Weekly Liquid Biopsy Insights

(3/30/2021) Liquid Biopsy March Round Up

The month of March was full of exciting developments for the liquid biopsy field. Below is a selection of headlines that caught our eye but be sure to check out all of the highlights!

M&A and Partnerships

Agilent to acquire Resolution Biosciences for up to $695M ($550M cash, $145M in milestones). This combination will combine Agilent’s global clinical, regulatory and commercial experience and resources with Resolution’s budding liquid biopsy platform. Prior to the acquisition, Resolution had developed a liquid HRD assay with Breakthrough Device Designation, a partnership with LabCorp to offer Resolution ctDX Lung (an NSCLC genomic profiling assay), and a partnership with Mirati Therapeutics to identify NSCLC patients who may respond to a KRAS G12C inhibitor. This acquisition may allow for Agilent to expand out of its traditional tissue-based diagnostic portfolio and offer comprehensive blood and tissue testing.
Seer announced a commercial agreement with SCIEX to offer an end-to-end proteomics solution. Seer’s nanoparticle technology and automated Proteograph Product Suite when combined with mass spectrometry can reveal deep, precise insights over the whole dynamic range of the proteome (including in complex samples like serum or plasma) while remaining unbiased. This partnership may boost Seer’s commercial reach and initial customer base while enabling users to perform easy-to-use, fast, highly sensitive, and deep proteomic experiments on industry-leading mass spec instruments. Mass spec’s utilization is gated largely by cost, instrument complication, and informatics complication, the latter two barriers may be alleviated by this end-to-end solution. It is yet to be seen if this partnership will expand to PrognomiQ (an early detection-focused spin-off of Seer) but this solution may assist in creating a more clinically capable workflow compared to current mass spec instruments.
CellMax life and Sebela Pharmaceuticals entered a collaboration to develop and commercialize CellMax’s cell-based (cancer and pre-cancer cells) colorectal blood test, FirstSight. FirstSight has been to have an AUC of 0.897 for adenomas and 0.958 for CRC. This could benefit patients by detecting CRC early and identifying those who may benefit from the removal of pre-cancerous polyps. Sebela is a leader in the gastroenterology space and is well-positioned to assist in the development of this assay.

Regulatory Updates

Inivata’s RaDaR was granted Breakthrough Device Designation. Upon a successful expedited review process, Inivata could see rapid market uptake given the BDD / CMS coverage policy (which has been delayed) and its commercialization agreement with NeoGenomics.
Natera received two new Breakthrough Device Designations for Signatera. These designations are meant to support Signatera’s use in Ph. III trials and are likely related to its use in breast and bladder cancer, although the assay has been validated in lung cancer as well. Along these lines, Natera and Genetech initiated a Ph. III trial (IMvigor011) using Signatera as a CDx for atezolizumab based on post-surgery ctDNA status status in muscle-invasive bladder cancer.
Guardant 360 was CE-marked for comprehensive molecular profiling across all solid cancers. On a side note – Guardant360 was shown to predict pembrolizumab-based immunotherapy response in a small (N=51) NSCLC study. G360 was used to determine molecular response from baseline to up to 9 weeks post-Tx initiation. Patients with molecular response achieved improved durable clinic benefit (log mean 49.4% vs. 3.5%) and significantly longer PFS (median 14.1 vs. 4.4 months) and OS (median 22.1 vs. 12.0 months) compared to those without molecular response.

If you have further questions about these or any headlines not covered in this summary, please reach out to Reuben. Other updates of interest include movements from SomaLogic, Universal Diagnostics, Genetron, Helio Health, ExosomeDx, and others below.

Market Highlights

Research Highlights

(3/3/2021) GRAIL and Providence Partnership; New Data from Berry Oncology; Twist Launches EM-Seq Methylation Detection System

Building upon efforts to meet the proposed Q2 launch date, GRAIL announced another key partnership that will likely drive early / accelerated adoption of Galleri. GRAIL announced that Providence will be the first health system to offer Galleri. Starting with Washington, California, and Oregon locations Galleri will be used to complement existing single cancer tests with the potential to grow into Providence’s larger 5M patient network. This partnership could help grow Galleri’s recognition and reputation as a multi-cancer test with physicians currently ordering cancer screens, which is an important step in commercialization. In addition, this partnership could grow the body of evidence GRAIL is gathering to demonstrate the real-world clinical utility and health economic impact of Galleri and may support FDA approval and / or payor coverage.

On the single-cancer screening front, Berry Oncology released new data from a 3.5k patient study assessing an HCC diagnostic model named HiFi. The model was able to differentiate HCC from liver cirrhosis with a sensitivity of 95.42%, a specificity of 97.83%. It is interesting to note that this new approach from Berry Oncology appears to be different from the existing Herui Gene liver test, which is believed to use Berry’s novel circulating single-molecule amplification resequencing technology (cSMART) sample prep to analyze nucleosome footprint, 5′ end motif, and fragmentation of cfDNA via NGS. HiFi however, appears to add hydroxymethylcytosine (5hmC) analysis to the other analytes mentioned to discern HCC patients from those with liver cirrhosis. Methylation is well-known to be relevant for early detection and is widely explored by LBx companies, but hydroxymethylation is a more unique approach being explored by far fewer companies (i.e., Bluestar Genomics, Cambridge Epigentixs).

Another HCC player, HelioHealth, came up in headlines this week as being an early access customer to Twist’s new EM-seq based methylation reagents. Alternatives to bisulfite-sequencing are being actively integrated or assessed for developing EDx assays (i.e., Base Genomics, Bluestar, Dnamx and others) but the clinical and economic advantages of these approaches are still being assessed.

Lastly, Exosome Diagnostics’ / Bio-Techne’s ExoDx Prostate test (EPI) was awarded coverage by Humana. EPI is intended to guide both initial and repeat biopsy decisions and is already included in NCCN guidelines. This reimbursement decision will increase access to this assay and will allow for men and their physicians to make more informed biopsy decisions after an ambiguous PSA test.

Market Highlights

(2/25/2021)GRAIL and Quest partner to support Galleri; TGen publishes new data

There are quite a few headlines from February to browse below. The highlights cover the completion of fundraising rounds (AnchorDx, Inivata, Micronoma, Oncocyte, PGDx), the release of new data (Angle PLC, Epic Sciences, Exosome Dx, FMI, NuProbe, Predicine, Universal Dx) and new partnerships (GRAIL / Quest, Natera / Personalis, PGDx / Fox Chase) in the liquid biopsy space.

GRAIL announced that Quest Diagnostics will provide phlebotomy services to support Galleri. This includes nation-wide access to Quests testing centers as well as mobile phlebotomy units for at-home visits. GRAIL will still need to invest in a salesforce to educate and grow adoption with primary care physicians, but this partnership will simplify the ordering process and reduce barriers to ordering Galleri due to Quest’s integration/presence at many hospitals and use for common blood work. Access to primary care physicians will be incredibly important for the success of early detection companies, and we have seen how access to a broad salesforce can accelerate the adoption of screening assays (ex., Exact and Pfizer’s agreement around Cologuard). If GRAIL or any other early detection company can secure marketing and sales channels through partnerships, this could be a major competitive advantage. It does not appear that sales support is part of this agreement with Quest, but it may be an attractive expansion of this partnership.

TGen has been in the news recently due to the license of TARDIS and sale of Ashion Analytics to Exact but they also have released new data on breast cancer detection and the promise of urine cfDNA as an early cancer detection analyte. Using mass spectrometry, TGen researchers were able to identify and create a protein panel of Extracellular Matrix components that are released into the bloodstream even at early stages of breast cancer. The research involved the use of hydrogel nanoparticles during sample prep to enrich for these protein biomarkers, many of which have not been previously observed in blood. TGen researchers also assessed the potential of fragmentation patterns in cfDNA found in urine for cancer diagnosis. They found that certain regions (called recurrently protected regions) of the genome are protected from fragmentation in healthy patients but are fragmented in cancer patients. They used this fragmentation pattern in urine cfDNA to identify healthy patients from those with cancer with an AUC of 0.89. There has been a noticeable increase in interest in urine as a non-invasive sample type for early cancer detection, especially in GU cancers.

Market Highlights

Research Highlights

TGen-led study results suggest more accurate diagnostic for breast cancer 26 Jan 2021
nRichDX Announces Launch of the Revolution™ Sample Prep Semi-Automated Workflow | 27 Jan 2021
Study: New prostate cancer test could avoid unnecessary biopsies | 11 Feb 2021
Gene-Based Blood Test for Melanoma Spread Evaluates Treatment Progress | 12 Feb 2021
Liquid biopsy for colorectal cancer could guide therapy for tumors | 12 Feb 2021
Circulating Tumor DNA Provides Prognostic Clues in Advanced BRAF-Mutated Melanoma Cases | 16 Feb 2021
TGen-led study confirms cell-free DNA in urine as potential method for cancer detection | 18 Feb 2021

(1/27/2021) Epigenomics plans to challenge NCD

In contrast to the headlines following ASCO and JPM, this weeks news was on the lighter end.
Epigenomics is challenging CMS’s decision to cover their FDA approved Epi proColon screening test, but also announced a second assay for CRC screening. The new rtPCR assay incorporates new proprietary methylation targets and is intended to offer a quick and affordable approach to CRC screening.
On the research end, a pre-print article featured a CTC capture and quantification method that produced 95% viable cells that can be used for downstream rtPCR, immuno-cytometry, or cell culture. The method involves using fluorescent magnetic nanobeads conjugated with anti-EpCAM antibodies to isolate and count CTC cells in a blood sample with 70 – 95% capture efficiency.

Market Highlights

Research Highlights

Improved Prognostic Stratification Using Circulating Tumor Cell Clusters in Patients with mCRPC | 19 Jan 2021
Tumor Genomic Subtype Might Influence Level of ctDNA Shedding in NSCLC | 19 Jan 2021
Researchers immunoengineer nanobead system for circulating tumor cell detection | 21 Jan 2021
MMRF, Dana Farber Amassing Data to Develop Smoldering Multiple Myeloma Monitoring Test | 22 Jan 2021

(1/21/2021) JPM and ASCO GI Highlights, and much more!

There are quite a few interesting headlines released to start the year, although this can be expected with JPM and ASCO GI. Below are brief summaries of some of the major developments we noticed, but there are quite a few other headlines to peruse as well.

J.P. Morgan Health Care Conference Snapshot

Natera laid out plans to expand the utility of Signatera through two primary avenues. IO therapy response monitoring is a new growth opportunity the company plans to enter this quarter and receive reimbursement for by the summer. The more direct growth route is by targeting additional indications for MRD under the umbrella LCD. Natera has already collected data for their MRD approach in lung, bladder, breast, and esophageal cancer with other indications on the horizon.
GRAIL confirmed near-term launch intentions of their pan-cancer early detection assay, targeting Q2 2021 for the commercial launch of Galleri as an LDT. The 6.6k patient PATHFINDER study completed enrollment in Dec 2020 and is planned to readout mid-202; the data from this trial is intended to support the LDT launch. In addition, GRAIL announced partnerships with Amgen, AstraZeneca, and BMS to evaluate their platform for MRD detection in early-stage cancer. This move, combined with Illumina’s efforts to grow into clinical genomic profiling, could enable GRAIL / Ilummina to offer assays throughout a patient’s journey (i.e., screening, therapy selection and monitoring). Currently, Guardant is the only other main player with established efforts in offering comprehensive testing, but FMI and Predicine could follow suit.
Adaptive Biotechnologies announced that Clonoseq will soon offer blood-based testing, which could double the market size of this assay.
Exact Sciences announced an exclusive license to TGen’s TARDIS technology. TARDIS is a sensitive personalized MRD approach capable of detecting minute amounts of ctDNA in a patient’s blood and was shown to detect molecular response and residual disease during neoadjuvant breast cancer therapy. Exact also clarified that TAPS, an alternative to bisulfite conversion for methylation analysis that increases sensitivity and efficiency that would be built into the blood-based Cologuard 2.0, its pan-cancer early detection test, and potentially the MRD test along with TARDIS. Exact acquired this technology through Base Genomics, and it was previously unclear if they planned to license out or integrate this technology into their portfolio.

ASCO GI Snapshot

Guardant announced a target launch date for Guardant Reveal (the commercial name of the LUNAR-1 assay) of Feb 2021. Guardant Reveal is the only liquid only (i.,e does not require an initial tissue sample) MRD assay and is being launched based on the data from the COBRA trial, which investigated Reveal’s use in adjuvant therapy decision making for Stage II colon cancer. While Reveal is the only liquid only MRD assay, Guardant opted to focus on CRC mutation and methylation profiles and does not personalize the assay to patient-specific mutations, as Signatera does. Guardant also announced that ECLIPSE, the registrational trial for LUNAR-2, would complete enrollment in 2021.
Freenome announced additional data from AI-EMERGE that demonstrated their multi-omic assay count detect advanced adenomas with a sensitivity of 41% and a specificity of 90%. This shows that a blood-based method has comparable performance to stool-based methods for advanced adenoma detection. It was also shown that their assay detected 2x more advanced adenomas compared to methylation only or single protein approaches.

Other interesting headlines included fundraising efforts by interesting early detection companies Delfi ($100M) and Earli ($40M), SOLVD’s clinical study launch, CMS’s final coverage decision for blood-based CRC screening, and the deal between VolitionRx and 4D Lifetec. Be sure to give those a scan!

Market Highlights

Research Highlights

Pan-cancer circulating tumor DNA detection in over 10,000 Chinese patients | 4 Jan 2021
Liquid Biopsy Predicts Colon Cancer Relapse Months Before CT | 17 Jan 2021

(1/5/2021) Biodesix initiates ALTITUDE; Biocept expands access through SoCal IPAs

News has been on the lighter side since our last update, typical for the end of year lull.

Biodesix initiated their 2000 patient ALTITUDE trial for the Nodify XL2 Lung Classifier. This first in class trial is intended to assess the clinical utility of Nodify XL2 in patients that have new incidentally identified solid lung masses with < 50% risk of cancer using the Mayo algorithm. The company is hopeful that the assay can reduce the number of invasive surgeries performed on patients with benign disease using this blood test.

Market Highlights

(12/22/2020) Inivata to be used in iDx-LUNG; ctDNA model used to predict tumor size; GRAIL shows Galleri's potential utility through modeling

Inivata announced that its InVision LBx platform will be used in the iDx-LUNG initiative. This 15,000 patient UK-based program has £10 million in funding and is focused on identifying the best method for early detection of lung cancer. Many diagnostic companies (i.e., Lung Cancer Initiative at Johnson & Johnson, Roche, Oncimmune, BC Platforms, Inivata, and others) are going to be involved in this program, but the InVioson platform will be used to assess blood samples for ctDNA mutations in patients who have inconclusive CT scans. This program will serve as an opportunity for Inivata to validate their technology for early detection in a large patient population.

A research group out of Stanford published a paper showing how ctDNA shedding can be used to infer tumor size in NSCLC. It was found that on average 0.014% of a tumor cell’s DNA is shed into the bloodstream per cell death and this finding was incorporated into a model that could predict the tumor size for early detection and recurrence in lung cancer patients. The team researched how testing frequency, blood volume, panel size, number of mutations called and sequencing errors impacted the detection size of tumors using this ctDNA approach (CAPP-seq). It was found that increasing testing frequency, reduced sequencing error and the use of a panel calling up to 25 mutations all resulted in large decreases in the average size of detected tumors. Applying this model to an annual blood-based screening paradigm the team predicted that the average detected tumor size would be 2 – 2.3 cm. This is a reduction in size of about 40% compared to the current average detection size of 3.5 cm using imaging-based methods. It was also found that. These findings can be used to demonstrate the utility/performance of ctDNA based early detection assays and could assist in their development.

Related to proving clinical utility, GRAIL released a model showing how Galleri could reduce the number of Stage III / IV by more than half in the U.S. population the 50-79. If this were to hold true in clinical practice this could be a monumental decrease in 5-year cancer deaths (estimated to be 26%).

Market Highlights

Research Highlights

Stanford Team Develops Mathematical Model of ctDNA Shedding to Predict Lung Cancer Tumor Size | 17 Dec. 2020

(12/17/2020) Natera shows value in IMvigor010; CELLSEARCH pooled analysis that shows the value of CTCs in breast cancer monitoring

Signatera made some waves for its involvement in the IMvigor010 trial by highlighting the value ctDNA can play in adjuvant therapy decision making in immuno-oncology, as well as an endpoint in the clinical evaluation of therapy efficacy. The trial consisted of comparing the use of Genentech’s Tecentriq (PD-L1 inhibitor) for adjuvant therapy in muscle-invasive urothelial carcinoma (MIUC) vs observation following surgical resection. Results from the interim analysis showed that patients who were ctDNA+ following surgery had increased overall survival (~10 mo.) in the treatment arm vs the observational arm. It was also shown that patients who were ctDNA- derived no benefit from adjuvant therapy and that ctDNA clearance was higher in the treatment arm vs the observational arm. Activity involving solid tumor MRD assays in the I/O setting is relatively limited (compared to the adjuvant chemo setting) but a number of research collaborations have been announced this year which will no doubt drive activity and interest.

Menarini Silicon Biosystems released a pooled (14 clinical trials) analysis demonstrating the value of CTC count for metastatic breast cancer monitoring, including hormone-positive, HER2 type, and TNBC patients. CELLSEARCH was used to measure a patient’s CTC status after surgery and 29 days after treatment initiation. It was found that across all subgroups, the median OS survival was 47.05 mo. in CTC- patients compared to 17.87 mo. in CTC+ patients. Additionally, patients who switched from CTC+ to CTC- during the course of therapy had a two-fold increase in OS (32.2. mo.) compared to patients who stayed CTC-. Monitoring the presence of CTCs in breast cancer patients could assist in optimizing the course of therapy.

Lastly, Bluestar Genomics and the University of Chicago published a whole-genome map of 5hmC across multiple tissue types. The study proved the performance of 5hmC (a gene activation marker) as a biomarker for multiple illnesses such as chronic disease and cancer. Bluestar and Cambridge Epigentix are both interrogating the use of 5hmC for early cancer detection.

Market Highlights

Research Highlights

(12/2/2020) GRAIL and NHS partnership announced; Publication from I-SPY 2 shows value of Signatera in breast cancer

This week’s news was concentrated around two well-known names in the liquid biopsy space. GRAIL and the National Health Service of the UK have entered a partnership to test the economic performance of Galleri before the assay could be considered for routine use. The partnership will consist of using the assay for approximately 165k patients (140k patients over 50 with no suspicions of cancer and 25k patients over 40 with suspicion of cancer) beginning in 2021, with the potential to expand to 1M+ patients in 2024/25. Galleri is still expected to be commercially available in 2021 in the U.S.

A new publication from the I-SPY 2 trial, which involved the use of Natera’s Signatera to monitor breast cancer patients’ response to neoadjuvant chemotherapy. The study involved collecting blood samples from 84 patients before, during, and after treatment but before surgery. Detailed clinical outcomes were tracked for up to 6 yrs. post-surgery. The study found that personalized ctDNA clearance (even without complete pathological response) was associated with improved survival, but the lack of ctDNA clearance was a significant predictor of poor response and relapse. This shows that Signatera may have value in real-time monitoring of neoadjuvant chemotherapy response.

Market Highlights

(11/25/2020) Biocept to target CSF applications; Helio Health releases promising early data for HCC detection

Biocept has struggled to find footing in the early detection space, especially during the pandemic which should create favorable conditions for non-invasive technologies. Recently, the company has expressed interest in positioning their Target Selector platform for CTC isolation and ctDNA analysis in the realm of neuro-oncology, to detect when metastasis has spread to the central nervous system (initially in breast and lung cancer) using CSF. Their technology has shown potential in this space and could offer more timely identification of CNS involvement. Early detection of this form of metastasis can be critical to a patient’s trajectory, especially in patients who are appearing to be responding to treatment of cancer in the main body.

Helio Health released early data comparing their methylation-based HCC screen to AFP and ultrasound in HCC detection. In a group of 631 patients (291 HCC patients and 340 healthy controls) the Healio Liver Test was able to identify Stage I and Stage II HCC with 88.7% sensitivity, whereas AFP and ultrasound (current standard of care) had sensitivities of 57.5% and 47%, respectively. HCC is a very aggressive cancer and detecting it early when resectable is critical to improving outcomes.

Market Highlights

Research Highlights

THE ELSA-SEQ ASSAY PROVIDES EARLY DETECTION AND LOCALISATION INFORMATION IN MULTIPLE CANCERS | Nov 20, 2020

(11/11/2020) CTCs show diverse potential in breast cancer treatment

Several companies have recently highlighted the diverse potential of circulating tumor cell analysis in the breast cancer care paradigm.

Angle PLC is seeking FDA approval for Parsortix in metastatic breast cancer. Angle has produced data that whole transcriptome sequencing of CTCs captured by Parsortix provides comparable gene signatures compared to biopsies obtained at metastatic sites. This would allow for a cheaper, non-invasive alternative to tissue biopsies and enables ‘real-time’ measurement of the cancer over time through frequent measurements, which may aid in patient monitoring.
Menarini Silicon Biosystems recently released data in JAMA Oncology from a randomized 778 patient study showing that CTC count (via CellSearch) can complement physician’s decision algorithms when deciding between frontline chemotherapy or hormone therapy in ER+ and HER2- metastatic breast cancer patients. In the CTC count driven patient cohort, patients with 5 or greater CTCs per 7.5mL of blood received chemotherapy and those with less than 5 received hormone therapy. Those who received chemo showed significant PFS improvements, and those who received hormone therapy did not see reduced PFS or OS.
Savran Technologies uses an antibody-based, positive-selection microfluidic platform to count CTCs in TNBC patients. The company is targeting a 2022 launch of a paired CTC counting and ctDNA assay to detect / monitor TNBC MRD. When CTC enumeration was paired with FoundationOne and FoundationAct the combination yielded 90% sensitivity in detecting MRD. The company plans to validate these findings in clinical trials and also believes this platform has potential in early stage breast cancer detection as well as other indications.

Market Highlights

Research Highlights

(11/3/2020) CTCs continue to generate steam; Methylation based tests for NSCLC and HCC provide updates

This week’s news contained quite a few circulating tumor cell (CTC) headlines. In a small study, Rarecells’ ISET platform was used to detect PSA positive CTCs and found to have a positive predictive value of 99% and a negative predictive value of 97% for prostate cancer detection. While a promising start to improving prostate cancer detection, much more data needs to be generated as well as the inclusion of risk scoring to determine the Gleason Grade of detected cancers. Epic and Predicine have partnered to offer comprehensive genomic profiling and CTC analysis from a single blood draw. By allowing for genomic and phenotypic analysis from the same sample, the companies hope to provide richer data for cancer profiling, therapy response monitoring, and MRD detection in clinical trials. Lastly, after touting an FDA submission for Parsortix (a CTC capturing device), Angle plc raised £20m to continue its growth. The raise will be used to develop 2 laboratories to process patient samples as well as develop PD-L1 CTC assays for immunotherapies.

Factors such as favorable screening recommendations, adherence to screening, reimbursement conditions, well-understood cancer biology and market size (screening population) make colorectal cancer an ideal target indication for the development of early detection liquid biopsy assays. CRC is the assay candidate many companies are hoping to enter the early detection market with. Recently the United States Preventative Services Task Force (USPSTF) released a draft guidance document that drops the recommended screening age from 50 to 45. An expansion in the recommended screening population directly increases the market size of for CRC early detection assays and makes this indication even more attractive to target.

Be sure to check out the stories from Nucleix and Helio as well!

Market Highlights

Research Highlights

(10/29/2020) Exact to acquire Thrive Earlier Detection and Base Genomics

Exact lagged behind other LBx early cancer detection leaders and only recently unveiled initial data around its multi-cancer assay. However, the company pushed further into the space with two high-profile acquisitions this week. Exact is set to acquire Thrive Earlier Detection (CancerSEEK) for $2.15B. Through this acquisition Exact now has a developed multi-cancer detection assay backed by large-scale clinical data (with other trials in progress). Coupled with Exact’s already established infrastructure, primary care presence, R&D engine, regulatory / reimbursement experience, and other resources, CancerSEEK is poised to see accelerated time to market and penetration upon approval. CancerSEEK is differentiated from other LBx early detection assays since it is designed to be combined with a full-body PET-CT scan for a complete diagnosis and this may pose some regulatory and reimbursement challenges for the assay. But this may not be the version of CancerSEEK that is taken to market, as the assay will continue to be developed with Exact’s extensive resources.

Exact is also acquiring UK-based Base Genomics for $410M. Base’s technology could be incorporated into CancerSEEK to improve its overall detection performance or enable tissue of origin calling. Base Genomics is developing TAPS, a methylation analysis method that increases sensitivity and enables mutation analysis on the same sample. TAPS could replace bisulfite sequencing, the current gold standard for methylation analysis. TAPS improves upon bisulfite’s high levels of DNA degradation and incomplete conversion while reducing overall sequencing costs. This technology could be used throughout Exact’s cancer diagnostic efforts.

Recent Headlines

Market Highlights

Nature Communications publishes Bluestar Genomics’ technology for cancer detection study | Oct 20, 2020
Burning Rock to Present Data on Its Early Detection ELSA-seq at ESMO Asia Virtual Congress 2020 | Oct 20, 2020
FDA accepts review for ANGLE’s Parsortix system for metastatic breast cancer | Oct 20, 2020
Summit Biolabs Commercializing Tests for Head and Neck Cancer Recurrence, COVID-19 | Oct 22, 2020
Genetron Health Licenses ImmuQuad Technology for Blood Cancer Testing | Oct 22, 2020
Immunovia Announces Completion of Analysis from the IMMray PanCan-d Verification Study | Oct 26, 2020
Exact Sciences to Acquire Thrive Earlier Detection, Becoming a Leader in Blood-Based, Multi-Cancer Screening | Oct 27, 2020

Research Highlights

(10/21/2020) CMS proposes new NCD for liquid biopsies for early CRC detection; mIR Scientific receives breakthrough device designation

Centers for Medicare & Medicaid Services (CMS) proposed a National Coverage Decision last week that would instate rolling coverage of new blood-based early colorectal cancer detection tests that meet specific criteria. To be covered under this NCD proposal new CRC early detection LBx assays must:

Be FDA approved
Establish 74% sensitivity and 90% specificity
Be endorsed by the USPSTF or major guideline association

No such tests currently exist, but by removing the NCD approval phase (6 – 12 months) this new approach would reduce the time and effort companies need to invest to gain CMS coverage. This new NCD could incentivize investment by assay developers looking to enter the space, but also will allow quicker entry by CRC LBx leaders who have been developing this test for years. Colorectal and Prostate detection assays/technologies currently have an alternative and shorter pathway to CMS coverage relative to assays for other indications and this draft NCD would further expedite coverage for CRC assays. If you would like to learn about this proposed NCD and its impacts, feel free to watch this video by Dr. Bruce Quinn, who is a leading Medicare Specialist and friend of DeciBio.

Other news includes progress on the early detection assay space. miR Scientific announced receiving Breakthrough Device Designation for their Sentinel Prostate Test. This designation grants miR a more intimate and expedited review process by the FDA as the company seeks approval. While not a liquid biopsy, Veracyte released positive data for their nasal swab test for lung cancer detection. Veracyte showed that the 248-gene smoking index (which identifies genomic changes related to smoking damage) performs with not only lung brushing from the main airway but on nasal samples as well. The company is still developing its assay but this data further establishes the viability of a non-invasive sample type that could be used to guide treatment decisions for patients with lung nodules.

Recent Headlines

Market Highlights

Research Highlights

(10/14/2020) Genetron receives BDD for HCC assay; Findings from I/O biomarker studies

The continual effort to better understand which biomarkers can predict the response (or be used to monitor a patient’s response to immune checkpoint inhibitors (ICI) made some progress and revealed additional utility for liquid biopsies in ICI therapy decision making. Two studies, one from Stanford + MSK and another from Assistance Publique Hopitaux De Marseille reported data on which biomarkers may improve ICI response prediction.

The Stanford + MSK study found pre-treatment ctDNA (e.g., TMB) and circulating CD8 T cell levels were independently associated with durable clinical benefit. Furthermore, they showed a greater ability to predict durable clinical benefit when these measures were combined with another ctDNA measurement a few weeks into therapy and that this assay (dubbed DIREct-on) avoided the need to measure PD-L1 status. This multi-parameter and multi-timepoint assay is completely non-invasive and may guide more informed treatment decisions
Initial data (100 patients) from the Assistance Publique Hopitaux De Marseille trial (PIONeeR) found that in addition to tumor PD-L1 status the number of circulating activated T cells, serum IL-6 and number of cytotoxic T cells in the tumor were associated with progression-free survival (PFS) in lung cancer patients. In addition, overall survival (OS) was associated with circulating T cells (activated and non-activated) serum IL-6 and TNFa levels.

On the early detection front, Genetron received the breakthrough device designation for their HCC LBx assay, which has the potential to detect this aggressive cancer in high-risk populations (chronic HBV infections and / or liver cirrhosis) early on when it is potentially curable.

Recent Headlines

Market Highlights

Research Highlights

Immunotherapy Response Prediction Improved by Baseline, On-Treatment Biomarker Combo | Oct 06, 2020
Characterization of Predictors of Response or Resistance to ICIs in NSCLC | Oct 6, 2020

(9/29/2020) Draft LCD with expanded coverage for MRD testing, Exact Sciences presents early detection data

2020 continues to be a big year for the MRD and treatment response monitoring market, as this week, CMS released a draft LCD for “Minimal Residual Disease Testing for Cancer”, which expands upon covered use cases from the final LCD Natera Signatera received earlier this month. Of note, highlights of the proposed LCD in comparison to the previous final LCD include:

The expanded LCD is pan-cancer, vs. colorectal cancer only, noting that MRD testing and validation studies have been performed in multiple cancer types (both solid tumors and hematopoietic malignancies)
- DeciBio Note: To date, most of the focus has been on MRD for CRC Stage II & III given the high perceived utility in this space and established use case for blood-based testing with CEA. However this LCD could greatly accelerate the adoption of other MRD / ctDNA monitoring use cases
Coverage of therapy response monitoring, specifically calling out immunotherapy monitoring
- DeciBio Note: Improved methods of predicting and detecting IO response could significantly reduce unnecessary treatment, associated costs, and side effects; however, clinician willingness to take patients off of IO upon detection of non-responders is yet to be seen and may impact actual clinical adoption in this setting. In the INSPIRE study published in Nature Cancer last month, 11 of the 30 patients who showed ctDNA increases continued to receive additional cycles of pembrolizumab despite having early progression. Natera (via Foundation Medicine) and Guardant are both decently well-positioned in this space from the perspective of commercial reach
The test should be “considerably more accurate than other established (non-MRD) forms of surveillance or monitoring” and “medically acceptable that the test being utilized precludes other surveillance or monitoring tests unless they are required to follow-up or confirm the findings of this test”
- DeciBio Note: In CRC and other cancers, ctDNA testing has shown to be more sensitive and detect recurrence with lead times over current methods (including CEA and imaging). CEA is known to be a mediocre marker for surveillance, so MRD assays should see limited push back here. However, whether MRD assays will be broadly used in place of imaging is yet to be determined – given the strong entrenchment of imaging methods, we expect the actual clinical implementation will be impacted by clinician preference.
To receive coverage, the test performance of an assay must be comparable to that of existing tests that are already covered
- DeciBio Note: We expect that this provides Signatera with a competitive edge given their first-to-coverage status to-date

The running list of companies vying for the MRD market (to varying extents) now includes Natera (& Foundation Medicine via partnership), Guardant, Archer DX, Inivata, Caris, GRAIL, Exact Sciences, and Genosity.

In the early detection space, Exact Sciences presented data on their multi-cancer liquid biopsy test, demonstrating overall 86% sensitivity and 95% specificity across esophageal, liver, lung, ovarian, pancreatic, and stomach cancers. Although Exact Sciences enters the early detection space behind key players (GRAIL, Guardant, Thrive, to name a few), we expect that their commercial reach in the primary care physician segment developed through Cologuard in addition to promising preliminary sensitivity/specificity (albeit in a limited data set not concentrated in early stage) can likely set them up for success.

Recent Headlines

Market Highlights

Universal Diagnostics Presents New Promising Data on Early (Pre) Cancer Detection from Cell Free DNA at ESMO | Sept 21, 2020
LabCorp to roll out Resolution Bio’s lung cancer liquid biopsy test | Sept 23, 2020
Medicare Issues Draft Local Coverage Determination for Signatera™ in Immunotherapy Response Monitoring | Sept 24, 2020
Exact Sciences Stock Soars on New Data Around Pan-Cancer Liquid Biopsy Test | Sept 24, 2020
Angle Files De Novo FDA Submission for CTC Collection Device in Breast Cancer | Sept 28, 2020

(9/24/2020) Illumina to acquire Grail

Illumina and Grail continued to generate buzz as the companies solidified an $8B acquisition deal in which Illumina will buy out the portion of Grail it didn’t already own. Grail is planning to launch its commercial assay, named Galleri, in 2021. With this deal, Illumina will be competing with other liquid biopsy / early detection companies that use Illumina’s sequencing products as part of their offering. But as a multi-cancer early detection leader Grail has a lot of potential to revolutionize cancer screening – we shall see how the major acquisition pans out for the sequencing giant.

Other news was on the lighter end with a few companies and researchers releasing new data for the use of liquid biopsies in CRC, lung, and breast cancer. ESMO concluded earlier this week but major liquid biopsy headlines were slimmer than they have been in previous years.

Recent Headlines

Market Highlights

Startup Stitch Bio Bets on CRISPR Tech to Render Cancer Cells With Gene Fusions Druggable | Sep 16, 2020
Foundation Medicine and Takeda Announce Collaboration To Develop CDx for Takeda’s Late-Stage Lung Cancer Portfolio | Sep 18, 2020
Natera to Present New Gastrointestinal Cancer Data at the ESMO | Sep 18, 2020
Arna Genomics Raises $3.5M In Series A Financing | Sep 21, 2020
Universal Diagnostics Presents New Promising Data on Early (Pre) Cancer Detection from cfDNA at ESMO | Sep 21, 2020
Biocept Announces that Highmark Has Made a Positive Coverage Determination on Target Selector | Sep 21, 2020
I llumina to Acquire Grail for $8B in Cash and Stock | Sep 21, 2020
Clinical Genomics Announces Publication of Additional Clinical Data for COLVERA® Recurrence monitoring Blood Test for Colorectal Cancer Patients | Sep 22, 2020

Research Highlights

(9/17/2020) Epic Sciences and MSK find a potential prognostic marker for mCRPC

Epic Sciences and researchers from MSK identified that a chromosomal instability marker on circulating tumor cells found in metastatic prostate cancer may have prognostic value and could be used to guide therapeutic decisions. The researchers found that the number of large scale transitions (LSTs) found in CTCs was associated with poor outcomes and developed an algorithm that can analyze CTC images captured as a result of Epic’s immunofluorescent staining platform. In a prospective study using samples from 294 patients (10,240 CTCs) a cutoff of 9 or more LSTs in a single CTC had a clinical sensitivity 68% and 84% specificity of predicting worse overall survival.

Other news includes the 9% stock drop Illumina saw after rumors of a potential acquisition of Grail (which came shortly after Grails IPO announcement) and Natera’s plan to look for a combined value for their Prospera and Signatera assay for oncology treatment decisions.

Recent Headlines

Market Highlights

Natera Launches Proposed Follow-On Offering | Sep 9, 2020
Streck Cell-Free DNA BCT® receives U.S. FDA De Novo clearance | Sep 11, 2020
Genetron develops testing kit for China’s nationwide cancer screening program | Sep 14, 2020
Natera Launches Initiative to Transform the Management of Cancer Patients in Organ Transplantation | Sep 14, 2020
Canexia Health Closes New Financing Round to Accelerate Precision Oncology Roadmap | Sep 16, 2020
Illumina’s Stock Falls 9 Percent on Grail Acquisition Rumors | Sep 16, 2020

Research Highlights

Epic Sciences, MSK Identify Potential Prostate Cancer Therapy Response Biomarker | Sep 10, 2020
Helio Health Announces Collaboration with Top National Cancer Centers | Sep 10, 2020

(9/10/20) FoundationOne Liquid CDx approval; Sysmex Inostics publishes on value of OncoBEAM in mPDAC

Liquid biopsies are pushing further into routine clinical care by receiving favorable approval/ coverage decisions by regulatory/ reimbursement bodies. In late August, Foundation Medicine’s liquid assay was approved as a CDx for Rubraca (a PARP inhibitor for prostate cancer) and three TKI’s for NSCLC treatment. The company intends to leverage the broad range of targets of FoundationOne Liquid CDx (a comprehensive genomic profiling assay) to pursue additional CDx claims. A potential expansion would be to seek CDx status for BluePrint’s and Genetech’s Gavreto, which received accelerated approval for metastatic NSCLC patients harboring RET fusions. Guardant and FMI can both detect RET fusions however only Thermo’s Oncomine tissue test is the only approved CDx platform for RET fusions. Additionally, Natera received a final local coverage decision of Signatera for serial monitoring of MRD in stage II / III CRC patients from CMS. This final local coverage decision is in line with the draft decision that was issued in Aug of 2019.

In other news, Sysmex Inostics announced a publication highlighting the potential value of their digital PCR assay, OncoBEAM RAS for metastatic pancreatic ductal adenocarcinoma. The study showed that levels of circulating RAS mutations may be an improved biomarker to CA19-9 (a non-tumor specific protein biomarker) for prognostic evaluation and real-time tumor response monitoring. This assay could add to the information on hand when oncologists are making clinical decisions, which is key when treating such an aggressive cancer.

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Market Highlights

Research Highlights

(8/5/2020) Singlera narrows focus to CRC; miR Scientific named as Fierce Innovation Finalist; More news on ArcherDx, Natera and Personalis

While Singlera’s 10 yr. retrospective study generated positive data for PanSeer (4 cancers) the company has decided to narrow its near-mid term commercialization efforts on colorectal cancer with an assay named ColonES. Reducing the scope to one cancer with clear screening guidelines and proven efficacy of assays for detection instead of imaging (e.g., ultrasound, MRI etc.) should lighten the lift required for Singlera to prove clinical utility and gain reimbursement. This path was forged by Exact Sciences but is crowded by the likes of Freenome and Guardant who are in hopeful pursuit. The pivotal study for ColonES is expected to launch in later 2020.

Another indication with an approved blood test to aid in cancer detection is prostate cancer. However, it is no secret that there needs to be a better tool than PSA for detecting high-grade prostate cancer. This week, miR Scientific was selected as a finalist for the 2020 Life Sciences Fierce Innovation Awards. miR’s Sentinal Prostate Test detects small-non-coding RNAs from a urinary exosomes to detect cancer as well as clasify the risk category of the cancer. The assay’s validation data revealed that Sentinal detects cancer with 94% sensitivity / 92% specificity, and correctly categorizes Gleason Grade (GG) 1 from GG 2 – 4 with 93% sensitivity / 90% specificity, as well as GG 1 – 2 from GG 3 – 5 with 94% sensitivity / 96% specificity. Correct categorization of a patients risk can save them from unnecessary and risky prostate biopsies.

Additionally, Natera, Personalis, and ArcherDx had stories this week. Be sure to take a look at them in the links below!

Recent Headlines

Market Highlights

Research Highlights

New Prostate Test Could Help African American Men | Jul 29, 2020
Cell-Free DNA in Blood Reveals Significant Cell, Tissue and Organ Specific injury and Predicts COVID-19 Severity | July 29, 2020
Efficient mutation screening for cervical cancers from circulating tumor dna in blood | Jul 29, 2020
Two thirds of lung cancers detected at early stage using blood test and CT scans | Jul 31, 2020
Patient specific circulating tumor DNA fingerprints to monitor treatment response across multiple tumors | Aug 1, 2020

(7/28/20) - Singlera releases preliminary PanSeer Data, suggesting a 4 year lead time; Methylation markers may help predict CPI Tx response

The largest buzz in headlines this week was generated by Singlera when they released positive preliminary data from the Taizhou Longitudinal (TZL) Study for PanSeer. PanSeer uses ctDNA methylation markers to detect stomach, esophageal, colorectal, lung or liver cancers and will compete with the likes of Thrive Earlier Detection (~10 cancers) and GRAIL (>50 cancers) as a blood-based pan-cancer screening assay. The TZL study collected samples from 123,115 healthy patients over time while they were monitored for cancer occurrence. The preliminary analysis consisted of a group of 605 asymptomatic patients, 191 of whom developed one of the 5 cancers measured by PanSeer. It was found that PanSeer detected cancer in 88% of these patients post-diagnosis at 96% specificity. PanSeer was able to identify 95% of asymptomatic individuals who were later diagnosed with cancer within 4 years of their blood draw. Further validation is needed, but the prospects of identifying cancer 4 years prior to conventional diagnosis is certainly exciting.

ctDNA methylation has established itself as a crucial analyte for the early detection of cancer and may prove to be useful later in cancer care. Genome Profiling and Fox Chase Cancer Center are collaborating to develop a potential predictive marker for checkpoint inhibitors in lung cancer patients. Immuno-oncology is known to only have drastic results in a limited group of patients. Markers like PD-L1 status and Tumor Mutation Burden are still being understood and are primarily determined by a tissue sample. The goal of this collaboration is to determine if methylation sites on circulating immune cells can predict a lung cancer patient’s response to CPIs. If successful, this test could save a patient from undergoing a risky biopsy as well as better inform treatment decisions.

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Market Highlights

Research Highlights

(7/21/20) - AnchorDx collaborating with J&J; Canadian consortium led by Canexia Health to improve targeted cancer treatment

AnchorDx is launching a clinical study through their partnership with Johnson &m Johnson. The study will enroll 3000 patients with lung nodules identified by a CT scan and will be used to determine if Anchor’s ~$100 methylation based blood test has clinical utility in detecting lung cancer early by differentiating benign nodules from malignant nodules.

Angle announced that Parsortix, a CTC capture device, identified targetable mutations in metastatic breast cancer that were missed in single site biopsies. The company plans to file their FDA submission for Parsortix in Q3 2020. This announcement comes amidst other research movements for liquid biopsy in breast cancer, which is exciting since this cancer is known to be low shedding and difficult to develop assays for.

Canexia Health (formerly Contextual Genomics) is leading a consortium whose initiative is to improve testing and treatment of Canadian cancer patients during this pandemic. The project is called ACTT (Access to Cancer Testing and Treatment) and will offer Canexia’s liquid biopsy test (Follow It) to recurrent or metastatic lung, breast, or colon cancer. Many patients have forgone genomic profiling during the corona pandemic out of fear of contraction. Other patients are facing long wait times to get surgery due to hospital congestion and may not be able to have a tissue biopsy collected. Time is critical in cancer care and having access to targeted therapies could improve patient outcomes. The consortium is using LBx to help alleviate the complications caused by the pandemic and could have long lasting impacts on cancer care.

Recent Headlines

Market Highlights

Research Highlights

Presence of cfDNA, CTCs Predicts Recurrence in Triple-Negative Breast Cancer | July 10, 2020
The Distribution of Circulating Tumor Cells Is Different in Metastatic Lobular Compared to Ductal Carcinoma of the Breast—Long-Term Prognostic Significance | July 17, 2020 (PDF download)

(7/10/20) - AnchorDx presents positive data for $100 methylation assay; Natera releases data at ESMO GI; Guardant to develop CDx for Janssen

AnchorDX presented early results for their Aurora early cancer detection assay at AACR last week. Aurora uses 100 – 200 methylation markers to detect 6 common cancer types (lung, breast, colorectal, esophagus, and liver) and was created using both TCGA and Anchor’s in-house database of 2,000 tissue and 4,000 plasma samples. Anchor’s in-house data is skewed towards early cancer patients, which they claim helped their test achieve superior sensitivity and specificity compared to other early detection assays. Aurora was tested using 246 lung, breast and colorectal cancer patient samples, and 141 normal controls. At a pre-specified specificity of 99% the test showed 82%, 63%, and 55% sensitivity in Stage 1 lung, breast, and colorectal cancers, respectively. On top of this impressive performance, the company, and wisely so, is targeting a price point of ~$100 which is expected to increase access if Aurora can continue proving clinical utility. Other companies targeting early detection assays have amassed higher levels of clinical data on their road to commercialization, so it will be interesting to see how Anchor’s data holds in a larger prospective dataset.

Natera announced further evidence of it’s Singatera platform at ESMO GI 2020. The studies showed that Signatera was able to detect 100% of oligometastatic patient’s pre-surgery, as well as highlighted the study design for a prospective and observational trial (GALAXY) which is part of the CIRCULATE-Japan trial. CIRCULATE-JAPAN is aimed at optimizing ctDNA guided treatment strategies in Stage II-III CRC patients. In a press release, Natera’s Senior Medical Director of Oncology claimed that “Now that Signatura is being used in prospective interventional trials, we’re seeing confirmation that it can help inform treatment decisions after oligometastatic resection in the 20 percent to 30 percent of patients with metastatic CRC,”.

In an interesting analysis of reimbursement coverage of liquid biopsies it was found that the ~40% of payers offer some coverage of ctDNA panels as of mid -2019 – a sharp increase from 0% in 2016. Coverage also expanded from just NSCLC to 12 cancers as well as from single-gene tests to 73 gene tests. A limitation of coverage for monitoring assays was noted, with only 11% of payers having positive claims towards ctDNA for monitoring purposes.

Recent Headlines

Market Highlights

Research Highlights

Study Supports Using Comprehensive ctDNA Testing in Patients with NSCLC | Jul 3, 2020
Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention | Jul 3, 2020

(7/1/20) - Guardant launches clinico-genomic platform GuardantINFORM, Inivata showcases RaDaR monitoring studies at AACR

Guardant has launched the GuardantINFORM platform, a dataset that combines de-identified longitudinal clinical information and genomic data collected from the Guardant360 liquid biopsy test. Notable applications for the platforms include targeted drug development, clinical trial optimization, and post-marketing studies. As the market leader in liquid biopsy testing, the size of Guardant’s dataset is impressive, with samples from over 100,000 patients have been accumulated over the past 5 years, according to Helmy Eltoukhy, Guardant Health co-founder and CEO. Across the industry, there is significant appetite for real-world evidence and clinico-genomics data to inform research and product development (note the Roche Group’s Prospective Clinical-Genomic study launched a month ago), and we are just starting to leverage its potential.
At the AACR meeting last week, Inivata and collaborators at the Cancer Research UK Cambridge Institute presented results from two studies using the RaDaR ctDNA monitoring assay. As part of one study regarding the analytical development, the RaDaR assay was used against a variety of cancer cell lines, DNA reference material, and tissue samples to assess performance at various dilutions. Tracking 48 mutations, the RaDaR assay demonstrated 97% sensitivity using 20,000 copies, and 63% sensitivity using 4,000 copies of DNA input.

In a separate study focused on early stage NSCLC, 90 patients were recruited from the LUng Cancer CIrculating Tumour DNA (LUCID) Study and monitored post-surgical resection and every 3 months for 9 months. ctDNA was identified in 35% of baseline samples from stage I patients, and >90% of samples from stage II and stage III patients, and the results suggest that that RaDaR could identify ctDNA 6-12 months ahead of typical disease progression in 60% of patients.

The RaDaR assay partitions the sample before sequencing, presumably increasing the signal-to-noise ratio to detect low-frequency variants prior to sequencing. Combined with the approach of using a personalized, mid-sized NGS panel, RaDaR could prove to be strong competition against other companies in the monitoring market (including Natera, Guardant, and ArcherDX).

Recent Headlines

Market Highlights

Biocept reaches deal to cover out-of-network patients for its liquid biopsy tests | June 24, 2020
Guardant Health Launches Real-World Clinical-Genomic Platform to Accelerate Precision Oncology Drug Development | June 23, 2020
Inivata Demonstrates Potential of ctDNA Assay for Cancer Recurrence, MRD Applications | June 25, 2020
NeoGenomics Launches Comprehensive Suite of Solid Tumor Liquid Biopsy Tests for Cancer Patients | June 29, 2020

Research Highlights