Page S60, https://doi.org/10.1093/ofid/ofy209.141 [Article]
[1] Blauwkamp TA, Thair S, Rosen MJ, et al. Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease. Nat Microbiol. 2019;4(4):663–674. doi:10.1038/s41564-018-0349-6 [Article]