What changed in this filing

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Item 1. Business

2025-02-20 compared with 2024-02-22 · 88 added, 61 removed, 568 unchanged (21% of the section changed)

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In addition, in March 2023, we submitted a premarket approval application, or PMA, for our Shield blood test to the FDA.

The FDA’s Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee intends to review the PMA.

We also expect to expand into lung and multi-cancer screening with our investigational, next-generation Shield assay.

Our objective is to be the leading provider of precision oncology and screening products for cancer management across all stages of the disease and drive commercial adoption of our products.

In July 2024, we received FDA approval of our Shield blood test for colorectal cancer screening in adults age 45 and older who are at average risk for the disease, and in August 2024, our Shield blood test became commercially available in the U.S.

as the first blood test approved by the FDA for primary colorectal cancer screening, meaning healthcare providers can offer Shield in a manner similar to all other non-invasive methods recommended in screening guidelines.

Shield is also the first blood test for colorectal cancer screening that meets coverage requirements by Medicare.

We also expect to expand into lung cancer screening and multi-cancer detection with our Shield platform.

Our objective is to be the leading provider of therapy selection, minimal residual disease detection, and early cancer screening products for cancer management across all stages of the disease and drive commercial adoption of our products.

To achieve this, we intend to:

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▪ providing earlier insights into emerging clinically relevant biomarkers;

▪ providing seamless customer experiences through collaborations with electronic medical record partners;

▪ expanding lab capabilities and services through partnerships.

• Expand our product portfolio by:

▪ using our commercial engine as a force multiplier of returns on research and development investment to generate data and analytical insights to enable development of new products;

▪ taking a disciplined and systematic approach to product and market development, by starting with therapy selection and then expanding sequentially towards early cancer detection;

▪ taking a disciplined and systematic approach to product and market development for cancer management across all stages of the disease;

▪ utilizing our data, sample biobank and insights into biology of circulating tumor-related biomarkers in blood to develop our new products;

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Our Guardant360 CDx test is a 74-gene test to provide tumor mutation profiling to be used by qualified health professionals in accordance with professional guidelines in oncology for cancer patients with any solid malignant neoplasm.

Our Guardant360 CDx test has also been approved by the FDA for use as a companion diagnostic to identify NSCLC patients who may benefit from treatment with TAGRISSO® (osimertinib), RYBREVANT® (amivantamab-vjmw), LUMAKRASTM (sotorasib) and ENHERTU® (fam-trastuzumab deruxtecan-nxki), and breast cancer patients who may benefit from treatment with ORSERDUTM (elacestrant), marketed by biopharmaceutical companies.

Our Guardant360 CDx test has also been approved by the FDA for use as a companion diagnostic to identify NSCLC patients who may benefit from treatment with TAGRISSO® (osimertinib), RYBREVANT® (amivantamab-vjmw), LUMAKRAS™ (sotorasib) and ENHERTU® (fam-trastuzumab deruxtecan-nxki), and breast cancer patients who may benefit from treatment with ORSERDU™ (elacestrant), marketed by biopharmaceutical companies.

Additional gene content and immune-oncology biomarkers (e.g.

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The number of personalized therapy options for advanced cancer patients continues to grow, giving patients who may have cycled through standard of care therapies additional options.

Our Guardant360 LDT test measures 80+ cancer-related genes and supports new guideline-recommended biomarkers, to help inform which therapy may be effective for advanced stage cancer patients with solid tumors, without the need to obtain archival tissue or subject the patient to another invasive biopsy.

Results are typically delivered within ten days following receipt of sample and delivered by a clinical report.

Our Guardant360 LDT test measures 730+ genes and supports all guideline-recommended biomarkers, to help inform which therapy may be effective for advanced stage cancer patients with solid tumors, without the need to obtain archival tissue or subject the patient to another invasive biopsy.

Our Guardant360 LDT test has been migrated to the Smart Liquid Biopsy platform which enables more sensitive epigenetic tumor fraction detection.

Results are typically delivered within seven days following receipt of sample and delivered by a clinical report.

Guardant360 Response Test

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Guardant360 TissueNext Test

To complement our liquid biopsy-based products, Guardant360 TissueNext, our first tissue-based test, is designed to identify patients with advanced cancer who may benefit from biomarker-informed treatment.

To complement our liquid biopsy-based products, Guardant360 TissueNext, our first tissue-based test with AI-powered PD-L1 detection, is designed to identify patients with advanced cancer who may benefit from biomarker-informed treatment.

Tissue genotyping is currently widely available to physicians and patients.

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We therefore believe our Guardant360 TissueNext test, together with our liquid biopsy-based products, have the potential to help address the challenges with tissue genotyping products currently in the market.

Recurring Monitoring / Minimum Residual Disease

Minimal Residual Disease Detection and Recurrence Monitoring

Guardant Reveal Test

In the management of early-stage cancer, current tools do not identify all high-risk patients who will benefit from adjuvant therapy or detect recurrence early enough when it is most curable.

We plan to address this need, first in early-stage colorectal, breast and lung cancers, with our Guardant Reveal test for residual disease and recurrence monitoring.

We expect to address this need, first in early-stage colorectal, breast and lung cancers, with our Guardant Reveal tissue-free blood test for residual disease and recurrence monitoring.

We believe the Guardant Reveal test has the potential to enable oncologists to improve the care of early-stage cancer patients by correctly identifying more high-risk patients than clinicopathologic review alone and by detecting recurrent disease months earlier than current standard of care methods like imaging carcinoembryonic antigen tests.

We believe the Guardant Reveal test can improve turnaround by simultaneously interrogating both genomic and epigenomic signals from a single blood draw without the need for tissue.

Similar to our data development effort for our Guardant360 tests, we are investing heavily in establishing clinical validity and utility for the use of Guardant Reveal in adjuvant treatment settings.

In addition, our Guardant Reveal test has been migrated to the Smart Liquid Biopsy platform which could maximize detection sensitivity without requiring tissue.

Similar to our data development effort for our Guardant360 tests, we are investing heavily in establishing clinical validity and utility for the use of Guardant Reveal in adjuvant treatment and surveillance settings.

We also believe our Guardant Reveal test may help biopharmaceutical companies identify new drug development opportunities.

In return, these relationships could help us establish clinical utility for our tests and create new testing opportunities related to emerging therapies.

In return, these relationships could help us establish clinical utility for our tests and

create new testing opportunities related to emerging therapies.

Results are typically delivered within seven days following receipt of sample and delivered by a clinical report.

According to American Cancer Society:

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Based on these study results, in March 2023, we submitted a PMA for our Shield blood test to the FDA.

The FDA’s Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee intends to review the PMA.

We also expect to expand into lung and multi-cancer screening with our investigational, next-generation Shield assay.

To clinically validate the performance of our next-generation Shield blood test in detecting lung cancer in high-risk individuals ages 50-80, in January 2022, we enrolled the first patient in a nearly 10,000-patient prospective, registrational study, which we refer to as the SHIELD LUNG study.

Shield is also the first blood test for colorectal cancer screening that meets coverage requirements by Medicare.

We also expect to expand into lung cancer screening and multi-cancer detection, or MCD, with our Shield platform.

To clinically validate the performance of our next-generation Shield blood test in lung cancer screening in high-risk individuals ages 50-80, in January 2022, we initiated a nearly 10,000-patient prospective, registrational study, which we refer to as the SHIELD LUNG study.

In addition, in January 2025, our Shield MCD test was selected for the Vanguard study funded by the National Cancer Institute, part of the National Institutes of Health.

The Vanguard study is a four-year pilot study which will enroll up to 24,000 people to inform the design of a randomized controlled trial evaluating the use of MCD tests for cancer screening.

We believe that developing a blood test for early detection of cancer requires a vast amount of molecular and clinical data across all stages of the disease in order to better understand the biology and clinical relevance of tumor-specific biomarkers in blood.

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Biopharmaceutical Offerings

GuardantINFINITY Test

Our GuardantINFINITY test is a next-generation Smart Liquid Biopsy test that provides new, multi-dimensional insights into the complexities of tumor molecular profiles and immune response to advance cancer research and therapy development.

Our GuardantINFINITY assay provides a more comprehensive molecular profile of tumors than earlier assays, giving researchers access to novel genomic and epigenomic insights to provide a simultaneously deeper and more complete understanding of a tumor’s biology, its system-wide interactions and the associated immune response in a range of applications, from therapy selection to molecular response and longitudinal monitoring.

The assay’s extensive methylome panel helps identify the unique methylation pattern that each tumor delivers, providing an important new dimension of research insights that has been largely unexplored in clinical development to date.

GuardantINFINITY is available as a single modular assay with flexible configurations that can be tailored to fit a current application, along with the ability to unlock additional content modules at any time, without incurring the burden or delay of additional sample collection.

The core module offers genotyping coverage

of more than 800 genes with sample-level methylation detection and tumor fraction score for biomarker discovery, clinical research, therapy selection and response monitoring.

GuardantOMNI Test

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In addition, the broad genomic footprint of our GuardantOMNI test enables accurate measurement of tumor mutational burden.

GuardantINFINITY Test

In September 2022, we launched GuardantINFINITY, a next-generation smart liquid biopsy test that provides new, multi-dimensional insights into the complexities of tumor molecular profiles and immune response to advance cancer research and therapy development.

The core module offers genotyping coverage of more than 800 genes with sample-level methylation detection and tumor fraction score for biomarker discovery, clinical research, therapy selection and response monitoring.

GuardantINFORM

GuardantINFORM complements our core diagnostic business with aggregated data obtained through real world genomic testing.

This genomic and epigenetic data is first matched with clinically relevant information, and through AI-enabled analytical tools and expertise, unlocks important insights into disease progression and treatment impact that can be fed back into drug discovery and development, as well as clinical research and practice.

Given the trend for oncologists to use liquid biopsy to monitor changes over time, our GuardantINFORM database uniquely provides longitudinal biological insight into tumor evolution alongside longitudinal clinical outcomes, which is particularly valuable for both resistance characterization of disease and as testing moves earlier in the cancer journey.

GuardantConnect

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At the same time, biopharmaceutical companies need to fill clinical studies that require screening hundreds of thousands of patients.

Despite these needs, clinical study enrollment in oncology has severely lagged, with only approximately 6.3% of cancer patients enrolling in clinical studies.

Despite these needs, clinical study enrollment in oncology has severely lagged.

GuardantConnect is our integrated software-based solution designed for our clinical and biopharmaceutical customers, seeking to connect patients tested with our assays with actionable alterations with potentially relevant clinical studies.

GuardantINFORM

GuardantINFORM complements our core diagnostic business with aggregated data obtained through real world genomic testing matched with clinically relevant information, which enables important insights into disease progression and treatment impact that can be fed back into drug discovery and development as well as clinical research and practice.

Given the trend for oncologists to use liquid biopsy to monitor changes over time, our GuardantINFORM database uniquely provides longitudinal biological insight to go alongside longitudinal clinical outcomes, which is particularly valuable for a disease characterized by resistance, and for which testing will move earlier and earlier in the cancer journey.

Smart Liquid Biopsy Platform

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While products continue to evolve by leveraging commonality in equipment, reagents, and staffing, this platform also provides a foundation for future product evolutions and data integration.

We expect to migrate our products to the platform and we believe our smart liquid biopsy platform has the potential to unlock the power of the epigenome, broaden the view of what drives cancer biology, and provide industry leading high-sensitivity genomic and epigenomic detection at ultra-high specificity and low cost.

Guardant Galaxy

Our Guardant Galaxy suite of advanced analytical technologies have been developed internally and through outside partnerships to enhance the performance and clinical utility of our portfolio of cancer tests, and to power the next generation of biomarker and drug discovery.

The first application in the Guardant Galaxy suite is an AI-backed digital pathology platform developed by Lunit®, for the enhanced Guardant360 TissueNext PD-L1 test, which improves detection of the cancer biomarker compared to manual pathologist interpretation in NSCLC cases.

Future planned applications include deep learning-driven genomic, epigenomic and spatial biomarker discovery via collaboration with biopharmaceutical partners and integration with GuardantINFORM real-world clinical data platform.

We believe our Smart Liquid Biopsy platform has the potential to unlock the power of the epigenome, broaden the view of what drives cancer biology, and provide industry leading high-sensitivity genomic and epigenomic detection at ultra-high specificity and low cost.

Clinical Studies and Publications

We are proactively pursuing studies to support the use of our tests as a preferred alternative or complementary to tissue testing to inform first line treatment right after diagnosis and at time of disease progression, with the goal to provide evidence that our tests detect genomic alterations at a similar rate compared to standard of care tissue testing and detects mutations that may not be detected by tissue based testing in the United States, Europe and Asia.

Such a strategy is predicated on the tests’ ability to offer accurate, reliable and fast guideline-directed comprehensive genotyping for all adult solid tumors without exposing patients to invasive biopsy procedures’ risks, delays or chance of failure.

Such a strategy is predicated on the tests’ abilities to offer accurate, reliable and fast guideline-directed comprehensive genotyping for all adult solid tumors without exposing patients to invasive biopsy procedures’ risks, delays or chance of failure.

We publish peer-reviewed studies in order to influence treatment guidelines, to educate clinicians and other oncology stakeholders about the value proposition of our test and to set the stage for reimbursement with private and public payers.

We have over 140 targeted therapy outcomes studies, more than 450 peer-reviewed publications and more than 900 scientific abstracts.

Commercialization

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For clinicians, endorsement by KOLs, utilization by academic centers and inclusion in national treatment guidelines are important, especially for adoption in the local community setting.

We believe that our relationships with key stakeholders across the oncology space have helped facilitate the use of our tests by clinicians and biopharmaceutical companies.

We believe that our relationships

with key stakeholders across the oncology space have helped facilitate the use of our tests by clinicians and biopharmaceutical companies.

clinical commercial efforts

We sell our tests to clinical customers in the United States through our targeted sales organization.

Our clinician-focused sales organization in the United States is engaged in sales efforts and promotional activities primarily targeting oncologists and cancer centers.

Our clinician-focused sales organization in the United States is engaged in sales efforts and promotional activities primarily targeting oncologists, cancer centers and primary care physicians.

Our sales representatives typically have extensive sales-related backgrounds in laboratory testing, therapeutics and oncology.

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In addition, we have established, and as these studies progress and we near commercial opportunities in these jurisdictions, will continue to seek to establish in-country laboratories and direct sales organizations.

In preparation for wider commercialization in the European Union, or the EU, we obtained a CE mark for our Guardant360 CDx, Guardant360 LDT, and Guardant Reveal tests.

In preparation for wider commercialization in the European Union, or the EU, we obtained a CE mark for our Guardant360 CDx test.

In December 2020, we signed our first public private partnership agreement with Vall D'Hebron Institute of Oncology, or VHIO, one of Europe’s leading cancer research institutions, and in May 2022, the first blood-based cancer testing services in Europe based on our digital sequencing platform became available at the VHIO testing facility in Spain.

In October 2021, we signed a partnership agreement with The Royal Marsden NHS Foundation Trust, or Royal Marsden, a premier cancer center within the United Kingdom, or the UK, for patient care, research and teaching of all types of cancer, and in April 2023, the blood-based cancer testing services based on our digital sequencing platform became available at Royal Marsden testing facility in the UK.

In September 2024, we signed a partnership agreement with the Agostino Gemelli University Polyclinic Foundation IRCCS, one of Italy’s largest and most renowned hospitals known for its advanced oncology services, including diagnostics, treatment, and research, to establish an in-house liquid biopsy testing service within its hospital system.

In May 2018, we formed and capitalized Guardant Health AMEA, Inc., with SoftBank, which we refer to as Guardant AMEA, relating to the sale, marketing and distribution of our tests generally outside the Americas and Europe and to accelerate commercialization of our products in Asia, the Middle East and Africa.

In June 2022, we purchased all of the shares held by SoftBank and its affiliates, and upon completion of the transaction, we obtained full control over operations of Guardant AMEA throughout the Asia, Middle East and Africa region.

In June 2022, we

purchased all of the shares held by SoftBank and its affiliates, and upon completion of the transaction, we obtained full control over operations of Guardant AMEA throughout the Asia, Middle East and Africa region.

In Japan, we have received regulatory approval of our Guardant360 CDx test as a companion diagnostic for identifying patients who may benefit from treatment with LUMAKRAS™ (sotorasib), Keytruda® (pembrolizumab), Opdivo® (nivolumab), and ENHERTU® (trastuzumab deruxtecan), from Japan's Ministry of Health, Labour and Welfare, or the MHLW.

In February 2022, we received accreditation from College of American Pathologists, or CAP, and in October 2022, we received In Vitro Diagnostic, or IVD, sample processing approval from the MHLW for our laboratory in Japan.

In addition, in July 2023, the MHLW granted national reimbursement approval for our Guardant360 CDx test for patients with advanced or metastatic solid tumor cancers in Japan.

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We have experienced situations where commercial payers proactively reduced the amounts they were willing to reimburse for our tests, and where commercial payers have determined that the amounts previously paid were too high and sought to recover those perceived excess payments by deducting such amounts from payments owed to us.

In addition to our existing covered and contracted payers, various laboratory benefit managers and evidence review organizations working with commercial payers have endorsed coverage of our Guardant360 CDx test, Guardant360 LDT test, Guardant360 TissueNext test and Guardant Reveal test.

In addition to our existing covered and contracted payers, various laboratory benefit managers and evidence review organizations working with commercial payers have endorsed coverage of Guardant360 CDx, Guardant360 LDT, Guardant360 TissueNext and Guardant Reveal.

We are actively engaged to expand coverage among existing commercial payers and to achieve coverage with the remaining key commercial payers, laboratory benefit managers and evidence review organizations.

This includes addressing variable coverage requirements and evidence required, and the need for enhanced guideline support.

As we broaden our coverage amongst commercial payers to include additional tests of ours, we may begin to experience increases in average revenue per test performed;

As we broaden our coverage amongst commercial payers to include additional tests, we may begin to experience increases in average revenue per test performed;

however, we cannot make any assurances that we will be successful in broadening our coverage on a timely basis or at all.

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Effective January 1, 2024, Medicare has increased the reimbursement rate for our Guardant360 LDT test to the same rate as our Guardant360 CDx test.

In January 2025, Palmetto GBA granted coverage for our Guardant Reveal test to monitor disease recurrence in patients with colorectal cancer in the surveillance setting following curative intent therapy.

This represents an expansion from the prior Medicare coverage of our Guardant Reveal test for colorectal cancer in the early post-surgical setting only.

In August 2024, following the FDA approval, our Shield blood test met the coverage requirements by Medicare based on the criteria established in its NCD for blood-based colorectal cancer screening tests.

The test is covered once every three years for eligible Medicare beneficiaries.

State Medicaid programs make individual coverage decisions for diagnostic tests and have taken steps to control the cost, utilization and delivery of healthcare services.

We believe that additional state and federal health care reform measures may be adopted in the future, any of which could have a material adverse effect on the clinical laboratory industry and our ability to successfully commercialize our tests.

We believe that additional state and federal healthcare reform measures may be adopted in the future, any of which could have a material adverse effect on the clinical laboratory industry and our ability to successfully commercialize our tests.

Any of these or other changes could substantially impact our revenues and increase costs.

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Other Considerations

As of January 2024, 15 states, including California, have enacted laws that require biomarker testing to be covered for the purposes of diagnosis, treatment, appropriate management, or ongoing monitoring of disease or condition if the test is supported by medical and scientific evidence, and these enacted laws will mandate coverage for our Guardant360 CDx test, Guardant360 LDT test, Guardant360 TissueNext test, Guardant Response test and Guardant Reveal test when certain criteria are met.

As of January 2025, 21 states, including California, have enacted laws that require biomarker testing to be covered for the purposes of diagnosis, treatment, appropriate management, or ongoing monitoring of disease or condition if the test is supported by medical and scientific evidence, and these enacted laws will mandate coverage for Guardant360 CDx, Guardant360 LDT, Guardant360 TissueNext, Guardant Response and Guardant Reveal when certain criteria are met.

In addition, several more states have current legislation in progress.

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This variability and unpredictability could increase the risk of future revenue reversal and result in our failing to meet any previously publicly stated guidance we may provide.

We currently perform our tests in our laboratories located in Redwood City, California, and San Diego, California.

We currently perform clinical, research use only, and investigation use only tests in our laboratory located in Redwood City, California.

Our Redwood City laboratory is certified pursuant to the Clinical Laboratory Improvement Amendments of 1988, or CLIA, accredited by the College of American Pathologists, or CAP, permitted by the New York State Department of Health, or NYSDOH, and licensed in California and four other states.

Our San Diego laboratory is CAP-accredited, CLIA-certified and licensed in California.

In addition, our Palo Alto, California laboratory is currently operated as a center for our research and technology development.

We have also received CAP accreditation and IVD sample processing approval from the MHLW for our laboratory in Japan.

We also perform research use only tests in our laboratory located in San Diego, California.

In addition, our Redwood City, San Diego and Palo Alto, California laboratories are currently operated as centers for our research and technology development.

The proprietary validated methods utilize robust semi-automated workflows designed for high throughput sample testing.

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In September 2014, we entered into a supply agreement with Illumina, Inc., or Illumina, for Illumina to provide products and services that can be used for certain research and clinical activities, including certain sequencers, reagents, and other consumables for use with the Illumina sequencers, as well as service contracts for the maintenance and repair of the sequencers.

The initial term of the supply agreement, as amended, continues until January 2033, and automatically renews for additional one-year terms thereafter unless either we or Illumina terminate the supply agreement for the other’s uncured material breach, bankruptcy or insolvency-related events, or in the event a regulatory authority notifies such party that continued performance under the supply agreement would violate applicable laws or regulations.

in the event a regulatory authority notifies such party that continued performance under the supply agreement would violate applicable laws or regulations.

We may also terminate the supply agreement for convenience upon 90 days’ prior written notice.

Growing understanding of the importance of biomarkers linked with therapy selection, response and early screening is leading to more companies offering services in genomic profiling.

Growing understanding of the importance of biomarkers linked with therapy selection, minimal residual disease detection, and early cancer screening is leading to more companies offering services in genomic profiling.

The promise of liquid biopsy testing is also leading to more companies attempting to enter the space and compete with us.

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Our competitors within the liquid biopsy space for therapy selection include Foundation Medicine, Inc., which was acquired by Roche Holdings, Inc.

Roche Molecular Systems, Inc., Thermo Fisher Scientific, Inc., Illumina, Inc., Qiagen N.V., Invitae Corporation, Caris Life Science, and Tempus Labs, Inc.

In addition, NeoGenomics Laboratories, Inc., Natera, Inc., Exact Sciences Corp., and Tempus Labs, Inc., among others, are our competitors in minimal residual disease testing.

Additionally, our competitors in the early screening testing space include GRAIL, Inc., Exact Sciences Corp., Freenome Holdings, Inc., Delfi Diagnostics and InterVenn Biosciences.

Competitors within the broader genomics profiling space based on tissue include laboratory companies such as Bio-Reference Laboratories, Inc., Laboratory Corporation of America and Quest Diagnostics, Inc., as well as Myriad Genetics, Inc., and most if not all of the competitors within the liquid biopsy space for therapy selection, that sell molecular diagnostic tests for cancer to physicians and have or may develop tests that compete with our tests.

Caris Life Science;

Tempus AI, Inc.;

NeoGenomics Laboratories, Inc.;

Exact Sciences Corp.;

Myriad Genetics, Inc.;

and Laboratory Corporation of America.

In addition, Natera, Inc., Tempus AI, Inc., Exact Sciences Corp., Myriad Genetics, Inc., Caris Life Science, Foundation Medicine, Inc.

and Quest Diagnostics, Inc., among others, are our competitors in minimal residual disease detection.

Additionally, our competitors in the early screening testing space include GRAIL, Inc., Exact Sciences Corp., Freenome Holdings, Inc., and Delfi Diagnostics.

Competitors within the broader genomics profiling space based on tissue include laboratory companies such as Bio-Reference Laboratories, Inc., Laboratory Corporation of America and Quest Diagnostics, Inc., and most if not all of the competitors within the liquid biopsy space for therapy selection, that sell molecular diagnostic tests for cancer to physicians and have or may develop tests that compete with our tests.

In addition, we are aware that certain of our customers are also developing their own tests and may decide to enter our market or otherwise stop using our tests.

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Our patent portfolio includes owned and licensed patents and patent applications, generally falling into three broad categories:

• issued patents and patent applications relating to our digital sequencing platform, including claims directed to methods for sequencing cell-free DNA, identifying CNVs, SNVs, indels and fusions in cell-free DNA and techniques for enriching nucleic acid samples;

• issued patents and patent applications relating to detecting and monitoring cancer and other diseases by determining genetic variations in biological samples;

• issued patents and patent applications relating to our digital sequencing platform, including claims directed to methods for preparing and sequencing cell-free DNA, techniques for enriching nucleic acid samples, identifying CNVs, SNVs, indels and fusions in cell-free DNA, and detecting epigenomic variations (such DNA methylation) in biological samples;

• issued patents and patent applications relating to detecting residual disease and monitoring cancer and other diseases by determining genetic and epigenomic variations in biological samples;

• issued patents and patent applications relating to early-stage cancer detection.

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Regulatory framework for medical devices in the United States

Pursuant to its authority under the Federal Food, Drug and Cosmetic Act, or the FDCA, the FDA has jurisdiction over medical devices, which are defined to include, among other things, IVDs.

Pursuant to its authority under the Federal Food, Drug and Cosmetic Act, or the FDCA, the FDA has jurisdiction over medical devices, which are defined to include, among other things, in vitro diagnostics, or IVDs.

The FDA regulates, among other things, the research, design, development, pre-clinical and clinical testing, manufacturing, safety, effectiveness, packaging, labeling, storage, recordkeeping, pre-market clearance or approval, adverse event reporting, marketing, advertising and promotion activities, sales, distribution and import and export of medical devices to ensure that medical devices distributed domestically are safe and effective for their intended uses and otherwise meet the requirements of the FDCA.

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As a practical matter, clearance often takes longer, and clearance is never assured.

FDA may issue a hold letter requesting additional information, which would stop the review clock for FDA.

The applicant has 180 days to respond to such additional information request, after which the FDA review clock will resume.

Although many 510(k) premarket notifications are cleared without clinical data, the FDA may require further information, including clinical data, to make a determination regarding substantial equivalence, which may significantly prolong the review process.

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The PMA process

We currently market our Guardant360 CDx test pursuant to an approved PMA.

We currently market our Guardant360 CDx test and the Shield test pursuant to an approved PMA.

The PMA process is more demanding than the 510(k) premarket notification process.

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Certain changes to an approved device, such as changes in manufacturing facilities, methods, or quality control procedures, or changes in the design performance specifications, which could affect the safety or effectiveness of the device, require submission of a PMA supplement.

PMA supplements often require submission of the same type of information as a PMA, except that the supplement is limited to information needed to support any changes from the device covered by the original PMA and may not require as extensive clinical data or the convening of an advisory panel.

PMA supplements often require submission of the same type of

information as a PMA, except that the supplement is limited to information needed to support any changes from the device covered by the original PMA 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.

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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:

The goal of the program is to provide patients and healthcare 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.

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On November 18, 2016, the FDA announced that it would not finalize either guidance document to allow for further public discussion on an appropriate oversight approach to LDTs and to give Congressional authorizing committees the opportunity to develop a legislative solution, and the FDA issued a discussion paper on possible approaches to LDT regulation in January 2017.

The FDA could ultimately modify its current approach to LDTs in a way that would subject LDTs to additional regulatory requirements.

Moreover, legislative measures could likewise result in a change to the approach to FDA’s regulation over LDTs, including a requirement for premarket review of LDTs, among other things.

In May 2024, the FDA finalized a rule requiring LDTs to undergo premarket review as medical devices.

While the rule is set to be implemented in the spring of 2025, it has been challenged in two separate lawsuits in federal court.

The FDA could ultimately subject LDTs to additional regulatory requirements.

Moreover, legislative measures could result in a change to the approach to FDA’s regulation over LDTs, including a requirement for premarket review of LDTs, among other things.

Research use only or investigational use only devices

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We must also operate within the bounds of the fraud and abuse laws of the states in which we do business which may apply to items or services reimbursed by non-governmental third-party payers, including private insurers.

In addition, the Physician Payments Sunshine Act imposes, among other things, reporting requirements on manufacturers of certain devices, drugs and biologics for certain payments and transfers of value by them and in some cases their distributors to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other health care providers such as physician assistants and nurse practitioners, and teaching hospitals, as well as ownership and investment interests held by physicians (as defined by the statute) and their immediate family members.

In addition, the Physician Payments Sunshine Act imposes, among other things, reporting requirements on manufacturers of certain devices, drugs and biologics for certain payments and transfers of value by them and in some cases their distributors to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare providers such as physician assistants and nurse practitioners, and teaching hospitals, as well as ownership and investment interests held by physicians (as defined by the statute) and their immediate family members.

Manufacturers must submit reports by the 90th day of each calendar year.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business