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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 10-K

 

(Mark One)

ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the year ended December 31, 2020

TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the transition period from to            

Commission File Number: 001-36571

 

T2 Biosystems, Inc.

(Exact name of registrant as specified in its charter)

 

 

Delaware

 

20-4827488

(State or other jurisdiction of

incorporation or organization)

 

(I.R.S. Employer

Identification No.)

 

 

 

101 Hartwell Avenue, Lexington, MA

 

02421

(Address of principal executive offices)

 

(Zip code)

 

Registrant’s telephone number, including area code: 781-761-4646

Securities registered pursuant to Section 12(b) of the Act

Title of each class

 

Trading

Symbol(s)

 

Name of each exchange on which registered

Common Stock, par value $0.001

 

TTOO

 

The Nasdaq Global Market

 

 

Securities registered pursuant to Section 12(g) of the Act: None

 

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act of 1933, as amended.    Yes      No  

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Securities Exchange Act of 1934, as amended.    Yes       No  

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports) and (2) has been subject to such filing requirements for the past 90 days.    Yes      No  

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).    Yes      No  

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See definitions of “large accelerated filer,” “accelerated filer” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

 

Large accelerated filer

 

  

Accelerated filer

 

Non-accelerated filer

 

 

  

Smaller reporting company

 

 

 

 

 

Emerging growth company

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report.  

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act).    Yes       No  

As of June 30, 2020, the last business day of the registrant’s most recently completed second fiscal quarter, the aggregate market value of the registrant’s common stock held by non-affiliates was approximately $147.9 million based on the closing price for the common stock of $1.27 on that date. Shares of common stock held by each executive officer, director, and their affiliated stockholders have been excluded from this calculation as such persons may be deemed to be affiliates. This determination of affiliate status is not necessarily a conclusive determination for other purposes.

The number of outstanding shares of the registrant’s common stock on March 26, 2021 was 148,491,673.

 

DOCUMENTS INCORPORATED BY REFERENCE

None.

 

 

 


 

 

TABLE OF CONTENTS

 

 

 

 

 

Page

PART I.

 

 

 

 

 

 

 

 

 

Item 1.

 

Business

 

4

 

 

 

 

 

Item 1A.

 

Risk Factors

 

33

 

 

 

 

 

Item 1B.

 

Unresolved Staff Comments

 

59

 

 

 

 

 

Item 2.

 

Property

 

59

 

 

 

 

 

Item 3.

 

Legal Proceedings

 

59

 

 

 

 

 

Item 4.

 

Mine Safety Disclosures

 

59

 

 

 

 

 

PART II.

 

 

 

 

 

 

 

 

 

Item 5.

 

Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities

 

60

 

 

 

 

 

Item 6.

 

[Reserved]

 

60

 

 

 

 

 

Item 7.

 

Management’s Discussion and Analysis of Financial Condition and Results of Operations

 

60

 

 

 

 

 

Item 7A.

 

Quantitative and Qualitative Disclosures about Market Risk

 

71

 

 

 

 

 

Item 8.

 

Financial Statements and Supplementary Data

 

72

 

 

 

 

 

Item 9.

 

Changes in and Disagreements with Accountants on Accounting and Financial Disclosure

 

103

 

 

 

 

 

Item 9A.

 

Controls and Procedures

 

103

 

 

 

 

 

Item 9B.

 

Other Information

 

104

 

 

 

 

 

PART III.

 

 

 

 

 

 

 

 

 

Item 10.

 

Directors, Executive Officers and Corporate Governance

 

105

 

 

 

 

 

Item 11.

 

Executive Compensation

 

108

 

 

 

 

 

Item 12.

 

Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters

 

115

 

 

 

 

 

Item 13.

 

Certain Relationships and Related Transactions, and Director Independence

 

117

 

 

 

 

 

Item 14.

 

Principal Accountant Fees and Services

 

119

 

 

 

 

 

 

 

 

 

 

PART IV.

 

 

 

 

 

 

 

 

 

Item 15.

 

Exhibits and Financial Statement Schedules

 

119

 

 

 

 

 

Item 16.

 

Form 10-K Summary

 

124

 

 

 

 

 

 

 

 

 

 

 

 

Signatures

 

125

 

 

 

 

 

 

 

 

1

 


 

FORWARD-LOOKING STATEMENTS

This Annual Report on Form 10-K contains forward-looking statements about us and our industry that involve substantial risks and uncertainties. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, or the Exchange Act. All statements other than statements of historical facts contained in this Annual Report on Form 10-K, including statements regarding our future results of operations and financial position, business strategy, prospective products and product candidates, their expected performance and impact on healthcare costs, marketing clearance from the U.S. Food and Drug Administration, or the FDA, regulatory clearance, reimbursement for our product candidates, research and development costs, timing of regulatory filings, timing and likelihood of success, plans and objectives of management for future operations and future results of anticipated products, are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “forecast,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this Annual Report on Form 10-K are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition and results of operations. These forward-looking statements speak only as of the date of this Annual Report on Form 10-K and are subject to a number of risks, uncertainties and assumptions described under the sections in this Annual Report on Form 10-K entitled “Item 1A.—Risk Factors”. Unless required by U.S. federal securities laws, we do not intend to update any of these forward-looking statements to reflect circumstances or events that occur after the statement is made or to conform these statements to actual results.

Summary of Principal Risk Factors

We operate in a rapidly changing environment that involves a number of risks, some of which are beyond our control. In evaluating our company, you should consider carefully the summary risks and uncertainties described below together with the other information included in this Annual Report on Form 10-K, including our consolidated financial statements and related notes included in Part II, Item 8, "Financial Statements and Supplementary Data" in this Annual Report on Form 10-K. The occurrence of any of the following risks may materially and adversely affect our business, financial condition, results of operations and future prospects.

 

 

our ability to continue as a going concern;

 

our status as an early commercial-stage company;

 

our expectation to incur losses in the future;

 

the market acceptance of our T2MR technology;

 

our ability to timely and successfully develop and commercialize our existing products and future product candidates;

 

the length and variability of our anticipated sales and adoption cycle;

 

our relatively limited sales history;

 

our ability to gain the support of leading hospitals and key thought leaders and publish the results of our clinical trials in peer-reviewed journals;

 

our ability to successfully manage our growth;

 

our future capital needs and our ability to raise additional funds;

 

the performance of our diagnostics;

 

our ability to compete in the highly competitive diagnostics market;

 

our ability to obtain marketing clearance from the FDA or regulatory clearance for new product candidates in the United States or any other jurisdiction;

 

impacts of and delays caused by future federal government shutdowns;

 

federal, state, and foreign regulatory requirements, including diagnostic product reimbursements and FDA regulation of our products and product candidates;

 

our ability to protect and enforce our intellectual property rights, including our trade secret-protected proprietary rights in T2MR;

 

our ability to recruit, train and retain key personnel;

 

our dependence on third parties;

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manufacturing and other product risks;

 

the impact of the adoption of new accounting standards;

 

the impact of cybersecurity risks, including ransomware, phishing, and data breaches on our information technology systems;

 

the impact of short sellers and day traders on our share price;

 

the impact of cost-cutting measures;

 

unforeseen interruptions in our supply chain;

 

our ability to maintain compliance with Nasdaq listing requirements;

 

the Tax Cuts and Jobs Act of 2017 (Tax Reform) and the impact of future tax legislation;

 

the impact of the COVID-19 pandemic on our business, results of operations and financial positions; and

 

the continued market demand for SARS-CoV-2 testing and our ability to convert T2SARS-CoV-2 customers to our other test panels.

 

3

 


 

 

PART I.

Item 1.

BUSINESS

Overview

We are an in vitro diagnostics company and leader in the rapid detection of sepsis-causing pathogens, and are dedicated to improving patient care and reducing the cost of care by helping clinicians effectively treat patients faster than ever before. We have developed an innovative and proprietary technology platform that offers a rapid, sensitive and simple alternative to existing diagnostic methodologies. We are using our T2MR technology to develop a broad set of applications aimed at lowering mortality rates, improving patient outcomes and reducing the cost of healthcare by helping medical professionals make targeted treatment decisions earlier. T2MR enables rapid detection of pathogens, biomarkers and other abnormalities in a variety of unpurified patient sample types, including whole blood, plasma, serum, saliva, sputum and urine, and can detect cellular targets at limits of detection as low as one colony forming unit per milliliter, or CFU/mL. Our products include the T2Dx Instrument, T2Candida Panel, the T2Bacteria Panel, the T2Resistance Panel, and the T2SARS-CoV-2 Panel that are all powered by our proprietary T2MR technology. Our development efforts target sepsis, which is an area of significant unmet medical need in which existing therapies could be more effective with improved diagnostics.

On September 22, 2014, we received market clearance from the FDA for our first two products, the T2Dx® Instrument, or the T2Dx and the T2Candida® Panel, or T2Candida, which have the ability to rapidly identify the five clinically relevant species of Candida, a fungal pathogen known to cause sepsis, directly from whole blood. On May 24, 2018, we received market clearance from the FDA for the T2Bacteria® Panel, or T2Bacteria, which runs on the T2Dx Instrument and has the ability to rapidly identify five of the most common and deadly sepsis-causing bacteria directly from whole blood. We have also developed and sell a research use only Candida auris assay, the T2Cauris™ Panel, for the rapid identification of Candida auris, a species of Candida that is highly drug resistant. We have developed a T2Resistance™ Panel for the early and sensitive detection of resistance markers, which can assist clinicians in selecting effective antibiotics. The T2Resistance Panel received FDA Breakthrough Device designation in February 2019 and was granted a CE Mark in November 2019. An additional diagnostic application in development is the T2Lyme™ Panel, or T2Lyme, which is focused on the detection of the bacteria that cause Lyme disease. Diagnostic applications for additional bacteria species and resistance markers were developed as part of a collaboration with CARB-X, a public-private partnership with the U.S. Department of Health and Human Services, or HHS, and the Wellcome Trust of London, focused on combatting antibiotic resistant bacteria. On August 2, 2019, the Centers for Medicare & Medicaid Services, or CMS, granted approval for a New Technology Add-on Payment (NTAP) for the T2Bacteria Panel for fiscal year 2020 and in September 2020, CMS extended the approval for 2021. In September 2019, the Biomedical Advanced Research and Development Authority (“BARDA”) awarded us a milestone-based contract, with an initial value of $6 million, and a potential value of up to $69 million, for the development of new direct-from-blood diagnostic panels that will run on the T2Dx. In September 2020, BARDA exercised the first contract option valued at $10.5 million. On June 30, 2020, we announced the U.S. launch of our COVID-19 molecular diagnostic test, the T2SARS-CoV-2 Panel, after validation of the test meeting the FDA’s requirements for an Emergency Use Authorization (EUA). In August 2020, the FDA issued EUA for the T2SARS-CoV-2 Panel. The test is designed to detect the presence of the SARS-CoV-2 virus extracted from a nasopharyngeal swab sample. The existing reimbursement codes support our sepsis products and anticipate the same for our Lyme disease product candidates. In 2020, CMS authorized Medicare fixed reimbursement to Clinical Laboratory Improvement Amendments, or CLIA, certified laboratories for materials and services to perform COVID testing. The T2SARS-CoV-2 Panel is covered under this reimbursement. The economic savings associated with our sepsis products are realized directly by hospitals. In the United States, we have a commercial team that is primarily targeting hospitals with the highest concentration of patients at risk for sepsis-related infections. Internationally, we have primarily partnered with distributors that target large hospitals in their respective international markets.

Sepsis is one of the leading causes of death in the United States, claiming more lives annually than the top three cancers combined: lung, colorectal and breast cancer, and it is the most expensive hospital-treated condition. Most commonly afflicting immunocompromised, critical care, and elderly patients, sepsis is a severe inflammatory response to a bacterial or fungal infection with a mortality rate of approximately 30%. Based on a 2020 study from the Department of Health and Human Services (HHS), it was estimated that the annual cost of sepsis to the US healthcare system was $62 billion. The rate of Medicare beneficiaries hospitalized with sepsis has increased by 40% over from 2012 to 2018, the HHS study found. The CDC estimates that sepsis causes more than 270,000 American deaths per year. Sepsis is typically caused by one or more of five Candida species or over 25 bacterial pathogens, and effective treatment requires the early detection and identification of these specific target pathogens in a patient’s bloodstream. Today, sepsis is typically diagnosed through a series of blood cultures followed by post-blood culture species identification if a blood culture tests positive. These methods have substantial diagnostic limitations that lead to a high rate of false negative test results, a delay of up to several days in administration of targeted treatment, and the incurrence of unnecessary hospital expense. In addition, the Survey of Physicians’ Perspectives and Knowledge About Diagnostic Tests for Bloodstream Infections in 2015 reported that negative blood culture results are only trusted by 36% of those physicians. Without the ability to rapidly identify pathogens, physicians typically start treatment of at-risk patients with broad-spectrum antibiotics and switch therapies every 12 to 24 hours if a patient is not responding. These drugs, which can be costly, are often ineffective and unnecessary and have contributed to the spread of antimicrobial resistance. The speed to getting the patient on the right targeted therapy is critical. According to a study published by Critical Care Medicine in 2006, in sepsis patients with documented hypotension, administration of effective antimicrobial therapy within the first hour of detection was associated with a survival rate of 79.9% and, over the ensuing six hours, each hour of delay in initiation of treatment was associated with an average decrease in survival of 7.6%.

4

 


 

Candida is the fourth leading hospital-acquired bloodstream infection, afflicting more than 135,000 patients per year in the United States, and the most lethal form of common bloodstream infections that cause sepsis, with an average mortality rate of approximately 40%. This high mortality rate is largely due to a delay in providing targeted therapy to the patient due to the elapsed time from Candida infection to positive diagnosis. According to a study published in Antimicrobial Agents and Chemotherapy, the Candida mortality rate can be reduced to 11% with the initiation of targeted therapy within 12 hours of presentation of symptoms. Additionally, a typical patient with a Candida infection averages 40 days in the hospital, including nine days in intensive care, resulting in an average cost per hospital stay of more than $130,000 per patient. In a study published in the American Journal of Respiratory and Critical Care Medicine, providing targeted antifungal therapy within 24 hours of the presentation of symptoms decreased the length of hospital stay by approximately ten days and decreased the average cost of care by approximately $30,000 per patient.

We believe our sepsis products, which include T2Candida, T2Bacteria, T2Resistance, and T2Cauris, will redefine the standard of care in sepsis management while lowering healthcare costs by improving both the precision and the speed to detection of sepsis-causing pathogens. According to a study published in the Journal of Clinical Microbiology in 2010, targeted therapy for patients with bloodstream infections can be delayed up to 72 hours due to the wait time for blood culture results. In another study published in Clinical Infectious Diseases in 2012, the delayed administration of appropriate antifungal therapy was associated with higher mortality among patients with septic shock attributed to Candida infection and, on that basis, the study concluded that more rapid and accurate diagnostic techniques are needed.

Our pivotal clinical trial for T2Candida demonstrated that it can deliver actionable results in as few as three hours, with an average time to result during the trial of 4.2 hours, compared to the average time to result of one to six or more days typically required for blood-culture-based diagnostics and the pivotal clinical trial for T2Bacteria demonstrated that it can deliver actionable results in an average of 5.4 hours, compared to an average of 60 hours for detecting the same species by blood culture. We believe the speed of the T2Candida and T2Bacteria tests will enable physicians to potentially make treatment decisions and administer targeted treatment to patients in four to six hours versus 24 to 144 hours for blood culture. Furthermore, in April 2015, Future Microbiology published the results of an economic study regarding the use of T2Candida conducted by IMS Health, a healthcare economics agency. In that economic study, IMS demonstrated that an average hospital admitting 5,100 patients at risk for Candida infections could save approximately $5.8 million annually due to decreased hospital stays for patients, reduction in use of antifungal drugs and other associated savings. The economic study further showed T2Candida can potentially reduce the costs of care by $26,887 per Candida patient and that rapid detection of Candida reduces patient deaths by 60.6%. Results from a data analysis of T2Candida for the detection and monitoring of Candida infection and sepsis were published comparing aggregated results from the use of T2Candida to blood culture-based diagnostics for the detection of invasive candidiasis and candidemia. The analysis included samples acquired from more than 1,900 patients. Out of 55 prospective patient cases that were tested with T2Candida and blood culture and determined to be positive or likely to be positive for a Candida infection, T2Candida detected 96.4% of the patients (53 cases) compared to detection of 60% of the patients (33 cases) with blood culture.

In addition, due to the high mortality rate associated with Candida infections, physicians often will place patients on antifungal drugs while they await blood culture diagnostic results which generally take at least five days to generate a negative test result. Antifungal drugs are toxic and may result in side effects and can cost over $50 per day. The speed to result of T2Candida and T2Bacteria coupled with their higher sensitivity as compared to blood culture may help reduce the overuse of ineffective, or even unnecessary, antimicrobial therapy which may reduce side effects for patients, lower hospital costs and potentially counteract the growing resistance to antifungal therapy. The administration of inappropriate therapy is a driving force behind the spread of antimicrobial-resistant pathogens, which the United States Centers for Disease Control and Prevention, or the CDC, recently called “one of our most serious health threats.” The addition of the use of our products, T2Bacteria and T2Candida, which both run on the T2Dx Instrument, with the standard of care for the management of patients suspected of sepsis, enables clinicians to potentially treat 90% of patients with sepsis pathogen infections with the right targeted therapy within the first twelve hours of development of the symptoms of disease. Currently, high risk patients are typically initially treated with broad spectrum antibiotic drugs that typically cover approximately 60% of patients with infections. Of the remaining 40% of patients, approximately 30% of the patients typically have a bacterial infection and 10% typically have Candida infections. T2Candida and T2Bacteria are designed to identify pathogens commonly not covered by broad spectrum antibiotic drugs.

Our Strategy

T2MR enables rapid and sensitive direct detection of a range of targets, and we believe it can be used in a variety of diagnostic applications that will improve patient outcomes and reduce healthcare costs. Our objective is to establish T2MR as a standard of care for clinical diagnostics. To achieve this objective, our strategy is to:

 

Sell T2Dx Instruments to Establish a Recurring, Consumables-Based Business. We are pursuing a consumables-based business model for our products by building an installed base of T2Dx Instruments at hospitals and driving utilization of our diagnostic panels, including T2Candida, T2Bacteria, and T2Resistance. We believe this strategy will foster a sustainable and predictable business model with recurring revenue streams.

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Drive Further Commercial Adoption of Our Sepsis Products. We expect our sepsis products to meaningfully improve patient outcomes while reducing costs to hospitals. We have established a direct sales force in the United States, and have partnered with distributors internationally, to demonstrate our clinical and economic value proposition to hospitals that have the highest populations of at-risk critical care and immunocompromised patients. We believe a sustained focus on these hospitals will drive adoption of the T2Dx Instrument, T2Candida, T2Bacteria, T2Resistance and future T2MR-based diagnostics. As a part of this effort, we will continue to work with thought leaders, conduct clinical and health economic studies and seek publication and presentation of these studies.

 

Convert T2SARS-CoV-2 Customer to Our Core Sepsis Test Products. In 2020, with the commercial launch of our molecular diagnostic test for COVID-19, the T2SARS-CoV-2 Panel, we initiated a targeted market penetration strategy to sell T2Dx Instruments and T2SARS-CoV-2 tests to U.S hospitals. We strategically focused on U.S. hospitals treating critical care patients including both COVID-19 patients and sepsis patients. While most of these instruments sold during 2020 were dedicated to COVID-19 testing, our strategy is to convert these new U.S. hospital accounts to our sepsis test panels.

 

Broaden Our Addressable Markets in Infectious Disease.  Our product development pipeline includes additional diagnostic panels that provide near-term and complementary market expansion opportunities. We will seek to expand our panels through partnerships to share the costs of our development of certain additional products, as well as through funding from other non-dilutive and government sources. We also are utilizing T2MR to address the challenges of providing a rapid and sensitive diagnosis of Lyme disease.

 

Broaden Our Addressable Markets Beyond Infectious Disease.  We may expand our product offerings by applying T2MR to new applications beyond sepsis and Lyme disease. We may conduct internal development and will continue to work with thought leaders, physicians, clinical researchers and business development partners to pursue new applications for T2MR. We believe the benefits of our proprietary technology, including the ability to rapidly and directly detect a broad range of targets, in a wide variety of sample types, may have potential applications within and outside of the in vitro diagnostics market, including environmental, food safety, industrial and veterinary applications. 

 

Expand International Distribution Channels. We are currently selling the T2Dx Instrument, T2Candida, T2Bacteria, and T2Resistance internationally through distributors that target large hospitals in their respective markets. We intend to continue to expand in international markets through similar distribution channels.  

Our Technology Platform

T2 Magnetic Resonance Technology Overview

We have built an innovative and proprietary technology platform that offers a rapid, sensitive and simple alternative to existing diagnostic methodologies. T2MR is a miniaturized, magnetic resonance-based approach that measures how water molecules react in the presence of magnetic fields. Our proprietary platform is capable of detecting a variety of targets, including:

 

molecular targets, such as DNA;

 

immunodiagnostics targets, such as proteins; and

 

a broad range of hemostasis measurements.

For molecular and immunodiagnostics targets, T2MR utilizes advances in the field of magnetic resonance by deploying particles with magnetic properties that enhance the magnetic resonance signals of specific targets. When particles coated with target-specific binding agents are added to a sample containing the target, the particles bind to and cluster around the target. This clustering changes the microscopic environment of water in that sample, which in turn alters the magnetic resonance signal, or the T2 relaxation signal that we measure, indicating the presence of the target.

We also believe T2MR is the first technology that can rapidly and accurately detect the presence of molecular targets within samples without the need for time- and labor-intensive purification or extraction of target molecules from the sample, such as that required by traditional polymerase chain reaction, or PCR, where 90% or more of the target can be lost. We can eliminate these steps because the T2 relaxation signal is not compromised or disrupted by the sample background, even the highly complex sample background that is present after a target amplification process, such as thermocycling. This enables T2MR’s low limit of detection, such as 1 CFU/mL, compared to the 100 to 1,000 CFU/mL typically required for PCR-based methods. More than 100 studies published in peer-reviewed journals have featured T2MR in a breadth of applications, including the direct detection and measurement of targets in various sample types, such as whole blood, plasma, serum, saliva, sputum and urine. We believe our T2MR technology will have potential applications within and outside of the in vitro diagnostics market, including environmental, food safety, industrial and veterinary applications.

Our Instruments

Utilizing T2MR, we have developed and received FDA marketing clearance for the T2Dx Instrument, a bench-top instrument for detecting pathogens associated with sepsis and Lyme disease, as well as other applications.

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T2Dx

 

 

Our FDA-cleared T2Dx Instrument is an easy-to-use, bench-top instrument that is capable of running a broad range of diagnostic tests and is fully automated from patient sample input to result, eliminating the need for manual workflow steps such as pipetting that can introduce risks of cross-contamination. To operate the system, a tube containing the patient’s sample is snapped onto a disposable test cartridge, which is pre-loaded with all necessary reagents. The cartridge is then inserted into the T2Dx Instrument, which automatically processes the sample and then delivers a diagnostic test result. Test results are displayed on screen and printed out.

By utilizing our proprietary T2MR technology for direct detection, the T2Dx Instrument eliminates the need for sample purification and analyte extraction, which are necessary for other optical-detection devices. Eliminating these sample processing steps increases diagnostic sensitivity and accuracy, enables a broad menu of tests to be run on a single platform, and greatly reduces the complexity of the consumables. The T2Dx Instrument incorporates a simple user interface and is designed to efficiently process up to seven specimens simultaneously.

The panels designed to run on the T2Dx are T2Candida, T2Bacteria, T2Resistance, and T2Cauris, which are focused on identifying life-threatening pathogens associated with sepsis and COVID-19. In 2014 we received FDA market clearance for the T2Dx and T2Candida. In May 2018, we received FDA market clearance for T2Bacteria. In November 2019, we received CE Mark for T2Resistance. In August of 2020, we received FDA EUA clearance for the T2SARS-CoV-2 Panel, which runs on the T2Dx.

Sepsis

Overview

Sepsis is an illness in which the body has a severe, inflammatory response to a bacterial or fungal infection. It is a life-threatening condition to which individuals with weakened immune systems or chronic illnesses are highly susceptible. Sepsis can lead to shock and organ failure, and is a leading cause of death in the United States with a mortality rate of approximately 30%, almost double the mortality rate of acute myocardial infarction, or heart attack. One out of every two hospital deaths in the United States is attributable to sepsis.

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Sepsis is one of the leading causes of death in the United States, claiming more lives annually than the top three cancers combined: lung, colorectal and breast cancer, and it is the most expensive hospital-treated condition. Most commonly afflicting immunocompromised, critical care, and elderly patients, sepsis is a severe inflammatory response to a bacterial or fungal infection with a mortality rate of approximately 30%. Based on a 2020 study from HHS, it was estimated that the annual cost of sepsis to the US healthcare system was $62 billion.  The rate of Medicare beneficiaries hospitalized with sepsis has increased by 40% over from 2012 to 2018, the HHS study found. The CDC estimates that sepsis causes more than 270,000 American deaths per year. The high cost of treating sepsis is primarily driven by the extended hospitalization of patients. We believe there are many effective, targeted therapeutic choices that could reduce overall hospitalization costs if applied earlier, but clinicians need to more rapidly identify the specific sepsis-causing pathogens in order to make more informed, targeted treatment decisions. Today, the diagnostic standard to identify these pathogens is blood culture-based, despite typically requiring one to six or more days to generate species-specific results and despite blood cultures inherent low sensitivity of 50% to 65%.

 

Sepsis contributes to 1 in 5 deaths globally. Virtually all of these patients are rapidly treated with broad-spectrum antibiotic drugs because there is no diagnostic manner for determining the type of infection. Of these 1.35 million patients with sepsis and at high risk for infection, approximately 40% do not respond to broad-spectrum antibiotic treatment. Of these patients that are non-responsive, approximately 25% of them have a Candida infection, with the remaining patients having a bacterial infection. Broad-spectrum antibiotics do not treat these Candida and bacterial infections; therefore more targeted drugs are required.

We estimate that approximately 15 million patients are tested for bloodstream infections in the United States annually. Of these, approximately 8.75 million are at high risk for a Sepsis infection, 90% of whom are at a high risk for a bacterial infection and 10% of whom are at a high risk for a Candida infection. Of these 8.75 million patients, 6.75 million patients present in in-patient settings and an additional 2.0 million present in emergency departments. We believe that our sepsis products have the potential to enable clinicians to make earlier therapeutic decisions that can reduce the mortality rate for sepsis by over 50% and save the hospitals an estimated $12 billion annually by testing all high risk patients with T2Candida and T2Bacteria.

Each year, over 30 million people worldwide are affected by sepsis with approximately 11 million mortalities, according to Rudd et al, (2020). Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. The Lancet, VOLUME 395, ISSUE 10219, P200-211, making sepsis a leading cause of death worldwide.

Limitations of Traditional In Vitro Diagnostics for Sepsis

The current standard for identifying bloodstream infections that cause sepsis requires a series of lengthy and labor-intensive analyses that begin with blood culture. Completing a blood culture requires a large volume of a patient’s blood, typically 20 mLs or more, which is obtained in two 10 mL draws and placed into two blood culture bottles containing nutrients formulated to grow fungi and bacteria. Before blood culture indicates if a patient is infected, pathogens typically must reach a concentration of 1,000,000 to 100,000,000 CFU/mL. This growth process typically takes one to six or more days because the pathogen’s initial concentration in the blood specimen is often less than 10 CFU/mL. A negative test result always requires a minimum of five days. A positive blood culture typically means that some pathogen is present, but additional steps must be performed to identify the specific pathogen in order to provide targeted therapy. These additional steps, which typically must be performed by a highly trained technician, may involve any of (i) a staining procedure for inspection on a microscope slide, (ii) PCR amplification and (iii) mass spectrometry. These steps require a preceding positive blood culture specimen because they need a high concentration of cells generated by the blood culture process for analysis.

For most PCR-based diagnostics, nucleic acid extraction of target cells from the sample is performed to remove inhibitory substances that may interfere with the amplification reaction. While PCR amplifies the target signal, this loss of target cells impairs the ability to detect, resulting in typical limits of detection of 100 to 1,000 CFU/mL, which is insufficient for species-specific sepsis diagnostics.

Blood culture-based diagnostics have substantial limitations, including:

 

Time to Result Delays Targeted Treatment.  Blood culture-based diagnostics typically require a minimum of one and as many as six or more days to identify a pathogen species, and blood culture always requires at least five days to generate a negative test result.

 

Antimicrobial Therapy Can Cause False Negative Results.  Antimicrobial therapies may be administered to a patient prior to taking a blood sample. As a result, the therapeutic agent is contained in the blood sample and its ability to stop or slow the growth of pathogens can delay or completely inhibit the growth of the pathogen during the blood culture process leading to time delays in detection or false negative results.

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Slow-Growing Pathogens Can Cause False Negative Results.  Some sepsis pathogens grow slowly or not at all and can require up to five or more days to reach sufficient concentrations to be detected by blood culture-based diagnostics. Blood culture procedures are typically stopped after five days and declared negative. Often, pathogens that grow too slowly are not detected by blood culture during this time frame, leading to a false negative diagnosis. For example, C. glabrata, one of the most lethal species of Candida due to its growing resistance to antifungal therapy, often requires more than five days of growth to reach a detectable concentration, and therefore is frequently undetected by blood culture.

 

Labor-Intensive Workflow Increases Costs and May Delay Targeted Treatment.  Blood culture is only the first step in identifying a pathogen that causes sepsis. After a blood culture is determined to be positive, highly trained technicians are required to perform multiple post-culture procedures on the blood culture specimen to identify the specific pathogen. These additional procedures can be expensive and time-consuming and may delay targeted treatment.

Given the typical one-to-six day time to result for blood culture-based diagnostics, the first therapy for a patient at risk of sepsis is often broad-spectrum antibiotics, which treat some but not all bacteria types and do not address fungal infections. Some physicians may use first-line, antifungal therapy for patients at very high risk for fungal infection, or use antifungal therapy if the patient is not responding to broad-spectrum antibiotics while they are still awaiting the blood culture-based result. This therapeutic approach may still not treat the growing number of patients infected with the antimicrobial-resistant species nor may it be the best choice, as the type of therapy is dependent on the specific pathogen causing the infection, which is unknown.

This inefficient therapeutic approach has resulted in unnecessary treatment of a significant number of high-risk patients with expensive and often toxic therapies that can worsen a patient’s condition. Such treatments may extend for many days while clinicians await blood culture-based diagnostic results. The overuse of ineffective, or even unnecessary, antimicrobial therapy is also a driving force behind the spread of antimicrobial-resistant pathogens, which the CDC recently called “one of our most serious health threats.” The CDC has specifically noted increasing incidence of Candida infections due to azole- and echinocandin-resistant strains and considers it a “serious” threat level. According to the CDC, at least two million people in the United States acquire serious infections each year that are resistant to one or more of the antimicrobial therapies used to treat these patients. At least 23,000 of these people are estimated to die as a direct result of the resistant infections and many more may die from other conditions that are complicated by a resistant infection. Further, antimicrobial-resistant infections add considerable and avoidable costs to the already overburdened U.S. healthcare system, with the total economic cost estimated to be as high as $20 billion in excess of direct healthcare costs, with additional costs to society as high as $35 billion, due to lost productivity.

Our T2Biosystems Product Portfolio

We believe T2MR delivers what no conventional technology currently available can: a rapid, sensitive and simple diagnostic platform to enable sepsis applications that can identify specific sepsis pathogens directly from an unpurified blood sample in hours instead of days at a level of accuracy equal to or better than blood culture-based diagnostics. The addition of the use of our products, T2Bacteria and T2Candida, with the standard of care for the management of patients suspected of sepsis enables clinicians to potentially treat 90% of patients with sepsis pathogen infections with the right targeted therapy within the first twelve hours of developing the symptoms of disease. Currently, high risk patients are typically initially treated with broad spectrum antibiotic drugs that typically cover approximately 60% of patients with infections. Of the remaining 40% of patients, approximately 30% of the patients have a bacterial infection and 10% have Candida infections. T2Candida and T2Bacteria are designed to identify pathogens commonly not covered by broad spectrum antibiotic drugs.

We believe our products provide a pathway for more rapid and targeted treatment of infections, potentially reducing the mortality rate by as much as 50% if a patient is treated within 12 hours of suspicion of infection and significantly reducing the cost burden of sepsis. Each year, more than 270,000 patients in the United States die from sepsis. According to a study published by Critical Care Medicine in 2006, in sepsis patients with documented hypotension, administration of effective antimicrobial therapy within the first hour of detection was associated with a survival rate of 79.9% and, over the ensuing six hours, each hour of delay in initiation of treatment was associated with an average decrease in survival of 7.6%. According to such study, the survival rate for septic patients who remained untreated for greater than 36 hours was approximately 5%. The toll of sepsis on a patient’s health can be severe: more than one-in-five patients die within two years as a consequence of sepsis. Sepsis is also the most prevalent and costly cause of hospital readmissions.

We believe the T2Biosystems Product Portfolio addresses a significant unmet need in in vitro diagnostics by providing:

 

Limits of Detection as Low as 1 CFU/mL. T2MR is the only technology currently available that can enable identification of sepsis pathogens directly from a patient’s blood sample at limits of detection as low as 1 CFU/mL.

 

Rapid and Specific Results in as Few as Three Hours. T2MR is the only technology that can enable species-specific results for pathogens associated with sepsis, directly from a patient’s blood sample, without the need for blood culture, to deliver an actionable result in three hours.

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Accurate Results Even in the Presence of Antimicrobial Therapy. T2MR is the only technology that can reliably detect pathogens associated with sepsis, including slow-growing pathogens, such as C. glabrata, directly from a patient’s blood sample, even in the presence of an antimicrobial therapy.

 

Easy-to-Use Platform. T2MR eliminates the need for sample purification or extraction of target pathogens, enabling sample- to-result instruments that can be operated on-site by hospital staff, without the need for highly skilled technicians.

Our first U.S. Food and Drug Administration, or FDA-cleared products, the T2Dx and T2Candida, focus on the most lethal form of common blood stream infections that cause sepsis, Candida, which has an average mortality rate of approximately 40%. According to a 2005 report published in Antimicrobial Agents and Chemotherapy, this high mortality rate can be reduced to 11% with the initiation of targeted therapy within 12 hours of presentation of symptoms. Currently, a typical patient with a Candida infection averages 40 days in the hospital, including nine days in intensive care, resulting in an average cost per hospital stay of over $130,000 per patient. In a study published in the American Journal of Respiratory and Critical Care Medicine in 2009, providing targeted antifungal therapy within 24 hours of the presentation of symptoms decreased the length of hospital stay by approximately ten days and decreased the average cost of care by approximately $30,000 per patient. In addition, many hospitals initiate antifungal drugs, such as caspofungin or micafungin, while waiting for blood culture-based diagnostic results. We estimate this practice costs approximately $500 per patient and is currently in use for over 40% of high-risk patients on average and for all high-risk patients in some hospitals. A negative result from T2Candida can provide timely data allowing physicians to avoid unnecessary antifungal treatment and potentially reduce the treatment cost further.

We believe that by identifying the specific species of Candida, physicians can administer the most effective therapy, significantly improving patient outcomes and reducing hospital costs. We further believe that the adoption of the T2Dx and T2Candida can decrease both the high mortality rate and excessive costs of Candida infections because these products can enable clinicians to make earlier and more informed decisions by providing positive test results to direct therapy and negative test results to reduce the use of antifungal drugs.

T2Bacteria, a multiplex diagnostic panel that detects the major bacterial pathogens associated with sepsis that are frequently not covered by first-line antibiotics, is FDA-cleared in the United States and CE-Marked and available commercially in Europe and other countries that accept the CE mark. T2Bacteria runs on the T2Dx and addresses the same approximately 6.75 million symptomatic high-risk patients as T2Candida while also expanding our reach to an additional two million people presenting with symptoms of infection in the emergency room setting. We believe that these factors make the United States market opportunity for T2Bacteria over $1.0 billion, and that T2Bacteria has the potential to achieve similar performance capabilities and provide similar benefits as T2Candida.

On August 2, 2019, CMS granted approval for an NTAP payment for the T2Bacteria Panel for fiscal year 2020. In its fiscal 2020 inpatient prospective payments system final rule, CMS explained: “the T2Bacteria Test Panel represents a substantial clinical improvement over existing technologies because it reduces the proportion of patients on inappropriate therapy, thus reducing the rate of subsequent diagnostic or therapeutic intervention as well as length of stay and mortality rates caused by sepsis causing bacterial infections.” With this designation, hospitals in the United States treating Medicare inpatients with sepsis will now be eligible for an NTAP, in addition to the standard payment amount. In the final rule, CMS determined a maximum NTAP amount of $97.50 for the T2Bacteria Panel in addition to the diagnosis-related group (MS-DRG)-based reimbursement that hospitals receive under the Medicare Hospital Inpatient Prospective Payment System (IPPS). Hospitals were eligible for the NTAP payment for any in-patient T2Bacteria Panel tests performed on Medicare patients beginning October 1, 2019. The maximum NTAP reimbursement for a qualifying case involving the use of the T2Bacteria Panel is $97.50, (65 percent of the list price of one T2Bacteria Panel test) in addition to the standard hospital payment under the appropriate sepsis MS-DRG codes. According to CMS there are more than 30 million Medicare patients in the United States enrolled in Medicare fee-for-service.

Clinical Utility

T2Candida

DIRECT Clinical Trial—Clinical Infectious Disease

In 2013 and 2014, we conducted a pivotal clinical trial for our T2Dx Instrument and T2Candida, or the DIRECT trial. Our DIRECT trial consisted of two patient arms. The first arm, known as the Prospective Arm, consisted of 1,501 samples from patients with a possible infection. The second arm, known as the Contrived Arm, consisted of 300 samples, of which 250 patient specimens were labeled contrived because each contained a known quantity of Candida CFUs that were manually added to each sample, or spiked, at clinically relevant concentrations, while the remaining 50 patient specimens were specifically known not to contain Candida. The DIRECT trial was designed to evaluate the sensitivity and specificity of T2Candida on the T2Dx.

Sensitivity is the percent concordance, or the percentage of sample results that agree with a reference, or comparative, method for positive results. Specificity is the percent concordance to a reference method for negative results. If a sample does not agree with the result of a referenced method, it is considered discordant. In our clinical trial, the Prospective Arm was compared to blood culture and the Contrived Arm was compared to the known state, which means that it was in the known presence or absence of added Candida organisms.

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The design of the DIRECT trial was reviewed by the FDA as part of pre-submission communications. The purpose of the DIRECT trial was to determine the clinical performance of T2Candida running on the T2Dx by identifying the following:

 

clinical specificity of T2Candida results as compared to Candida negative blood culture results in specimens collected from patients in the Prospective Arm;

 

clinical specificity of T2Candida results as compared to Candida negative samples collected from patients in the Contrived Arm;

 

clinical sensitivity of T2Candida results as compared to the known Candida-positive specimens collected from patients in the Contrived Arm; and

 

clinical sensitivity calculations of T2Candida results compared to the Candida-positive blood culture results in specimens collected from patients in the Prospective Arm.

50 known negative samples and 250 contrived samples (50 samples for each of the five Candida species included in the T2Candida Panel) were prepared and run in a blinded manner at the same clinical sites used for processing the prospective samples. The positive contrived samples were prepared by spiking clinical isolates into individual patient specimens at concentrations determined through publications and discussions with the FDA to be equivalent to the clinical state of patients who presented with symptoms of a Candida infection. 20% of the positive contrived samples were spiked at concentrations levels of less than 1 CFU/mL. The contrived samples were collected from patients referred for a diagnostic blood culture per routine standard of care — the same population of patients from whom prospective samples were collected. Unique isolates of the species were used for each patient sample, which means a total of 50 unique isolates were tested for each of the five species of Candida for a total of 250 unique isolates.

In addition to the pivotal clinical trial data that we submitted to the FDA, we also provided data from an analytical verification study to determine the limit of detection, or LoD, for each species identified by our T2Candida. The LoD was defined as the lowest concentration of Candida that can be detected in 95% of at least 20 samples tested at a single concentration.

The T2Candida Panel reports three results, where species are grouped together according to their responsiveness to therapy. Candida albicans and/or Candida tropicalis are reported as a single result, Candida parapsilosis is a single result, and Candida krusei and/or Candida glabrata are reported as a single result. Specificity and sensitivity are calculated for each reported result.

There are five relevant species of Candida, each of which were analyzed in the DIRECT trial. Each are listed in abbreviated form in the tables below. These species are Candida albicans, Candida tropicalis, Candida parapsilosis, Candida krusei, and Candida glabrata. The typical naming convention for a species is to abbreviate by using the first letter of the first word and the full second word; for example, Candida krusei is abbreviated as C. krusei. In the tables below, we also abbreviate each species name by the first letter of the second word; for example, Candida albicans and Candida tropicalis is A/T.

The following tables illustrate the results of the DIRECT trial. The primary sensitivity and specificity analysis is presented in Table A, followed by sub-analyses in Tables B and C. Additional data on the LoD and the time to results of T2Candida and the T2Dx are included in the remaining tables.

Table A

T2Candida Performance Characteristics

 

 

 

Overall

 

Overall

 

 

Sensitivity

 

Specificity

Number of Tests (%)

 

234/257 (91.1%)

 

5114/5146 (99.4%)

 

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Table B

Overall Sensitivity and Specificity by Test

 

 

 

 

 

95% Confidence

 

 

 

 

 

Interval

 

Specificity:

 

 

 

 

 

 

 

 

A/T (C. albicans/C. tropicalis )

 

1679/1697 (98.9%)

 

98.3 -

 

 

99.4

%

P (C. parapsilosis)

 

1736/1749 (99.3%)

 

98.7 -

 

 

99.6

%

K/G (C. krusei/C. glabrata)

 

1699/1700 (99.9%)

 

99.7 -

 

 

100.0

%

Total:

 

5114/5146 (99.4%)

 

99.1 -

 

 

99.6

%

Sensitivity:

 

 

 

 

 

 

 

 

A/T (C. albicans/C. tropicalis)

 

96/104 (92.3%)

 

85.4 -

 

 

96.6

%

P (C. parapsilosis)

 

49/52 (94.2%)

 

84.1 -

 

 

98.8

%

K/G (C. krusei/C. glabrata)

 

89/101 (88.1%)

 

80.2 -

 

 

93.7

%

Total:

 

234/257 (91.1%)

 

86.9 -

 

 

94.2

%

Table C

Study Arm Sensitivity and Specificity by Test

 

 

 

 

 

95% Confidence

 

 

 

 

 

Interval

 

Specificity (Prospective tests):

 

 

 

 

 

 

 

 

A/T (C. albicans/C. tropicalis )

 

1479/1497 (98.8%)

 

98.1 -

 

 

99.3

%

P (C. parapsilosis)

 

1487/1499 (99.2%)

 

98.6 -

 

 

99.6

%

K/G (C. krusei/C. glabrata)

 

1499/1500 (99.9%)

 

99.6 -

 

 

100.0

%

Total:

 

4465/4496 (99.3%)

 

99.0 -

 

 

99.5

%

Sensitivity (Prospective tests):

 

 

 

 

 

 

 

 

A/T (C. albicans/C. tropicalis)

 

2/4 (50.0%)

 

6.8 -

 

 

93.2

%

P (C. parapsilosis)

 

2/2 (100.0%)

 

15.8 -

 

 

100.0

%

K/G (C. krusei/C. glabrata)

 

1/1 (100.0%)

 

2.5 -

 

 

100.0

%

Total:

 

5/7 (71.4%)

 

29.0 -

 

 

96.3

%

Specificity (Contrived tests):

 

 

 

 

 

 

 

 

A/T (C. albicans/C. tropicalis)

 

200/200 (100.0%)

 

98.2 -

 

 

100.0

%

P ( C. parapsilosis)

 

249/250 (99.6%)

 

97.8 -

 

 

100.0

%

K/G (C. krusei/C. glabrata)

 

200/200 (100.0%)

 

98.2 -

 

 

100.0

%

Total:

 

649/650 (99.8%)

 

99.1 -

 

 

100.0

%

Sensitivity (Contrived tests):

 

 

 

 

 

 

 

 

A/T (C. albicans/C. tropicalis)

 

94/100 (94.0%)

 

87.4 -

 

 

97.8

%

P (C. parapsilosis)

 

47/50 (94.0%)

 

83.5 -

 

 

98.7

%

K/G (C. krusei/C. glabrata)

 

88/100 (88.0%)

 

80.0 -

 

 

93.6

%

Total:

 

229/250 (91.6%)

 

87.4 -

 

 

94.7

%

 

Table D

T2Candida Limit of Detection

 

 

 

Final LoD

 

Species

 

CFU/mL

 

C. albicans

 

2

 

C tropicalis

 

1

 

C. parapsilosis

 

3

 

C. glabrata

 

2

 

C. krusei

 

1

 

 

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Table E

Sensitivity Sub-Analysis: Sensitivity by Species Relative to LoD

 

 

 

 

 

>  LoD

 

 

< LoD

 

 

 

LoD

 

 

 

95% Confidence

 

 

 

 

95% Confidence

 

 

 

(CFU/ml)

 

Sensitivity

 

Interval

 

 

Sensitivity

 

Interval

 

C. albicans

 

2

 

39/39 (100.0%)

 

91.0 -

 

 

100.0

%

 

9/11 (81.8%)

 

48.2 -

 

 

97.7

%

C. glabrata

 

2

 

35/37 (94.6%)

 

81.8 -

 

 

99.3

%

 

7/13 (53.8%)

 

25.1 -

 

 

80.8

%

C. krusei

 

1

 

40/40 (100.0%)

 

91.2 -

 

 

100.0

%

 

6/10 (60.0%)

 

26.2 -

 

 

87.8

%

C. parapsilosis

 

3

 

32/32 (100.0%)

 

89.1 -

 

 

100.0

%

 

15/18 (83.3%)

 

58.6 -

 

 

96.4

%

C. tropicalis

 

1

 

38/40 (95.0%)

 

83.1 -

 

 

99.4

%

 

8/10 (80.0%)

 

44.4 -

 

 

97.5

%

Total:

 

 

 

184/188 (97.9%)

 

94.6 -

 

 

99.4

%

 

45/62 (72.6%)

 

59.8 -

 

 

83.1

%

 

Table F

Sensitivity Sub-Analysis: Sensitivity by Titer Level

 

 

 

 

 

1 — 10 CFU/ml

 

11 — 30 CFU/ml

 

31 — 100 CFU/ml

 

 

<1 CFU/ml Sensitivity

 

Sensitivity

 

Sensitivity

 

Sensitivity

C. albicans

 

8/10 (80.0%)

 

18/18 (100.0%)

 

17/17 (100.0%)

 

5/5 (100.0%)

C. glabrata

 

5/10 (50.0%)

 

16/18 (88.9%)

 

16/17 (94.1%)

 

5/5 (100.0%)

C. krusei

 

6/10 (60.0%)

 

18/18 (100.0%)

 

17/17 (100.0%)

 

5/5 (100.0%)

C. parapsilosis

 

8/10 (80.0%)

 

17/18 (94.4%)

 

17/17 (100.0%)

 

5/5 (100.0%)

C. tropicalis

 

8/10 (80.0%)

 

16/18 (88.9%)

 

17/17 (100.0%)

 

5/5 (100.0%)

Total:

 

35/50 (70.0%)

 

85/90 (94.4%)

 

84/85 (98.8%)

 

25/25 (100.0%)

 

Table G

Sensitivity Sub-Analysis: Sensitivity by Species Relative to Clinically Relevant Concentrations

 

 

 

Clinically Relevant

 

Sensitivity <

 

 

Sensitivity >

 

Species

 

Concentration

 

Relevant CFU

 

 

Relevant CFU

 

C. tropicalis

 

1-10 CFU/mL

 

 

80

%

 

 

95

%

C. krusei

 

11-30 CFU/mL

 

 

85.7

%

 

 

100

%

C. glabrata

 

11-30 CFU/mL

 

 

75

%

 

 

96

%

C. albicans

 

1-10 CFU/mL

 

 

80

%

 

 

100

%

C. parapsilosis

 

11-30 CFU/mL

 

 

89.3

%

 

 

100

%

Total

 

 

 

 

82.7

%

 

 

98

%

 

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Table H

Time to species identification or negative result for T2MR and Blood Culture

 

 

 

Blood Culture

 

 

T2Dx

 

Time to Results (hours)

 

 

 

 

 

 

 

 

Mean ± SD (N)

 

126.5 ± 27.3 (1470)

 

 

4.2 ± 0.9 (1470)

 

Median

 

 

121.0

 

 

 

4.1

 

(Min, Max)

 

(12.4, 247.2)

 

 

(3.0, 7.5)

 

Time to Positive Results(1),(2) (hours)

 

 

 

 

 

 

 

 

Mean ± SD (N)

 

43.6 ± 11.1 (4)

 

 

4.4 ± 1.0 (4)

 

Median

 

 

46.1

 

 

 

4.6

 

(Min, Max)

 

(28.1, 54.1)

 

 

(3.2, 5.4)

 

Time to Negative Results(1),(2) (hours)

 

 

 

 

 

 

 

 

Mean ± SD (N)

 

126.7 ± 27.0 (1466)

 

 

4.2 ± 0.9 (1466)

 

Median

 

 

121.1

 

 

 

4.1

 

(Min, Max)

 

(12.4, 247.2)

 

 

(3.0, 7.5)

 

 

(1)

Includes samples that are 100% concordant for both methods (i.e. does not include discordant results). We do not include discordant results because a comparison of the duration of time to positive result requires that both the blood culture result and the T2Candida result be positive for a given specimen.  Similarly, a comparison of the duration of time to negative result requires that both the blood culture result and the T2Candida result be negative for a given specimen.  We therefore would exclude any sample with a discordant result where blood culture yields one result and T2Candida yields the opposite result.

(2)

Refers to time to species identification or final negative result.

Results from the study were published in Clinical Infectious Disease in 2015 in an article entitled: “T2 Magnetic Resonance Assay for the Rapid Diagnosis of Candidemia in Whole Blood: A Clinical Trial.” The study findings include:

 

the overall sensitivity (Prospective and Contrived Arm combined) of T2Candida was 91.1%;

 

the average specificity of the three test results for the Prospective and Contrived Arms combined was 99.4% (see Table A) with the specificity by test result ranging from 98.9% to 99.9% (see Table B);

 

in the Contrived Arm of the study, the average specificity was 99.8%, with the specificity by test result ranging from 99.6% to 100% (see Table C);

 

in the Prospective Arm of the study, the average specificity was 99.3%, with the specificity by test result ranging from 98.8% to 99.9% (see Table C);

 

in the Contrived Arm of the study, the average sensitivity was 91.6%, with the sensitivity by test result ranging from 88.0% to 94.0% (see Table C); and

 

in the Prospective Arm of the study, the average sensitivity was 71.4% (see Table C).

In this study, the following observations were reported:

 

within the Prospective Arm, T2Candida accurately detected a rare co-infection in one study patient with C. albicans and C. parapsilosis in their bloodstream;

 

T2Candida detected at least one infection that was not identified by blood culture, which was determined to be a Candida infection seven days after the T2Candida result was obtained. This case is considered a discordant result for the purposes of the FDA filing because of the disagreement between T2Candida and the blood culture-based results, despite the accurate identification by T2Candida. Along with ten other patients with clinical symptoms or microbiological evidence of infection, the study findings indicate that the true sensitivity and specificity of T2Candida may be higher than the reported values;

 

the LoD of T2Candida was demonstrated to be 1 to 3 CFU/mL depending upon the species of Candida (see Table D). In the Contrived Arm of the study, T2Candida positively detected 97.9% of the samples spiked at and above the LoD while also detecting 72.6% of all samples spiked at concentration levels below the LoD (see Table E);

 

in the Contrived Arm of the study, T2Candida detected 97% of cases at or above 1 CFU/mL and 70% of cases below 1 CFU/mL (see Table F);

 

in the Contrived Arm of the study, T2Candida detected 98% of cases at or above clinically relevant concentrations of Candida, ranging from 95% to 100% detection depending on the Candida species (see Table G);

 

T2Candida demonstrated an average time to positive result of 4.4 hours compared to blood culture average time to result of 129 hours;

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T2Candida demonstrated an average time to negative result of 4.2 hours compared to blood culture average time to result of >120 hours; and

 

T2Candida has a negative predictive value of 99.8% in a standard population. Negative predictive value is the probability that subjects with a negative result truly do not have the disease.

The authors of the study made the following conclusions based on the study results:

 

Because mortality due to invasive candidiasis has remained high and unchanged for the past two decades and early initiation of appropriate antifungal therapy has been reported to reduce mortality by at least two-thirds, the rapid and accurate diagnostic capability offered by this novel technology has the potential to change the management and prognosis of the disease.

 

The ability to rapidly and accurately exclude the possibility of candidemia can have significant implications in clinical practice, by decreasing the number of patients who need to be on empiric antifungal therapy, and thus decreasing the incidence of resistant strains, the potential of side effects of antifungal treatment, and substantial healthcare costs.

 

A key advantage of T2MR over other biosensors is that it does not require culture and sample purification or preparation.

Massachusetts General Hospital Study — Science Translational Medicine

We co-authored a study with investigators from Massachusetts General Hospital, or MGH, to evaluate the sensitivity and specificity of T2MR to detect Candida compared to blood culture-based diagnostics. Results from the study were published in an article entitled “T2 Magnetic Resonance Enables Nanoparticle-Mediated Rapid Detection of Candidemia in Whole Blood” in Science Translational Medicine in 2013. In this study:

 

T2MR was tested across 320 contrived whole blood samples, each containing one of the five clinically relevant species of Candida, and was able to detect each of the species at a LoD ranging from 1 to 3 CFU/mL.

 

T2MR was tested across 24 whole blood specimens from patients exhibiting symptoms of sepsis, with eight Candida positive, eight bacteria positive and eight negative samples. Results showed 100% sensitivity and 100% specificity of T2MR when compared with blood culture results for identification of Candida.

 

In patients with Candida treated with antifungal therapy, T2MR detected the presence of Candida in patient samples drawn up to four days after antifungal administration, while blood culture failed to identify the infection upon administration of antifungal therapy.

University of Houston Study — Diagnostic Microbiology and Infectious Disease

We sponsored an independent study at the University of Houston to directly compare the sensitivity and time to result of T2Candida running on the T2Dx and blood culture-based diagnostics. In this study, contrived blood samples were split between T2Candida using the T2Dx and standard blood culture. The study showed improved performance of T2Candida over blood culture in terms of speed and sensitivity. The following findings were published in an article entitled “Comparison of the T2Dx Instrument with T2Candida Diagnostic Panel and Automated Blood Culture in the Detection of Candida Species Using Seeded Blood Samples” in Diagnostic Microbiology and Infectious Disease in 2013:

 

T2Candida detected all of the samples of C. glabrata at concentrations of 2.8 CFU/mL, while blood culture was not able to detect C. glabrata in any of the samples, even at a higher concentration of 11 CFU/mL and with the standard five-day run time.

 

T2Candida detected all of the samples for all of the species of Candida at concentration levels of 3.1 to 11 CFU/mL.

 

The average time to species identification was approximately three hours for T2Candida, as opposed to over 60 hours for blood culture.

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The following table summarizes the results of our University of Houston study. The five relevant species of Candida were analyzed in the University of Houston study.

Contrived blood samples at concentrations between 3.1 — 11 CFU/mL

 

 

 

Blood Culture

 

 

T2Candida

 

 

 

(n=20 per species)

 

 

(n=13-20 per species)

 

Average time to positive result

 

63.23 ± 30.27 hours

 

 

 

 

 

 

3 hours

 

 

 

 

 

 

 

C. albicans

=

 

 

100

%

 

C. albicans

=

 

 

100

%

 

 

C. tropicalis

=

 

 

100

%

 

C. tropicalis

=

 

 

100

%

Detection rate

 

C. parapsilosis

=

 

 

100

%

 

C. parapsilosis

=

 

 

100

%

 

 

C. glabrata

=

 

 

0

%

 

C. glabrata

=

 

 

100

%

 

 

C. krusei

=

 

 

100

%

 

C. krusei

=

 

 

100

%

Sensitivity

 

 

 

 

 

 

 

 

100%

 

 

 

 

 

Specificity

 

 

 

 

 

 

 

 

98%

 

 

 

 

 

 

Clinical Data Review of T2MR and T2Candida—Future Microbiology

Dr. Michael Pfaller (former T2 Biosystems Chief Medical Officer), Donna Wolk, PhD (Geisinger Health System), and Tom Lowery, PhD (T2 Biosystems’ former Chief Scientific Officer) collaborated to perform a meta-analysis of T2MR and T2Candida data that was published in Future Microbiology in 2015 with the title T2MR and T2Candida: novel technology for the rapid diagnosis of candidemia and invasive candidiasis. The article had the following overall summary statements and conclusions:

 

There is an urgent need to rapidly and accurately detect and identify fungal pathogens. Current culture-based methodologies are too slow and, with some organisms like C. glabrata, may fail altogether due to the insensitivity of some blood culture systems to detect this slow-growing species. 

 

The development and FDA approval of T2Candida represents the advent of a new class of infectious disease diagnostics that enable rapid, direct detection and identification of pathogens in a culture-independent manner. The new panel will reduce the time to detection and species identification for common Candida species.

 

As of the date of publication of the article, the T2Candida Panel had identified over 31 cases of candidemia and 12 cases of candidiasis. In the latter 12 cases, blood culture was unable to detect any of those proven infections. There were an additional ten patients with probable or suspected invasive candidiasis, but patient record review was not available to include these cases. More specifically, across all studies to date, T2Candida had successfully detected 43 of 45 patients with confirmed candidemia (31/33) or candidiasis (12/12). When including patients with probable candidiasis, T2Candida detected 10 of 10 patients, totaling 53 of 55 cases detected for candidemia or candidiasis. In this aggregate population, blood culture only detected 33 of 55 patients.  Table 7 from the article summarizes the data showing increases in sensitivity for T2Candida vs. blood culture.

 

 

 

-

Across all studies to date, T2Candida had an overall specificity of greater than 99.4% from more than 1,560 patients.

 

-

Application of the T2Candida Panel facilitates the diagnosis of candidemia and other forms of invasive candidiasis and promises to have major clinical impact resulting from the diagnosis of previously unrecognized, deep-seated candidiasis as well as from the ‘real-time’ (hours) detection of candidemia.  The earlier species-level diagnosis provided by T2Candida will allow targeted pre-emptive antifungal therapy which should result in a decrease in Candida -associated morbidity, mortality, and excess length of stay in the hospital and at the same time reduce unnecessary empiric antifungal therapy.  T2Candida provides breakthrough performance in the detection and identification of Candida direct from patient samples and may significantly impact patient mortality and hospital costs.

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DIRECT2 Pivotal Clinical Trial – Clinical Infectious Diseases

The DIRECT2 study, published in Clinical Infectious Diseases, was a multi-center study involving 14 sites and evaluated the performance of T2Candida and blood culture in N=152 candidemic patients. T2Candida detected 89% of infections across this patient population, validating the 91.1% clinical sensitivity reported from the FDA pivotal study for the T2Candida in a much larger patient population. Additionally, T2Candida detected almost twice as many confirmed infections as blood culture in patients receiving antifungal therapy. This indicates that T2Candida is a more effective diagnostic tool for patients treated with pre-emptive or empiric antifungal therapy. Consistent with other studies, the time savings afforded by T2Candida was significant. The median time to detection of Candida by diagnostic blood cultures and subsequent species identification was 3.4 days. In comparison, T2Candida provides diagnostic results in an average time of 4.4 hours. The authors noted that T2Candida “ushers in a new era in which rapid molecular testing for invasive candidiasis will serve as an adjunct to microbiologic cultures.”

STAMP Study – Journal of Clinical Microbiology

The STAMP study, published in the Journal of Clinical Microbiology, compared blood culture to T2Candida for monitoring the clearance of an infection when a patient is being treated with antifungal drugs. The study demonstrated that T2Candida can detect the ongoing presence of a Candida infection while blood culture often yields false negative test results because the administration of antifungal drugs can impede the growth of cells that blood culture requires to detect an infection. These observations are consistent with the DIRECT2 study. The authors concluded that T2Candida can be an effective tool for reliably identifying patients that have cleared an infection, which can reduce the unnecessary and expensive antifungal therapy. The STAMP study evaluated running multiple diagnostic tests for patients with confirmed Candida infections who were receiving antifungal drugs. The study demonstrated that T2Candida outperforms blood culture for monitoring the clearance of Candida infections.

 

T2Candida was positive in 23 patient samples, compared to only 7 for blood culture in cases of true infection.

 

T2Candida identified every infection that was detected by blood culture and provided actionable results 3 days earlier than blood culture.

 

T2Candida detected a Candida infection that blood culture missed in one patient during the study.

 

T2Candida results were a better indicator of disease clearance than blood culture, as two consecutive T2Candida negative results indicated that the patient no longer had an active infection in the blood that required aggressive management.

 

STAMP study data suggest that serial testing of patients with the T2Candida Panel may enable more timely management of infections, de-escalation of therapy, better source control and overall reduced costs of care.

T2 Magnetic Resonance Assay Improves Timely Management of Candidemia – The Journal of Antimicrobial Stewardship

Another study published in The Journal of Antimicrobial Stewardship entitled “T2 Magnetic Resonance Assay Improves Timely Management of Candidemia” compared the management of candidemic patients before and after the implementation of T2Candida and was designed to evaluate time to appropriate therapy. Patients tested with the T2MR platform were treated in a median of 5 hours, a more than 8-fold reduction as compared to that based on blood culture, which delayed appropriate therapy by a median of 44 hours. This speed advantage demonstrates that the T2MR platform may be a valuable clinical tool to aid antifungal stewardship’s goal to deliver timely antifungal therapy for infected patients. In addition to speed, the use of the T2MR platform provided increased identification of Candida infections. Consistent with the performance of blood culture and T2MR published in other studies, the Candida species was definitively identified in 93% of patients after implementation of T2MR and in only 57% of patients prior to implementation of T2MR. Prior to implementation of T2Candida, the only diagnostic tests used at Henry Ford Health System were blood culture and beta-D-glucan (BDG). The authors also identified an additional clinically relevant improvement in patient outcomes after the implementation of T2MR: a significant reduction of Candida ocular involvement from 30% to 12% was observed. The authors point out this could be associated with improved sensitivity of T2MR or due to improved timeliness of patient management by T2MR. Although the study was not adequately powered to evaluate reduction in patient mortality rates, the authors note that appropriately treating patients within 24 hours of the onset of disease is proven to reduce mortality rates from 41% to below 16%. T2MR is the only diagnostic method presented in this study with the speed and accuracy necessary to enable therapeutic decisions that achieve this reduction in mortality.    

Customer Presentations

Since receiving FDA clearance in 2014, customers have regularly reported on their experiences with T2Candida at conferences and in publications. Below is a summary of some those reports.

 

-

Investigators at the Henry Ford Health System reported data that demonstrated that after the implementation of T2Candida in their hospital system, the hospital system projected that it may save an estimated $2.3M annually, reduced median ICU length of stay by seven days per patient (p=0.009), and reduced total length of stay by four days per patient (p=0.164). Additionally, 75% of negative patients had antifungals discontinued or deescalated.

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-

Investigators at the Lee Health System reported that after the implementation of T2Candida, they have experienced a reduction in the average length of stay per patient by 7 days, unnecessary antifungal therapy was avoided in 41% of patients, and unnecessary antifungal therapy was discontinued after 1 dose in another 15% of patients, and the average net antifungal savings was $195 for every patient tested with T2Candida.

 

-

Investigators at Riverside Community Hospital reported that implementation of T2Candida led to therapy being discontinued for 100% of patients who tested negative, and for patients who tested positive and had not been on antifungals prior to testing, 83% of patients who tested positive received appropriate therapy within six hours of blood drawing and 100% within nine hours of blood draw.

 

-

Investigators at the University Di Roma reported that T2Candida detected invasive candidiasis that were not identified by blood culture. T2Candida identified three cases of C. albicans and one case of C. glabrata that were proven accurate with additional in vitro diagnostic testing and diagnostic imaging.

 

-

An investigator from Rigshospitalet, Denmark evaluated the performance of T2Candida, Mannan Ag and blood culture for diagnosis of invasive candidiasis infections across 126 patients. The sensitivity for invasive candidiasis was higher for T2Candida compared to blood culture and Mannan Ag and the positive predictive value was highest for T2Candida.

 

-

Investigators from Bambino Gesu Pediatrics Hospital in Rome, Italy presented a comparison of T2Candida, SeptiFast and blood culture in pediatric and neonatal patients showing an 89% concordance between blood culture and T2MR.

 

-

Investigators in Detroit, Michigan evaluated the impact of utilizing T2Candida on anti-fungal de-escalation in patients with malignancy/chemotherapy, transplant, and immunosuppression. T2Candida testing decreased turnaround time for results from 4 days to 6 hours compared with blood culture. For C. albicans/tropicalis, 50% of patients were de-escalated to fluconazole in 4 days.

 

-

Investigators in Huntsville, Alabama evaluated the utility of T2Candida for managing candidemia at a large community hospital, comparing 89 patients diagnosed using T2Candida to 163 patients diagnosed using blood culture. Candidemia was detected in an average of 9 hours with T2Candida vs 41 hours with blood culture. Antifungal therapy was initiated within 4 hours with T2Candida vs 37 hours with blood culture. The same group evaluated the impact of T2Candida on antifungal stewardship in a 900 bed hospital. The patient population included critical care and febrile neutropenic patients. 628 T2Candida results were evaluated. Antifungal therapy was avoided in 60.4% of negative cases. Additionally, antifungal optimization occurred in 54% of patients on antifungals at the time of test.

T2Bacteria

T2Bacteria Panel Pivotal Clinical Study Information

On May 24, 2018, we received market clearance from the FDA for T2Bacteria, a multiplex diagnostic panel that runs on the T2Dx instrument and detects five major bacterial pathogens associated with sepsis and, in conjunction with T2Candida and standard empiric therapy regimens, may enable the early, appropriate treatment of 90% of sepsis patients. T2Bacteria addresses the same approximately 6.75 million symptomatic high-risk patients as T2Candida and also a new population of patients who are at increased risk for bacterial infections, including an additional two million patients presenting with symptoms of infection in the emergency room setting.  

On August 4, 2017 we completed a pivotal clinical study of T2Bacteria, which is a qualitative T2MR assay designed for the direct detection of bacterial species in human whole blood specimens from patients with suspected bacteremia. T2Bacteria is designed to identify five species of bacteria directly from human whole blood specimens: Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Outside of the United States, the CE marked T2Bacteria panel identifies all 5 of these species along with a 6th species, Acinetobacter baumannii.

To the extent that T2Bacteria is performed on an outpatient basis, third-party payors may separately reimburse our customers using existing CPT codes for patients who are not admitted to the hospital. By way of example, Medicare payment for outpatient clinical laboratory services is the lesser of the amount billed, the local fee for a geographic area, or the national limit established by the CMS under the Clinical Laboratory Fee Schedule, or CLFS, on an annual basis. For 2020, the national limit for the series of CPT codes used to bill T2Bacteria is approximately $175. Effective January 1, 2018, CLFS rates are based on weighted median private payor rates as required by the Protecting Access to Medicare Act of 2014. We believe that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our diagnostic products or additional pricing pressures.

The performance characteristics of T2Bacteria were evaluated through a series of analytical studies as well as a multi-center clinical study.  The clinical study evaluated the performance of T2Bacteria in comparison to the current standard of care, blood culture. 

18

 


 

The clinical study consisted of two arms, a prospective arm and a seeded arm. In the prospective arm, a total of 1,427 subjects were tested at eleven geographically dispersed and demographically diverse sites in the United States.  In the seeded arm, 300 specimens of known bacterial composition were evaluated at three sites. Seeded specimens were prepared by spiking whole blood with multiple strains of the bacterial species detected by T2Bacteria at defined concentrations (CFU/mL). Fifty negative blood samples also were evaluated as part of the seeded arm of the study.  In total, 1,777 (1,427 prospective specimens and 350 seeded and negative) clinical samples were tested to evaluate the clinical performance of T2Bacteria.

Data from the pivotal clinical trial was presented at the Association of Molecular Pathology annual meeting in November 2017. Results from the trial demonstrated that T2Bacteria can deliver actionable results in an average of 5.4 hours, compared to an average of 60 hours for detecting the same species by blood culture. In addition, T2Bacteria identified 63 infected patients that were missed by the paired blood culture that was simultaneously run. The reported sensitivity was 96%, compared to a sensitivity of 38% for the paired blood culture as measured by the total of 102 patients with confirmed infections by any culture result.  More specifically, the study findings include:

 

The overall sensitivity for the prospective and seeded arms combined was 95.8% (see Table I below);

 

In the seeded arm of the study, the average sensitivity was 96.8% (see Table K), with the sensitivity by bacterial target ranging from 90.9% to 100.0% (see Table L);

 

In the prospective arm of the study, the average sensitivity was 89.7% (see Table M), with the sensitivity by bacterial target ranging from 81.3%% to 100.0% (see Table N);

 

The average specificity for the prospective and seeded arms combined was 98.1% (see Table I);

 

In the seeded arm of the study, the average specificity of the test was 99.0% (see Table K), with the specificity by bacterial target ranging from 97.3% to 100.0% (see Table L);

 

In the prospective arm of the study the average specificity of the test was 97.9% (see Table M), with the specificity by bacterial target ranging from 95.0% to 99.4% (see Table N);

 

In the prospective arm of the study, results that were identified as positive by T2Bacteria but negative by blood culture were evaluated by looking at additional blood culture results obtained +/- 14 days of the paired T2 / blood culture draw.  36% of the T2 positive / blood culture negative results were found to be culture positive for the organism identified by the T2Bacteria Panel within the defined 14 day window (Table N).

 

In the prospective arm of the study, four specimens that were identified as negative by T2Bacteria but positive by blood culture were evaluated by running a second archived blood sample.  Two of the four samples generated positive results by T2Bacteria that were in agreement with blood culture, one for S. aureus and the other for E.coli.

Table I: T2Bacteria Panel Overall Performance for Prospective and Seeded Arms

 

Sensitivity

 

95% CI

 

Specificity

 

95% CI

95.4% (209 / 219)

 

91.8%-97.5%

 

97.9% (8,416/8,596)

 

97.6%-98.2%

 

Table J: T2Bacteria Panel Combined Performance for Prospective and Seeded Arms

 

 

 

Sensitivity (PPA)

 

Specificity (NPA)

Species

 

Sensitivity

 

95% CI

 

Specificity

 

95% CI

E. coli

 

90.9% (30/33)

 

76.4% - 96.9%

 

95.4% (1637/1716)

 

94.3% - 96.3%

E. faecium

 

100.0% (41/41)

 

91.4% - 100.0%

 

99.5% (1717/1726)

 

99.0% - 99.7%

K. pneumoniae

 

100.0% (46/46)

 

92.3% - 100.0%

 

98.6% (1697/1721)

 

97.9% - 99.1%

P. aeruginosa

 

97.7% (43/44)

 

88.2% - 99.6%

 

97.7% (1682/1722)

 

96.9% - 98.3%

S. aureus

 

89.1% (49/55)

 

78.2% - 94.9%

 

98.4% (1683/1711)

 

97.6% - 98.9%

 

 

PPA (sensitivity) calculated against samples with titer levels at or above limit of detection (LoD) in Seeded Arm and blood culture positives in Prospective Arm

 

NPA (specificity) calculated from all samples (including below LoD and unspiked negative samples) as the total number of negative channels divided by total number of non-spiked channels in Seeded Arm and blood culture negatives in Prospective Arm.

 

Table K: T2Bacteria Panel Seeded Sample Performance

 

Sensitivity

 

95% CI

 

Specificity

 

95% CI

96.7% (174 / 180)

 

92.9%-98.5%

 

98.9% (1,483/1,500)

 

98.2%-99.3%

 

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PPA (sensitivity) calculated against samples with titer levels at or above limit of detection (LoD)

 

Table L: T2Bacteria Panel Seeded Sample Performance

 

 

 

Sensitivity (PPA)

 

Specificity (NPA)

Species

 

PPA

 

95% CI

 

NPA

 

95% CI

E. coli

 

90.9% (20/22)

 

72.2 - 97.5%

 

97.3% (292/300)

 

94.8 - 98.6%

E. faecium

 

100% (40/40)

 

91.2 - 100%

 

100% (300/300)

 

98.7 - 100%

K. pneumoniae

 

100% (40/40)

 

91.2 - 100%

 

99.3% (298/300)

 

97.6 - 99.8%

P. aeruginosa

 

97.4% (38/39)

 

86.8 - 99.5%

 

97.7% (293/300)

 

95.3 - 98.9%

S. aureus

 

92.3% (36/39)

 

79.7 - 97.3%

 

100% (300/300)

 

98.7 - 100%

 

 

PPA (sensitivity) calculated against samples with titer levels at or above limit of detection (LoD)

 

Table M: T2Bacteria Panel Overall Performance for Prospective Arm

 

Sensitivity

 

95% CI

 

Specificity

 

95% CI

89.7% (35/39)

 

76.4%-95.9%

 

97.7% (6,933/7,096)

 

97.3%-98.0%

 

Table N: T2Bacteria Panel Performance as Compared to Blood Culture — Prospective Arm

 

 

 

Sensitivity (PPA)

 

Specificity (NPA)

Species

 

Sensitivity

 

95% CI

 

Specificity

 

95% CI

E. coli

 

90.9% (10/11)

 

62.3 - 98.4%

 

95.0% (1345/1416)

 

93.7 - 96.0%

E. faecium

 

100.0% (1/1)

 

20.7 - 100%

 

99.4% (1417/1426)

 

98.8 - 99.7%

K. pneumoniae

 

100.0% (6/6)

 

61.0 - 100%

 

98.5% (1399/1421)

 

97.7 - 99.0%

P. aeruginosa

 

100.0% (5/5)

 

56.6 - 100%

 

97.7% (1389/1422)

 

96.8 - 98.3%

S. aureus

 

81.3% (13/16)

 

57.0 - 93.4%

 

98.0% (1383/1411)

 

97.1 - 98.6%

 

Table O:  Summary of T2(+)/BC(-) Results in Prospective Arm

 

 

Species

 

T2(+) / BC(-) total

 

Other Blood Culture positive1

 

Sequencing positive2

 

T2(+) / BC(-)

associated with strong evidence of infection3

 

T2(+) / BC(-) associated with other evidence of infection Non-Blood Matrices Culture Positive4

 

T2(+) / BC(-) associated with no evidence of infection

E. faecium

 

9

 

2

 

2

 

44.4% (4/9)

 

33.3% (3/9)

 

22.2% (2/9)

E. coli

 

63

 

12

 

9

 

33.3% (21/63)

 

12.7% (8/63)

 

54.0% (34/63)

K. pneumoniae

 

22

 

6

 

8

 

63.6% (14/22)

 

13.6% (3/22)

 

22.7% (5/22)

P. aeruginosa

 

33

 

3

 

8

 

33.3% (11/33)

 

12.1% (4/33)

 

54.5% (18/33)

S. aureus

 

28

 

16

 

3

 

67.9% (19/28)

 

17.9% (5/28)

 

14.3% (4/28)

Total

 

155

 

39

 

30

 

44.5% (69/155)

 

14.8% (23/155)

 

40.7% (63/155)

 

1Blood cultures positive for the T2 species identified other than the paired blood culture and processed within ± 14 days of collection of the T2 sample.

2 Sequencing from blood samples drawn at the same time as collection of the T2 sample and positive for the T2 species identified, where this sequencing assay was only run on subjects without positive evidence from other sample sources (footnote 1 and 4).

3 Strong evidence defined as a T2 positive result associated with a blood culture positive from a different draw than T2 draw or a sequencing positive result from a blood sample drawn concurrently with the T2 draw.

4 Other cultures from non-blood sample matrices positive for the T2 species identified within ± 14 days of collection of the T2 sample.

 

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Customer Presentations

 

Investigators at the Catholic University School of Medicine in Rome, Italy, presented interim data from a study in which T2Bacteria achieved 100% sensitivity and 97% specificity in analytical studies, and in clinical studies, it identified patients with infection in as fast as four hours, while blood culture took up to five days, inclusive of multiple cases where T2Bacteria identified patients missed by blood culture with proven infections.

 

Investigators at the Gemelli Hospital in Rome, Italy published a study in the Journal of Antimicrobial Chemotherapy (April 2018) entitled “T2Bacteria magnetic resonance assay for the rapid detection of ESKAPE pathogens directly in whole blood. This prospective study was with 129 adult patients in the ICU and ED. It showed that T2Bacteria achieved faster time to species ID than blood culture, or BC: 5.5h ±1.4h vs. BC 25.2h ± 15.2h (P<0.001) and faster time to negative results 6.1h ± 1.5h vs. BC 120.0h ± 0.0h (p<0.001). Additionally, T2Bacteria performed with a sensitivity and specificity of 90% and 98%, respectively, according to true infection criteria.

 

Investigators at Lee Health in Fort Myers, FL reported at MAD-ID in May 2018 a study entitled “Early experience with the T2Bacteria Research Use Only (RUO) Panel at a community hospital”. This prospective study was conducted at Lee Health, Fort Myers, FL in 28 adult patients presenting to the ED. It showed that T2Bacteria allowed testing from whole blood samples and provided final results within 4 hours. T2Bacteria provided positive and negative results approximately 20 hours and 122 hours sooner than BCs, respectively (p<0.001). It detected 5 organisms not identified by BC and in these 28 patients greater than 30 opportunities for de-escalation of coverage based on negative results for S. aureus or P. aeruginosa were identified.

 

Another group of investigators presented at ASM Microbe in June 2018 a study entitled “Validation of a rapid diagnostic test on whole blood for early identification of pathogens in patients in the intensive care unit.” This a combined prospective and retrospective study conducted by Northwestern University with 91 retrospective samples and 58 prospective samples from patients admitted to the ICU. Overall, T2Bacteria was 87% sensitive and 95% specific for the detection of six different organisms compared to BC; The calculated specificity is limited by comparison to BC because many studies demonstrate that BC itself is poorly sensitive. As further support, T2Bacteria detected organisms in the blood when BC was negative but evidence of infection in the kidney, bone, soft-tissue, intra-abdominal area, or lungs was available; a positive T2Bacteria result in this setting may indicate poor source control, inappropriate antibiotics or poor host defenses.

 

Researchers from UPMC presented at ASM Microbe 2018 and ID Week in October 2018 on the pivotal T2Bacteria study in a presentation entitled “Clinical performance of T2Bacteria among patients with bloodstream infections due to five common bacterial species.” This pivotal, clinical multicenter prospective trial was conducted in 11 U.S. Centers with 1427 subjects from presenting to the ICU or ED. They further reported in the pivotal study manuscript that overall, T2Bacteria detected ~66% of BSIs, excluding common contaminants. The mean time to BC+ was 38.5h ± 32.8h; the mean time to BC speciation was 71.7h ± 39.3h; mean time to T2B result was 3.6h ± 0.2h – 7.70hr ± 1.38h; T2Bacteria demonstrated 90% per patient specificity in detecting Blood Stream Infection (BSI) and per assay specificity of 90%. The study pointed out that potential advantages of T2Bacteria over Blood Culture include detection of bacteremia several days before Blood Culture (3-5 hours versus 2-3 days), diagnosing infections missed by Blood Culture, identifying patients with incorrect antibiotics and patients with extra-blood site infections.

 

At the 2019 ECCMID conference, Dr. Tom Walsh from New York Presbyterian / Cornell Hospital highlighted the clinical utility of T2Bacteria in the hematologic malignancy and stem cell transplant patient population. Within his institution, T2Bacteria showed a 75% positive predictive agreement with blood culture and 98% negative predictive agreement and covered 80% of significant species detected by blood culture.

 

Also at ECCMID 2019 and EIM 2019, Dr. Christopher Voigt reported on the performance of T2Bacteria in the emergency department of Ochsner Medical Center and Tampa General Hospital.  Data from 137 emergency department patients were evaluated and relative to blood culture, T2Bacteria showed 100% positive percent agreement and 99.2% negative percent agreement. In addition, for species on T2Bacteria, the T2Bacteria assay detected 4 more positive results associated with infection than blood culture, the average time to identification was 56.6 hours faster than blood culture and T2Bacteria covered 70.5% of all species