It’s been another busy and exciting year here at BioInformatics, now part of Science and Medicine Group. Together with our sister brands, Instrument Business Outlook, IMV Medical Information, Kalorama Information and Strategic Directions International, we’ve been helping clients achieve success through our quantitative and qualitative custom research services, our market research reports and industry data files.

 

After a busy January kicking off new projects, we attended the 2019 Society for Laboratory Automation and Screening (SLAS) in early February right here in our hometown of Washington, DC. More than 300 companies, including many of our clients, were exhibiting and we got to see the tremendous effort they’re making to improve the productivity of their customers.

For example, our friends at Bio-Rad introduced a new API for their ZE5 flow cytometer. The API allows the device to interact directly with an ecosystem of liquid handlers and other components, allowing use in high-throughput screening applications. The API is now available and offered as an upgrade for current as well as newly sold systems.

PerkinElmer was there too with a wide range of instrumentation and consumables to provide labs with a total solution and scalability. At their booth, the company exhibited a number of different systems that can be combined into an automated workflow including the chemagic Prime workstation for DNA and RNA extraction and liquid processing of 96 samples at a time. The Prime has the ability to bundle with other PerkinElmer products, such as reagents and plates.

Tecan also took the opportunity to launch the Tecan NGS DreamPrep system, an automated solution for NGS library preparation, leveraging its Fluent liquid handling automation platform and Infinite plate-reader technology as well as their newly acquired NuGEN Technologies to provide a complete solution for library preparation and online sample QC.

 

But the big news in February was when Danaher announced its plans to purchase GE Healthcare’s $3.2 billion biopharma business for $21.4 billion. This was Danaher’s largest acquisition to date and in many ways a culmination of Danaher’s commitment to the bioprocessing market. Danaher has emphasized the strategic priority of biopharma manufacturing tools to the company due to the rapidly growing market for biologic drugs and the high percentage of consumables sales, which are also specified into product manufacturing, providing a captive user base. Seventy-five percent of GE BioPharma’s revenues are recurring. According to SDi’s recent market report, Bioprocessing Technologies 2018, GE holds the largest market share in the process chromatography market (defined as systems, aftermarket and service).

In March, a large contingent of us traveled to Philadelphia for Pittcon. More than 700 exhibitors were on the floor. Although Pittcon may not be the hub of press announcements and new products that it once was, the show did mark announcements by Rigaku and Anton Paar. Rigaku debuted a new branding strategy to highlight the unification of the company’s operational units. Anton Paar USA detailed changes to its operational structure, forming four regional organizations in order to be closer to its customer base, provide faster response times and offer more training centers.

Our intrepid reporters from Instrument Business Outlook sat down with senior executives from three major instrument system and lab product suppliers—Shimadzu Scientific Instruments (SSI) (the North American unit of Japanese firm Shimadzu), Thermo Fisher Scientific and Waters. Discussing company priorities, R&D approaches and the current state of informatics development, the companies indicated the influence of major industry themes such as increasing instrument ease of use to growth usage, integrating larger amounts of data and access to them, and providing more tightly integrated workflow solutions

Dan Shine, senior vice president and president of the Analytical Instruments Group told us “[Customers] are under increasing pressure to get more samples analyzed more quickly and make use of the data, so we’re doing a lot on both the front end, with sample prep, and the back end, data analysis and data integrity, to automate that process as best we can and put the pieces together.”

Jeff Mazzeo, PhD, vice president of Marketing at Waters told us that along with new products, Waters plans to enhance its market focus. “We are now trying to focus more on customer input and that’s where the market segment teams really have to understand what do our customers need to be successful with our technology today, and so how do we build the right products for the future.”

Patrick Fromal, vice president of sales at Shimazdu also said this year will include include workflow solutions as well as new markets. “We see our position around HPLC enhancing greatly in pharma, in environmental [and] the emerging markets of cannabis and hemp.”

 

Then it was off to the American Association of Cancer Research (AACR) annual meeting in Atlanta. Over 500 exhibitors filled AACR 2019’s exhibition hall. Several product announcements presented new imaging solutions designed to address many of the shortcomings of IHC or combined multi-parameter measurements into one system. Single-cell analysis continued to be a major focus for research instrumentation, especially improvements and extensions of current flow cytometry and cell sorting technology. Meanwhile, mass spec exhibitors emphasized new applications specific to cancer research. In addition, many companies debuted product line expansions built upon technology acquisitions.

NanoString Technologies’ used the occasion to unveil the GeoMx Digital Spatial Profiler (DSP) system, which employs NanoString’s digital optical barcodes technology and a microscope for high-plex protein or RNA counting and spatial imaging of FFPE or fresh frozen tissue samples

We also saw Miltenyi Biotec preview its MACSima Imaging Platform for high-content imaging of fixed cell and tissue samples using epifluorescence microscopy. An unlimited number of markers can be detected through repeated sample scanning using up to 3 antibodies and 3 fluorochromes at a time. Applications include target discovery, biomarker discovery and deep phenotyping.

ACEA Biosciences, now a part of Agilent, used AACR as a soft launch for its xCELLigence RTCA eSight, which combines ACEA Biosciences’ real-time, label-free biosensor technology with live-cell imaging for the first time, according to the company, to allow simultaneous visualization of cellular characteristics and activities.

Another product introduction that caught our attention was Bio-Rad’s ddPCR single-cell assay for transposase accessible chromosome sequencing (scATAC- Seq) that maps the epigenetic profile to understand why different gene expressions patterns occur.

Finally we got some vindication for naming Fluidigm the “2019 Company to Watch” at the Life Science Industry Awards last year. Fluidigm launched its Maxpar Direct Immune Profiling System, which can aid in quantifying 37 different immune cell populations from human peripheral blood mononuclear cells as well as whole blood. The Maxpar Direct can allow a researcher to look at 30 different biomarkers (7 of the researcher’s own choice) from the same sample tube and provide results in 5 minutes.

In April, we saw a few niche suppliers unveil some very interesting new products. Jackson ImmunoResearch launched a new range of products for scientists developing single-domain VHH antibodies while Cygnus Technologies, an assay and services provider, introduced the EndonucleaseGTP ELISA Kit for the detection and quantitation of residual endonuclease impurities in recombinant vaccines and viral vectors used for gene therapy.

 

Meanwhile, Illumina and BGI filed dueling lawsuits against each other. Illumina’s complaint, filed in Denmark, details infringement of its sequencing-by-synthesis chemistry patent EP 3 002 289 B1. The suit also accuses BGI of trademark infringement of “MGISEQ” under EU Trademark No. 8972127. Illumina also has case pending against BGI in Germany alleging infringement of EP 1 530 578 B1.

In the US, Complete Genomics, a BGI business held by its MGI subsidiary, filed suit against Illumina in Delaware alleging infringement of US Patent No. 9,222,132 (Methods and Compositions for Efficient Base Calling in Sequencing Reactions). The complaint states, “use of Illumina’s ‘two-channel’ sequencing systems in combination with Illumina’s ‘Library Preparation Kits’ and ‘Cluster Generation and Sequencing Kits’ in the United States by Illumina and its customers constitutes direct infringement of at least claims 1–4 of the ’132 patent.” Defining a two-channel system, it states, “On information and belief, during ‘two-channel sequencing,’ the identity of each nucleotide is deduced from two signals.” Two-channel systems include Illumina’s NovaSeq 6000, the NextSeq series and MiniSeq systems. In a press release, MGI called  two-channel sequencing a “key technology in the DNBSEQ sequencing technology.”

Illumina faced a further headache in June when the UK’s Competition and Market Authority (CMA) found that Illumina’s proposed acquisition of Pacific Biosciences could limit competition in the UK sequencer market.

Does the onset of summer make companies more litigious? In July the US District Court for the District of Delaware granted Bio-Rad Laboratories’ motion for a permanent injunction against 10x Genomics’ sale of its single-cell droplet products in the US. In a letter to customers, 10x CEO and Co-founder Serge Saxonov wrote, “We strongly disagree with both this ruling and the jury’s verdict and we will appeal.”

Shortly thereafter, in light of the ongoing CRISPR patent dispute between the University of California (UC) and the Broad Institute, Sigma-Aldrich, part of Merck KGaA, has filed an urgent petition with the US Patent and Trade Office (USPTO) regarding its patent application related to CRISPR-Cas9-based methods in eukaryotic cells. In the petition, Sigma-Aldrich requests a so-called “parallel interference,” or an interference proceeding (an interference is conducted to determine which party is first responsible for invention) between the company and UC that would occur at the same time as current interference between UC and Broad. Sigma-Aldrich emphasized in its filing, “Of critical importance here, Sigma-Aldrich’s benefit applications pre-date the earliest possible benefit applications involved in the UC v. Broad Inst. interference with respect to their respective disclosures of CRISPR-Cas9 in eukaryotic cells.” Sigma-Aldrich also argued that it is being unfairly treated, stating, “Indeed, the USPTO has now granted Broad Inst. over a dozen issued patents. In direct contrast, the USPTO continues to reject Sigma-Aldrich’s CRISPR-Cas9 eukaryotic claims as not patentable over those same UC CRISPR-Cas9 prokaryotic provisional applications that the USPTO has repeatedly found have been successfully overcome by Broad Inst.’s eukaryotic claims.”

Then in August,10x Genomics filed for a public offering of its common stock. As of June 30, the company’s installed base stood at 1,284. Instruments, consumables and services revenues represented 25%, 74% and 1% of 2018 sales, respectively, with a consumable pull-through per instrument of $148,000. In its filing, 10x detailed the effects of Bio-Rad’s 2015 infringement case, which found 10x guilty of patent infringement. To avoid infringement, in the second quarter, 10x launched its Next GEM microfluidic chip for Single Cell Gene Expression, Single Cell Immune Profiling and Single Cell ATAC, but has yet to develop the new chips for its Single Cell CNV and Linked-Read solutions. The company expects the new chips to make up nearly all of its consumables sales by the end of next year. In the third quarter this year, the company anticipates all new Chromium instruments will only use Next GEM solutions. A few weeks later, 10x Genomics disclosed in its September 12 prospectus filing that the US Federal Court of Appeals has granted a partial interim stay of the injunction against the company’s sales of GEM chips. They began trading on the NASDAQ Global Select Market at a price per share of $39.00, raising an estimated $357.5 million in proceeds before expenses.

 

Also in August, our colleagues at Kalorama released the 12th edition of their highly anticipated report on the Global IVD Market. Kalorama reported that the world market for diagnostics is estimated at $69.2 billion in 2019 and is expected to grow 4% annually to $85.2 billion by 2024. This figure includes all laboratory- and hospital-based products, and over-the-counter (OTC) product sales. Tissue-based testing for cancer and molecular tests for both cancer and infectious diseases are the growth engines among larger market segments, each growing 50% faster than the overall IVD market. Concerns over sepsis and respiratory conditions should ensure that infectious disease will also remain in the fast-growth categories. Specialty immunoassays, continuous glucose tests, MS and inherited diseases are other large and high-growth segments. The IVD market continues to grow, but what the dollars represent is changing. Twenty years ago, clinical chemistry and immunoassays represented most of the testing. Still today, the traditional core lab test segments—chemistry/immunoassay, hematology and coagulation—make up 34% of the dollar value of the IVD market and over 60% of tests run. But as molecular, infectious disease and cancer tests increase in importance, the market share of these core tests will decrease to 29% by 2024.

 

September saw us launch RateMyProduct – an automated product assessment tool that provides life science suppliers with customer feedback about their product concept, product, or service. RateMyProduct enables life science marketing and product managers to create an online presentation about a lab product or service, have it reviewed by a chosen target market, and get an online report within five days. The automatically generated online report provides feedback from prospective customers and indicates the likelihood of market success. Over the previous several months, our clients had been testing RateMyProduct by deploying it in their own product development cycles. Using this tool, they’ve been able to test different price points and see how well they’re communicating their product’s value. Our clients have been overwhelmingly positive about the outcomes.

In late September, Illumina and PacBio amended their merger agreement’s expected time for completion, extending it to December 31, with Illumina having the option to further extend it to March 31, 2020. Among the highlights of the CMA’s summary were comments on competitive dynamics, stating that, “Almost all customers said that long-read technologies will be more prevalent in the future, and a large proportion of these said that this will be at the expense of short-read technologies.” Regarding long-read sequencer firm Oxford Nanopore (ONT), the document reads, “Customers often mentioned ONT as a competitor to PacBio, and made comments suggesting that the choice between PacBio and ONT is closely balanced.” Recounting researcher’s opinions of the deal, the document states, “Most customers said that they felt that PacBio’s offering would improve under Illumina, either due to concerns about PacBio’s current financial situation or due to Illumina’s track record of acquiring and improving technology.”

SGI-DNA, a company developing synthetic genomics technologies and DNA data storage solutions, completed a $25 million series A financing round in September, led by Northpond Ventures. Proceeds of the financing will support the global commercial launch of the BioXp 3200 System, which it called the industry’s first fully automated gene synthesis platform.

September wrapped up with Gyros Protein Technologies introducing PurePep Chorus, its next generation automated peptide synthesis platform. The system can be purchased with or lab-upgraded to include, 2, 4 or 6 channels, with independent induction heating, and real-time UV monitoring on 2 or more channels.

In October, Illumina and QIAGEN N.V. announced a 15-year partnership intended to broaden the availability and use of NGS-based in-vitro diagnostic (IVD) kits, including companion diagnostics, for patient management. The agreement grants QIAGEN non-exclusive rights to develop and globally commercialize IVD kits to be used together with Illumina’s MiSeq™ Dx and NextSeq 550Dx Systems. The agreement also includes rights for expansion of the partnership on future Illumina diagnostic systems. Both companies are also exploring opportunities for QIAGEN to develop and market companion diagnostics based on Illumina’s TruSight Oncology assays that enable comprehensive genomic profiling of tumor samples in immunotherapy.

 

Our team was on the road again in October for the American Society of Human Genetics (ASHG) annual meeting in Houston. The exhibition hall featured 271 exhibitors and we noted several notable trends among exhibitors. The word “democratize” was prevalent in product ads, flyers and at technology talks. In the context of analytical instrumentation, democratization means to increase accessibility through simplification of operation and analysis. Vendors have come to recognize that specialized skills and training are significant barriers to product use, and ease-of-use is a highly marketable feature.

RNA sequencing products were featured by many exhibitors, with multiple new products showcased for RNA library preparation. RNA-seq is one of the fastest-growing portions of the sequencing market; more information on demand and growth can be found in SDi’s recently published market report, Sample Preparation for Next-Generation Sequencing.

There was a growing presence of data service companies at the conference, with Amazon Web Services presenting its partnership with Illumina, and Microsoft exhibiting its collaboration with the Broad Institute. With the explosive growth of sequencing data generated, large data companies have found opportunities to become increasingly involved in secondary analysis and data storage.

New England Biolabs showcased its recently launched NEBNext Enzymatic Methyl-seq (EM-seq) kit. The EM-seq kit, instead, uses an initial protection step followed by a deamination step to achieve the same conversion as the sodium bisulfite method, while minimizing damage. The higher yields require fewer PCR amplification cycles, provide more uniform coverage and results in more complex libraries.

Inscripta introduced the Onyx Digital Genome Engineering platform, calling it the world’s first fully automated benchtop instrument for genome-scale engineering. The CRISPR-mediated, massively parallel platform enables researchers to engineer microbial libraries containing the full breadth and scope of possible edit types, in their own labs.

As we returned from ASHG, Danaher agreed to divest three businesses—FortéBio label-free biomolecular characterization, chromatography hardware and resins, and SoloHill microcarriers and particle validation—in order to gain regulatory approval of its planned acquisition of GE Healthcare’s biopharma business. Sartorius will acquire the businesses for $750 million. The three businesses had combined 2018 revenues of $140 million and double-digit margins. According to SDi’s 2018 report, Bioprocessing Technologies 2018.MilliporeSigma and Pall are the largest vendors of bioprocessing filtration and concentration products, with Sartorius a distant third.

The UK Competition and Markets Authority (CMA) put up another obstacle to the Illumina/Pacbio merger in October when it issues its provisional findings stating, “We provisionally conclude that the adverse effect arising from the identified SLC [substantial lessening of competition] would be that the Merged Entity would have less incentive to complete and that this would result in reduced choice, an increase in prices, deterioration in quality, deterioration in service and/or loss of innovation or refocus their own innovation.”

On the last day of October Mesa Laboratories, which provides instruments and consumables QC applications purchased Gyros Protein Technologies from AP6, Ampersand Capital and individual shareholders for $180 million.

 

live cell imaging

Modern microscope station with tissue section on the screen

November saw us on the road again – this time to Association for Molecular Pathology. Early detection is key to improving treatment outcomes for most cancers, but despite advancements, the challenge of early detection remains. So it came as no surprise that exhibitors showcased innovations designed to improve detection time and testing relevance.

A notable product introduction was Thermo Fisher Scientific’s same-day NGS system, the Ion Torrent Genexus. Thermo Fisher highlighted the durability of the Genexus’ design and IT features, including reporting and documentation of all aspects of the sample run. Andy Felton, vice president of Product Development at Thermo Fisher, spoke with IBO about the system. He said the Genexus is designed to make NGS on par with immunohistochemistry (IHC) systems in terms its influence on oncologists’ decisions. “At the current time, the IHC result comes in a few hours, and the next generation sequencing test is generally outsourced and comes in weeks,” he said. “By then, the treatment recommendation has been made. If you can perform NGS on site, it can also be part of the process.” To do this, Genexus boasts a workflow time of less than 24 hours for some cancer type and same day with most others. This speed, Mr. Felton said, is due to the system’s use of a greatly improved clonal amplification process that reduces processing time from 14 hours to 3 hours.

Illumina made news with the debut of a liquid biopsy NGS offering for oncology. As of 2019, over 40 companies are active in the global market for liquid biopsy diagnostics and monitoring tests. The market is expected to surpass $1.5 billion by 2023, according to a recent Kalorama Information report, with a CAGR of 27.9% over the next five years. Illumina’s TruSight Oncology 500 ctDNA is its first liquid biopsy solution for detecting cancer biomarkers. According to the company, TruSight provides labs with the flexibility to analyze both tissue and liquid biopsy samples. Consequently, it can uncover biomarkers using liquid biopsy when tissue samples are limited or unavailable, or it can complement tissue results by detecting biomarkers in circulating tumor DNA (ctDNA).

Agena Bioscience showcased its combined RT-PCR and mass spec system. The company’s UltraSeek chemistry is designed to be an economical method for validating mutations of interest identified through NGS and RT-PCR, to confirm or rule out borderline results. The company said that following whole-exome sequencing, targeted detection on its MassARRAY system has been proved to confirm low-threshold mutations.

Promega announced at AMP a global collaboration with Merck for companion diagnostics (CDx). The collaboration will develop Promega’s MSI technology as an on-label, solid tumor CDx for use with Merck’s anti-PD-1 therapy, KEYTRUDA. The presence of MSI represents phenotypic evidence that DNA mismatch repair (MMR) is not functioning normally. Cells with abnormally functioning MMR are unable to correct errors that occur during DNA replication and consequently accumulate errors.

Mission Bio displayed its Tapestri Platform, which the company calls the first and only single-cell multi-omics platform that is capable of simultaneously providing both genotype and phenotype data from the same cell, across thousands of cells. The system can directly assess the clonal architecture of a sample and uncover the true distribution of genotypes and their segregation patterns across subclones. These subclonal mutations can escape current treatments, and NGS alone can miss what is happening in rare cell within a population.

The Illumina saga took a new twist when the company submitted its response to the UK Competition and Market Authority’s if Illumina were to acquire Pacbio. In its first response to the CMA, Illumina proposed granting Oxford Nanopore Technologies a perpetual, royalty-free license to certain PacBio patents for use in nanopore sequencing, or alternatively granting this license to any third party. But Oxford Nanopore responded, “The Parties’ proposal is egregiously misleading. It includes offering patents that have been revoked, while also excluding substantially relevant patents and applications from PacBio’s intellectual property (IP) portfolio and pipeline. In addition, the offer does not include any of the relevant Illumina patents and/or patent applications.”

In a second proposed remedy document submitted eight days after the first, Illumina removed specific references to Oxford Nanopore stating “A perpetual, royalty-free, irrevocable, license of PacBio’s and Illumina’s patents to any interested third-party undertaking for use in the field of single-molecule, native long-read sequencing systems and associated sequencing chemistries would be a fully effective, reasonable and proportionate undertaking to remedy the SLC provisionally identified by the CMA.” Oxford Nanopore wasn’t impressed, “As an IP package, the offer has serious limitations and appears to be confined to a very restricted field of use: ‘single-molecule, native long-read sequencing and associated sequencing chemistries.’ As of this writing, the CMA has moved its timeline for its revised statutory decision to February 5, 2020 from the previous date of December 31.

 

Since 2002, the Life Science Industry Awards have recognized the innovative manufacturers of the “tools of science” that help advance biological research and drug discovery. Traditionally, the Life Science Industry Awards have been a biennial event where thousands of life scientists nominate and vote for the best performing supplier in 10 distinct customer support, service and communications categories. Beginning in 2019, the Life Science Industry Awards have expanded to include three new categories to recognize the most innovative new products released this year. The editors of Instrument Business Outlook and the scientists who comprise BioInformatics’ market insights team will select winners.

This year, the LSIAs were awarded in three categories: cell biology, genomics and protein analysis. Speaking about the Awards, BioInformatics Inc. CEO Craig Overpeck enthused, “The amazing life transformations from a therapy often overshadows the fact that these discoveries resulted from the labors of small groups of dedicated scientists who themselves are supported by the relatively small number of companies that produce the ‘tools of science.’”

2019 LSIA Award Winners for Most Innovative New Product

 

Cell Biology
Gold Fluidigm Maxpar Direct Immune Profiling System The System enables researchers to easily quantify 37 different immune cell populations from human peripheral blood mononuclear cells (PBMCs) and whole blood using a simple single-tube workflow and CyTOF technology on the Helios system.
Silver Tecan Spark Cyto plate reader with real-time image cytometry The first live-cell plate reader to offer real-time detection and analysis of biological, chemical and physical events.
Bronze Agilent Technologies xCELLigence RTCA eSight The System provides label-free, real-time biosensor measurements and kinetic imaging of the same live cell populations, independently or simultaneously.
Genomics
Gold Pacific Biosciences Sequel II System The System includes the new SMRT Cell 8M, as well as chemistry, instrument control software and the SMRT Link software package that reduce project costs and timelines with approximately eight times the data output compared to the previous Sequel System.
Silver Agilent Technologies Magnis NGS Prep System The fully automated System includes reagents and protocols that make it easy to assay multiple genes and complex genetic aberrations from genomic DNA, including degraded samples such as FFPE.
Bronze Thermo Fisher Scientific QuantStudio 6 and 7 Pro Real-Time PCR Systems The Systems include facial authentication, voice commands, RFID-enabled plate scanning, and quick access to service and support to improve the user-instrument interaction.
Protein Analysis
Gold Thermo Fisher Scientific Orbitrap Exploris 480 Mass Spectrometer A benchtop MS that unlocks the power of an advanced differential ion mobility interface option and internal standard–triggered methods to deliver high levels of performance in high-throughput lab environments.
Silver Gyros Protein Technologies PurePep Chorus The scalable instrument and software platform enables production of even the most challenging sequences at the highest possible crude purity and yield. PurePep Chorus has a modular design, enabling in-lab upgrades aligned with the growing needs of peptide researchers.
Bronze Bruker TimsTOF FleX The MS, which includes a software-switchable MALDI source adapted to the ESI TimsTOF Pro platform. This new combined ESI/MALDI capability enables spatially resolved omics, which the company calls SpatialOMx, on a single instrument.

 

Towards the end of November, private equity firms Astorg and Cinven, leading a consortium of buyers, agreed to purchase LGC from KKR for an undisclosed amount. LGC is a provider of genomics reagents, standards for supply chain assurance, proficiency testing schemes, among other products, to end-markets that include the health care, agri-food and environment sectors.

So here we are in December. Inscripta announced an early holiday present in the form of $125 million in a Series D round. Inscripta will use the funding to commercialize and develop new applications for its Onyx Digital Genome Engineering platform. Twist Bioscience reported that revenues for its fiscal fourth quarter 2019 rose 87 percent year over year. Dolomite Bio and S2 Genomics just announced they were joining forces to automate library preparation of tissue samples for single-cell RNA sequencing.

 

Like I said, it’s been a busy year! 2019 marked our 25th year in business delivering market insights and Voice of Customer to our clients in the life science and analytical instrument market. On behalf of everyone here at BioInformatics, we wish you a happy and peaceful holiday season and we look forward to working with you in 2020.

 

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