The market for liquid biopsy will near $1.6 billion by 2023, according to a new report from Kalorama Information. This represents double-digit growth over the course of the period researched in the market research firm’s report. Liquid biopsies are a set of minimally invasive diagnostic methods that analyze tumor-derived materials that can be found

circulating in biological fluids, to provide information for the diagnosis, treatment, and monitoring of cancer. The market for liquid biopsy testing, still in its infancy, is rapidly evolving as vendors develop and commercialize innovative new technologies to meet the needs of the clinical diagnostic market, according to The World Liquid Biopsy Market, from Kalorama Information. https://kaloramainformation.com/product/the-world- liquid-biopsy-market/

The most frequently targeted analyte in liquid biopsy is
ctDNA, which encompasses small fragments of DNA that are
believed to originate from the natural and abnormal necrosis and
apoptosis processes undergone by solid tumor cells as well as
normal cells during regular cellular turnover. As of 2019, over 40 companies are active in the global market for liquid biopsy diagnostics and monitoring tests.

Demand Stems from Tissue Biopsy Disadvantages

Several drawbacks and limitations are associated with tissue biopsies. First, they are highly invasive surgical procedures that may expose patients to risks. The tumor site must be known and surgically accessible in the first place. Because of the invasive nature of the procedure, tissue biopsies are usually restricted to a single sample site, and repeat tissue biopsies are impractical; a single biopsy provides only a snapshot of a tumor’s characteristics. Furthermore, tissue biopsy samples may not reflect the genomic heterogeneity of tumors. Tissue biopsies are also quite costly to perform; a typical surgical biopsy can cost $15K-45K to perform.

In comparison, liquid biopsies offer several key advantages over tissue biopsies. They are less or non- invasive, lower risk, lower cost, and offer faster turnaround times for results. Moreover, liquid biopsies provide the opportunity for repeat testing, to monitor treatment progression over the course of

$1.6BN Market for Liquid Biopsy, and 20%+ growth, according to Kalorama Information’s new report.

therapy, and/or to test for recurrence after surgical removal of tumors. Liquid biopsies provide a more comprehensive picture of tumor heterogeneity, providing genomic insights for both intra-tumor, and of metastatic lesions. Liquid biopsies, in general, are better able to capture the heterogeneity of cancer than tissue biopsies, as cells, DNA, and exosomes are shed from multiple parts of the primary tumor or metastatic lesions in various locations of the body, into the vascular and lymphatic systems. With this information, clinicians can form a more comprehensive understanding of the disease burden, and druggable variants may be identified.

Comparison of Tissue and Liquid Biopsy

Tissue Biopsy

Liquid Biopsy

Invasive and expensive

Non-invasive and less costly

Provides information specific to the localized tumor site

May provide information from both primary and metastatic sites

Available in limited quantities

Can be collected frequently, in larger volumes

Information provided is limited to the section of biopsy analyzed

Can reflect tumor heterogeneity

Serial biopsies are difficult/impossible

Serial evaluation of disease possible

Difficult to obtain from some organs / Not available if primary tumor is not visible in imaging or has been surgically removed

Blood/urine specimens are easy to collect

Source: Kalorama Information

Liquid Biopsy Limitations

While liquid biopsies offer many advantages, the technique is still early in its development, and challenges have been identified. Several studies examining tests offered by major liquid biopsy companies have found discordance between how results compare with tissue biopsy sequencing, as well as inconsistent results between various liquid biopsy assays conducted by different companies. Discrepancies and false negative results can be attributed to low occurrence of CTCs and ctDNA, akin to looking for a needle in a haystack, which makes detection difficult. However, false positive detection of biomarkers is also a common occurrence. Discrepancies may also be a product of differing assay characteristics between providers, which are difficult to assess as tests are proprietary. Because of these issues, a joint literature review conducted by the American Society of Clinical Oncology and the College of American Pathologists conducted in 2018 concluded that there is no evidence of clinical utility for ctDNA testing in early-stage cancer, treatment monitoring, or residual detection. However, the review also noted that given the rapid pace of research into liquid biopsy, re-evaluation will be required shortly.

Yet despite these limitations, the global market for liquid biopsy diagnostic and monitoring test is expected to grow at a rapid pace over the forecast period of five years in the report.

Growth Prognosis

Kalorama forecasts growth as liquid biopsy gains clinical acceptance. A market size of 1.6 billion and growth of more than 20% is much higher revenue growth than IVDs generally experience, but it is lower than some estimates put forth by investment concerns or non-specialist market researchers. Clinical uses will drive growth. Currently, there are more than 130 approved therapeutics that target various cancer biomarkers, and a large number of drugs are in the late stages of clinical development, prompting the need for diagnostic and monitoring tests that inform the use of these therapies.

Most liquid biopsy tests commercialized in this segment focus on the detection of distinct, clinically actionable markers on single genes or small panels of genes, which offer the advantages of lower cost and complexity, faster turnaround, and easier to interpret results. The majority of companies focus on testing a single analyte, such as ctDNA, CTCs or exosomes, from blood specimens, but a few companies, such as Biocept and LungLife AI, incorporate multiple analytes, such as the combination of ctDNA and CTCs, to expand the test’s performance and the range of detectable biomarkers.

Growth for diagnostic/screening applications will be driven by several factors. As the incidents of many cancers increases globally, clinical guidelines have adopted screening recommendations, such as colonoscopies and mammograms, into regular patient management. While liquid biopsy-based screening tests have yet to be incorporated clinical care guidelines, clinicians and patients can choose to use them in place of more invasive procedures, or as a screening method to decide whether a more invasive diagnostic method is necessary.

This White Paper by necessity can only offer a limited amount of information. Our complete market assessment, reflecting our considered analysis of liquid biopsy can provide useful understanding and business planning information.

The molecular diagnostics segment is the fastest growing segment within the global IVD market. The global market is estimated to be $8,760 million in 2019. Infectious diseases diagnostics represent the largest segment within the market, accounting for more than half of the global molecular diagnostics market. The global market is forecasted to grow at a compound average growth rate (CAGR) of 8.1% to reach $12,955 million in 2024. Major segments that are expected to drive the growth are infectious diseases, cancer, and transplant diagnostics. These are all broken out and forecasted in Kalorama’s The World Molecular Diagnostics Market, 8th Edition. The discovery of the structure of DNA in 1953 is one of the earliest scientific advancements that facilitated the development of molecular methods as diagnostic tools, even though it took more than 4 decades for the first tests to get commercialized. The pioneers in the molecular diagnostics field include Roche Diagnostics, Gen-Probe, and Becton Dickinson. The main focus of the initial molecular diagnostics products were infectious diseases such as HIV, Chlamydia Trachomatis/Neisseria Gonorrhoea (CT/NG), and TB. Some of the initial molecular diagnostics products include Roche’s PCR test for HIV and CT/NG, Gen Probe’s tests for TB and CT/NG based on transcription mediated amplification (TMA) method, and Becton Dickinson’s CT/NG test based on branched chain DNA 0 2 4 6 8 10 12 14 8.7 12.9 2019 2024 This White Paper is derived from Kalorama Information’s market research reports: For more information, visit: www.kaloramainformation.com (bDNA) signal amplification technology. Focus on infectious diseases was maintained even during the early years of the last decade by companies that ventured into the molecular diagnostics sector, and commercial molecular assays were introduced for hepatitis and respiratory diseases. The blood banking sector became one of the key application areas during this period, since the high sensitivity offered by molecular diagnostics brought significant value for donor blood screening for pathogens of high concern. Currently, the use of molecular diagnostics methods is not limited to infectious diseases. Other disease segments where molecular assays have high demand include inherited diseases, coagulation, transplant medicine, prenatal and postnatal screening, and cancer. Molecular Diagnostics Market Facts Kalorama Information made the following findings about the market in its report: • Fast Growth: The global market is forecasted to grow at a compound average growth rate (CAGR) of 8.1% to reach $12,955 million in 2024. • Microbiology leads: Infectious diseases diagnostics represents the largest market within the market, accounting for more than half of the global molecular diagnostics market. • Watch Reimbursements: Even though the demand for molecular diagnostic tests is growing at a high single-digit growth rate in spite of affordability concerns, reimbursement has been a major factor for this segment. This is particularly true in the case of tests for supporting drug decisions. • IT is Central: The molecular diagnostics market is evolving with the effective integration of information technology (IT), including various bioinformatics platforms, cloud computing, and big data analysis methods. From data sharing to developing well-curated gene variations to integration of clinical insights for better outcomes, to development of automated sample-toinsight systems, only improved information technology will enable the realization of these concepts. • Watch NGS: Though a small segment now, we are right on the cusp of next-generation sequencing becoming an essential part of clinical decision making. Clinical usage is behind many installations and consumable purchases and has been touted by the major sequencing providers. NOW PUBLISHED – KALORAMA INFORMATION’S World Market for Molecular Diagnostics, 8 TH Edition This White Paper is derived from Kalorama Information’s market research reports: For more information, visit: www.kaloramainformation.com The first-generation molecular testing methods were time consuming and labor intensive, which included techniques such as the Southern Blot, DNA probes, capillary electrophoresis and pulsed field gel electrophoresis. The sector has seen significant advancements and most popular molecular technologies used for developing molecular diagnostic tests include nucleic acid amplification technologies (NAATs) including polymerase chain reaction (PCR) and other NAAT methods, sequencing, mass spectroscopy, microarrays, and biochips. Currently, molecular diagnostics is one of the fast-growing segments in the clinical diagnostics market. The field has witnessed innovation in multiple levels during the past two decades, leading to increasing significance in the clinical diagnostics sector. “Infectious diseases diagnostics account for more than half of the global molecular diagnostics market.” A majority of the molecular tests that are CE-marked and FDA-approved are based on new genetic markers that are validated for clinical utility. Innovations in biomedical engineering have enabled automation of many steps including sample preparation steps, reducing the labor and time for testing. Emerging Trends Influencing the Market Landscape Molecular diagnostics is a fast evolving and dynamic field and is the fastest growing segment within the in vitro diagnostics (IVD) market. Molecular diagnostics have become indispensable tools in clinical medicine that touch all aspects of healthcare including treatment decisions in terms of identifying antimicrobial resistant (AMR) infections at the earliest, companion diagnostics assisting in the evaluation of suitability of various cancer treatment options, pharmacokinetics or patient metabolism of drugs for HIV, psychiatric conditions or blood thinners; cancer prognosis and therapy, organ matching, blood safety, and the diagnosis of latent and neonatal conditions. Rather than replacing other major IVD modalities such as immunodiagnostics, the molecular diagnostics market has expanded by meeting clinical needs unmet or never envisioned with other major testing disciplines. As they become more affordable, displacement of other diagnostics such as immunodiagnostics has also occurred owing to the high sensitivity and unique insights molecular diagnostic methods offer. Certain IVD segments have been or are in the course of being remade worldwide through the application of molecular methods including blood screening, POC diagnostics, cytogenetics, and tissue typing. Some of the key market trends of the industry that are influencing the market landscape in a big way are as below: This White Paper is derived from Kalorama Information’s market research reports: For more information, visit: www.kaloramainformation.com Democratization of Molecular Testing with Sample-to-Result and POC Systems Opposing trends of centralization and decentralization are expected to reshape the molecular diagnostic market landscape. While democratization of molecular tests is becoming a reality with advancements in automation and information technology, the opposite trend is also strong, as many tests are moving from local clinical labs to large reference labs due to the economies of scales that can be achieved. Advancements in automation and information technologies (IT) have created a new level of optimism in the molecular diagnostics markets as evident from the research investments, university spin-offs, mergers, and acquisitions in the segment. The holy grail for molecular testing is the ability to load an untreated sample onto a cartridge or cassette, push start and then come back when the test has been completed. The “sample-to-result” table-top systems fast entering the market represent an important milestone towards achieving this goal. Some of the leading global companies focusing on offering such table-top systems include Cepheid, Spartan, Qiagen, Hologic, GenMark, and Enigma. The investments by such leading companies and government agencies who partner with them are pushing the existing limits of automation and IT, facilitating fast advancement towards near-patient and point-of-care diagnostics solutions. Table-top systems are considered the prerequisite technology advancement to providing molecular testing in small laboratories and resource-limited test sites anywhere in the world. The market is moving beyond these systems and the next generation of sample-to-result molecular test instruments is focusing on bringing genetic medicine to a much broader audience. The commercialization of these platforms and tests are the next major development towards democratization of molecular diagnostics as they have the potential to improve the quality of healthcare by improving the affordability and accessibility to advanced diagnostic solutions even in remote areas where challenges of skilled manpower and infrastructure are acute. Government investments into academic research and initiatives to support startup companies in the field are also driving the growth of the molecular diagnostics sector. This White Paper is derived from Kalorama Information’s market research reports: For more information, visit: www.kaloramainformation.com Major Companies in the Market The following companies participate in the market segments of molecular testing. Full profiles, notices of product launches and mergers, as well as market assessments are included in Kalorama’s World Market for Molecular Diagnostics, 8 th Edition. • Abbott Diagnostics • Advanced Cell Diagnostics (Biotechne) • Agilent Technologies • Amoy Diagnostics • Applied Spectral Imaging • Becton, Dickinson & Co. (BD) • Beijing Genomics Institute (BGI) • Berry Genomics • bioMérieux • Bio-Rad Laboratories • CareDx, Inc. • Danaher (Cepheid and Leica Biosystems) • Eiken Chemical • GenMark Diagnostics • Genotypic Technology Pvt. Ltd. • Grifols, S.A. • Illumina • Immucor, Inc. • Meridian Bioscience, Inc. • Molbio Diagnostics Pvt. Ltd. • PerkinElmer, Inc. • QIAGEN N.V. • Quidel Corporation • Roche Diagnostics • Thermo Fisher Scientific, Inc. • Vela Diagnostics