Macro view of LIQUID BIOPSY sector

Back on 4/3/2017, my “Macro View of the CAR T-cell sector” post here related that other efforts were ongoing in pursuit of the holy grail of treating and curing cancer, e.g., Johns Hopkins Kimmel Cancer Center scientists who reported data from a new study providing evidence that random, unpredictable DNA copying “mistakes” account for nearly two-thirds of the mutations that cause cancer. Their research is grounded on a novel mathematical model based on DNA sequencing and epidemiologic data from around the world.…
Bert Vogelstein, M.D., co-director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center, stated, ”We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations. However, many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed.” This effort is in the realm of what is called liquid biopsy, a sector that I have been watching and conducting my own due diligence since 2016.

Since only one so far - Foundation Medicine Inc. (FMI) - of many competing interests in this sector has been brought to the attention of this board, I will share and provide a macro view of what’s going on, who are some of the players (public and private companies and academic research centers), and what are the most promising business plans and progress in research and development of diagnostic products to deliver to the marketplace. So here goes a long heads up post, intended to whet your appetite and, if interested, to conduct your own deep dive research and due diligence.


According to the NIH National Cancer Institute, liquid biopsy is a test done on a sample of blood to look for cancer cells from a tumor that are circulating in the blood or for pieces of DNA from tumor cells that are in the blood. A liquid biopsy may be used to help find cancer at an early stage. It may also be used to help plan treatment or to find out how well treatment is working or if cancer has come back. Being able to take multiple samples of blood over time may also help doctors understand what kind of molecular changes are taking place in a tumor.…

Liquid biopsy is a minimally invasive technology for detection of molecular biomarkers without the need for costly or invasive procedures. It is a simple and non-invasive alternative to surgical biopsies which enables medical doctors to discover a range of information about a disease or a tumor through a simple blood sample. Circulating cancer cells or traces of cancer’s RNA or DNA in the blood can give clues about which treatments are most likely to work for the patient. Circulating nucleic acids are protected by extracellular micro-vesicles, mainly exosomes.


There are two highly recognized/acknowledged pioneer developers and giants of liquid biopsy:

Bert Vogelstein, M.D., co-director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center, is one of the most highly cited scientists in the world. In the 1980s, Dr. Vogelstein was acknowledged as having broken into “the cockpit of cancer” after he and coworkers at Johns Hopkins University showed for the first time exactly how a series of DNA mutations, adding up silently over decades, turn cells cancerous. Damaged DNA, he helped prove, is the cause of cancer. Here’s an excellent article about Dr. Vogelstein’s professional background and accomplishments:…
We’re not winning the war on cancer, and the death of ­Vogelstein’s brother shows why. Too many cancers are caught when they have become incurable. Each year, $91 billion is spent on cancer drugs worldwide, but most of those medicines are given to patients when it’s too late. The newest treatments, created at staggering expense, cost $10,000 a month and often extend life by only a few weeks. Pharmaceutical firms develop and test more drugs for late-stage cancer than for any other kind of disease.
“We as the public and as scientists have been entranced by this idea of curing advanced cancers,” says Vogelstein. “That is society’s Plan A. I don’t think that has to be the case.” There are other ways to reduce cancer deaths: wearing sunscreen, not smoking, and getting screened to catch cancer early. To ­Vogelstein, all these preventive steps represent “Plan B” because they receive so much less attention and funding. Yet when prevention works, it has better results than any drug. In the United States, the chance of dying from colorectal cancer is 40 percent lower than it was in 1975, a decrease mostly due to colonoscopy screening. Melanoma skin cancer, too, is treatable with surgery if caught early. “We think Plan B needs to be Plan A,” says Vogelstein.
The new blood tests could make that possible.

Dennis Lo, who is a molecular anatomist, Director of the Li Ka Shing Institute of Health Sciences, the Li Ka Shing Professor of Medicine, and Professor of Chemical Pathology of The Chinese University of Hong Kong, China, has worked for nearly 20 years on a technique called the “liquid biopsy,” which is meant to detect cancers very early—even before symptoms arise—by sequencing the DNA in a few drops of a person’s blood. Lo was the first scientist to discover the presence of fetal DNA in a pregnant mother’s blood-plasma that in recent years has led to a much safer, simpler screening test for Down syndrome.
Here’s an interesting March/April 2015 MIT Technology Review article about Lo’s background:
On May 31, 2017, GRAIL, Inc., a life sciences company whose mission is to detect cancer early when it can be cured, announced it has entered into a definitive agreement to combine with Cirina, Ltd., a Hong Kong-based, privately held company co-founded by Dennis Lo and others and also focused on the early detection of cancer. Lo was named a scientific co-founder of the combined entity and joined GRAIL’s scientific advisory board.

I’ll refer to these two giant pioneers later in my post.


The currently available liquid biopsy technologies employ the analysis of various types of analytes, including:
• circulating tumor DNA (ctDNA) - aka circulating cell-free DNA (cfDNA),
• circulating tumor cells (CTCs),
• extracellular vesicles,
• proteins,
• miRNA and
• mRNA

Among these, ctDNA and CTCs have been the most explored technologies for commercial applications up to the present time.

Circulating tumor DNA (ctDNA)
ctDNA encompasses the small fragments of DNA that are believed to originate from the natural and abnormal necrosis and apoptosis processes that tumor cells undergo regularly. ctDNA fragments have the advantage of being available from different types of specimens, including urine, plasma, blood, and cerebrospinal fluid, but are rare and have a short half-life in the bloodstream, which makes their isolation and identification highly challenging. Since many cancer patients shed only very small DNA fragments into the bloodstream, ctDNA-based diagnostic technologies need to be highly sensitive in order to detect such rare events. Furthermore, ctDNA cannot provide information about protein expression, and the analysis of RNA is also difficult and limited using ctDNA. ctDNA may also result from tumor cells killed by therapeutic drugs, and does not capture information about the residual cancer that may not respond to the particular therapy or has become resistant to it.

Current companies with ctDNA-based liquid biopsy tests include the following:
• Adaptive Biotechnologies
• Biodesix
• Epigenomics
• Foundation Medicine
• Genomic Health
• Guardant Health
• Myriad Genetics
• Pathway Genomics
• Personal Genome Diagnostics
• Roche Diagnostics
• Sysmex-Inostics
• Trovagene

Companies with ctDNA-based liquid biopsy tests in development include the following:
• Adaptive Biotechnologies
• Biocartis
• Epigenomics
• Exact Sciences
• Foundation Medicine
• Genomic Health
• Inivata
• Natera
• Trovagene

Circulating tumor cells (CTCs)
CTCs are cancer cells that are believed to detach from primary or secondary tumors and enter the bloodstream, traveling to distant organs, initiating the process of metastasis, and forming new tumors. Similarly to ctDNA, CTC-based tests could offer significant advantages compared to tissue biopsies, as they may be able to capture the heterogeneity of tumors and their genetic evolution during the disease progression and therapy. Compared to ctDNA, CTCs have a longer half-life in blood, and the analysis of viable cells could provide information about protein expression, such as PD-L1 or ER, which is not possible with ctDNA. Also, since CTCs contain intact genomic material from tumors, their analysis can reveal additional information about the biology of cancer and metastasis that is not possible to obtain from ctDNA.

Current companies with CTCs-based liquid biopsy tests include the following:
• Biocept
• Cynvenio Biosystems
• Epic Sciences
• Menarini-Silicon Biosystems

Companies with CTCs-based liquid biopsy tests in development include the following:
• Angle
• Biocept
• Epic Sciences
• Janssen Diagnostics

Exosomes are nanometer-sized extracellular membrane vesicles secreted by cells in the extracellular environment on a continuous basis. Exosomes circulate in great abundance and are highly stable in all biological fluids, and contain molecular information from their parental cells, included in proteins and various nucleic acids. Moreover, exosomes are involved in many cellular processes and carry information about tumor growth, metastasis, and drug resistance, which is not available from the analysis of circulating free DNA. Despite their advantages, the analysis of exosomes for diagnostic purposes poses various challenges that complicate considerably their use in the development of commercial diagnostics. Due to the complex composition of biological fluids, the detection and isolation of high purity exosomes is a long process that imposes the use of multiple techniques based on various parameters.

Companies with liquid biopsy tests based on extracellular vesicles/other analytes include the following:
• Biodesix
• Exosome Diagnostics
• Gensignia
• Hologic
• MMDxHealth
• OncoCyte
• Vermillion
• VolitionRx

The aforementioned companies are not a catchall listing.


At present, the market is heterogeneous and very fragmented with many companies commercializing various liquid biopsy diagnostic products and developing new ones for a broad range of applications. But only a few top competitors can be expected to hang in and survive long-term, e.g., Roche, Qiagen, Biocept and Myriad Genetics are among the aforementioned companies active in the global market for liquid biopsy diagnostic and monitoring tests.

Liquid biopsy encompasses various diagnostic methods that use liquid, non-tissue specimens to provide information that can aid in the diagnosis, treatment and monitoring of cancer. Currently, tissue biopsies, along with imaging techniques, are the standard methods used in the diagnosis of solid cancers, but despite their widespread use, they have many limitations that open the door for other diagnostic technologies in oncology clinical settings.

The overall market competitiveness increased in recent years as a result of new product introductions, and is projected to continue to increase within the next five years, as many companies are developing new products that are expected to reach the market in the near future. The market growth will be influenced by factors such as the rising incidence and prevalence of cancer at the global level, increasing use of personalized medicine, regulatory hurdles, reimbursement considerations, and adoption and integration issues of these.

ctDNA and CTCs have been the most explored technologies for commercial applications up to the present time. Given the advantages of isolating and analyzing ctDNA compared to CTCs and other analytes, along with the lower barriers to entry in this segment, the ctDNA-based liquid biopsy tests market segment is the most active one, with many competitors engaged in the development and commercialization of such tests.


As Saul once responded to one of my much too lengthy, but hopefully pithy CAR T-cell therapy deep dives, So Ray, after working your way all the way through that, what did you think about … any one or more of these companies???

In my ongoing due diligence since 2016, after applying the following filters among others, i.e.,
• Business plan, goals and objectives
• Disruptive, break through technology
• Barriers of Entry
• Massive user market
• Using modern technology
• Strong financial support
• High profile scientific advisory board,
I’ve narrowed my focus on primarily the direction and R&D efforts of the two liquid biopsy pioneers - Bert Vogelstein and Dennis Lo - given in the following private companies:
• GRAIL (associated with Denis Lo)
• Personal Genome Diagnostics/PGDx as well as other companies associated with Dr. Vogelstein, who is a member of the scientific advisory boards of Morphotek, Exelixis GP, and Syxmex Inostics, and is a founder of PapGene and Personal Genome Diagnostics. Morphotek, Syxmex Inostics, PapGene, and Personal Genome Diagnostics, as well as other companies, have licensed technologies from The Johns Hopkins University on which Vogelstein is an inventor. These licenses and relationships are associated with equity or royalty payments to Vogelstein. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict of interest policies. PGDx is a spin-off of Johns Hopkins University and co-founded by Vogelstein and his proteges Luis Diaz and Victor E. Velculescu, both oncologists at Hopkins Kimmel Cancer Center.

What attracts me to Lo and Vogelstein are their similar goals to shoot for the “whole enchilada,” i.e., develop one test that ideally will detect all cancers early on in supposedly healthy people and will be affordable enough to be included with other normal tests taken in annual physical examinations of patients - a massive global population and market.


At the Johns Hopkins Kimmel Cancer Center, Dr. Vogelstein said that his ultimate goal is to turn the blood tests into a way to routinely screen everyone for cancer. The Hopkins researchers believe they have a version of the test that can do that. Instead of tracking a few key cancer genes, they sequence a person’s entire genome using DNA from the blood sample. This lets them count how often chunks of genetic material are misplaced or appear scrambled. A large amount of rearranged DNA is a molecular side effect seen only on the chromosomes of cancer cells—a tip-off that cancer is present. But a full genome sequence is still expensive. “If a person has cancer, you don’t mind spending $5,000 on a DNA test. But you can’t have a test that costs $1,000 that you can do at an annual physical,” said Vogelstein. “The goal is to get the technology cheap enough to use in screening.” That could take time. The cost of DNA sequencing has been falling very rapidly, yet a $100 genome - the price that might be low enough for a general screening test - could be 10 years away.

Hopkins has begun several studies, mostly on individuals predisposed to cancer, to determine whether the techniques can catch tumors early in healthy people. One involves 800 people at risk for pancreatic cancer. In these unusual cases, people have cysts on the pancreas that sometimes turn into cancer but sometimes don’t. The clinical trial began following patients in 2012.

In August 2017, In a bid to detect cancers early and in a noninvasive way, Hopkins scientists reported they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to accurately identify more than half of 138 people with relatively early-stage colorectal, breast, lung and ovarian cancers. The test, the scientists say, is novel in that it can distinguish between DNA shed from tumors and other altered DNA that can be mistaken for cancer biomarkers. The researchers took blood samples from 200 people with different stages of breast, lung, ovarian, and colorectal cancer. The test was able to identify 62 percent of stages 1 and 2 cancers. There were no false-positives among 44 healthy people who were also tested. “This study shows that identifying cancer early using DNA changes in the blood is feasible, and that our high accuracy sequencing method is a promising approach to achieve this goal,” according to Dr. Victor Velculescu, professor of oncology at the Johns Hopkins Kimmel Cancer Center and co-founder of the cancer genomics company Personal Genome Diagnostics. For those interested in more details, check this Hopkins website:…

In September 2017, Johns Hopkins scientists say they have developed a blood test that spots tumor-specific DNA and protein biomarkers for early-stage pancreatic cancer. The combined “liquid biopsy” identified the markers in the blood of 221 patients with the early-stage disease. Their results, published online the week of Sept. 4 in the Proceedings of the National Academy of Sciences, show that detection of markers from both DNA and protein products of DNA was twice as accurate at identifying the disease as detection of DNA alone. Such liquid biopsies aim to fish out DNA molecules specific for cancer amid a wide sea of normal DNA circulating in the blood. Tumors tend to shed their mutated DNA into the bloodstream, making it possible for scientists to use genomic sequencing tools to sift through the blood and find such cancer-linked DNA. While their test is not ready to be used outside of a research setting, they say, mutated DNA of the type that is shed from tumors and found in blood is “exquisitely specific” for cancer. “If cancer-linked DNA can be found in the blood of an individual, it is very likely that person has cancer,” says Bert Vogelstein, M.D. Studies by Vogelstein’s team and others have shown that DNA can be identified in the blood of more than 85 percent of patients with advanced cancers. However, the sensitivity of detecting such small bits of DNA in the blood of patients with early cancers, without prior knowledge of the genetic status of the cancers, was unknown prior to this study, say the scientists.…


GRAIL is a life sciences company whose mission is to detect cancer early when it can be cured. GRAIL is using the power of high-intensity sequencing, population-scale clinical trials, and state of the art Computer Science and Data Science to enhance the scientific understanding of cancer biology and develop blood tests for early-stage cancer detection.

Strong Financial Support

The company has experience exceptionally strong funding, led by ARCH Venture Partners with the following investors: Amazon, Bezos Expeditions, Bill Gates, Bristol-Myers Squibb, Celgene, GV, Illumina, Johnson & Johnson Innovation, Merck, McKesson Ventures, Sutter Hill Ventures, Tencent, Varian Medical Systems, and other financial partners.

The following are key financial events:
• On January 10, 2016, Illumina, Inc. (ILMN) announced GRAIL, a new company formed to enable cancer screening from a simple blood test. Powered by Illumina sequencing technology, GRAIL would develop a pan-cancer screening test by directly measuring circulating nucleic acids in blood. The testing concept being pursued by Illumina, sometimes called a “liquid biopsy,” is to use high-speed DNA sequencing machines to scour a person’s blood for fragments of DNA released by cancer cells. If DNA with cancer-causing mutations is present, it often indicates a tumor is already forming, even if it’s too small to cause symptoms or be seen on an imaging machine.
Detecting cancer at the earliest stages dramatically increases long-term survival, hence the successful development of a pan-cancer screening test for asymptomatic individuals would make the first major dent in global cancer mortality.
GRAIL’s unique structure enabled it to take on this grand challenge. GRAIL was formed as a separate company, majority owned by Illumina. GRAIL was initially funded by over $100 million in Series A financing from Illumina and ARCH Venture Partners, with participating investments from Bezos Expeditions, Bill Gates and Sutter Hill Ventures. GRAIL’s unique relationship with Illumina provided the ability to economically sequence at the high depths necessary to create a screening test with the required sensitivity and a hoped for level of specificity never before achievable for cancer screening…

• On March 01, 2017, GRAIL announced that it has raised over $900 million through the first close of its previously announced Series B financing which was led by ARCH Venture Partners and includes Johnson & Johnson Innovation1 as the largest investor in the financing.
GRAIL will use the proceeds of the financing for continued product development and validation of blood tests for early-stage cancer detection, including the previously announced Circulating Cell-free Genome Atlas (CCGA) study and other large-scale clinical trials that are expected to enroll hundreds of thousands of patients. The CCGA study will characterize the landscape of cell-free DNA profiles in individuals with cancer and in healthy non-cancer participants using GRAIL’s high-intensity (ultra-broad and ultra-deep) sequencing approach, leveraging Illumina sequencing technology. Some of the proceeds were used to repurchase a portion of Illumina’s stake in GRAIL such that Illumina now owns slightly less than 20 percent of the Company.…

• On March 1, 2018, it was reported that GRAIL is considering a $500 million Hong Kong IPO. Last year, GRAIL completed a $900 million Series B fundraising, the largest ever. In June, GRAIL merged with Cirina, a Hong Kong cancer diagnostics company, which was co-founded by Dennis Lo, an early scientific leader in the field of molecular diagnostics. GRAIL is considering Hong Kong for its IPO venue following new HKEX rules that allow companies to IPO even if they aren’t profitable and to offer two classes of stock, one with voting rights (for the original owners) and one without.

Using modern technology

Initially, at the helm of GRAIL was CEO Jeff Huber best-known in the technology world as the senior engineering leader behind a 12-year hit parade of massive data businesses at Google, including Google Ads, Apps, and Maps. At Grail, he moved from mapping the world to mapping genomes, using Illumina’s cutting edge HiSeq sequencers?—?which, working in a pod of ten, can sequence 18,000 genomes in a year, a throughput of roughly one every few hours. Huber’s plan was to spin up scores and possibly hundreds of sequencing machines, each of which spit out a gigabit of data per second during operation. His long-term goal is nothing short of breathtaking?—?the creation of a living map of human biology, a platform spanning data and biology capable of delivering personalized cures not only for cancer, but quite possibly many other seemingly insoluble diseases.…
On 8/2/17 founding CEO Huber was appointed Vicd Chairman of the Board of Directors, and Bill Rastetter was appointed interim CEO. Subsequently, Jennifer Cook (formerly head of Clinical Operations in Product Development for Roche Pharmaceuticals) was appointed chief executive officer, effective January 2, 2018. Bill Rastetter, who has been acting as interim chief executive officer since August 2017, continues in his role as chairman of the Board of Directors, focusing on governance of the company.

Disruptive, break through technology and R&D

• The GRAIL 2016 Investor Presentation gave a target liquid biopsy test price range of $500 to $1,000 to make it attractive and affordable as part of an individual’s physical exam. [Note: earlier I mentioned that Dr. Vogelstein believes $1,000 is too much and strives for a more affordable cost, say $100.]…
• On December 1, 2016, GRAIL announced that it has commenced its first multi-center clinical study, the Circulating Cell-free Genome Atlas (CCGA) study to facilitate the development of GRAIL’s blood test for early-stage cancer detection.…

The purpose of the CCGA Study is to characterize the landscape of cell-free nucleic acid (cfNA) profiles in individuals with and without cancer. The observational CCGA Study will enroll at least 15,000 individuals with and without cancer (70% with cancer and 30% without cancer), interrogating the biology of both tumor biopsy tissue samples and the circulating, tumor-derived nucleic acids in blood. cfDNAs in the blood are an emerging biomarker for earlier cancer detection. GRAIL and its collaborators will collect clinical outcomes on the enrolled participants for at least five years. The result is intended to be a detailed atlas of cancer genomics that will be used to support development of GRAIL products for early cancer detection. The database, upon analysis, may be expanded to enroll additional individuals with specific cancers or without cancer.
Collaborators include Avera Research Institute, Benaroya Research Institute at Virginia Mason, Christ Hospital Health Network - The Lindner Cancer Center Research Division, Cleveland Clinic, Guardian Research Network, Hartford HealthCare Cancer Institute, Icahn School of Medicine at Mount Sinai, Lahey Hospital & Medical Center, Mayo Clinic (Arizona, Florida, and Minnesota), Memorial Sloan Kettering, Oregon Health & Science University Knight Cancer Institute, Tennessee Oncology, UHN Princess Margaret Cancer Centre (Canada), University of Miami Sylvester, and US Oncology Network.
• On May 31, 2017, GRAIL announced it has entered into a definitive agreement to combine with Cirina, Ltd., a privately held company that is also focused on the early detection of cancer. Cirina was co-founded by world renowned scientist in non-invasive molecular diagnostics, Dennis Lo, his colleagues Rossa Chiu and Allen Chan at the Chinese University of Hong Kong (CUHK), and lead investor, Decheng Capital. The company is headquartered in Hong Kong with research and development teams in Hong Kong and South San Francisco.…

• On June 03, 2017, GRAIL, Inc. announced results from a study evaluating a novel high-intensity sequencing approach for detecting tumor signals in the bloodstream. Historically, research has focused on detecting a small number of clinically-actionable mutations in circulating cell-free DNA (cfDNA). This study evaluated the ability of a high-intensity sequencing approach to detect a more diverse range of tumor signals, including those that are less common. This broader and deeper approach will be required to develop tests that can detect the tiny amounts of tumor DNA in the blood, and accurately capture the diversity in genomic alterations that characterize the tumors of every person with cancer.…

• A New England Journal of Medicine article dated August 10, 2017 addressed a study by Hong Kong doctors, led by researcher Dennis Lo, that showed that liquid biopsy tests can spot cancer early and was the first major field study of a new type of blood test to detect cancer early that showed the technique can probably save lives, at least in certain circumstances. This study in Hong Kong in which about 20,000 men were tested and then followed for three years found that nasopharyngeal cancer could be detected and treated early. That cancer, which grows in the throat, is exceptionally common in south China. The result provided a peek at the promise and limitations of “liquid biopsies”—tests that may be able to spot tumor DNA in a person’s blood even before they have any overt symptoms.
Here’s the New England Journal of Medicine Abstract.
Circulating cell-free Epstein–Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. We conducted a prospective study to investigate whether EBV DNA in plasma samples would be useful to screen for early nasopharyngeal carcinoma in asymptomatic persons.
We analyzed EBV DNA in plasma specimens to screen participants who did not have symptoms of nasopharyngeal carcinoma. Participants with initially positive results were retested approximately 4 weeks later, and those with persistently positive EBV DNA in plasma underwent nasal endoscopic examination and magnetic resonance imaging (MRI).
A total of 20,174 participants underwent screening. EBV DNA was detectable in plasma samples obtained from 1112 participants (5.5%), and 309 (1.5% of all participants and 27.8% of those who initially tested positive) had persistently positive results on the re- peated sample. Among these 309 participants, 300 underwent endoscopic examination, and 275 underwent both endoscopic examination and MRI; of these participants, 34 had nasopharyngeal carcinoma. A significantly higher proportion of participants with naso- pharyngeal carcinoma that was identified by screening had stage I or II disease than in a historical cohort (71% vs. 20%, P<0.001 by the chi-square test) and had superior 3-year progression-free survival (97% vs. 70%; hazard ratio, 0.10; 95% confidence interval, 0.05 to 0.18). Nine participants declined to undergo further testing, and 1 of them presented with advanced nasopharyngeal carcinoma 32 months after enrollment. Nasopharyngeal carcinoma developed in only 1 participant with negative EBV DNA in plasma samples within 1 year after testing. The sensitivity and specificity of EBV DNA in plasma samples in screening for nasopharyngeal carcinoma were 97.1% and 98.6%, respectively.
Analysis of EBV DNA in plasma samples was useful in screening for early asymptomatic nasopharyngeal carcinoma. Nasopharyngeal carcinoma was detected significantly earlier and outcomes were better in participants who were identified by screening than in those in a historical cohort. (Funded by the Kadoorie Charitable Foundation and the Research Grants Council of the Hong Kong government; number, NCT02063399.)

• On April 17, 2018, GRAIL, Inc. announced initial results from its Circulating Cell-Free Genome Atlas (CCGA) Study. Data from three prototype genome sequencing assays showed it may be feasible to develop a blood test for early detection of multiple cancer types with greater than 99 percent specificity.…

High profile scientific advisory board

GRAIL currently has an exceptionally strong Scientific Advisory Board, comprised of the following members:
• Dennis Lo, MD, PhD, Is the Director of the Li Ka Shing Institute of Health Sciences, the Li Ka Shing Professor of Medicine, and Professor of Chemical Pathology of The Chinese University of Hong Kong (CUHK).
• José Baselga, MD, PhD, is the Physician-in-Chief and Chief Medical Officer at Memorial Sloan Kettering Cancer Center (MSK) and Professor of Medicine at Weill Cornell Medical College.
• Vikram (Vik) Bajaj, Ph.D, is a Managing Director at Foresite Capital and previously was the Chief Scientific Officer of GRAIL, where he led laboratory and data science teams at the forefront of industrial cancer genomics and diagnostics development. He is the Co-Founder and former Chief Scientific Officer of Verily (formerly Google Life Sciences) and serves as the Chair of Verily’s Scientific Advisory Board.
• Hal V. Barron, MD, is Chief Scientific Officer and President, R&D, GSK
• Donald Berry is Professor and founding chair of the Department of Biostatistics of the University of Texas M.D. Anderson Cancer Center
• Timothy Church, Ph.D., is a professor in the Division of Environmental Health Sciences in the School of Public Health at the University of Minnesota. His expertise is in cancer screening, colorectal cancer, medical device evaluation, biostatistics, epidemiologic methods, and clinical trial design
• Christina Curtis, PhD, is an Assistant Professor of Medicine (Oncology) and Genetics at Stanford University School of Medicine, where she leads the Cancer Computational and Systems Biology Group.
• Jeff Dean, PhD, joined Google in 1999 and is currently a Google Senior Fellow in Google’s Research Group, where he leads the Google Brain team, Google’s deep learning research team in Mountain View, working on systems for speech recognition, computer vision, language understanding, and various predictive tasks.
• Brian Druker M.D., is Director of the Oregon Health & Science University (OHSU) Knight Cancer Institute, JELD-WEN Chair of Leukemia Research, OHSU, and an Investigator of the Howard Hughes Medical Institute
• Sanjiv Sam Gambhir, MD, PhD, is the Virginia & D.K. Ludwig Professor of Cancer Research, Chairman of Radiology at Stanford University School of Medicine, and heads the Canary Center for Cancer Early Detection at Stanford.
• William N. Hait, M.D., Ph.D., is Global Head, External Innovation at Johnson & Johnson.
• Richard Klausner, MD, is Founder and Director of Juno Therapeutics and Executive Chairman of Wisdo, a third generation internet company.
• Dr. Franz Och, PhD, is an expert in machine learning, artificial intelligence, large-scale data processing, and data analysis, specifically in the areas of natural language processing, machine translation, and genomics
• Mostafa Ronaghi, Ph.D., joined Illumina in August 2008. As Senior Vice President and Chief Technology Officer, he is responsible for leading internal research and the Illumina accelerator program.
• Sir Mike Stratton, PhD, is Director of the Wellcome Trust Sanger Institute. His primary research interests have been in the genetics of cancer.
• Charles Swanton, MD, PhD, is Senior Clinical Research Fellow at Cancer Research UK and Group Leader of the Translational Cancer Therapeutics laboratory at the London Research Institute.
• Karen Vousden is the Chief Scientist of Cancer Research UK, responsible for overseeing the organization’s scientific research.


While I want all endeavors in the liquid biopsy sector to succeed, I realize that only a few top competitors can be expected to survive long-term. So for now, my primary interests favor the ultimate goals and ongoing efforts pursued by the GRAIL collaboration and the Vogelstein-lead team at the John Hopkins Kimmel Cancer Center and its associated collaborators. I have any forthcoming GRAIL IPO on my watch list.

I continue to conduct my due diligence and try to keep abreast of current efforts by other companies and academic research centers, e.g., the University of California - San Diego where a new blood test has been developed that could detect cancer – and locate where in the body the tumor is growing. “We made this discovery by accident. Initially, we were taking the conventional approach and just looking for cancer cell signals and trying to find out where they were coming from. But we were also seeing signals from other cells and realized that if we integrate both sets of signals together, we could actually determine the presence or absence of a tumor, and where the tumor is growing,” reported Kun Zhang, a bioengineering professor and senior author of the study that could provide a way to diagnose cancer early on without having to do invasive surgical procedures like biopsies.…
Just another example of lots of good progress being made in this sector.

As always, conduct your own due diligence and decision-making.



Amazing post Ray. Thank you so much for this. So informative and so hope filled. It is not only promising for the investment potential, but much more importantly for the promise of a better future for us all.


Awesome job, Ray.


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I forgot to mention…I wish there was a “super-rec” because your post is worth 10 of most ordinary rec’d posts.


Amazing post. I’d rec it a 100 times if I could. I haven’t looked into this tech much. I might need to do that.



Thanks for the info, Ray,

Fascinating field. At the risk of sounding greedy, are there any public companies that you find worthy
of further study due to your research?

With the deep-pocketed donors, it wouldn’t be impossible for them to fund a startup without going
public, wouldn’t you agree?


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Wow - amazing post!

Have you seen, and do you have any thoughts on what ITUS claims is possible with their Ccheck process?…



That was a terrific write up. I will definitely put GRAIL on my watchlist too. I’m a little more sanguine about FMI prospects and usefulness. Difficulty doesn’t necessarily eliminate it from the conversation. The only thing I would add to the discussion is the size of the genetics database is critical as well. FMI has a tremendous data advantage over anyone. That leads to more testing and more data.

Thanks for your hard work.



Long FMI Calls

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There are some big genetic databases out there
Vanderbilt Medical has info on over 250,000 patients.
Other hospitals are starting to do the same.
Before too long I expect to see some major advances as they start matching diseases and genetics.

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Certainly, the most disappointing thing about GRAIL is that one can’t invest in it …

Saw this news and remembered the discussion on liquid biopsy. Seems like FMI will be a player in this arena.…


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