UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM10-K

(Mark One)

For the year ended December 31, 20202021

For the transition period from to         

Commission File Number: 001-36571

T2 Biosystems, Inc.

(Exact name of registrant as specified in its charter)

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

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

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.

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, 2020,2021, 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$188.7 million based on the closing price for the common stock of $1.27$1.19 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, 202118, 2022 was 148,491,673.171,036,992.

DOCUMENTS INCORPORATED BY REFERENCE

None.

TABLE OF CONTENTS

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.

PART I.

Overview

We are an in vitro diagnostics company and leader in the rapid detection of sepsis-causing pathogens and antibiotic resistance genes. We 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 platformproducts that offersoffer a rapid, sensitive and simple alternative to existing diagnostic methodologies. We are using our T2MR technology to developdeveloping a broad set of applications aimed at lowering mortality rates, improving patient outcomes, and reducing the cost of healthcare, and lowering mortality rates by helping medical professionals make earlier targeted treatment decisions earlier. T2MRdecisions. Our technology 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. We are currently targeting a range of critically underserved healthcare conditions, focusing initially on those for which a rapid diagnosis will serve an important dual role – saving lives and reducing costs. 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. Ourcurrent development efforts primarily target sepsis, which is an area of significant unmet medical need in which existing therapies could be more effective with improved diagnostics.

OnOur primary commercial products include the T2Dx^® Instrument, the T2Candida^® Panel, the T2Bacteria^® Panel, the T2Resistance^® Panel, and the T2SARS-CoV-2™ Panel.

History

In September 22, 2014, we received market clearancemarketing authorization from the United States Food and Drug Administration, or 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 most clinically relevant species of Candida, a fungal pathogen known to cause sepsis, directly from whole blood. Onblood specimens. The T2Dx Instrument and T2Candida Panel were CE marked in the European Union, or EU, in July 2014.

In 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,blood specimens. The T2Bacteria Panel was CE marked in the T2Cauris™EU in June 2017.

In February 2019, our T2Resistance®™ 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. Theor T2Resistance, Panel receivedwas granted FDA Breakthrough Device designation in February 2019 and was granted a CE Mark in November 2019. An additional diagnostic application2019, it was CE marked 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.EU.

In September 2019, the Biomedical Advanced Research and Development Authority, (“BARDA”) or 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-blooda next-generation diagnostic panels that will run on the T2Dx.instrument, a comprehensive sepsis panel, and a multi-target biothreat panel. In September 2020, BARDA exercised the first contract option valued at $10.5 million. OnIn April 2021, BARDA agreed to modify the contract to accelerate product development by advancing future deliverables, and adding a U.S. T2Resistance Panel into Option 1 of the BARDA contract. In September 2021, BARDA exercised Option 2A valued at approximately $6.4 million to further advance the new product development initiatives. In December 2021, we initiated the U.S. clinical trials for the T2Resistance and T2Biothreat Panels.

In June 30, 2020, we announcedlaunched the U.S. launch ofT2SARS-CoV-2 Panel, our COVID-19 molecular diagnostic test, the T2SARS-CoV-2 Panel, after validation of the test meetingpursuant to the FDA’s requirements forpolicy permitting COVID-19 tests to be marketed prior to receipt of an Emergency Use Authorization, (EUA).or EUA, subject to certain prerequisites. In August 2020, the FDA issuedgranted an EUA to the T2SARS-CoV-2 Panel for the T2SARS-CoV-2 Panel.qualitative direct detection of nucleic acid from SARS-CoV-2 in upper respiratory specimens (such as nasal, mid-turbinate, nasopharyngeal, and oropharyngeal swab specimens) and bronchoalveolar lavage specimens from individuals suspected of COVID-19 by their healthcare provider. 

Clinical Need

Sepsis is the body’s overwhelming and life-threatening response to infection that can lead to tissue damage, organ failure, and death. 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.

SepsisIt 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),or HHS, it was estimated that the annual cost of sepsis to the USU.S. 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 United States Centers for Disease Control and Prevention, or CDC, estimates that sepsis causes more than 270,000 American deaths per year. SepsisThe most common cause of sepsis is typically caused by one or morebacterial, Gram positive and Gram negative pathogens, while Candida species are the most common cause of five Candida species or over 25 bacterial pathogens, and effective treatment requires the earlyfungal sepsis. Early detection and identification of these specific targetsepsis causing pathogens in a patient’s bloodstream. is critical for effective treatment and positive patient outcomes.

Today, sepsis issepsis-causing pathogens are typically diagnoseddetected through a series of blood cultures, followed by post-blood culture species identification if a blood culture tests positive.and antimicrobial susceptibility testing. These methods have substantial diagnostic limitations that lead to a high rateincluding the risk of false negative test results, a delay of up to several days in administration of targeted antimicrobial treatment, and the incurrence of unnecessary hospital expense. 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.

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%.

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 believeIn 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, coupled with 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 CDC called “one of our sepsis products,most serious health threats.” Currently, high risk patients are typically initially treated with broad spectrum antibiotic therapy that 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 either resistant to, or not covered by, broad spectrum antibiotic therapy.

Products - Commercially Available

T2Dx Instrument

Our T2Dx Instrument, which includeis FDA-cleared for use with our T2Candida and T2Bacteria panels and CE marked in the EU for use with our T2Candida, T2Bacteria and T2Resistance Panels, is a fully automated, easy-to-use, bench-top instrument that is capable of running a broad range of diagnostic tests from patient samples, 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 placed onto a disposable test cartridge, which is pre-loaded with all necessary reagents and consumables. 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 can be printed or connected directly to the hospital or laboratory information system.

The T2Dx Instrument eliminates the need for sample purification and analyte extraction often required by other diagnostic technologies, which increases sensitivity and specificity, 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 commercially available test panels designed to run on the T2Dx Instrument are T2Candida, T2Bacteria, T2Resistance, and T2Cauris, will redefineT2SARS-CoV-2, which are focused on identifying life-threatening pathogens associated with sepsis and COVID-19.

T2Candida

Our T2Candida Panel, which is FDA-cleared in the standardU.S. and CE marked in the EU, is a direct-from-blood test that identifies the most lethal form of care incommon blood stream infections that cause sepsis, management while lowering healthcare costs by improving both the precisioncandidemia, which has an average mortality rate of approximately 40%. T2Candida identifies five species of Candida, directly from certain human whole blood specimens, including Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, and the speed to detectionCandida parapsilosis. These species account for 90% of sepsis-causing pathogens. Candida blood stream infections.

According to a 2005 report published in Antimicrobial Agents and Chemotherapy, the high mortality rate associated with Candida infection 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 Clinical MicrobiologyRespiratory and Critical Care Medicine in 2010,2009, providing targeted

antifungal therapy for patients with bloodstream infections can be delayed up to 72within 24 hours due toof the wait timepresentation 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 cultureculture-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.In another study published2014 we received FDA marketing authorization for the T2Candida Panel in Clinical Infectious Diseasesthe U.S. and in 2012,July 2014 the delayed administration of appropriate antifungal therapyT2Candida Panel was associated with higher mortality among patients with septic shock attributed to Candida infection and, on that basis,CE marked in the study concluded that more rapid and accurate diagnostic techniques are needed.EU.

OurIn our pivotal clinical trial for T2Candida, we demonstrated that it can deliver actionabledelivered 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.diagnostics. 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 four4 to six6 hours versus 24 to 144 hours for blood culture. In the pivotal clinical trial, the T2Candida Panel also demonstrated overall sensitivity of 91.1% and overall specificity of 99.4%. 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 reducereduced the costs of care by $26,887 per Candida patient and that rapid detection of Candida reducesreduced 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:

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:

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.

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 thatT2Candida 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.

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 studyfound. 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:

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:

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, faster, significantly improving patient outcomes and reducing hospital costs. We further believe that the adoption of the T2Dx Instrument 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

Our T2Bacteria Panel, which is FDA-cleared in the U.S. and CE marked in the EU, is a multiplex diagnostic paneldirect-from-blood test that detects the majorcertain bacterial pathogens associated with sepsis that are frequently not covered by first-line antibiotics, often referred to as the “ESKAPE pathogens.” The T2Bacteria Panel is FDA-cleareddesigned for the detection of most of the ESKAPE pathogens from human whole blood specimens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and the CE marked T2Bacteria Panel in addition identifies a sixth species, Acinetobacter baumannii, with a positive percent agreement ranging from 81.3% to 100% and the negative percent agreement ranging from 95.0% to 100.0%. The ESKAPE pathogens are responsible for the majority of nosocomial infections and are often capable of “escaping” the biocidal action of antimicrobial agents, exhibiting multidrug resistance and virulence. These pathogens cause over 2 million illnesses and 23,000 deaths per year. In the pivotal clinical trial the T2Bacteria Panel also demonstrated overall sensitivity of 90% and overall specificity of 98%.

A systematic review of the clinical and economic impact of antibiotic resistance reveals that the ESKAPE pathogens are associated with the highest risk of mortality, thereby resulting in increased health care costs. In the T2Bacteria clinical trial, the mean time for the T2Bacteria Panel to result was 6.46 hours, while the result for blood culture was substantially longer with a mean time to result of 123.8 ± 9 hrs. for a negative result and 51.0 ± 43.0 hrs. for a positive result, and the mean time to species identification was 83.7 ± 47.6 hours. A study published in the United StatesMicrobiologyOpen found that the T2Bacteria Panel decreased the time to species identification on average by 55 hours faster than blood culture. The rapid detection and CE-Marked and available commerciallyidentification of the pathogens by the T2Bacteria Panel in Europe and other countries that acceptpositive specimens also allowed for the CE mark.early antimicrobial stewardship interventions with faster initiation of an effective targeted antibiotic therapy, in some of the patients which was captured in another study presented by Paggi R, et al. July 2021 with 29.2% of patients with T2Bacteria runspositive results switched to an appropriate therapy. Seitz T et al presented on the T2Dx and addressesEvaluation of the same approximately 6.75 million symptomatic high-risk patients as T2Candida while also expanding our reachclinical impact of the T2MR for the Diagnosis of Blood Stream Infections, where the data showed that the use of T2Bacteria led to an additional two million people presenting with symptomsa shorter length of infection in the emergency room setting. We believe that these factors make the United States market opportunitystay for T2Bacteria over $1.0 billion,of 10 days as compared with the 13 days for blood culture. The T2Bacteria Panel can ensure prompt diagnosis, assist clinicians in making clinical decisions about patient management such as the escalation or de-escalation of therapy faster, with improvement in patient care and that T2Bacteria hasoutcomes, by potentially shortening the potentialtime of exposure to achieve similar performance capabilitiesineffective antibiotics, which may reduce the chances of developing anti-microbial resistance. Our sepsis panels are to be used in conjunction with whole blood cultures, and provide similar benefits as T2Candida.

Ondetecting the ESKAPE pathogens directly from whole blood in 3-5 hours, potentially enables therapy targeted to these organisms, which are often resistant to common empiric therapies. Detecting these commonly resistant organisms in 3-5 hours pre-culture is more critical than rapidly detecting those organisms which typically respond to common empiric therapies. In August 2, 2019, CMS granted approval for ana New Technology Add-on Payment, or NTAP, payment for the T2Bacteria Panel, foreffective October 1, 2019, which has been extended through the 2022 fiscal year 2020.year. 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, U.S. 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 wereare eligible for the NTAP payment for any in-patient T2Bacteria Panel teststesting performed on Medicare patients, beginning October 1, 2019. Theto a 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)per 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.

The design ofWe believe T2Bacteria can enable clinicians to achieve targeted antimicrobial therapy, faster, significantly improving patient outcomes and reducing hospital costs. We further believe that 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:

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

Table B

Overall Sensitivity and Specificity by Test

Table C

Study Arm Sensitivity and Specificity by Test

Table D

T2Candida Limit of Detection

Table E

Sensitivity Sub-Analysis: Sensitivity by Species Relative to LoD

Table F

Sensitivity Sub-Analysis: Sensitivity by Titer Level

Table G

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

Table H

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

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:

In this study, the following observations were reported:

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

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:

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 “Comparisonadoption of the T2Dx Instrument with T2Candida Diagnostic Panel and Automated Blood Culture in the Detection of Candida Species Using Seeded Blood Samples” in Diagnostic MicrobiologyT2Bacteria can enable clinicians to make earlier and Infectious Disease in 2013:

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

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:

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.

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 Candidaantimicrobial drugs. 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.

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 6^th 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. 

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:

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

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

Table K: T2Bacteria Panel Seeded Sample Performance

Table L: T2Bacteria Panel Seeded Sample Performance

Table M: T2Bacteria Panel Overall Performance for Prospective Arm

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

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

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.

Customer Presentations

T2Resistance

We have also developed theOur T2Resistance Panel, which is CE marked in the EU, is a direct-from-blood test that simultaneously detects 13thirteen resistance genes from both gram-positive and gram-negative pathogens. These targets includeT2Resistance is designed to identify the most clinically important carbapenem resistance genes (KPC,KPC, OXA-48, NDM, VIM, IMP), which areand IMP. Carbapenem resistance has been listed on the CDC Urgent Threat list for antibiotic resistance; CTXM-14 and CTXM-15,resistance. The T2Resistance Panel also detects a major source of extended spectrum beta lactamases, (ESBLs);or ESBLs, CTXM-14 and CTXM-15; AmpC beta-lactamase genes (CMY, DHA); detection of vanA/BvanA vanB resistance genes, which are responsible for vancomycin resistant gram-positive enterococcus; and the detection of the methicillin resistance genes mecC and mecA, which cause methicillin resistant Staphylococcus aureus (MRSA).  Initial clinicalaureus. Clinical performance data demonstrates the carbapenemase targets ondemonstrated that the T2Resistance Panel identify theseidentified carbapenemase resistance genes with an average time of 5.3 hours compared to an average of 30 hours (and up to 95 hours) with conventional methods.hours. Antibiotic resistance is recognized by the WHO as ‘one“one of the biggest threats to global health, food security, and development today’. today.”

We believe the T2Resistance Panel has the potentialcan help to prevent the spread of multidrug-resistant organisms and improve patient outcomes by enabling rapid identification of the genes and species associated with antibiotic resistance – enabling correct targeted therapy and the reduction of unnecessary antibiotic use, which is thea primary cause of antibiotic resistance. Most importantly, these tests canhave the potential to enable more patients to get on the rightappropriate targeted therapy quicker, potentially reducingfaster, and thereby reduce mortality and hospitalization cost. Finally, these tests could also be used to accelerate clinical trials for new antibiotics and reduce the time to commercial availability.costs. The T2Resistance Panel received FDA Breakthrough Device designation in February 2019 and was granted a CE Markmarked in the EU in November 2019 and is available for purchase in the United States as a Research Use Only product.Research-Use-Only, or RUO product, meaning that it is in the laboratory research phase of development and is being shipped or delivered for an investigation that is not subject to FDA regulations governing investigational device studies. In December 2021 we initiated a U.S. clinical trial for the T2Resistance Panel. The clinical trial is expected to be completed in 2022, and we believe the data from this trial may enable filing a submission to the FDA in 2022.

T2SARS-CoV-2 Panel

Our T2SARS-CoV-2 Panel, which is commercially available in the United States under an EUA is designed to detect SARS-CoV-2, the virus that is responsible for COVID-19 infections, in certain patients. The T2SARS-CoV-2 Panel provides sample-to-answer results in less than two hours, utilizing a nasopharyngeal swab sample. Clinical testing on known positive and negative patient samples showed a sensitivity of 95% and specificity of 100%. The T2SARS-CoV-2 Panel runs on our T2Dx Instrument, and is capable of performing seven tests simultaneously. The Company has conducted a number of in silico analyses which have demonstrated that the T2SARS-CoV-2 was capable of detecting currently known variants of the SARS-CoV-2 virus.

In March 2020, we announced that we had licensed certain technology for the development of a rapid test for COVID-19 from the Center for Discovery and Innovation, or CDI, at Hackensack Meridian Health. Under this license agreement, T2 Biosystems is authorized to use the CDI technology and adapt the CDI-developed COVID-19 test to the T2 Biosystems platform, and market and distribute the test in places of need amid the expanding pandemic. In August 2020, we received an EUA from the FDA to market the T2SARS-CoV-2 Panel for thequalitative direct detection of nucleic acid from SARS-CoV-2 in upper respiratory specimens (such as nasal, mid-turbinate, nasopharyngeal, and oropharyngeal swab specimens) and bronchoalveolar lavage specimens from individuals suspected of COVID-19 by their healthcare provider. COVID-19 has since become a global pandemic infecting over 450 million individuals and causing over 6 million deaths as of March 10, 2022.

SARS-CoV-2 has a wide-ranging clinical manifestation that contributes to increased morbidity and mortality from mild symptoms to hypoxic respiratory failure, acute respiratory distress syndrome, thromboembolic disease, cytokine release syndrome, multiorgan failure, and in some, secondary infections. A study by David R. Little et al has shown that patients who are hospitalized with COVID-19 are more likely to develop sepsis and septic shock when compared to patients admitted with influenza during the 2016, 2017, or 2018 flu seasons. COVID-19 pneumonia typically presents with fever, cough and dyspnea and this has led to the use of empirical antibiotics in patients by the physicians while waiting for laboratory and radiological results further compounding the problem of rational antimicrobial agent usage.

In a multicenter clinical study published in 2021 of hospitalized patients that were tested for COVID-19, the investigators found that SARS-CoV-2 positive patients were almost 2 times as likely to have a secondary pathogen detected during hospital onset period (42.4% vs 22.2%). There was also an increase in length of hospital stay for COVID-19 positive patients with a secondary positive pathogen detected vs patients with a negative pathogen specimen (13.7 vs 8.2 days). The data from the study additionally showed that 6 out of the top 10 pathogens detected by blood cultures of admitted patients are identified by the T2Bacteria and T2Candida panels. The existing reimbursement codes support our sepsis products and COVID-19 product and we anticipate the same for our product candidates in development.

Products - in Development

T2Biothreat

Our T2Biothreat Panel is a direct-from-blood test panel that is designed to run on the T2Dx Instrument and to simultaneously detect six biothreat pathogens identified as threats by the U.S. Government, including Bacillus anthracis, Burkholderia mallei, Burkholderia pseudomallei, Francisella tularensis, Richettsia prowazekii and Yersinia pestis. In December 2021, the Company initiated a U.S. clinical trial for the T2Biothreat Panel that includes positive samples being prepared and analyzed at a high-containment Biosafety Level 3 laboratory and negative samples being analyzed at a clinical site. The clinical trial is expected to be completed in 2022, and we believe the data from this trial may enable filing a submission to the FDA during 2022.

Comprehensive Sepsis Panel

Our comprehensive sepsis panel is a direct-from-blood test panel that is designed to run on our next generation instrument. The new test panel is designed to detect greater than 95% of all bloodstream infections caused by bacterial and Candida species, and antibiotic resistant markers identified as threats by the CDC, in a single test and to provide a time to result of approximately 3 hours. We believe this test panel, if successfully developed and authorized by the FDA, could be positioned as the primary test for patients at risk of sepsis, and substantially change the blood culture based laboratory workflow.

Next Generation Instrument

Our next-generation instrument, which is being developed in conjunction with our comprehensive sepsis panel, is designed to be fully automated, on-demand, and random access. This design is similar to our current T2Dx Instrument but incorporates faster turnaround times and is designed to detect an increased number of pathogens and resistance genes from a single, whole blood sample.

T2Cauris

In September 2017, we entered into an agreement with the CDC, pursuantOur T2Cauris™ Panel is designed to which the CDC agreed to validate the T2Dx in its laboratory for potentially testing and monitoring the emergence and outbreaksprovide direct detection of the emerging superbug Candida auris.auris in patient skin, patient blood, and hospital environmental samples and is now available for RUO. The CDC evaluated the T2Cauris™ Panel swab test on patient skin samples and published their findings in Mycoses.

Candida auris is a multi-drug resistant pathogen recognized by the CDC as a serious global health threat because it can be resistant to all three major classes of antifungal drugs and is difficult to identify. The CDC has also reported that more than one-in-three patients with Candida auris infections have died. Unlike most other species of Candida, Candida auris can spread quickly in a hospital making rapid identification and hospital environment surveillance a critical component of containing these outbreaks. Existing laboratory methods that detect Candida auris, including blood culture, suffer from prolonged detection times and low accuracy, which exacerbates the challenge in the fight to contain the superbug. Recently, reported cases have surged internationally, and the CDC has reported a significant increase in infected patients in the United States. According to the European Centre for Disease Prevention and Control, hospital outbreaks have occurred in the United Kingdom and Spain. Because Candida auris can be resistant to most treatment options and can spread so quickly, these hospital outbreaks have been difficult to contain by even the most enhanced control measures.

The goals of the CDC collaboration were to use the T2Dx Instrument to (i) validate the detection of Candida auris from patient skin samples and hospital environmental samples, (ii) validate a process for surveillance of Candida auris in healthcare facilities from skin and environmental samples, and (iii) assist state and local public health labs in combating the outbreak. In a study presented at ASM Microbe 2018 regarding the detection of Candida auris, it was found that the T2MRour technology provided accurate diagnostic results from patient skin samples. The study concluded

T2Lyme

Our T2Lyme Panel is a direct-from-blood test panel designed to run on the T2Dx Instrument to identify the bacteria that T2MR could be usedcause Lyme disease. We believe the T2Lyme Panel may benefit from similar advantages provided by our technology, including the potential for high sensitivity, high specificity, ease of use and rapid time to result. T2Lyme is designed to provide a more rapid detectionaccurate and timely diagnosis ofCandida auris in patient skin swabs. This study was subsequently published as an article entitled “Evaluation of a new T2 Magnetic Resonance assay for rapid detection of emergent fungal pathogen Candida auris on clinical swab samples” in the journal Mycoses.  

T2Lyme

We believe that T2MR can also address the significant unmet need associated with Lyme disease a tick-borne illness that can cause prolonged neurologicalcausing pathogens, with the goal of preventing the evolution of the disease and musculoskeletal disease. For patientsto its later stages with Lyme disease, early diagnosis and appropriate treatment significantly reduces both the likelihood of developingassociated neurological and musculoskeletal disorders, as well as the significant costs associated with treating these complications. Multiple diagnostic methods are used to test for Lyme disease today, which are labor-intensive, can take weeks to process, and are subject to high false negative rates due to their inability to detect the disease, making each method unreliable in the diagnosis of the condition. Because of these limitations, patients are frequently misdiagnosed or are delayed in the diagnosis of this disease.diseases. 

According to the CDC, Lyme disease affects approximately 30,000 people in the U.S. each year, but the CDC also estimates that the actual number is closer to 360,000 due to under-reporting because of poor diagnostic methods. Approximately 3.4 million tests are run for Lyme disease each year, including serology testing, PCR techniques and blood culture, which has low sensitivity and takes approximately two to three weeks to provide results. Inadequate identification of Lyme disease may lead to antibiotic resistance, significant costs, and transmission of the disease through healthcare procedures such as blood transfusion. The misdiagnosis of Lyme disease has been reported to have an annual cost of more than $10,000 per patient in the United States, representing over $3 billion per year.

Our product candidate, T2Lyme, will identifyWe believe that our technology can address the bacteria that cause Lyme disease directly from the patient’s blood, without thesignificant unmet need for blood culture which, for the bacteria associated with Lyme disease, a tick-borne illness that can take several weeks. The test panel is expected to be run on the T2Dx, the same instrument currently used to run all commercially available test panels. We anticipate the T2Lyme test panel to benefit from similar advantages provided by T2MR, including high sensitivity, high specificity, ease of usecause prolonged neurological disease and rapid time to result. T2Lyme may provide accurate and timely diagnosis ofmusculoskeletal disease. For patients with Lyme disease, early diagnosis and may preventappropriate treatment

significantly reduces both the evolutionlikelihood of the disease to its later stages with associateddeveloping neurological and musculoskeletal diseases. disorders, as well as the significant costs associated with treating these complications. Multiple diagnostic methods are used to test for Lyme disease today, which are labor-intensive, can take weeks to process, and are subject to high false negative rates due to their inability to detect the disease, making each method unreliable in the diagnosis of the condition. Because of these limitations, patients are frequently misdiagnosed or are delayed in the diagnosis of this disease.

Based on feedback from the FDA and the dynamics of the Lyme disease testing market, we believe that the most expeditious path for commercializing the T2Lyme panelPanel may be by offering the test with a single partner as a lab developed test our and our current goalpartner.

Strategy

Our objective is to potentiallyestablish our products as the standard of care for clinical diagnostics. To achieve this objective, our strategy is to focus on the following three corporate objectives:

In 2021, we entered into contracts for 32 T2Dx Instruments, including 17 instruments during the fourth quarter. Our installed base of T2Dx Instruments includes 89 in the U.S. and 55 internationally. We generated sepsis panel revenue of $5.1 million representing an increase of 46% compared to the prior year. In the U.S., we achieved annualized sepsis test utilization of $118,000 per legacy T2Dx Instrument, an increase of 37% compared to the prior year. We continue to believe that, over time, annualized sepsis test utilization will reach $200,000 per instrument in the U.S.

To further penetrate the market we have T2Lyme validatedmaterially expanded our commercial team. In the U.S., we have 20 sales territories providing geographic hospital coverage; increased from just 2 sales territories in 2020. We recently hired Brett Giffin as Chief Commercial Officer, and he leads our commercial growth initiatives and is directly responsible for global sales, marketing, service and customer support.

As recently announced, we continue to expand our international distribution network which allows our products to be marketed and sold in more countries. Hospitals around the world face similar challenges when caring for patients suspected of sepsis and we are leaning into this opportunity. In the second half of 2021, we initiated commercialization in Singapore, South Korea, Taiwan, and Mexico by entering into distributor agreements in each of these countries. Shipments to our distribution partners were initiated in the second half of 2021, with 2 T2Dx Instruments shipped to Singapore during the third quarter and 4 T2Dx Instruments shipped to South Korea during the fourth quarter. Early in 2022, we have continued to expand our distribution networks with agreements in Norway, Finland and Turkey and have hired an International Business Manager to focus on the Asia Pacific and Latin America regions.

While sepsis remains the primary focus and the top commercial priority for T2 Biosystems, the introduction of our T2SARS-CoV-2 Panel in 2020 has allowed us to significantly increase our installed base of T2Dx Instruments and gain access to U.S. hospitals that were previously unfamiliar with our products and services. The expanded installed base of 45 T2Dx instruments being used for COVID-19 testing will eventually play a partner’s labmeaningful role in increasing sepsis test panel sales because each of these customers has committed to evaluating our sepsis tests.

Despite the broad use of at-home COVID-19 antigen tests, hospitals continue to rely on molecular or PCR tests, including the T2SARS-CoV-2 Panel, to identify acute COVID-19 infections. The early 2021 surge in COVID-19 infection rates has translated to strong demand for commercial launch.

We expect that existing CPT codesour T2SARS-CoV-2 Panel from U.S. hospitals during the first quarter of 2021, and while we believe there will be used to facilitate reimbursement ofcontinued demand for our T2Lyme diagnostic panel.

T2Lyme identifies the microorganisms responsible for most cases of Lyme diseaseT2SARS-CoV-2 Panel, we expect a decrease in North America and Europe and are detected directly in whole blood using T2MR and the same methodology used in the T2Candida and T2Bacteria tests. Preliminary data demonstrate that the detection of three species of Borrelia at limits of detection as low as 10 cells/mL was achieved in spiked whole blood and detection of spirochetes in clinical samples from patients with early stage Lyme disease using T2MR.  

T2SARS-CoV-2

On March 24, 2020, we announced that we had licensed certain technology for the development of a rapid test for COVID-19 from the Center for Discovery and Innovation (CDI) at Hackensack Meridian Health. Under this license agreement, T2 Biosystems is authorized to use the CDI technology and adapt the CDI-developed COVID-19 test to the T2 Biosystems platform, and market and distribute the test in places of need amid the expanding pandemic. On June 30, 2020, we announced the US launchsales of our COVID-19 molecular diagnostic test compared to 2021.

Enhancing our Operations. To sustain growth and drive adoption and utilization of our products over the T2SARS-CoV-2 Panel, after validationlong-term we continue to implement changes to our operations that enable a more efficient business model.

We have focused on scaling our manufacturing capabilities and strengthening our supply chain. Over the past year, we have increased our manufacturing capabilities from being able to produce 2,000 tests per week to over 7,000 tests per day. To achieve this level of production, we reviewed and refined our business and manufacturing processes, as well as our business systems. We assessed multiple tools and determined that one of the best ways to improve our efficiency was by implementing a new Oracle ERP system, which we implemented during the third quarter of 2021.

In the third quarter of 2021, we signed a lease that will consolidate our existing operations into a single 70,000 square foot, state-of-the-art life sciences facility in Billerica, Massachusetts, to accommodate current and future growth. This new facility will serve as our corporate headquarters and main manufacturing hub. It will also house all of our R&D labs that will aid in the advancement of our future products. This move, which we expect will commence in the second half of 2022, will produce a significant reduction in rent expense, accommodate our manufacturing expansion, and reduce costs through efficiencies gained in working in and maintaining one facility.

During 2022, we also plan to make strategic investments in tooling, automation, and efficiency projects to further scale our manufacturing capabilities and continue to improve cost of goods.

Our scientific team successfully completed the milestones described under Option 1 of the BARDA contract. BARDA subsequently chose to exercise Option 2A of the contract, which is planned for the period between October 2021 and March 2022 and is valued at $6.4 million. Upon the successful completion of Option 2A, we are optimistic that BARDA will choose to exercise Option 2B.

In December 2021, we initiated the U.S. clinical trials for the T2Resistance Panel and the T2Biothreat Panel, both ahead of our previously announced schedule. The clinical trials are designed to evaluate the performance of the T2Resistance and T2Biothreat panels and support submission of marketing applications to the FDA.

The T2Resistance Panel, which runs on our T2Dx Instrument, is a direct-from-blood test meetingpanel that simultaneously detects thirteen antibiotic resistance genes from both Gram-positive and Gram-negative bacterial pathogens, which are known to cause antibiotic-resistant infections that may lead to sepsis. It provides accurate results in 3-5 hours without the FDA’s requirementsneed to wait days for a positive blood culture. The T2Resistance Panel, which is currently marketed and sold in the EU under a CE-mark, was granted Breakthrough Device designation from the FDA, which offers manufacturers an Emergency Use Authorization (EUA). On July 1, 2020, we submitted an EUA requestopportunity to interact with the FDA's experts through several different program options to efficiently address topics as they arise during the premarket review phase, and may help manufacturers receive feedback from the FDA in a timely way. All submissions for devices designated as Breakthrough Devices will receive priority review, meaning that the review of the submission is placed at the top of the appropriate review queue and receives additional review resources at FDA, as needed. The clinical trial for the T2Resistance Panel, which will include up to 1,500 patients across 10 U.S. hospitals, is estimated to cost T2 Biosystems $2.5 million and is expected to be completed in 2022, potentially enabling submission of a marketing application to the FDA forduring 2022.

The T2Biothreat Panel, which also runs on our T2Dx Instrument, is a direct-from-blood test panel that is designed to provide results in 3-5 hours, and to simultaneously detect six biothreat pathogens identified as threats by the T2SARS-CoV-2 Panel. In August 2020,CDC. The clinical trial, which includes positive samples being prepared and analyzed at a high-containment Biosafety Level 3 laboratory and negative samples being analyzed at a single site, is estimated to cost T2 Biosystems $450,000 and is expected to be completed in 2022, potentially enabling submission to the FDA issued EUA for our T2SARS-CoV-2 Panel.during 2022.

The T2SARS-CoV-2 Panelcomprehensive sepsis panel is a direct-from-blood test panel that is designed to run on our next generation instrument. This test panel is designed to detect SARS-CoV-2,greater than 95% of all bloodstream infections caused by bacterial and Candida species, and antibiotic resistant markers identified as threats by the virus thatCDC, in a single test and to provide a time to result of approximately 3 hours. We believe this test panel, if successfully developed and authorized by the FDA, could be positioned as the primary test for patients at risk of sepsis, and substantially change the blood culture based laboratory workflow.

The next-generation instrument, which is responsible for COVID-19 infections. The T2SARS-CoV-2 Panel provides sample-to-answer resultsbeing developed in less than two hours, utilizing a nasopharyngeal swab sample. Clinical testing on known positiveconjunction with our comprehensive sepsis panel, is designed to be fully-automated, on-demand, and negative patient samples showed a sensitivity of 95% and specificity of 100%. The T2SARS-CoV-2 Panel runs onrandom access. This design is similar to our FDA-clearedcurrent T2Dx Instrument but incorporates faster turnaround times and is capabledesigned to detect an increased number of performing seven tests simultaneously. An pathogens and resistance genes from a single, whole blood sample. The design is approaching completion, and based on the currently outlined schedule, we expect to have a fully functioning Beta unit in silico analysis conducted by the Company in Marchfirst half of 2021 demonstrated that2022. Once the T2SARS-CoV-2build-out is capable of detecting all known variants ofcomplete, we will merge prototypes with the SARS-CoV-2 virus.

Clinical data from Wuhan, China showed that for COVID-19 patients, bacterialassay and fungal co-infections are a significant burden with 71% of patients treated for potential bacterial infections and 15% treated for potential fungal infections. Given the high incidence of bacterial and fungal co-infections, we believe the T2 Biosystems technology has the potential to address the diagnostic needs of COVID-19 patients by helping identify these secondary infections associated with coronavirus and detecting the virus directly. Taken together, these capabilities have the potential to enable clinicians to diagnose and target therapy for patients with secondary bacterial or fungal infections associated with primary COVID-19 infections.    begin full scale system wet testing.

Sales, Marketing and Distribution

We are working to drive awareness and adoption of our T2MR technology and related products by buildingwith a direct sales force in the United States, targetingthat targets hospitals that treat critical care patients, and continuing to educate physicians, key decision makers and thought leaders through publishing scientific data in peer-reviewed journals, presenting at major industry conferences and conducting and supporting clinical studies.We have a small team of employees in Europe and the Middle East primarily to support our network of distributors in those regions.

patients. At the end of 2020,2021, our commercial organization consisted of 1331 people, including 922 people in sales and marketing and 4 people in medical affairs. In January 2021, we separated the medical affairs team from the commercial organization and hired a Chief Medical Officer to lead the team, which is comprised of United States based Doctor of Pharmacy (PharmD) clinicians. marketing.

Our sales team employs a strategic approach focusing on clinical value of our products highlighting clinical data, the clinical performance of our products, improved patient outcomes and the economic value for hospitals, including providing these hospitals with a customized budget-impact analysis. They also demonstrate the ease-of-use of our products and highlight the advantages of our products over existing diagnostics and empiric therapy practices. We plan to continue to invest in our sales force as we execute our strategy of converting COVID accounts to sepsis accounts and expand our customer reach.

Today, our sales forceteam markets and sells the T2Dx Instrument, T2Bacteria, T2Candida T2Bacteria and T2SARS-CoV-2 products directly to hospitals in the United States, targeting large hospitals that treat the largest number of high-risk patients.States. If these institutions optimize the full extent of our technology, we expect a positive network effect in the hospital community, accelerating adoption of T2CandidaT2Bacteria and T2Bacteria.T2Candida. We believe key aspects of healthcare reform, including a sensitivity to the growing problem of antimicrobial resistance, the focus on cost containment, risk-sharing, and outcomes-based treatment and reimbursement, are aligned with the value proposition of our sepsis products, contributing positively to their adoption.

Outside of the United States, we have received marketing authorizations or certifications in the EU, Australia, and certain countries in the Middle East and Africa, and expect to seek regulatory authorizations or certifications in additional international markets. We market our products primarily through distribution partners who utilize a similar model as our sales approach in the United States. We have obtained CE mark for our products as follows: T2Candida and T2Dx Instrument in July 2014, T2Bacteria in September 2017, and T2Resistance in November 2019. As of the end of 2021, we had distributors throughout the EU, and in a growing number of countries in Asia Pacific, Latin America and the Middle East. These distributors typically have strong, existing relationships with key opinion leaders, have relationships with important hospitals in their

respective countries, and have experience in infectious diseases and/or microbiology. We continue to develop partner relationships in other key international markets and plan to further expand our distribution channels in other key markets around the world. We have employed a small regionally-focused commercial team of business managers and field service personnel primarily to support the efforts of our distributors. 

Medical and Clinical Affairs

We continue to educate physicians, key decision makers and thought leaders through publishing scientific data in peer-reviewed journals, presenting at major industry conferences and conducting and supporting clinical studies. At the beginning of 2021, we hired Aparna Ahuja, MD as Chief Medical Officer. She has led a total rebuild of our medical, clinical, and regulatory teams. In the past, our medical affairs team was limited to Pharm Ds, and today we have a highly diverse and experienced medical and clinical affairs team of 15 people, which is comprised of infectious disease MDs, laboratory professionals, and Pharm Ds. Our clinical and medical affairs teams are raising awareness by amplifying clinical value messaging for our products. The team is actively engaged with Key Opinion Leaders to generate and share real world data via scientific journal publications, at medical conferences, and at industry trade shows. During 2021, our products were mentioned in over 50 publications, posters, and presentations.

We believe the key decision-makers at hospitals are infectious disease and critical care physicians, laboratory directors, hospital pharmacy, Chief Medical Officers, and hospital administrators. In response to the severity and complexity of managing bloodstream infections, a growing number of hospitals have instituted sepsis committees or antimicrobial stewardship committees to control hospital practices related to infections, including the use of antibiotic and antifungal therapy. These committees typically include key decision-makers, and we believe they can provide a central forum to present the benefits of our products. In addition, we plan to continue to publish scientific data in peer-reviewed journals, present at major industrymedical and scientific conferences and conduct and support clinical trials to provide additional data relative to the performance of T2Candida and T2Bacteria to these decision-makers.

Outside of the United States, we have received regulatory approvals in Europe, Australia, and certain countries in the Middle-East and Africa, and expect to seek regulatory approvals in additional international markets. We market our platform primarily through distribution partners who utilize a similar model as our sales approach in the United States.  In July 2014, we received CE marking for T2Candida and the T2Dx, in September 2017 we received CE marking for T2Bacteria and in November 2019, we received CE marking for T2Resistance. As of the end of 2020, we had distributors throughout the European Union (EU), Caribbean, Australia and the Middle East. These distributors have knowledge of infectious diseases and/or microbiology.  They typically have strong, existing relationships with international thought leaders in these areas and have good relationships with important hospitals in their respective countries.  We continue to develop partner relationships in other key international markets and will further investigate potential distribution channels in other key markets around the world.  We have employed a small team of regional distributor managers and field service personnel primarily to support the efforts of our distributors in the EU and Middle East. 

For the year ended December 31, 2020, we derived approximately 36% of our total revenue from one customer, 11% from a second customer and 6% from a third customer.

Manufacturing

We manufacture our proprietary T2Dx Instrument and our sepsis test panels at our manufacturing facilityfacilities in Lexington, MassachusettsMA and our T2Candida, T2Bacteria, T2SARS-CoV2-2 and T2Resistance reagent trays at our manufacturing facility in Wilmington, Massachusetts.MA. We perform all instrument and tray manufacturing and packaging of final components in accordance with applicable guidelines for medical device manufacturing. We outsource manufacturing of our T2Candida, T2Bacteria, T2Resistance and T2SARS-CoV-2 consumable cartridges to a contract manufacturer. Our particles are supplied by a sole source supplier, GE Healthcare. We believe we can secure arrangements with other suppliers on commercially reasonable terms for the products and parts we outsource.

We have implemented a quality management system designed to comply with FDA regulations and International Standards Organization, or ISO, standards governing medical device products. These regulations govern the design, manufacture, testing, release and service of diagnostic products as well as raw material receipt and control. We have received ISO 13485:20122016 registration from the National Standards Authority of Ireland. Our key outsourcing partners are also ISO-certified.

We plan to continue to manufacture components that we determine are proprietary or require special processes to produce, while outsourcing the manufacturesupply of more commodity-like components. We expect to establish additional outsourcing partnerships as we manufacture more products. We believe our facilities in Lexington and Wilmington, Massachusetts are adequate to meet our current manufacturing needs and that additional manufacturing space is readily available for future expansion.

In November 2021, we entered into a lease for 70,125 square feet of office, research, laboratory and manufacturing space in Billerica, Massachusetts. We plan to consolidate all manufacturing facilities into this facility by 2023.

Raw Materials

We purchase many different types of raw materials, including plastics, magnets, metals, electronic and mechanical sub-assemblies and various biological and chemical products. We seek to ensure continuity of raw material supply by securing multiple options for sourcing and also review relevant sources for compliance with conflict minerals requirements. Some of our components are custom-made by only a handful of external suppliers. In certain instances, we have a sole source supply for key product components of the T2Dx Instruments and certain components for our test kits. We have entered into supply agreements with most of our suppliers to help ensure component availability and flexible purchasing terms with respect to the purchase of such components. We have reviewed our suppliers and quantities of key materials and believe we have sufficient stocks and alternate sources of critical materials should our supply chains become disrupted, although raw materials and plastics for the manufacturing of reagents and consumables are in high demand, and interruptions in supply are difficult to predict. We are also experiencing unprecedented cost increases from many of our suppliers, primarily as a result of the ongoing COVID-19 pandemic, labor and supply disruptions and increased inflation. The areas of cost increases include raw materials, components, and value-add supplier labor. We believe that we can continue to take actions to limit the impact of cost increases on such devices, including bulk purchases and entering into long term supply agreements. See “Risk Factors - Risks Related to Our Business and Strategies - We utilize third-party, single-source suppliers for some components and materials used in our products and product candidates, and the loss of any of these suppliers could have an adverse impact on our business.” for additional information.

Intellectual Property

We strive to protect and enhance the proprietary technologies that we believe are important to our business, and seek to obtain and maintain patents for any patentable aspects of our product and product candidates, including their methods of use and any other inventions that are important to the development of our business. Our success will depend significantly on our ability to obtain and maintain patent and other proprietary protection for commercially important proprietary technology, inventions and know-how related to our business, including our methods, processes and product candidate designs, and our ability to defend and enforce our patents, maintain our licenses to use intellectual property owned by third parties, preserve the confidentiality of our trade secrets and operate without infringing the valid and enforceable patents and other proprietary rights of third parties. We also rely on trademarks, copyrights, know-how, continuing technological innovation and in-licensing opportunities to develop, strengthen, and maintain our proprietary position in the fields targeted by our products and product candidates. Protecting these rights is a primary focus in our relationships with other parties, and we seek to protect such rights, in part, by entering into confidentiality and non-disclosure agreements with such third parties and including protections for such proprietary information and intellectual property rights in our other contracts with such third parties, including material transfer agreements, licenses and research agreements.

We own or exclusively license over 35 issued U.S. patents and over 15 pending U.S. patent applications, including provisional and non-provisional filings. We also own or license over 50 pending or granted counterpart applications worldwide. We possess substantial know-how and trade secrets which protect various aspects of our business and products. The patent families comprising our patent portfolio are primarily focused on protection of a range of general and specific attributes of our proprietary assay architecture and assay instrumentation for our T2Candida, T2Bacteria, T2Resistance, T2Cauris products, and our T2Lyme product candidates, as well as protection of certain aspects of the conduct of the assays and detection of analytes. The issued patents in our patent families that cover T2Candida and T2Bacteria are expected to expire between 2023 and 2034, while additional pending applications covering T2Candida and T2Bacteria would be expected, if issued, to expire as late as 2037. The issued patents in our patent families that cover T2Lyme are expected to expire between 2023 and 2034, while additional pending applications covering T2Lyme would be expected, if issued, to expire as late as 2037. In all cases, the expiration dates are subject to any extension that may be available under applicable law.

Our success will depend significantly on our ability to obtain and maintain patent and other proprietary protection for commercially important proprietary technology, inventions and know-how related to our business, including our methods, processes and product candidate designs, and our ability to defend and enforce our patents, maintain our licenses to use intellectual property owned by third parties, preserve the confidentiality of our trade secrets and operate without infringing the valid and enforceable patents and other proprietary rights of third parties. We also rely on trademarks, copyrights, know-how, continuing technological innovation and in-licensing opportunities to develop, strengthen, and maintain our proprietary position in the fields targeted by our products and product candidates. Protecting these rights is a primary focus in our relationships with other parties, and we seek to protect such rights, in part, by entering into confidentiality and non-disclosure agreements with such third parties and including protections for such proprietary information and intellectual property rights in our other contracts with such third parties, including material transfer agreements, licenses and research agreements.

Proprietary Rights and Processes

We rely, in some circumstances, on proprietary technology and processes (including trade secrets) to protect our technology. However, these can be difficult to protect. We require all full-time and temporary employees, scientific advisors, contractors and consultants working for us who have access to our confidential information to execute confidentiality agreements in order to safeguard our proprietary technologies, methods, processes, know-how, and trade secrets. We also seek to preserve the integrity and confidentiality of our proprietary technology and processes by maintaining physical security of our premises and physical and electronic security of our information technology systems. All of our full-time and temporary employees and independent contractors and consultants are also bound by invention assignment obligations, pursuant to which rights to all inventions and other types of intellectual property conceived by them during the course of their employment are assigned to us.

While we have confidence in these individuals, organizations and systems, agreements or security measures may be breached, and we may not have adequate remedies for any breach. To the extent that our employees, consultants, scientific advisors, contractors, or any future collaborators use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions. Further, any of our intellectual property and proprietary rights could be challenged, invalidated, circumvented, infringed or misappropriated, or such intellectual property and proprietary rights may not be sufficient to provide competitive advantages. For more information, please see “Risks Related to Intellectual Property.”

Trademarks

We have trademarks and intend to continue to seek trademark protection.

License Agreements

License Agreement with Massachusetts General Hospital

In 2006, we entered into an exclusive license agreement with Massachusetts General Hospital, or MGH, pursuant to which MGH granted to us an exclusive, worldwide, sublicensable license under certain patent rights to make, use, import and commercialize products and processes for diagnostic, industrial and research and development purposes. In 2008 and 2011, we amended our agreement with MGH to add patent rights and to modify, among other things, our diligence and payment obligations.

We are required to use reasonable commercial efforts to develop and make available to the public products and processes covered by the agreement, and to achieve specified organizational, development and commercialization milestones by specified dates. To date, we have met all of our diligence obligations pursuant to this agreement.

We paid MGH an upfront fee and issued to MGH shares of our common stock equal to a low single-digit percentage of our then-outstanding common stock, subject to limited adjustments to prevent dilution in certain circumstances. In addition, we are responsible for reimbursing MGH’s costs associated with prosecution and maintenance of the patent rights licensed to us under the agreement. We will also be required to make payments for achievement of specified regulatory milestones with respect to products and processes covered by the agreement. In addition, we

are required to pay an annual license maintenance fee, which is creditable against any royalty payments we are obligated to make to MGH under the agreement.

We are required to pay royalties to MGH on net sales of products and processes that are covered by patent rights licensed to us under the agreement at percentages in the low single digits, subject to reductions and offsets in specified circumstances. The products and processes covered by the agreement include T2Bacteria, T2Candida T2Bacteria and other particle-based T2MRtest panels that we may develop in the future. Our royalty obligations, if any, and their duration, will depend on the specific patent rights covering the product or process being sold, and the particular category of product or process, as noted above. With respect to T2Bacteria, T2Candida and T2Bacteria and other potential particle-based T2MRtest panels we may develop in the future, our obligation to pay royalties to MGH will expire upon the later of ten years after the first commercial sale of the first product or process in the particular category and the expiration of the patent rights licensed to us under the agreement. We will also be required to pay to MGH a low double-digit percentage of specified gross revenue that we receive from our sublicensees. In addition, we will be required to pay royalties to MGH of less than one percent on net sales of specified products and processes that are not covered by the patent rights licensed to us under the agreement. Our obligation to pay royalties to MGH with respect to such products and processes will expire upon the earlier of 12 years after the first commercial sale of the first such product or process and the termination by MGH of all of the licenses granted to us under the agreement.

We have the right to terminate our agreement with MGH for any reason upon 90 days’ written notice to MGH. MGH may terminate our agreement in its entirety if we fail to make a payment required under the agreement and do not cure such failure within a specified time period, if we fail to maintain adequate insurance coverage or if we become insolvent. MGH may also terminate our agreement, with respect to a given category of products or processes, on 60 days’ notice for our uncured breach with respect to such category of products or processes. Absent earlier termination, our agreement with MGH will remain in force until the later of the expiration or abandonment of the licensed patents and patent applications, and the expiration of our obligations under the agreement.

Supply Agreement with SMC Ltd.

We are currently party to a supply agreement with SMC Ltd. for the supply and manufacture of plastic injection molded products are used across all T2 product lines. The agreement contains other terms and conditions generally consistent with an agreement for the manufacture and supply of materials or products for use in the development and commercialization of biotechnology products such as our products and product candidates, including with respect to ordering, supply of such product in accordance with specifications, and quality assurance and quality control activities.

The supply agreement may be terminated prior to the end of its term upon the occurrence of certain specified events and further provides that upon termination, including upon the expiration of the term, SMC shall continue to manufacture and ship products subject to outstanding purchase orders and we shall be responsible for purchasing finished products, inventory, raw materials and work-in-progress held by SMC to the extent SMC, after the use of commercially reasonable efforts to use such inventory, cannot use such inventory in a financially viable way.

BARDA Contract

In September 2019, BARDA awarded the Company a milestone-based contract, with an initial value of $6.0 million, and a potential value of up to $69.0 million, if BARDA awards all contract options. BARDA operates within the Office of the Assistant Secretary for Preparedness and Response, or ASPR, at HHS. If BARDA awards and the Company completes all options, the Company’s management believes it will enable a significant expansion of the Company’s current portfolio of diagnostics for sepsis-causing pathogen and antibiotic resistance genes. In September 2020, the Company completed the initial award and BARDA exercised the first contract option valued at $10.5 million. In September 2021, BARDA exercised Option 2A valued at approximately $6.4 million. In April 2021, BARDA agreed to accelerate product development by modifying the contract to advance future deliverables into the currently funded Option 1 of the BARDA contract for the next generation instrument, T2Biothreat, T2Resistance and comprehensive sepsis panel. Should BARDA reduce, cancel or not grant additional milestone projects, our ability to continue our future product development may be impacted.

Competition

While we believe that we are currently the only diagnostic company with FDA-cleared or CE marked commercial products capable of detecting sepsis-causing pathogens associated with bloodstream infections from directand antibiotic resistance genes directly from whole blood, samples, at limits of detection as low as 1 CFU/mL, without the need of culturing colony growth, we compete with commercial diagnostics companies for the limited resources of our customers. Our principal competition is from a number of companies that offer platforms and applications in our target sepsis markets, most of which are more established commercial organizations with considerable name recognition and significant financial resources.

Companies that currently provide traditional blood culture-based diagnostics include Becton Dickinson & Co. and bioMerieux, Inc. In addition, companies offering post-culture species identification using both molecular and non-molecular methods include bioMerieux, Inc. (and its affiliate, BioFire Diagnostics, Inc.), Bruker Corporation, Accelerate Diagnostics, Luminex, Genmark,Roche, Cepheid and Beckman Coulter, a Danaher company. These post-culture competitors rely on a positive result from blood culture in order to perform their tests, significantly prolonging their results when compared to T2MR.our technology. Some of the products offered by our competitors require hours of extensive hands-on labor by an operator, while some rely on high concentrations of pathogens present in a positive blood culture, which can require a final concentration of at least 1,000,000 CFU/mL. In addition, there may be a number of new market entrants in the process of developing other post-blood culture

diagnostic technologies that may be perceived as competitive with our technology. Karius, Inc. offers a lab developed culture independent diagnostic test for the identification of pathogens that has not been cleared by the FDA but may be perceived as competitive with our technology.

We believe that we have a number of competitive advantages, including:

In addition to identifying sepsis-causing pathogens, T2MR technologywe can also identify the existence of the SARS-CoV-2 virus. Competition for molecular testing of the SARS-CoV-2 virus includes the same large commercial organizations named above, and extends to other large companies like Abbott, Roche, Bio-Rad, PerkinElmer, Hologic, Thermo Fisher and others. In 2020 and 2021, many of these companies have experienced supply shortages for the tests due to high demand. We believe one competitive advantage in this space is the availability of tests due to our ability to produce more tests than our installed base of customers can consume.

Government Regulation

Our products under development and our operations are subject to significant government regulation. In the United States, our products are regulated as medical devicesregulation by the FDA and other federal, state, and local regulatory authorities.

FDA Regulation of Medical Devicesauthorities, as well as comparable authorities in other jurisdictions. Our products are subject to regulation as medical devices under the Federal Food, Drug, and Cosmetic Act, or FDCA, as implemented and enforced by the FDA.

The FDA and other U.S. and foreign governmental agencies regulate, among other things, with respect to medical devices:

In the United States, numerous laws and regulations govern all the processes by which medical devices are brought to market and marketed. These include the Federal Food, Drug and Cosmetic Act, or FDCA, and the FDA’s implementing regulations, among others.

FDA Pre-market Clearance and Approval Requirements

Each medical device we seek to commercially distribute in the United States must first receive 510(k) clearance, de novo down classification, or pre-market approval, or PMA, from the FDA, unless specifically exempted by the FDA. For someUnder the FDCA, medical devices we may seek Breakthrough Device Designation to aid in communications with the FDA during the pre-submission process. The FDA classifies all medical devicesare classified into one of three classes. Devices deemedclasses—Class I, Class II or Class III—depending on the degree of risk associated with each medical device and the extent of manufacturer and regulatory control needed to poseensure its safety and effectiveness. Class I includes devices with the lowest risk to the patient and are categorizedthose for which safety and effectiveness can be assured by adherence to the FDA’s General Controls for medical devices, which include compliance with the applicable portions of the FDA’s Quality System Regulation, or QSR, facility registration and product listing, reporting of

adverse medical events, and truthful and non-misleading labeling, advertising, and promotional materials. Class II devices are subject to the FDA’s General Controls, and special controls as eitherdeemed necessary by the FDA to ensure the safety and effectiveness of the device. These special controls can include performance standards, post-market surveillance, patient registries and FDA guidance documents. While most Class I ordevices are exempt from the 510(k) premarket notification requirement, manufacturers of most Class II which requires the manufacturerdevices are required to submit to the FDA a 510(k) pre-marketpremarket notification submission requesting clearanceunder Section 510(k) of the FDCA requesting permission to commercially distribute the device. The FDA’s permission to commercially distribute a device for commercial distribution in the United States. Some low risk devices are exempted from this requirement. subject to a 510(k) premarket notification is generally known as 510(k) clearance.Devices deemed by the FDA to pose the greatest risk, such as life-sustaining, life-supporting or implantable devices, or devices deemed not substantially equivalent to a previously 510(k) cleared device are categorized as Class III. These devices require submission and approval of a premarket approval, or PMA application.

Emergency Use Authorization

In response to the public health emergency association with the SARS-CoV-2 virus, the FDA has established an Emergency Use Authorization (EUA) submission and approval process for molecular diagnostics for SARS-CoV-2 detection.  FDA guidance for submission and approval for the testing of respiratory samples for SARS-CoV-2 virus is outlined in Section V.A. of the FDA guidance document “Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (January 27, 2020)”.  The T2SARS-CoV-2 Panel was approved by the FDA for EUA in August 2020.

Breakthrough Device Program

The FDA offers a voluntary Breakthrough Devices Program where companies can apply to be granted Breakthrough Device Designation from the FDA. To be eligible for Breakthrough Designation a device must (A) “provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating human disease or conditions and (B) one of the following: (1) represent breakthrough technology; (2) no approved or cleared alternatives can exist; (3) must offer significant advantages over existing approved or cleared alternatives; or (4) device availability is in the best interest of patients. The program offers manufacturers an opportunity to interact with the FDA's experts through several different program options to efficiently address topics as they arise during the premarket review phase, which can help manufacturers receive feedback from the FDA and identify areas of agreement in a timely way. Manufacturers can also expect prioritized review of their submission. The T2Resistance Panel received Breakthrough Device designation in February 2019.

510(k) Clearance Process

To obtain 510(k) clearance, we must submit a pre-market notification to the FDA demonstrating that the proposed device is substantially equivalent to a previously-cleared 510(k) device, a device that was in commercial distribution before May 28, 1976 for which the FDA has not yet called for the submission of pre-market approval applications, or is a device that has been reclassified from Class III to either Class II or I. In rare cases, Class III devices may be cleared through the 510(k) process. The FDA’s 510(k) clearance process usually takes from three to 12 months from the date the application is submitted and filed withaccepted by the FDA, but may take significantly longer and clearance is never assured. Although many 510(k) pre-market notifications are cleared without clinical data, in some cases, the FDA requires significant clinical data to support substantial equivalence. In reviewing a pre-market notification submission, thelonger. The FDA may requestrequire additional information, including clinical data, to make a determination regarding substantial equivalence. In addition, FDA collects user fees for certain medical device submissions and annual fees for medical device establishments. If the FDA agrees that the device is substantially equivalent to a predicate device currently on the market, it will grant 510(k) clearance to commercially market the device. If the FDA determines that the device is “not substantially equivalent” to a previously cleared device, the device is automatically designated as a Class III device. The device sponsor must then fulfill more rigorous PMA requirements, or can request a risk-based classification determination for the device in accordance with the de novo classification process, which may significantly prolong the review process.  is a route to market for novel medical devices that are low to moderate risk and are not substantially equivalent to a predicate device.

After a device receives 510(k) clearance, any subsequent modification of the device that could significantly affect its safety or effectiveness, or that would constitute a major change in its intended use, will require a new 510(k) clearance or, depending on the modification, could require pre-market approval.approval or de novo classification. The FDA requires each manufacturer to make this determination initially, but the FDA may review any such decision and may disagree with a manufacturer’s determination. If the FDA disagrees with a manufacturer’s determination, the FDA may require the manufacturer to cease marketing and/or recall the modified device until 510(k) clearance, issuance of a de novo classification or approval of a PMA is obtained. Under these circumstances, the FDA may also subject a manufacturer to significant regulatory fines or other penalties. In addition,Our T2Bacteria Panel received 510(k) clearance from the FDA is currently evaluatingon May 24, 2018.

Over the last several years, the FDA has proposed reforms to its 510(k) clearance process, and such proposals could include increased requirements for clinical data and a longer review period, or could make it more difficult for manufacturers to utilize the 510(k) clearance process and may make substantial changesfor their products. For example, in November 2018, FDA officials announced steps that the FDA intended to industry requirements, including whichtake to modernize the premarket notification pathway under Section 510(k) of the FDCA. Among other things, the FDA announced that it planned to develop proposals to drive manufacturers utilizing the 510(k) pathway toward the use of newer predicates. These proposals included plans to potentially sunset certain older devices are eligible forthat were used as predicates under the 510(k) clearance pathway, and to potentially publish a list of devices that have been cleared on the abilitybasis of demonstrated substantial equivalence to rescind previously grantedpredicate devices that are more than 10 years old. These proposals have not yet been finalized or adopted, although the FDA may work with Congress to implement such proposals through legislation. More recently, in September 2019, the FDA issued revised final guidance describing an optional “safety and performance based” premarket review pathway for manufacturers of “certain, well-understood device types” to demonstrate substantial equivalence under the 510(k)s clearance pathway by showing that such device meets objective safety and additional requirementsperformance criteria established by the FDA, thereby obviating the need for manufacturers to compare the safety and performance of their medical devices to specific predicate devices in the clearance process. The FDA has developed and maintains a list of device types appropriate for the “safety and performance based” pathway and continues to develop product-specific guidance documents that may significantly impactidentify the process.performance criteria for each such device type, as well as recommended testing methods, where feasible.

Pre-market Approval Process

A PMA application must be submitted if the medical device is in Class III (although the FDA has the discretion to continue to allow certain pre- amendment Class III devices to use the 510(k) process) or cannotrequire PMA approval before they can be marketed, although some pre-amendment Class III devices for which FDA has not yet required a PMA are cleared through the 510(k) process. AThe PMA applicationprocess is more demanding than the 510(k) premarket notification process. In a PMA, the manufacturer must demonstrate that the device is safe and effective, and the PMA must be supported by among other things, extensive technical, preclinical,data, including data from pre-clinical studies and human clinical trials, as well astrials. The PMA must also contain a full description of the device and its components, a full description of the methods, facilities, and controls used for manufacturing, and labeling data to demonstrate to the FDA’s satisfaction the safety and effectiveness of the device.

proposed labeling. After a PMA application is submitted and filed by the FDA, the FDA begins an in-depth review of the submitted information, which typically takes between one and three years, but may take significantly longer. During this review period, the FDA may request additional information or clarification of information already provided. Also during the review period, an advisory panel of experts from outside the FDA will usuallymay be convened to review and evaluate the application and provide recommendations to the FDA as to the approvability of the device. The FDA may or may not accept the panel’s recommendation. In addition, the

FDA will conduct a pre-approval inspection of the manufacturing facility to ensure compliance with Quality System Regulation, orthe QSR, which imposes elaborate design development, testing, control, documentation and other quality assurance procedures in the design and manufacturing process.

The FDA will approve the new device for commercial distribution if it determines that the data and information in the PMA constitute valid scientific evidence and that there is reasonable assurance that the device is safe and effective for its intended use(s). The FDA may approve a PMA application with post-approval conditions intended to ensure the safety and effectiveness of the device including, among other things, restrictions on labeling, promotion, sale and distribution and collection of long-term follow-up data from patients in the clinical study that supported approval.approvalor requirements to conduct additional clinical studies post-approval. The FDA may condition PMA approval on some form of post-market surveillance when deemed necessary to protect the public health or to provide additional safety and efficacy data for the device in a larger population or for a longer period of use. In such cases, the manufacturer might be required to follow certain patient groups for a number of years and to make periodic reports to the FDA on the clinical status of those patients. Failure to comply with the conditions of approval can result in materially adverse enforcement action, including the loss or withdrawal of the approval. New PMA applications

Certain changes to an approved device, such as changes in manufacturing facilities, methods, or supplements are required for significant modifications toquality control procedures, or changes in the manufacturing process, labelingdesign performance specifications, which affect the safety or effectiveness of the product and designdevice, require submission of a device that is approved through the PMA process.supplement. PMA supplements often require submission of the same type of information as an original PMA application, except that the supplement is limited to information needed to support any changes from the device covered by the original PMA application, and may not require as extensive clinical data or the convening of an advisory panel.Certain other changes to an approved device require the submission of a new PMA, such as when the design change causes a different intended use, mode of operation, and technical basis of operation, or when the design change is so significant that a new generation of the device will be developed, and the data that were submitted with the original PMA are not applicable for the change in demonstrating a reasonable assurance of safety and effectiveness.

De novo Classification Process

Medical device types that the FDA has not previously classified as Class I, II, or III are automatically classified into Class III regardless of the level of risk they pose. The Food and Drug Administration Modernization Act of 1997 established a new route to market for low to moderate risk medical devices that are automatically placed into Class III due to the absence of a predicate device, called the “Request for Evaluation of Automatic Class III Designation,” or the de novo classification procedure. This procedure allows a manufacturer whose novel device is automatically classified into Class III to request down-classification of its medical device into Class I or Class II on the basis that the device presents low or moderate risk, rather than requiring the submission and approval of a PMA application. Prior to the enactment of the Food and Drug Administration Safety and Innovation Act, or FDASIA, in July 2012, a medical device could only be eligible for de novo classification if the manufacturer first submitted a 510(k) premarket notification and received a determination from the FDA that the device was not substantially equivalent. FDASIA streamlined the de novo classification pathway by permitting manufacturers to request de novo classification directly without first submitting a 510(k) premarket notification to the FDA and receiving a not substantially equivalent determination. Under FDASIA, FDA is required to classify the device within 120 days following receipt of the de novo application. If the manufacturer seeks reclassification into Class II, the manufacturer must include a draft proposal for special controls that are necessary to provide a reasonable assurance of the safety and effectiveness of the medical device. In addition, the FDA may reject the reclassification petitionde novo request if it identifies a legally marketed predicate device that would be appropriate for a 510(k) or determines that the device is not low to moderate risklow-to-moderate-risk or that general controls would be inadequate to control the risks andand/or that special controls cannot be developed. We utilizedOn September 22, 2014, the FDA granted de novo classification process to obtain marketing clearance for ourthe T2Dx and T2Candida, which were given aand classified these products as Class II designation.  We received marketing clearance for these devices from the FDA on September 22, 2014. We received marketing clearance for our T2Bacteria on May 24, 2018.medical devices.

Clinical Trials

A clinical trial isClinical trials are typically required to support a PMA application or de novo request, and isare sometimes required forto support a 510(k) pre-market notification. Clinical trials generally require submissionAll clinical investigations of an application for an Investigational Device Exemption,devices to determine safety and effectiveness must be conducted in accordance with the FDA’s investigational device exemption, or IDE, regulations which govern investigational device labeling, prohibit promotion of the investigational device, and specify an array of recordkeeping, reporting and monitoring responsibilities of study sponsors and study investigators. If the device presents a “significant risk” to human health, as defined by the FDA, the FDA requires the device sponsor to submit an IDE application to the FDA. TheFDA, which must become effective prior to commencing human clinical trials. If the device under evaluation does not present a significant risk to human health, then the device sponsor is not required to submit an IDE application to the FDA before initiating human clinical trials, but must still comply with abbreviated IDE requirements when conducting such trials. A significant risk device is one that presents a potential for serious risk to the health, safety or welfare of a patient and either is implanted, used in supporting or sustaining human life, substantially important in diagnosing, curing, mitigating or treating disease or otherwise preventing impairment of human health, or otherwise presents a potential for serious risk to a subject. An IDE application must be supported by appropriate data, such as animal and laboratory testingtest results, showing that it is safe to test the device in humans and that the investigationaltesting protocol is scientifically sound. The IDE applicationwill automatically become effective 30 days after receipt by the FDA unless the FDA notifies the company that the investigation may not begin. If the FDA determines that there are deficiencies or other concerns with an IDE for which it requires modification, the FDA may permit a clinical trial to proceed under a conditional approval.

Regardless of the degree of risk presented by the medical device, clinical studies must be approved in advance by, and conducted under the FDAoversight of, an Institutional Review Board, or IRB, for a specified numbereach clinical site. The IRB is responsible for the initial and continuing review of patients, unless the product is deemed a non-significant risk deviceIDE, and eligiblemay pose additional requirements for more abbreviated IDE requirements. Clinical trials for a significant risk device may begin once the conduct of the study. If an IDE application is approved by the FDA and one or more IRBs, human clinical trials may begin at a specific number of investigational sites with a specific number of patients, as well asapproved by the appropriate institutionalFDA. An IDE supplement must be submitted to, and approved by, the FDA before a sponsor or investigator may make a change to the investigational plan that may affect its scientific soundness, study plan or the rights, safety or welfare of human subjects. During a study, the sponsor is required to comply with the applicable FDA requirements, including, for example, trial monitoring, selecting clinical investigators and providing them with the investigational

plan, ensuring IRB review, boards,adverse event reporting, record keeping and prohibitions on the promotion of investigational devices or IRBs, at theon making safety or effectiveness claims for them. The clinical trial sites, and the informed consent of the patients participatinginvestigators in the clinical trial is obtained. Afterstudy are also subject to FDA’s regulations and must obtain patient informed consent, rigorously follow the investigational plan and study protocol, control the disposition of the investigational device, and comply with all reporting and recordkeeping requirements. Additionally, after a trial begins, the sponsor, the FDA may place it on holdor the IRB could suspend or terminate it if, among othera clinical trial at any time for various reasons, it concludesincluding a belief that the risks to study subjects outweigh the anticipated benefits.

Expedited Development and Review Programs

Following passage of the 21st Century Cures Act, the FDA implemented the Breakthrough Devices Program, which is a voluntary program offered to manufacturers of certain medical devices and device-led combination products that may provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions. The goal of the program is to provide patients and health care providers with more timely access to qualifying devices by expediting their development, assessment and review, while preserving the statutory standards for PMA approval, 510(k) clearance and de novo classification. The program is available to medical devices that meet certain eligibility criteria, including that the device provides more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions, and that the device meets one of the following criteria: (i) the device represents a breakthrough technology, (ii) no approved or cleared alternatives exist, (iii) the device offers significant advantages over existing approved or cleared alternatives, or (iv) the availability of the device is in the best interest of patients. Breakthrough Device designation provides certain benefits to device developers, including more interactive and timely communications with FDA staff, use of post-market data collection, when scientifically appropriate, to facilitate expedited and efficient development and review of the device, opportunities for efficient and flexible clinical subjects are exposed to an unacceptablestudy design, and prioritized review of premarket submissions.

Emergency Use Authorization

The Commissioner of the FDA, under delegated authority from the Secretary of HHS may, under certain circumstances in connection with a declared public health risk. Any trials we conduct must be conducted in accordanceemergency, allow for the marketing of a product that does not otherwise comply with FDA regulations by issuing an EUA for such product. Before an EUA may be issued by HHS, the Secretary must declare an emergency based a determination that public health emergency exists that effects or has the significant potential to affect, national security, and that involves a specified biological, chemical, radiological, or nuclear agent or agents, or CBRN, or a specified disease or condition that may be attributable to such CBRN. On February 4, 2020, the HHS Secretary determined that there is such a public health emergency that involves the virus now known as wellSARS-CoV-2, the virus that causes the COVID-19 infection. Once the determination of the threat or emergency has been made, the Secretary of HHS must then declare that an emergency exists justifying the issuance of EUAs for certain types of products (referred to as other federal regulationsEUA declarations). On February 4, 2020, the Secretary of HHS declared – on the basis of his determination of a public health emergency that has the potential to affect national security or the health and state laws concerning humansecurity of U.S. citizens living abroad that involves SARS-CoV-2 – that circumstances exist justifying authorization of in vitro diagnostic devices during the COVID-19 pandemic, subject protectionto the terms of any EUA that is issued.

Once an EUA declaration has been issued, the FDA can issue EUAs for products that fall within the scope of that declaration. To issue an EUA, the FDA Commissioner must conclude that (1) the CBRN that is referred to in the EUA declaration can cause serious or life-threatening diseases or conditions; (2) based on the totality of scientific evidence available, it is reasonable to believe that the product may be effective in diagnosing, treating, or preventing the disease or condition attributable to the CBRN and privacy.that the product’s known and potential benefits outweigh its known and potential risks; and (3) there is no adequate, approved, and available alternative to the product. Products subject to an EUA must still comply with the conditions of the EUA, including labeling and marketing requirements. Moreover, the resultsauthorization to market products under an EUA is limited to the period of time the EUA declaration is in effect, and the FDA can revoke an EUA in certain circumstances.

At certain points during the COVID-19 pandemic, the FDA has issued policies indicating that it would not object to test developers distributing or offering their validated tests prior to receipt of an EUA, provided the test developers met certain criteria set forth in published enforcement policies. In June 2020, we launched the T2SARS-CoV-2 Panel, our COVID-19 molecular diagnostic test, after validation of the test pursuant to the FDA’s policy permitting COVID-19 tests to be marketed prior to receipt of an EUA, subject to certain prerequisites. In August 2020, the FDA granted an EUA to the T2SARS-CoV-2 Panel for the qualitative direct detection of nucleic acid from SARS-CoV-2 in upper respiratory specimens (such as nasal, mid-turbinate, nasopharyngeal, and oropharyngeal swab specimens) and bronchoalveolar lavage specimens from individuals suspected of COVID-19 by their healthcare provider.

Research-use-only devices

Some of our products, including our T2Resistance Panel and T2Cauris Panel are currently available RUO. An RUO device is an in vitro diagnostic device, or IVD, that is in the laboratory research phase of development. IVDs that are marketed for RUO are not intended for use in a clinical trial may notinvestigation or for clinical diagnostic use outside an investigation and must be sufficientlabeled “For Research Use Only. Not for use in diagnostic procedures.” Products that are intended for RUO and are properly labeled as RUO are exempt from compliance with the FDA’s requirements applicable to obtainmedical devices more generally, including the requirements for clearance or approval and compliance with the FDA’s QSR. A product labeled RUO but intended to be used diagnostically may be viewed by the FDA as adulterated and misbranded under the FDCA and is subject to FDA enforcement activities. The FDA may consider the totality of the product.circumstances surrounding distribution and use of an RUO product, including how the product is marketed, when determining its intended use.

Pervasive and Continuing U.S. Food and Drug Administration Regulation

After a medical device is placed on the market, numerous FDA regulatory requirements apply, including, but not limited to the following: