GRAIL (company)

Last updated

GRAIL
Type Subsidiary
Industry Biotechnology
Founded2015;8 years ago (2015)
Headquarters,
United States
Products Galleri test
Parent Illumina, Inc.
Website grail.com

Grail (styled GRAIL) is an American biotechnology company, which began in 2016 as a start-up in San Francisco, California, seeking to develop an early cancer screening test for people who do not have symptoms. [1] Its headquarters is in Menlo Park, California, with locations in Washington, D.C., North Carolina, and the UK. Its parent company is Illumina in San Diego, California.

Contents

Their liquid biopsy, which was launched in June 2021 and is called the 'Galleri test', detects fragments of DNA in a blood sample via next-generation sequencing, which identifies DNA methylation, distinct patterns of which are associated with particular cancers, potentially allowing for the early detection of cancer and providing information of the origin of the cancer. It is one of three multicancer screening tests under investigation; the other two being the CancerSEEK assay and the PanSeer assay. On November 27, 2020, Grail announced a commercial partnership with the National Health Service (England) (NHS), to trial the Galleri test, reporting in 2026.

Origin

Grail began as a San Francisco biotechnology and pharmaceutical startup company in 2015, the parent company being Illumina of San Diego, which produces most of the DNA sequencing machines that scientists use to study human biology and diagnose rare genetic diseases. [2] [3] [4] [5] According to Forbes in 2017, 20% of Grail's profits are kept by Illumina. [2]

In September 2020, Illumina announced an agreement to purchase Grail outright for $7.1 billion. [6] In March 2021, the Federal Trade Commission sued to block the vertical merger. [7] [8] In September 2022, an administrative judge ruled against the FTC's position on antitrust grounds. [9]

Activities

Illumina's own research showed that repeatedly sequencing DNA in the bloodstream made it possible to detect floating bits of DNA from cancer cells more accurately. [2] It initially aimed to recruit greater than 100,000 people into its clinical trials in order to accumulate the sizeable data required to detect and interpret cancer biomarkers. [10]

Galleri test

Grail calls its liquid biopsy for early cancer the 'Galleri test' or the 'Galleri multicancer early detection (MCED) test', one of three multicancer screening tests under investigation and being validated as of November 2020; the other two being the CancerSEEK assay and the PanSeer assay. [11] [12] The Galleri test detects fragments of DNA in a blood sample via next-generation sequencing, which identifies DNA methylation, distinct patterns of which are associated with particular cancers, potentially allowing early detection of cancer and providing information of the origin of the cancer. [11]

Grail's first clinical trial for the Galleri test is the 'Circulating Cell-free Genome Atlas Study'. [10] The study looked at more than 50 distinctive cancer types in blood and tumour tissue samples from 15,254 people from 142 locations in North America, including people with new cancer and blood samples from people without a cancer diagnosis. [11] Subsequently the Galleri test entered into a further three trials; STRIVE, SUMMIT, and PATHFINDER studies. [11]

Galleri received breakthrough device designation from the U.S. Food and Drug Administration in May 2019. [13] Galleri is not yet approved by the FDA, but it is available by prescription under the agency's provision for laboratory developed tests. [14]

In November 2020 Grail announced a commercial partnership with the National Health Service (England) (NHS), to trial the 'Galleri test'; [15] [16] several scientists responded to the news. [17] [18]

The NHS England interventional randomised controlled trial includes two groups of participants; a group of 140,000 people aged 50 to 79 identified through NHS records who have no symptoms, who will have a yearly blood test over three years, and a second group of 25,000 people with possible cancer symptoms. [15] The trial started on August 31, 2021, with primary completion date estimated at July 15, 2024, and study completion on February 28, 2026. [19]

As of January 2023 at least seventeen clinical trials were in progress to investigate the performance and clinical utility of multicancer early detection tests, six of them involving Grail. [20]

In June 2023, Grail disclosed that its telemedicine vendor PWNHealth mistakenly informed 408 of its patients that they may have cancer. The company asserted that the incident was due to a software configuration issue at PWNHealth, not due to incorrect Galleri test results. [21] [22]

Related Research Articles

<span class="mw-page-title-main">Biopsy</span> Medical test involving extraction of sample cells or tissues for examination

A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a disease. The tissue is then fixed, dehydrated, embedded, sectioned, stained and mounted before it is generally examined under a microscope by a pathologist; it may also be analyzed chemically. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. An incisional biopsy or core biopsy samples a portion of the abnormal tissue without attempting to remove the entire lesion or tumor. When a sample of tissue or fluid is removed with a needle in such a way that cells are removed without preserving the histological architecture of the tissue cells, the procedure is called a needle aspiration biopsy. Biopsies are most commonly performed for insight into possible cancerous or inflammatory conditions.

<span class="mw-page-title-main">Qiagen</span> German biotechnology company

QIAGEN is a provider of sample and assay technologies for molecular diagnostics, applied testing, academic and pharmaceutical research. The company operates in more than 35 offices in over 25 countries. QIAGEN N.V., the global corporate headquarter of the QIAGEN group, is located in Venlo, The Netherlands. European, American, and Asian regional headquarters are located in respectively Hilden, Germany; Germantown, Maryland United States; and Shanghai, China. QIAGEN's shares are listed at the NYSE and at the Frankfurt Stock Exchange in the Prime Standard. Thierry Bernard is the company's Chief Executive Officer(CEO). The main operative headquarters are located in Hilden, Germany.

Genotyping is the process of determining differences in the genetic make-up (genotype) of an individual by examining the individual's DNA sequence using biological assays and comparing it to another individual's sequence or a reference sequence. It reveals the alleles an individual has inherited from their parents. Traditionally genotyping is the use of DNA sequences to define biological populations by use of molecular tools. It does not usually involve defining the genes of an individual.

Illumina, Inc. is an American biotechnology company, headquartered in San Diego, California, and it serves more than 140 countries. Incorporated on April 1, 1998, Illumina develops, manufactures, and markets integrated systems for the analysis of genetic variation and biological function. The company provides a line of products and services that serves the sequencing, genotyping and gene expression, and proteomics markets.

Digital polymerase chain reaction is a biotechnological refinement of conventional polymerase chain reaction methods that can be used to directly quantify and clonally amplify nucleic acids strands including DNA, cDNA, or RNA. The key difference between dPCR and traditional PCR lies in the method of measuring nucleic acids amounts, with the former being a more precise method than PCR, though also more prone to error in the hands of inexperienced users. A "digital" measurement quantitatively and discretely measures a certain variable, whereas an “analog” measurement extrapolates certain measurements based on measured patterns. PCR carries out one reaction per single sample. dPCR also carries out a single reaction within a sample, however the sample is separated into a large number of partitions and the reaction is carried out in each partition individually. This separation allows a more reliable collection and sensitive measurement of nucleic acid amounts. The method has been demonstrated as useful for studying variations in gene sequences — such as copy number variants and point mutations — and it is routinely used for clonal amplification of samples for next-generation sequencing.

COLD-PCR is a modified polymerase chain reaction (PCR) protocol that enriches variant alleles from a mixture of wildtype and mutation-containing DNA. The ability to preferentially amplify and identify minority alleles and low-level somatic DNA mutations in the presence of excess wildtype alleles is useful for the detection of mutations. Detection of mutations is important in the case of early cancer detection from tissue biopsies and body fluids such as blood plasma or serum, assessment of residual disease after surgery or chemotherapy, disease staging and molecular profiling for prognosis or tailoring therapy to individual patients, and monitoring of therapy outcome and cancer remission or relapse. Common PCR will amplify both the major (wildtype) and minor (mutant) alleles with the same efficiency, occluding the ability to easily detect the presence of low-level mutations. The capacity to detect a mutation in a mixture of variant/wildtype DNA is valuable because this mixture of variant DNAs can occur when provided with a heterogeneous sample – as is often the case with cancer biopsies. Currently, traditional PCR is used in tandem with a number of different downstream assays for genotyping or the detection of somatic mutations. These can include the use of amplified DNA for RFLP analysis, MALDI-TOF genotyping, or direct sequencing for detection of mutations by Sanger sequencing or pyrosequencing. Replacing traditional PCR with COLD-PCR for these downstream assays will increase the reliability in detecting mutations from mixed samples, including tumors and body fluids.

<span class="mw-page-title-main">Pacific Biosciences</span> American biotechnology company

Pacific Biosciences of California, Inc. is an American biotechnology company founded in 2004 that develops and manufactures systems for gene sequencing and some novel real time biological observation. PacBio has two principal sequencing platforms: single-molecule real-time sequencing (SMRT), based on the properties of zero-mode waveguides and sequencing by binding (SBB) chemistry, which uses native nucleotides and scarless incorporation for DNA binding and extension.

Natera, Inc. is a clinical genetic testing company based in Austin, Texas that specializes in non-invasive, cell-free DNA (cfDNA) testing technology, with a focus on women’s health, cancer, and organ health. Natera’s proprietary technology combines novel molecular biology techniques with a suite of bioinformatics software that allows detection down to a single molecule in a tube of blood. Natera operates CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in San Carlos, California and Austin, Texas.

<span class="mw-page-title-main">Molecular diagnostics</span> Collection of techniques used to analyze biological markers in the genome and proteome

Molecular diagnostics is a collection of techniques used to analyze biological markers in the genome and proteome, and how their cells express their genes as proteins, applying molecular biology to medical testing. In medicine the technique is used to diagnose and monitor disease, detect risk, and decide which therapies will work best for individual patients, and in agricultural biosecurity similarly to monitor crop- and livestock disease, estimate risk, and decide what quarantine measures must be taken.

Dennis Yuk Ming Lo is a Hong Kong molecular biologist, and an important contributor to the development of non-invasive prenatal testing. He is the current Associate Dean (Research) and Li Ka Shing Professor of Medicine at the Chinese University of Hong Kong (CUHK), as well as the head of the Department of Chemical Pathology of CUHK and the director of the Li Ka Shing Institute of Health Sciences. His research focuses on the detection of cell-free fetal DNA in blood plasma.

<span class="mw-page-title-main">Circulating tumor DNA</span>

Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the bloodstream that is not associated with cells. ctDNA should not be confused with cell-free DNA (cfDNA), a broader term which describes DNA that is freely circulating in the bloodstream, but is not necessarily of tumor origin. Because ctDNA may reflect the entire tumor genome, it has gained traction for its potential clinical utility; "liquid biopsies" in the form of blood draws may be taken at various time points to monitor tumor progression throughout the treatment regimen.

A liquid biopsy, also known as fluid biopsy or fluid phase biopsy, is the sampling and analysis of non-solid biological tissue, primarily blood. Like traditional biopsy, this type of technique is mainly used as a diagnostic and monitoring tool for diseases such as cancer, with the added benefit of being largely non-invasive. Liquid biopsies may also be used to validate the efficiency of a cancer treatment drug by taking multiple samples in the span of a few weeks. The technology may also prove beneficial for patients after treatment to monitor relapse.

<span class="mw-page-title-main">Exact Sciences (company)</span> American company in Madison, United States

Exact Sciences Corp. is a molecular diagnostics company specializing in the detection of early stage cancers. The company's initial focus was on the early detection and prevention of colorectal cancer, in 2014 it launched Cologuard, the first stool DNA test for colorectal cancer. Since then Exact Sciences has grown its product portfolio to encompass other screening and precision oncological tests for other types of cancer.

<span class="mw-page-title-main">Surveyor nuclease assay</span>

Surveyor nuclease assay is an enzyme mismatch cleavage assay used to detect single base mismatches or small insertions or deletions (indels).

CAncer Personalized Profiling by deep Sequencing (CAPP-Seq) is a next-generation sequencing based method used to quantify circulating DNA in cancer (ctDNA). The method was introduced in 2014 by Ash Alizadeh and Maximilian Diehn’s laboratories at Stanford, as a tool for measuring Cell-free tumor DNA which is released from dead tumor cells into the blood and thus may reflect the entire tumor genome. This method can be generalized for any cancer type that is known to have recurrent mutations. CAPP-Seq can detect one molecule of mutant DNA in 10,000 molecules of healthy DNA. The original method was further refined in 2016 for ultra sensitive detection through integration of multiple error suppression strategies, termed integrated Digital Error Suppression (iDES). The use of ctDNA in this technique should not be confused with circulating tumor cells (CTCs); these are two different entities.

Circulating free DNA (cfDNA) (also known as cell-free DNA) are degraded DNA fragments released to body fluids such as blood plasma, urine, cerebrospinal fluid, etc. Typical sizes of cfDNA fragments reflect chromatosome particles (~165bp), as well as multiples of nucleosomes, which protect DNA from digestion by apoptotic nucleases. The term cfDNA can be used to describe various forms of DNA freely circulating in body fluids, including circulating tumor DNA (ctDNA), cell-free mitochondrial DNA (ccf mtDNA), cell-free fetal DNA (cffDNA) and donor-derived cell-free DNA (dd-cfDNA). Elevated levels of cfDNA are observed in cancer, especially in advanced disease. There is evidence that cfDNA becomes increasingly frequent in circulation with the onset of age. cfDNA has been shown to be a useful biomarker for a multitude of ailments other than cancer and fetal medicine. This includes but is not limited to trauma, sepsis, aseptic inflammation, myocardial infarction, stroke, transplantation, diabetes, and sickle cell disease. cfDNA is mostly a double-stranded extracellular molecule of DNA, consisting of small fragments (50 to 200 bp) and larger fragments (21 kb) and has been recognized as an accurate marker for the diagnosis of prostate cancer and breast cancer.

Sophia Genetics is a data-driven medicine software company with headquarters in Lausanne, Switzerland and Boston, Massachusetts. It provides genomic and radiomic analysis for hospitals, laboratories, and biopharma institutions. The company was ranked among the 50 smartest companies by the MIT Technology Review in 2017. The company went public on the Nasdaq in 2021, floating at $1.1B.

Clinical metagenomic next-generation sequencing (mNGS) is the comprehensive analysis of microbial and host genetic material in clinical samples from patients by next-generation sequencing. It uses the techniques of metagenomics to identify and characterize the genome of bacteria, fungi, parasites, and viruses without the need for a prior knowledge of a specific pathogen directly from clinical specimens. The capacity to detect all the potential pathogens in a sample makes metagenomic next generation sequencing a potent tool in the diagnosis of infectious disease especially when other more directed assays, such as PCR, fail. Its limitations include clinical utility, laboratory validity, sense and sensitivity, cost and regulatory considerations.

<span class="mw-page-title-main">Helmy Eltoukhy</span> American scientist and entrepreneur

Helmy Eltoukhy is an American scientist and a businessperson who co-founded startups Avantome and Guardant Health. He is best known for his contributions to genomics, semiconductor DNA sequencing, and personalized medicine. His startups were acquired by Illumina in 2008. Avantome was founded to develop and commercialize semiconductor-based DNA sequencing, during the race for the $1,000 genome. Guardant Health was founded to pioneer non-invasive liquid biopsy approaches for cancer diagnosis, monitoring, personalized medicine treatment, and research.

Cancer Likelihood in Plasma (CLiP) refers to a set of ensemble learning methods for integrating various genomic features useful for the noninvasive detection of early cancers from blood plasma. An application of this technique for early detection of lung cancer (Lung-CLiP) was originally described by Chabon et al (2020) from the labs of Ash Alizadeh and Max Diehn at Stanford.

References

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