The year 2019 comes to an end with significant advancements in precision medicine, genetics, genomics, CRISPR technology, liquid biopsy, and immunotherapy. Highlights and notable news included various technological advancements, genetics and genomics moving more and more into the clinic, the launch and recent successes of population studies, artificial intelligence and machine learning investments and AI potential, advancements and learnings in the area of CRISPR technology and the microbiome, immunotherapy further establishing itself as the leading weapon to attack cancer, and major acquisitions that change the landscape of pharma and biotech. The results speak a clear language: improved patient care via better diagnostic and more precise therapeutics.
Here below a few highlights – not an all-inclusive summary – of what made 2019 so exciting. Find a more complete list of 2019 news on the enlightenbio Industry News site.
The therapeutics sector – pharma / drug discovery
Some of the biggest news in this sector in 2019 followed the FDA approval of Novartis’ new gene therapy drug Zolgensma – a treatment for spinal muscular atrophy for children under 2 years of age – and its high drug price of $2.1M per patient/treatment regimen; the recent FDA approval of Vertex Pharmaceutical’s Trikafta, a gene-based therapy for children with cystic fibrosis; Biogen resurrecting the Alzheimer’s drug Aducanumab and submitting it for drug approval to the FDA, creating new hope for Alzheimer’s patients; while Roche scoring its first U.S. approval of immunotherapy for breast cancer with Tecentriq (atezolizumab) for advanced triple-negative breast cancer. All of these examples nicely demonstrate the ever increasing importance of understanding the molecular mechanisms that define a disease and with that enhancing and translating this knowledge into therapeutic approaches that enhance the success rate of targeted, individualized medicine. Also of note in this sector in 2019 is GSK’s formed partnership with CRISPR pioneer Doudna to establish drug discovery operations in new laboratories in search for new drugs in San Francisco and spending up to $67 million over five years.
Numerous acquisitions across the entire sector of health care
Starting with the January 2019 JP Morgan conference – typically a window into what the new year will have to offer – major acquisition took place throughout the entire year and included Eli Lilly buying Loxo Oncology for $8bn, BMS buying Celgene for $74bn, Roche purchasing gene therapy company Spark Therapeutics for approximately $4.8bn (Spark Therapeutic is the maker of Luxturna, a one-time gene therapy for individuals with an inherited retinal disease), Johnson & Johnson buying surgical robotics company Auris Health, Novartis buying cholesterol drug maker Medicine Co. for $9.7bn, Pfizer acquiring Array Biopharma, Merck buying Peloton Therapeutics in a transaction valued at $1.05bn and drug developer ArQule for $2.7bn, QIAGEN acquiring N-of-One (which enables QIAGEN to expand its decision-support solutions), Exact Sciences buying Genomic Health in a $2.8bn deal (expecting to generate $1.6bn in revenue and grow profit of $1.2bn in 2020), Invitae acquiring Singular Bio to help increase access to genetic screening in early pregnancy, all the while Google is buying Fitbit to position itself against Apple and its AppleWatch.
Major population studies and sequencing/genomics initiatives and partnerships are taking shape
Various population studies/initiatives were either launched or took shape this year, as demonstrated with projects such as… :
- Color announcing its new DNA10K initiative in partnership with the NorthShore University HealthSystem,
- Color moving whole genome sequencing into clinical care through a 100,000-person initiative,
- Helix partnering with AdventHealth for screening FH-linked genes via the WholeMe study,
- Intermountain Healthcare together with deCODE genetics launching the largest DNA mapping effort,
- Jefferson Health combining genomics, population health to enhance employee wellness with Color as its partner,
- Mayo Clinic collaborating with Regeneron to generate whole exome sequencing and genotyping data of 100,000 DNA samples and partnering with Google on digital health analytics as part of a 10-year partnership,
- Sanofi and GSK joining FinnGen, a project collecting genomic and health data from 500,000 participants in Finland,
- Verily Life Sciences launching the Baseline Health System Consortium with Duke University, Mayo Clinic, Vanderbilt University, University of Mississippi Medical Center, Regional Health in South Dakota, and University of Pittsburg,
- Verily partnering with two health systems – Atrius Health and Palo Alto Veterans Affairs – to experiment with ways to improve patient outcomes,
- NIH ‘All of Us’ precision medicine program sharing its first-year progress report,
- Five million volunteers (NHS patients) having their DNA analyzed in new genomics projects under a new Genomics England program,
- Nebula Genomics, Merck KGaA’s EMD Serono partnering on lung cancer pilot,
- Renown Health, Helix, and Genome Medical partnering to bring genetic counseling and educational services to patients for end-to-end genetic testing support,
- UK launching National Genomic Healthcare strategy
- Leading health and research organizations launching the Medical Genome Initiative – includes Baylor Genetics, Hudson Alpha Institute for Biotechnology, SickKids Foundation, Stanford University, Mayo Clinic, Broad Institute, Rady Children’s Hospital, and Illumina.
These various initiatives and partnerships are likely to accelerate advancements in precision medicine via the move of genomics into the clinical setting, thus increasing the diversity of data, and engaging participants to take ownership of their data.
To overcome the diversity issue challenging the healthcare sector and particular genome-based studies, the NIH funds new centers to expand and diversify the human reference genome. This $29.5M grant will enable to generate and maintain a completely new and comprehensive reference sequence of the human genome that represents human genetic diversity.
Genomic medicine with next-generation sequencing and genetic testing reached new milestones
The first month of 2019 already was rich in content and activities as it started out with a series of announcements emerging from the JP Morgan Healthcare Conference: Invitae exceeding the company’s own prior guidance in testing volume and was boasting double testing volume year over year, and Illumina’s deSouza highlighting that ~12M consumer tests were processed in 2018 alone, or more than the cumulative volume in the previous 3 years expecting consumer testing volumes would continue with this trajectory. While these announcements were highly significant for the genomic/genetic testing sector, Illumina later in the year lowered its full-year expectations, citing near term uncertainties in the direct-to-consumer (DTC) genetic testing market due to privacy concerns and the limited long-term value of genetic tests to consumers. In other news, 23andMe announced it is moving beyond consumer DNA tests and building a clinical trial recruitment business directly competing with Apple which also offers as a service the aggregation of this kind of health information.
Large investments in technologies and companies shaping the industry….
Investments were bountiful, especially in the sector of AI and machine learning (Tempus, Freenome, Sophia Genetics, Healx, Insilico, and PathAI), data platforms (DNAnexus), and in the therapeutic sector (BioNTech, Achilles Therapeutics, ArsenalBio, and Verve Therapeutics). Again, the list shown below is not comprehensive, but simply highlights a few select major investment rounds that took place in 2019:
- The German cancer-treatment research company BioNTech AG raised $325M from investors, one of the largest financing rounds ever by a European biotechnology company
- Tempus raised $200M in Series F financing, bringing total raised amount to $510M
- Freenome closes $160 Million Series B financing to advance its multiomics blood testing platform for early cancer detection
- New York Genome Center receives a $125M gift
- UK’s Achilles Therapeutics raised €110M (£100M) in Series B to test its personalized cancer cell immunotherapies in humans for the first time
- Health Catalyst Secures up to $100M in Series F and Dept financing
- ArsenalBio, a precision immunotherapy company backed by billionaire Sean Parker, launched with $85M from a Series A funding
- Sophia Genetics raises $77M in Series E
- Merck, BMS chip in to PathAI’s series B, bringing total to $75M
- DNAnexus Closes $68M Series F Round, bringing the biomedical informatics platform’s total funding to approximately $173M
- Verve Therapeutics launched with a $58.5M Series A financing round, focuses on gene therapies for cardiovascular disease
- Healx, the AI-powered technology company specializing in treatments for rare diseases, secured $56M in Series B financing
- Liquid biopsy company Inivata completed a $52.6M Series B funding round
- Bolt Biotherapeutics raised $54M
- Insilico raised $37M in Series B with plans to bring its AI to more drug discovery partnerships
- This the while Walgreens has started to invest $300M in digital health, and 10x Genomics filed for a $100M IPO among other companies.
The other side of 2019 included shutdowns and bankruptcies:
As is often the case in times of fast-paced development, there are also challenges and setbacks that need to be mentioned. Unfortunately, 2019 was no exception and delivered its share of not so good news in the area of precision medicine, including two major shutdowns: the wellness company Arivale and Veritas Genetics. uBiome had to declare bankruptcy amid an FBI investigation due to its billing practices, while a failing fundraising round of $1.5bn valuated Proteus Digital Health may now challenge its future. Arivale stated that they may have “simply been too early”, while Veritas’ challenges were based on a much needed fundraising round that was hampered by a previous Chinese investment [Note: Veritas only ceases operations in the US and continues to be served by Veritas Europe and Latin America services]. Interestingly, the Veritas Genetics shutdown follows a recent data breach announcement of which no further details are available. PatientsLikeMe, another company that faced fundraising challenges, was forced by U.S. to ditch Chinese investors, and was sold to UnitedHealth Group. Furthermore, an interesting potential data privacy precedent may have taken place in Florida which could open up all consumer DNA sites to law enforcement agencies across the country.
Additional noteworthy news to include in this section:
- The revisit of the anniversary of the “CRISPR-Cas9” twins by He Jiankui that are now a symbol of the broken basic medical mantra of “do no harm”. He Jiankui has since been fired from his research position, and just been sentenced to three years in prison.
- Illumina loses DNA sequencing patents in Europe, which of course is of interest to companies such as Qiagen, as well as MGI and the BGI Group, all of which are in the midst of patent infringement claims.
- While Illumina was making monthly cash payments to PacBio under extended merger agreement, the merger faced an obstacle when Britain’s Competition and Markets Authority expressed concerns that it may reduce competition and increase prices, and the UK government’s Competition and Markets Authority (CMA) said that it has launched an investigation into Illumina’s planned acquisition of Pacific Biosciences. Early in 2020 it was announced that the $1.2bn merger plans have been scraped.
Some of the recurring technological themes of 2019 included artificial intelligence/machine learning, and scientific innovations such as the CRISPR technology, liquid biopsy, single cell genomics, and spatial transcriptomics.
- AI/machine learning
- The Hôpitaux Universitaires Genève in Switzerland will be the first European university hospital to implement IBM’s Watson/AI to help doctors select treatments for complex cancer cases.
- Stanford University launch the Institute for Human-Centered Artificial Intelligencecommitted to studying, guiding and developing human-centered AI technologies & applications.
- Deep learning enables rapid identification of potent DDR1 kinase inhibitors
- DeepMind, Alphabet’s artificial intelligence lab, showed the power of AI when it beat a roomful of biologists in a contest to predict the shape of a protein based on its genetic code
- CRISPR technology
- The First lawful human trial for CRISPR in treating inherited blindness is now underway – First CRISPR study inside the body to start in U.S.
- Scientists create new, more powerful technique to edit genes to overcome some of the limitations of CRISPR which allows easier and more precise DNA editing.
- Liquid biopsy
- TGen reported encouraging results on using a liquid biopsy test, called Targeted Digital Sequencing (or TARDIS) which was shown to be up to 100 times more sensitive than other similar liquid-biopsy tests in picking up DNA shed by breast cancer cells into the blood.
- GRAIL announced significant progress with multi-cancer early detection test:
Early data from Grail showed its liquid biopsy test was not only able to detect the presence of 12 different kinds of early-stage cancer but could also identify the disease’s location within the body before it spreads using signatures found in the bloodstream.
- MIT and Broad Institute scientists isolated and preserved samples of nearly 8,000 human microbiome strains, while also clarifying their genetic and metabolic context, this library of human gut bacterial isolates paired with longitudinal multiomics data now enables mechanistic microbiome research.
Scientific research advancements
On the independent and academic research side, several scientific advancements took place that are noteworthy and listed below:
- Concerns of widespread misinterpretation of gene expression data due to frequent technical bias in data generated by current RNA-seq technology was raised.
- The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues, and to link these regulatory mechanisms to trait and disease associations.
- The largest pan-cancer study of metastatic solid tumor genomes was performed, including whole-genome sequencing data for 2,520 pairs of tumor and normal tissue, was analyzed at median depths of 106× and 38×, respectively, surveying more than 70 million somatic variants.
- The Landscape of Genetic Content in the Gut and Oral Human Microbiome was published
- The key gene behind hallmark of Lou Gehrig’s disease was identified
- Scientists from the German Cancer Consortium, German Cancer Research Center, and the University of Freiburg have created a comprehensive database of all synonymous mutations ever found in cancer.
The SynMIC database contains a total of 659,194 entries concerning 88 different types of cancer.
- Clinical use of current polygenic risk scores may exacerbate health disparities
- A single-cell atlas of the tumor and immune ecosystem of human breast cancer
- Spatial transcriptomics is considered one of the next big applications which combines RNA expression with single cell genomics
To sum it all up – 2019 was an eventful and exciting year creating a solid foundation for what is to come in 2020.
We should expect larger technological advancements, with AI/machine learning taking the lead and big data applications such as in drug discovery and clinical decision-making benefitting from these; Population initiatives are expected to be increasing its diversity to help explain genomic differences across populations; Whole genome sequencing will continue on its path of slowly but steadily increasing its footprint in the clinical space, ultimately improving our diagnostic capabilities. Furthermore, it is very conceivable that we’ll witness the potential of liquid biopsies to translate into cheap and accurate simple diagnostic tests. We’ll likely see an emerging elucidation of the role of the microbiome in multiple sclerosis, inflammatory bowel disease and even cancer. All these developments will help drive translation of genetic discoveries and expedite clinical applications. The 2020 JP Morgan healthcare conference, scheduled for this coming week, will surely again live up to its reputation of providing a first glimpse of what the new year has in store of us