Next-generation sequencing: not just the medical industry

Release date: 2014-04-09


JPMorgan's medical industry summit is the absolute protagonist of traditional medicine, and biotech companies have come to see what can help. This year, investment giants have turned to data analysis, digital healthcare, how to better serve patients and other companies related to next-generation gene sequencing (NGS) technology.
Looking at the industry changes from the experience of Google venture capitalists attending industry conferences Over the past 30 years, JPMorgan (JPMorgan Chase, the "godfather of the modern financial industry") in the medical industry summit is the absolute protagonist of traditional medicine, and biotechnology companies are Have a look at what can help.
The game rules for this conference on January 16, 2014 are somewhat different. Active on the stage, the company's cooperation intentions are medical insurance companies, software developers, data analysts, and various IT companies.
“I have been here five times. All of them used to be traditional medicine companies. They talked about how to treat certain diseases. But with the promulgation of the new medical reform bill (AffordableCareAct), there have been some business models that were completely absent a few years ago. Now Everyone is talking about data analysis, digital medicine, how to better serve patients. We asked an IT company to ask me, 'Do you think I should go to JPMorgan'? I will tell him five years ago. Necessary, but now I told him, 'You really should go'." One of the directions of the medical reform is to link the hospital reimbursement amount to the patient's treatment effect, not the number of patients. This prompted hospitals and other parties to purchase software and big data products for tracking. "These products have always been there, but there was no incentive before. Now do it or not."
The JPMorgan conference brought some new faces to all of the best health insurance providers in the industry. Change won't happen overnight, but everyone understands that major changes are brewing, so maybe just want to get closer to these changes.
Companies involved in GoogleVentures include the genetic analysis company FoundationMedicine (which served and was greatly appreciated by Jobs), the big data company DNANexus, and the consumer gene sequence company 23andMe (the founder of both is also the founder of Google, Brin wife).
Counting the changes in the new generation of sequencing industry NO.1: The cover of Time Magazine re-established "Human Longevity Company"
In 2000, he was once again selected with the representative of the Human Genome Project at the same time. CraigVenter, the ancestor of the magazine of the era magazine, re-launched HumanLongevity Inc in March 2014.
Venter's challenge this time is the world-class genetic research center, including the Broad Institute, which MIT and Harvard support. The company raised $70 million in the first round (expected to spend 18 months without problems), including Illumina, the world's largest provider of genetic testing equipment. This logic is not difficult to understand, Illumina needs a lot of research to promote (gene test) market demand.
"With Illumina's most advanced technology (Venter buys 20 HiSeqXTen), our goal is to become the world's largest human genetic sequencing center." The most advanced technology here refers to the most powerful sequencer HiSeqXTen announced by Illumina earlier this year. A set of 10 units, with a total price of $10 million, is suitable for a large-scale sequencing project and is interpreted as the first time that the $1,000 genome has been sequenced.
NO.2: Illumina's order status and market feedback heat exceeded expectations According to Seekingalpha's Illumina performance briefing on January 28 this year, some analysts asked that in the absence of competing competitors, new products were launched. How to consider.
According to Illumina's CEO: Not only is the technology reserve in place, but market demand is in place. The so-called demand means that the company has always judged that the wholehuman gene sequencing is the future direction. Now large-scale demand has broken out, and it was previously blocked by excessive prices. .
The CEO of Illumina also revealed that the company's product orders and market feedback are more than expected. The CEO also pointed out that the problem of restricting the comprehensive development of gene sequencing technology for many years is that the utilization rate of clinical samples is too low (10-15%), and it is difficult to achieve large-scale sequencing under the technical conditions of 2500 due to price factors. Now this platform may allow you to complete projects that you didn't do or want to do 10-15 years ago.
NO.3 "Human Longevity Company" masters gathered Venter is convened by experts in various fields, genomics, stem cell science, cancer, translational medicine, microbiology, and various emerging technology experts. Because of the ambitious plans that Venter has set for itself, these areas are related to the company's future mission. In addition to gene sequencing, they will also record microbiome and metabolome data from the test participants, with the goal of linking each person's genetic variants, their own bacterial composition, the molecules in the blood, and their history of visits. together.
Venter believes that data analysis can not only identify early signs of chronic diseases, provide interventional treatment for everyone in a timely manner, but also reduce the cost of medication. While HumanLongevity's technology that is now eye-catching looks a bit ridiculous, these massive and diverse data are meaningful in themselves, and at least we can expect some bright spots in the clinical arena. Venter said, "This will be one of the largest research data in science and medicine." Well, you can hardly argue with this statement, and Venter has always been.
He also has a feature that is very close to commercial organizations. "We are a commercial organization, and our business has to spend a lot of money, so the data generated must have commercial value." Venter's business model is based on The original data is charged externally, but it also raises concerns about how they get written consent from anonymous participants and patients.
Currently, the company is collaborating with the Moores Cancer Center. If patients in all centers do not explicitly withdraw, they agree to let HumanLongevity sequence the genome for itself and various tumor data. All data will be saved and used to find new therapeutic targets, pathways and biomarkers.
There are now two sets of Illumina's newest and most powerful HiSeqXTen sequencers, and the company has become destined to become the center of genetic research, and Venter decided to establish a case file for each recipient, even without considering the combination of microbial and metabolic data. There should also be business value that he mentioned, that is, I don’t know (we can only hope) that the clinical value is not so late.
Regarding the negative reports on "next generation sequencing" as related reports that are temporarily frustrated, any subversion, it is inevitable to encounter several "document risks" between "out of control".
Just before the Christmas shopping season last year, the FDA sent a letter prohibiting 23andMe from selling $99 in genetic testing products to consumers. There are already 500,000 consumers who have chosen this product. With just a cotton swab, you can learn more about your ancestors and 248 genetic characteristics (such as a particular health risk, a drug reaction) and Health information.
However, from the Wired (Connected) magazine January 2014 comment: 23andMe genetic test was called to stop, the battle is with the FDA, and will not be the entire genetic testing war.
In the FDA's allegations, 23andMe is classified as a diagnostic device (meaning the most stringent regulation), and it is believed that since it is to be used for diagnosis, it must be approved by the FDA with comprehensive research data as a support. Can be recommended for use by consumers. The letter pointed out that the most worrying thing is that consumers' various incorrect responses to these genetic information are either insufficient or excessive. Some consumers even force doctors to do unnecessary surgery or prescribe drugs for themselves. The FDA believes that the cost of misuse of genetic information will outweigh the benefits that may be brought to consumers.
Some reports show that when a patient takes genetic data to consult with his doctor, the doctor either does not know, or does not want to, or simply resists, because the doctor is part of the existing interest group, and the doctor-patient relationship will occur. Subversive changes, they must struggle. Various existing interest groups ran to the regulators to complain (previously did not happen, Uber, Lyft, Sidecar, Airbnb), but this time is 23andMe.
The company has softened to the FDA to ensure that information other than hereditary data is no longer available. Perhaps the company will reach a certain settlement with the FDA in the future. If it is difficult to ruin the FDA anger, the value of this emerging company and this technology will end. More than 23andMe is on the market, but a number of monitoring, testing, and sensing devices have emerged, allowing consumers to know if their health, sleep, food intake and other lifestyles are correct.
Perhaps, regulators in the future will be under pressure from consumers (huge demand) and industry insiders (new opportunities bring reshuffles).
The value of massive genetic data is not only to improve health, reduce costs, but also to put medical research on the right track, which may be the biggest change in medical health after the discovery of antibiotics in the early twentieth century. The possibility of testing less than $100 in the future is not just millions of genetic data, but all. Regardless of the final fate of 23andMe, the loser will be the one who believes he can win the future by blocking the trend.
With Illumina, the representative of the next-generation DNAsequencing (NGS), significantly lowering the price threshold and increasing the sequencing speed, scientists are now studying the genes on the basis of the open hypothesis rather than the past. Focus on the "hot" areas of the genome to find certain key mutations. The popular analogy is that you find the key in the dark, and the floodlight is always more likely to succeed than the flashlight.
We believe that the first beneficiaries of NGS are pharmaceutical companies, especially pharmaceutical companies. In the past, we used cancer sites to define cancer, such as lung cancer, breast cancer, prostate cancer, etc. More and more studies have shown that the genetic path and mutations that lead to lesions should be started, and the body parts of the lesions are only "by-products". . Many first-line treatments are not only ineffective, they can even cause side effects. With the development of NGS, the efficiency of R&D projects of pharmaceutical companies will be greatly improved in the future, and the drug fees paid by patients will also be reduced.
What about the bottleneck? Two. Bioinformatics and regulation. First of all, let's have a concept of the speed of the industry. By the end of 2013, a total of 50K genomes were sequenced. With Illumina's latest HiSeqXTen equipment, only one group (10 units) can complete the 18K genome in one year. The main participants will be the large laboratory Broad Institute (co-hosted by Harvard and MIT), the pharmaceutical company (represented by Regeneron, Amgen), and the new commercial laboratory (CraigVenter just founded HumanLongevity).
The massive amount of genetic data brought about by new technologies is faced with the lack of unified industry standards, how to define formats and quality, which will hinder the subsequent large-scale commercial application. So we see that the NGS value chain has quickly turned to software tools for large-scale interpretation of bioinformatics. The good news is that Illumina, Google, Merck & Co, and the New York Gene Center have established Global Alliance for Genomics and Health to help shape industry standards in the field of genetics. In the current lack of standards, in order to obtain genetic data, accelerate the development of new treatment methods (mainly in the field of cancer), pharmaceutical companies are also thinking about each. Some have teamed up with laboratory and clinical diagnostic companies (Foundation Medicine, FMI), and some have introduced external resources through mergers and acquisitions to establish internal laboratories (such as Amgen and deCODEGenetics).
The second major bottleneck in the clinical application of NGS is regulatory uncertainty (hysteresis). After Illumina's MiSeqDx received the FDA's clinical approval, the organization that uses this device for clinical diagnostic testing still needs to choose whether to obtain the FDA approval or to take the "shortcut" - count as a laboratory development test (lab-developed-test) , LDT), abandoning the approval of CLIA (CLIA-
Waived), also not regulated by the FDA.
The latter has become a desirable solution in the field of reproductive health and tumor gene sequencing. But the problem has also emerged, although it is not obvious but has a deepening trend, that is, LDT's competitive pressure on companion diagnostics (CD). Concomitant diagnosis is to cooperate with pharmaceutical companies to improve the efficiency of drug development. At present, the CDx market is mainly aimed at individual gene mutations. With the development of NGS, mutations across different gene pathways will become the next potential market for CDx.
Although CDx has been officially recognized, the FDA has not given a clear regulatory line, so the competitive advantage of LDT with significantly looser supervision is not obvious. On the one hand, the enthusiasm for diagnosing the company's investment with the important force of diagnosis will be reduced, on the other hand, insurance The company is not willing to support the uncertainty, so the diagnosis of the company's investment is likely to be unrecoverable.
In addition, as mentioned earlier, the new drug will be based on the genetic pathway in the future, and the existing FDA approval is still mainly based on the mutation site, so future research may find that the corresponding drug may not be FDA-approved, which has been reflected in FMI (Foundation Medicine). The patient's treatment is critical, doctors may be forced to prescribe drugs without FDA, and patients will increasingly face this embarrassing choice.

Source: Orient Securities

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