Grail (company)

Last updated

GRAIL
Company type Subsidiary
Industry Biotechnology
Founded2015;9 years ago (2015)
Headquarters
Menlo Park, California
,
United States
Products Galleri test
Parent Illumina, Inc.
Website grail.com

Grail (styled GRAIL) is an American biotechnology company in Menlo Park, California. It is a subsidiary of Illumina started as a startup seeking to develop an early cancer screening test for people who do not have symptoms. [1]

Contents

Their liquid biopsy (also called multi-cancer early detection test [2] ) 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 multi-cancer screening tests under investigation; the other two being the CancerSEEK assay and the PanSeer assay.

History

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. [3] [4] [5] [6] Richard Klausner, then chief medical officer at Illumina and former director of the National Cancer Institute, advocated for the new business. According to the San Francisco Business Times, he correctly predicted how DNA sequencing technology would make it possible to detect evidence of a tumor from a blood sample. [7] He also joined Grail's board of directors. [8] According to Forbes in 2017, 20% of Grail's profits are kept by Illumina. [3]

In September 2020, Illumina announced an agreement to purchase Grail outright for $7.1 billion. [9]

On November 27, 2020, Grail announced a commercial partnership with the National Health Service (England) (NHS), to trial the Galleri test, reporting in 2026.

In March 2021, the Federal Trade Commission (FTC) sued to block the vertical merger. [10] [11] In September 2022, an administrative judge ruled against the FTC's position on antitrust grounds. [12]

In June 2023, Grail disclosed that its telemedicine vendor PWNHealth mailed letters to 408 patients incorrectly informing them that they may have cancer. The company blamed the incident on PWNHealth, saying that it was due to a software configuration issue, not due to incorrect Galleri test results. [13] [14]

In July 2023, it was reported that three separate lawsuits were filed against Grail by former female employees; the allegations included that Grail created a "frat house” culture and a “sexually charged, hostile work environment”. [15]

In October 2023, the European Commission ordered Grail to be divested from Illumina within the next twelve months. [16] The European Commission (EC) has since approved Illumina's divestment plan for separating from Grail. Illumina has set a goal of finalizing the divestment terms by the end of the second quarter of 2024. In April 2024, the EC approved Illumina's plan, allowing Illumina to explore either a trade sale or a capital markets transaction (spin-off) to divest Grail. In May 2024, Illumina publicly filed a Form 10 registration statement with the U.S. SEC, a necessary step for a potential capital markets separation of Grail. If a capital markets transaction occurs, Illumina must capitalize Grail with around $1 billion to fund 2.5 years of operations per the EC's divestment plan. [17] [18] [19]

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. [3] 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. [20]

Galleri test

Grail calls its liquid biopsy for early cancer the Galleri test or the Galleri multi-cancer early detection (MCED) test, one of three multi-cancer screening tests under investigation and being validated as of November 2020; the other two being the CancerSEEK assay and the PanSeer assay. [21] [22] 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. [21]

Grail's first clinical trial for the Galleri test is the 'Circulating Cell-free Genome Atlas Study'. [20] 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. [21] Subsequently the Galleri test entered into a further three trials; STRIVE, SUMMIT, and PATHFINDER studies. [21] Results from PATHFINDER presented in September 2022 showed a 43.1% positive predictive value for the detection of early-stage cancer, with the test predicting the cancer signal origin with 97% accuracy in less than three months' time. [23]

Galleri received breakthrough device designation from the U.S. Food and Drug Administration in May 2019. [24] The test does not diagnose cancer; [25] rather, it detects possible signs of cancer in order to help direct follow-up diagnostic testing. [26] Galleri is not yet approved by the FDA, but it is available by prescription under the agency's provision for laboratory developed tests. [27] [28]

In November 2020 Grail announced a commercial partnership with the National Health Service (England) (NHS), to trial the Galleri test; [29] [30] several scientists responded to the news. [31] [32]

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. [29] The trial started on August 31, 2021, with primary completion date estimated at July 15, 2024, and study completion on February 28, 2026. [33] In June 2021, the company began selling Galleri tests in the U.S. [34]

As of January 2023 at least seventeen clinical trials were in progress to investigate the performance and clinical utility of multi-cancer early detection tests, six of them involving Grail. [35]

Related Research Articles

<span class="mw-page-title-main">Prostate-specific antigen</span> Mammalian protein found in humans

Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a glycoprotein enzyme encoded in humans by the KLK3 gene. PSA is a member of the kallikrein-related peptidase family and is secreted by the epithelial cells of the prostate gland in men and the paraurethral glands in women.

<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, an interventional radiologist, or an interventional cardiologist. The process involves the 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">Fecal occult blood</span> Medical condition

Fecal occult blood (FOB) refers to blood in the feces that is not visibly apparent. A fecal occult blood test (FOBT) checks for hidden (occult) blood in the stool (feces).

Prostate cancer screening is the screening process used to detect undiagnosed prostate cancer in men without signs or symptoms. When abnormal prostate tissue or cancer is found early, it may be easier to treat and cure, but it is unclear if early detection reduces mortality rates.

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. 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, and serves more than 155 countries.

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 qPCR 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.. 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.

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<span class="mw-page-title-main">Cancer screening</span> Method to detect cancer

The objective of cancer screening is to detect cancer before symptoms appear, involving various methods such as blood tests, urine tests, DNA tests, and medical imaging. The purpose of screening is early cancer detection, to make the cancer easier to treat and extending life expectancy. In 2019, cancer was the second leading cause of death globally; more recent data is pending due to the COVID-19 pandemic.

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">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.

<span class="mw-page-title-main">Circulating tumor DNA</span> Tumor-derived fragmented DNA in the bloodstream

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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.

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.

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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.

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References

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  2. ↑ Pyzocha, Natasha J. (October 2022). "Galleri Test for the Detection of Cancer". American Family Physician. 106 (4): 459–460. ISSN   1532-0650. PMID   36260909.
  3. 1 2 3 Herper, Matthew. "Company Will Raise $1 Billion To Create Blood Test To Detect Cancer". Forbes. Retrieved November 27, 2020.
  4. ↑ Rockoff, Jonathan D. (September 21, 2020). "Sequencing Firm Illumina to Pay $7.1 Billion for Liquid-Biopsy Firm Grail" . Wall Street Journal . ISSN   0099-9660 . Retrieved November 27, 2020.
  5. ↑ Novo Melo, Pedro; Machado, Carolina (2018). Management and Technological Challenges in the Digital Age. CRC Press. p. 157. ISBN   978-0-429-81623-9.
  6. ↑ Kuchler, Hannah; Aliaj, Ortenca (September 21, 2020). "Illumina agrees $8bn deal for cancer screening group Grail" . ft.com. Financial Times. Retrieved December 1, 2020.
  7. ↑ Leuty, Ron (May 27, 2021). "Biotech's elder statesman is still going strong". San Francisco Business Times. Retrieved June 25, 2023.
  8. ↑ "Illumina Launches GRAIL, Focused on Blood-Based Cancer Screening". GEN - Genetic Engineering and Biotechnology News. January 11, 2016. Retrieved June 25, 2023.
  9. ↑ Rockoff, Jonathan D. (September 21, 2020). "Sequencing Firm Illumina to Pay $7.1 Billion for Liquid-Biopsy Firm Grail". Wall Street Journal. Retrieved March 31, 2021.
  10. ↑ Kendall, Brent; Rockoff, Jonathan D. (March 31, 2021). "FTC Seeks to Block Illumina's $7.1 Billion Acquisition of Life Sciences Firm Grail". Wall Street Journal. Retrieved March 31, 2021.
  11. ↑ "FTC Challenges Illumina's Proposed Acquisition of Cancer Detection Test Maker Grail". FTC.gov. Federal Trade Commission. March 30, 2021. Retrieved March 31, 2021.
  12. ↑ Loftus, Peter (September 1, 2022). "Illumina Wins Case Against FTC on Grail Acquisition" . The Wall Street Journal .
  13. ↑ Smyth, Jamie; Smith, Ian (June 2, 2023). "More than 400 Grail patients incorrectly told they may have cancer". Financial Times.
  14. ↑ Sunny, Mariam (June 2, 2023). "Grail says about 400 patients incorrectly informed they may have cancer". Reuters.
  15. ↑ Smyth, Jamie; Kinder, Tabby (July 13, 2023). "Grail sued by three female ex-employees over 'toxic work culture'". Financial Times.
  16. ↑ Chee, Foo Yun (October 12, 2023). "Illumina ordered by EU antitrust regulators to sell Grail". Reuters.
  17. ↑ "Illumina's planned divestment of GRAIL approved by the European Commission". Illumina. May 6, 2024.
  18. ↑ "Statement Regarding Illumina's Decision to Divest Grail". Federal Trade Commission. December 18, 2023.
  19. ↑ "Illumina publicly files Form 10 registration statement ahead of planned divestiture of GRAIL". Illumina. February 1, 2019.
  20. 1 2 Harry Glorikian; Malorye Allison Branca (November 20, 2017). MoneyBall Medicine: Thriving in the New Data-Driven Healthcare Market. Taylor & Francis. pp. 109–110. ISBN   978-1-351-98433-1.
  21. 1 2 3 4 Beer, Tomasz M. (November 1, 2020). "Novel blood-based early cancer detection: diagnostics in development". The American Journal of Managed Care . 26 (14): S292–S299. doi: 10.37765/ajmc.2020.88533 . PMID   33200893.
  22. ↑ The Lancet Oncology (June 1, 2020). "Cancer detection: the quest for a single liquid biopsy for all". The Lancet Oncology. 21 (6): 733. doi: 10.1016/S1470-2045(20)30033-4 . ISSN   1470-2045. PMC   7266566 . PMID   32502435.
  23. ↑ "903O - A prospective study of a multi-cancer early detection blood test". ESMO Congress – OncologyPRO. September 11, 2022. Retrieved July 26, 2023.
  24. ↑ Tirumalaraju, Divya (May 14, 2019). "Grail gets FDA breakthrough designation for multi-cancer test". Medical Device Network. Retrieved June 26, 2023.
  25. ↑ "The Galleri Blood Test: What To Know". Health. December 21, 2022. Retrieved July 26, 2023.
  26. ↑ Sample, Ian (September 11, 2022). "Blood test spots multiple cancers without clear symptoms, study finds". The Guardian. Retrieved July 26, 2023.
  27. ↑ Kolata, Gina (June 10, 2022). "Blood Tests That Detect Cancers Create Risks for Those Who Use Them". The New York Times. Retrieved June 25, 2023.
  28. ↑ Sample, Ian (September 11, 2022). "Blood test spots multiple cancers without clear symptoms, study finds". The Guardian. Retrieved July 26, 2023.
  29. 1 2 Gregory, Andy (November 27, 2020). "NHS to trial 'game-changer' blood test for cancer in 2021". The Independent.
  30. ↑ "NHS England » NHS to pilot potentially revolutionary blood test that detects more than 50 cancers". NHS England. Retrieved November 30, 2020.
  31. ↑ Several experts (November 27, 2020). "Expert reaction to announcement of a new NHS pilot on a blood test for more than 50 cancers".
  32. ↑ Campbell, Denis (November 27, 2020). "NHS to trial blood test to detect more than 50 forms of cancer". The Guardian. Retrieved November 28, 2020.
  33. ↑ "Does Screening With the Galleri Test in the NHS Reduce the Likelihood of a Late-stage Cancer Diagnosis in an Asymptomatic Population? A Randomised Clinical Trial". ClinicalTrials.gov. November 10, 2022. NCT05611632.
  34. ↑ Nathan-Kazis, Josh (June 4, 2021). "Grail Will Begin Selling Its Multi-Cancer Blood Test". Barron's. Retrieved June 25, 2023.
  35. ↑ Johnson, Kate (January 10, 2023). "Cancer Clinics See Patients Demanding New Cancer Detection Tests". Medscape.
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