Guardant Throws Hat in Early Cancer Detection Ring with CRC Test

The combination of Bristol-Myers Squibb (BMS)'s marketed cancer immunotherapies Opdivo (nivolumab) plus a low dose of Yervoy (ipilimumab) showed durable clinical benefit in a Phase II trial as a first-line treatment in patients with microsatellite instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC)

Guardant Health will launch its first blood-based liquid biopsy for residual disease detection and recurrence monitoring next month—while later this year it will commercialize its first next-generation tissue-based test, as the diagnostics developer expands its focus beyond late-stage cancer and blood-based tests.

The new liquid biopsy, Guardant Reveal, is a plasma-only circulating tumor DNA (ctDNA) test that will be indicated for detection of early-stage colorectal cancer, with additional cancer types to follow. The minimal residue disease (MRD) test, which will have a turnaround time (TAT) of seven days, had been in development since 2016 under the name LUNAR-1, and was launched for research use only in 2019. launched for research use only in 2019 .

“These are stage 1 to stage 3 individuals that may have undergone curative treatment and are presumably cured of their cancer. The big question there is, Is there still something left? Did the surgeon get it all? This test is really going to be the first of its kind of blood-only test that really answers that question with groundbreaking performance,” said Guardant Health CEO Helmy Eltoukhy, Ph.D.

In targeting colorectal cancer, Guardant Health is competing with stool-based assay developers such as Exact Sciences, whose Cologard® is the only FDA-approved stool DNA test for colorectal cancer; and other blood-based colorectal cancer tests that include Epigenomics’ Epi proColon, the first such test to win FDA approval in 2016; and Signatera, whose developer Natera says is the first ctDNA test custom-built for molecular treatment monitoring and MRD assessment.

Eltoukhy said Guardant Reveal would stand out within what his company has projected is a $15-billion addressable market consisting of the nation’s 15 million early-stage cancer survivors, based on its 91% sensitivity and 100% positive predictive value for recurrence detection following completion of definitive therapy: “Not only will it be hugely impactful in terms of cancer patients, but obviously a big business opportunity as well.”

That opportunity is expected to grow, according to Guardant Health, which also envisions Guardant Reveal as helping its more than 60 biopharma partners identify new opportunities in developing adjuvant drugs and therapies designed to target earlier-stage cancers.

LUNAR Mission

Guardant Reveal is one of two earlier-stage cancer detection tests from Guardant Health’s LUNAR program. The other assay, known as LUNAR-2, is designed to address early cancer detection in asymptomatic individuals eligible for cancer screening and individuals at a higher risk for developing cancer with early detection.

Through the ECLIPSE clinical trial (Evaluation of the ctDNA LUNAR Test in an Average Patient Screening Episode; NCT04136002) — a 10,000-participant, 150-site registrational study launched in October 2019 — Guardant Health is evaluating the efficacy of LUNAR-2. That test potentially addresses a much larger market than Guardant Reveal by targeting the estimated 100+ million asymptomatic individuals at high cancer risk, a $50 billion (or more) market opportunity.

Guardant Health aims to generate clinical data that supports a premarket approval submission to the FDA through the ECLIPSE trial, which is assessing how well LUNAR-2 detects colorectal cancer in the trial’s participant population of individuals ages 45-84 who are at average risk for the disease.

“I think we’re on track to really finish enrollment of those 10,000 patients in the second half of this year,” Eltoukhy said. “And we’re thinking about another perhaps 12 to 16 months before that test could be FDA approved and launched.”

At the American Association for Cancer Research (AACR) Virtual Annual Meeting II, held last June, Guardant Health presented data showing LUNAR-2 to have demonstrated overall sensitivity of 90.3% and overall specificity of 96.6% in the early detection of colorectal cancer. Both exceed the 90% specificity and 74% sensitivity benchmarks set for coverage of blood-based biomarker screening tests set by the U.S. Centers for Medicare & Medicaid Services (CMS) in a draft local coverage determination.

Eltoukhy said Guardant Health chose colorectal cancer for Guardant Reveal and LUNAR-2 based on factors that include technology, ease of regulatory approval reimbursement compared with other cancers, and physician adoption.

“We’ve chosen colorectal cancer indications for both LUNAR-1 and LUNAR-2 as our beachhead application, but the technology is very extensible,” Eltoukhy said. “We’ve presented early detection data lung cancer before and we have very compelling data on other cancer types as well. So these tests will certainly expand to multiple cancer types if not pan-cancer.”

Beyond Therapy Selection

LUNAR-2 and Guardant reveal extend Guardant Health’s liquid biopsy franchise beyond the advanced therapy selection niche served by the company’s Guardant360 test. Launched in 2014, Guardant360 has guided advanced therapy selection on 700,000+ metastatic cancer patients representing $6B of market opportunity. More than 60% of orders for Guardant360 are from oncologists who practice in community settings, according to Eltoukhy.

In August, the FDA approved Guardant360 CDx for comprehensive genomic profiling (CGP), in patients with any solid tumor—and as a companion diagnostic to identify non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) alterations who may benefit from treatment with Tagrisso (osimertinib).

Since then, Guardant Health has submitted supplemental premarket approval applications seeking use of the test as a CDx with Amgen’s sotorasib, a KRASG12C inhibitor, for patients with locally advanced or metastatic NSCLC with KRAS G12C mutation; and Janssen Pharmaceutical Cos.’ amivantamab, indicated for NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. The company also plans to use Guardant360 CDx as a companion diagnostic with Radius Health’ elacestrant for ER+ breast cancer candidate.

“We’ve made a lot of progress on a number of those programs specifically Amgen and Jansen as well. It’s basically a commitment to having the Guardant360 CDx, which is a companion diagnostic for Tagrisso today,  continue to build on that foundation as a universal companion diagnostic addressing multiple drugs.”

Guardant Health says its market-size estimates are based on sources that include the U.S. Centers for Disease Control and Prevention, the U.S. Census, the American Cancer Society, a study published in the Society’s flagship journal CA: A Cancer Journal for Clinicians, Piper Jaffray, and Cowen Equity Research.

Tissue Assay Planned

During his presentation at JPM, Eltoukhy said Guardant Health plans to launch its first-ever tissue-based assay later this year. The test will provide comprehensive genomic profiling (CGP) for all solid tumors, including biomarkers recommended in screening guidelines such as homologous recombination deficiency (HRD), microsatellite instability (MSI), and tumor mutational burden (TMB).

“There is no single modality that’s perfect, in terms of addressing all open questions. There are some areas that liquid does better and for some patients, tissue is going to be better. There are also the sense of physicians as well, and having a one-stop shop really provides them all of the answers or, really, all of the products that they need or may desire, is going to be important,” Eltoukhy said.

“Tissue is still an important part of the equation. However, there are still a lot of challenges that I think haven’t been addressed in how tissue has performed in the market today. The product that we have come out with will try to address some of those challenges.”

Those challenges, he said, include the missing of as much as 15-20% of actionable alterations; a slow TAT of 21-28 days; a high failure rate; and the challenge of analyzing specimens based on input amounts.

“We as a company have often been focused on what is going to provide the greatest impact for patient care. And those largely have been in providing innovative technologies, where we were answering questions that couldn’t be answered before because the tools didn’t exist. That is why we were focused on the liquid biopsy side, and certainly early detection and early cancer management and so on, because tissue just can’t play in those areas,” Eltoukhy added. “Now that we’ve made a lot of progress in those areas, it’s also important to provide a total customer experience and a total solution for physicians.”

Guardant Health also plans to continue its launch of its Guardant-19 diagnostic for detecting COVID-19, for which the FDA granted emergency use authorization in August. Eltoukhy said the test does not augur Guardant Health reducing its focus on cancer.

“In terms of the disease areas, we’re very much focused on oncology. There’s so many different areas we can have that still need to be addressed. Within oncology clearly, it’s not a single disease,” Eltoukhy said. “Our primary focus in the company is continuing to help cancer patients and really develop innovative products across the cancer care continuum, but we’ll provide the Guardant-19 testing as needed.”

Cash Cushion

The tissue assay, LUNAR-2, and Guardant Reveal are among assays whose development Guardant Health plans to fund with some of its $2 billion-plus cash, cash equivalents, and marketable securities. The company doubled that cash cushion last month, when it completed a $1.15-billion convertible senior notes maturing in 2027—the original $1-billion issue, plus another $150,000 in notes that initial purchasers had the option to buy. Net proceeds from the notes offering were $1.132 billion.

Guardant Health said proceeds from the notes offering will be used toward general corporate purposes and working capital, including increasing investment in R&D and sales and marketing activities aimed at expanding the business, as well as general and administrative matters.

“Obviously it’s going to support some of the organic growth that we have as a company, whether it’s LUNAR-1 or a lot of the early detection programs which are even more expensive. But I think it also gives us an opportunity to be aggressive on the inorganic [growth] side in terms of mergers and acquisitions that may be worthwhile, and may allow us to move even faster in some of these areas.”

Guardant Health finished the third quarter of 2020 with $74.57 million in revenue, up 23% from the year-ago quarter, of which 81% ($60.38 million) came from precision oncology testing; the rest reflects development services and other sources. The company ended Q3 with a loss of $71.67 million, well above the $12.79 million loss of Q3 2019. For the first three quarters of 2020, Guardant generated $208.41 million, up about 38% from January-September 2019, but reported a net loss attributable to shareholders of $160.04 million compared with $50.44 million in Q1-Q3 2019.

San Diego Expansion

Another priority for Guardant Health is expanding its commercial infrastructure. Two weeks after the notes offering, the company disclosed plans to add 112 jobs to be based at a new site to be opened in March in the Torrey Pines Section of San Diego. The new site will include space for labs, R&D, and patient testing.

“San Diego is really just another place that we’ve always had a desire to move into because of the concentration of talent. It’s a big biotech hub, and we’ve had experience with Illumina”—which provides Guardant Health with products and services for research and clinical activities under a supply agreement signed in 2014.

The Torrey Pines site is a nearly seven-hour drive south of Guardant Health’s Silicon Valley headquarters in Redwood City, CA. Eltoukhy said the San Diego expansion reflects the company’s desire to broaden its operations geographically. Guardant Health already has two other domestic sites in Seattle and Spring City, TX; and has posted openings for jobs in Barcelona and Madrid, Spain; Berlin and Frankfurt, Germany; Fujisawa and Minato City, Japan; London; and Singapore.

“I think COVID really highlighted to an even larger extent the decentralization of the workforce, the fact that many types of roles could be decentralized, and that you could get very high productivity from remote workers,” Eltoukhy said.

“It’s really important to flex that muscle of decentralization, being able to attract talent, even when you know individuals do need to come in—for instance, those that work in the lab or R&D and so on,” Eltoukhy added. “And having really multiple locales, where you have those concentrations of talent, certainly allows us to build that muscle and make sure that we are getting the best and brightest, with geography not being really an impediment.”

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