Grail¶
Grail files for $100M IPO ahead of 2021 launch of multi-cancer liquid biopsy¶
[The artical link](https://www.medtechdive.com/news/grail-files-for-100m-ipo-ahead-of-2021-launch-of-multi-cancer-liquid-biops/584906/)
- Grail on Wednesday filed with the U.S. Securities and Exchange Commission to raise up to $100 million in an initial public offering ahead of the anticipated launch of its multi-cancer liquid biopsy screening test for use in asymptomatic individuals.
- The Illumina spinout expects to launch the product, Galleri, as a lab developed test (LDT) in 2021. Based on data generated to date, Grail estimates screening people aged 50 years and older using Galleri could avert 39% of deaths from cancers that would otherwise kill within five years.
- Grail’s SEC filing acknowledges that getting insurers’ support for asymptomatic screening could be challenging. Yet, with $686 million in the bank as of June 30 and more to come from the IPO, the company believes it has the resources to ride out near-term challenges and establish itself as a force in the nascent liquid biopsy market.
Dive Insight: Grail spun out of genome sequencing giant Illumina at the start of 2016 with the support of backers including ARCH Venture Partners, Bezos Expeditions and Bill Gates. Over the next few years, Grail raised a series of big financing rounds to fund a huge R&D program that saw it enroll 115,000 people across its foundational studies, with IPO rumors swirling along the way. While other liquid biopsy startups focused on detecting a single cancer, Grail set out to create a single test that screens for tens of tumors.
The work has now advanced to the point that Grail is gearing up for commercialization. If all goes to plan, the company will introduce Galleri and a test to “accelerate diagnostic resolution for patients for whom there is a clinical suspicion of cancer” first as LDTs next year before seeking FDA approval in 2023.
After bringing Galleri to market, Grail will push for the test’s integration into the management of the 40 million patients who already visit their physicians for standard-of-care cancer screening. Grail is pitching the test as a way to detect cancers earlier and, in doing so, reduce morbidity, mortality and costs associated with late-stage diagnoses.
Yet, the risk of false positives could mean Grail faces pushback from insurers hesitant to back the cost of additional diagnostic workup, the company outlined in its preliminary prospectus. Grail will try to counter those concerns with evidence of the value of its test, pointing to modeling that suggests Galleri may “detect nearly 70% of cancers resulting in death within five years at an earlier stage.” That would translate into the aversion of 39% of otherwise expected deaths.
Grail’s calculations are based on a study in which Galleri detected more than 50 cancers, including more than 45 types that are not explictly recommended for screening today. The study linked Galleri to a positive predictive value of 43% and found it would yield 7,000 false positives per million tests. That compares favorably to existing single-cancer screening tests such as mammograms.
Researchers at Grail achieved that level of performance by zeroing in on methylation patterns that indicate the presence and location of a cancer. Further work led to a targeted approach, eliminating the need to perform costly whole-genome methylation.
Other liquid biopsy companies have factored elements other than methylation into their tests. For example, Freenome, which raised $270 million last month, also looks at immune DNA signatures. The Form S-1 states Grail is assessing “multi-omic approaches including evaluation of additional analytes and biofluids” but is confident its existing approach can detect low level signs of cancer in the blood.
Some of the money from the IPO, which has a placeholder fundraising target of $100 million, will support such ongoing development work but the focal point is commercial preparations. Grail put another piece of the preparations in place in June when it leased space in North Carolina to add to its capacity. COVID-19 could disrupt the build, the paperwork warns, leaving Grail reliant on its existing site in California that may be unable to meet demand.
How much demand Galleri generates will partly depend on the success of Grail’s rivals. The IPO filing named Guardant Health, Exact Sciences, Freenome, Thrive Earlier Detection and ArcherDX among its competitors, several of which have tested liquid biopsies in studies of more than 10,000 people. However, Grail sees itself as partly insulated from competition, stating that not “many companies would have the financial resources to invest in population-scale clinical trials and rigorous analytics to compete with our products.”
Behind Grail, Illumina’s billion-dollar diagnostics startup (https://medcitynews.com/2017/03/behind-grail-illumina-startup/)
History¶
With a billion dollars in private financing and a test projected to generate a terabyte of data per person, Grail has seeded a new category of diagnostics and Big Data.
So who is Grail, the cancer diagnostics company that last week raised what could be the largest-ever equity financing round in biopharma history? How has it shaped a field of diagnostics into a billion-dollar venture in just over a year?
While the company hasn’t been particularly forthcoming with information, a lot can be gleaned from CEO Jeff Huber’s presentation at the Future of Genomic Medicine conference held in San Diego last week.
After over a decade at Google, Huber’s Big Data background led him to Illumina and then Grail, as fate cast him a personal role in the pursuit of early cancer detection.
Rochester Regional Health chooses Datos platform to minimize coronavirus pandemic mitigation risks Concerned with an influx of COVID 19 patients, Rochester Regional Health deployed Datos Health’s telehealth platform in only 4 days to protect hospital staff and better manage home hospitalized patients.
DATOS HEALTH
Science is full of coincidental success stories, most famously the discovery of penicillin. It’s not clear yet whether Grail will have the same impact, but a similar unintended observation by the Illumina research and discovery team led to its creation.
In 2013, Illumina acquired Verinata Health, a company focused on noninvasive prenatal testing (NIPT). That science came from the discovery that small fragments of fetal DNA cross the placenta during pregnancy. With sensitive tools, scientists learned how to isolate the fetal DNA to safely screen for any chromosomal abnormalities that might impact the infant’s development.
By the time Illumina acquired Verinata, the prenatal test had been run over 100,000 times, Huber said. It worked extremely well, except for a handful of cases — around 20 — where a foreign signal was detected.
The researchers struggled to identify the source of the signal, theorizing that it could be some rare fetal abnormality. Several months later, the 20-odd babies were all born healthy and the team went back to the drawing board.
Around the same time, Illumina hired the former director of the National Cancer Institute, Rick Klausner. He took a look at the data in question and promptly declared that it was cancer, Huber recounted.
Unfortunately for the 20 women involved, Klausner was right. The prenatal test had detected tumor fragments known as cell-free DNA (cfDNA) circulating in the bloodstream.
“They were finding cancers with perfect specificity, literally 100 percent accuracy,” Huber said.
Other NIPT companies and academic groups have reported similar findings. The catch was that the cancers were late-stage. The test couldn’t change patient outcomes.
“And that led to the light bulb within Illumina of saying, OK, if this test that was developed for this other purpose, that doesn’t have the kind of sensitivity that it would need to have but is still detecting the signal, what would it take to be able to go from the late-stage diagnoses that are happening here, to be able to detect cancer in its earliest stages,” Huber said.
Illumina’s R&D team began working on the science, embarking on a partnership with Memorial Sloan-Kettering that continues to this day. As the potential of the technology came to light, Huber said the discussions turned from, “wow this is a really good business idea,” to the realization that they had a moral and ethical imperative to make this test a reality.
The vision
Grail has a concise way of explaining its overarching aim. For cancers discovered in the earliest stages, stage one and stage two, the prognosis is typically positive; a 70-90 percent survival rate depending on the cancer type.
Cancer that is discovered late-stage, stage three and stage four, is roughly the inverse, Huber said. Some 80-90 percent of patients die.
Grail wants to drastically shift the odds in the patient’s favor by detecting cancer early. It would take the form of an omnipotent blood test that is routine, preventive and actionable.
Is that a moonshot or a logical extension of the technology?
It’s too early to know. Grail spun out of Illumina just over one year ago. During that time, the company built a dedicated facility in Menlo Park, California, which Huber believes to be the highest capacity sequencing lab in the world. From an initial team of 40 ex-Illumina employees, the staff now number 160.
For a population-wide cancer screening test, Grail knows it needs to work on a large scale. To that end, it has already launched its first multicenter clinical trial, dubbed the Circulating Cell-free Genome Atlas (CCGA) study. The aim is to analyze blood samples from 10,000 participants; 7,000 with cancer and 3,000 controls to build a detailed reference library for what a normal blood profile looks like.
Huber said the studies will ultimately scale to hundreds of thousands of patients to generate enough data on different cancer types and stages.
To detect cancer in its very earliest stages requires sensitivity down to a handful of molecules in a tube of blood. That’s where the ultra-deep, ultra-wide sequencing comes in. Huber described the high-intensity approach as an order of magnitude deeper than traditional liquid biopsy sequencing.
“The net effect of that is that we’re generating on the order of a terabyte of data for every test that we do,” he said.
(This scale is one of the reasons why the company doesn’t refer to its tests as liquid biopsies, a Grail spokeswoman said via email.)
If the company can realize its aim to embed itself in the medical system as a routine test, the data calculations become enormous. Starting with just the adult population in the United States — approximately 100 million people per year — would make Grail the first “zettabyte-scale application,” Huber said.
That’s 1,000,000,000,000,000,000,000 bytes; roughly the size of the likes of Amazon, Google and Facebook.
Collecting, organizing and gleaning insights at that scale will be an immense challenge. However, it does readily explain the unprecedented scale of its Series B financing round.
It’s also partly why Huber is at the helm as well. As a 12-year veteran of Google, he was first recruited to join the Illumina board to inject some Big Data knowledge into the team. That path led to Grail.
It’s not all abstract
Behind the technology and the Silicon Valley idealism is a painful authenticity that stems from Huber himself. Long before the huge financing round was closed, he was burdened with the responsibility to do something meaningful in this space.
In 2014, Huber’s wife Laura was unexpectedly diagnosed with stage four colon cancer. He told the Future of Genomic Medicine audience that there were few warning signs and no risk factors. She was 46, healthy, and did not have a family history of the disease.
After 18 months of intense treatment, Laura passed away. It was November 2015. A month later, Huber was approached by the Illumina team about taking the helm at Grail, given his very personal connection.
It’s a tough topic to discuss with strangers, but undeniably relevant.
“I’m very confident that if Grail had existed three or four years earlier that Laura could have had a very different outcome,” Huber told the audience.