Next Generation Sequencing: Not Just Medical

JPMorgan's medical industry summit is the absolute protagonist of traditional medicine companies, and biotechnology companies are looking to see what can help. This year, investment bigwigs have turned to data analysis, digital health, how to better serve patients and other companies related to next-generation gene sequencing (NGS) technology.

From the perspective of Google venture capitalists attending industry conferences, we can see industry changes. In the past three decades, the medical industry summits of JPMorgan (JPMorgan Chase, the “godfather” of the US modern financial industry) have been the traditional protagonists of traditional pharmaceutical companies. Biotech companies are What can you do to help in the past?

The game rules for this meeting on January 16, 2014 are somewhat different. Active on the stage, the audience has reached a cooperation intention are some medical insurance companies, software developers, data analysts, and various IT companies.

“I’ve been there five times, and all of them were traditional pharmaceutical companies. They talked about how to treat a certain disease. But with the promulgation of the Affordable Care Act, there were some business models that were completely absent from a few years ago. Everyone talks about data analysis, digital health care, how to better serve patients, and we asked an IT company to ask me, 'Do you think I should go to JPMorgan?', and I will tell him five years ago Necessary, but now I told him, "You really should go."

One of the directions of medical reform is to connect the hospital's reimbursement quota with the patient's treatment effect more closely than to the number of patients. This prompted related parties such as hospitals to purchase software and big data products for tracking. "These products have been there all along. There was a lack of incentives before. Now either do it or not."

The JPMorgan conference came with new faces and all the best medical insurance service providers in the industry. Changes will not happen overnight, but everyone understands that major changes are brewing, so maybe just want to be closer to these changes.

GoogleVentures's related companies include Gene Analysis Company Foundation Medicine (who used to serve Jobs and was greatly appreciated), Big Data Corporation DNANexus, and 23genMe, a consumer gene sequence company (its founder is also one of Google's founders, Brin). wife).

The Next Generation Sequencing Industry Changes No.1: The Times Weekly cover figures once again formed the "Human Longevity Company".

In 2000, together with the representative of the Human Genome Project at the time, he was selected as the cover character of the era magazine. CraigVenter, the founder of the era, once again founded Human Longevity Inc. in March 2014.

Venter challenged the world-class genetic research center including the Broad Institute, which MIT and Harvard jointly supported. The company raised $70 million in the first round (expected to spend 18 months without any problem), and investors included 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 (genetic testing) market demand.

"With Illumina's most advanced technology (Venter buying 20 HiSeqXTen), our goal is to become the world's largest human gene sequencing center." The most advanced technology here refers to HiSeqXTen, the most powerful sequencer announced by Illumina earlier this year. A set of 10 units, with a total price of 10 million US dollars, is suitable for group-scale sequencing projects and was interpreted as the first time that the US$1,000 genome sequencing became a reality.

NO.2: Illumina's order status and market feedback fever exceeds expectations. According to Seekingalpha's Illumina January 28th performance exchange this year, some analysts asked about the launch of new products without competitor competitors. How to consider. Illumina's CEO said: Now that not only technical reserves are in place, but market demand is in place. The so-called demand means that companies have always determined that wholehuman gene sequencing is the future direction. Now that large-scale demand has erupted, it was previously blocked by high prices. .

Illumina’s CEO also revealed that the company’s product order status and market feedback have exceeded expectations. The CEO also pointed out that the problems that restrict the comprehensive development of gene sequencing technology over the years are 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 subject to price factors. This platform may now allow everyone to complete projects that were not done or wanted to be done 10-15 years ago.

NO.3 "Longevity Company" master gathered with Venter is definitely an expert in various fields, genomics, stem cell, cancer, translational medicine, microbiology, and big-name experts in various emerging technologies. Because of the ambitious plan Venter gave itself, these areas are related to the company's future mission. In addition to gene sequencing, they will also record the microbiome and metabolome data of the participants. The goal is to link each person’s genetic variants, self-contained bacterial components, molecules in the blood, and their medical history. together.

Venter believes that not only early signs of chronic diseases can be discovered through data analysis, but interventions can be provided to everyone in time, and the cost of medication can also be reduced. Although the technology that HumanLongevity has come up with to attract attention now looks a bit overblown, these massive and diverse data are meaningful in themselves. At least we can expect some bright spots in clinical practice. Venter said, "This will be one of the largest research data in science and medicine." Well, you can't argue this statement, and Venter has always been the same.

One of his characteristics is that he is very close to commercial organizations. “We are a commercial organization and we spend a lot of money on our business. Therefore, the data generated must have commercial value.” The business model in Venter's mind is Raw data was charged to the outside world, but it also caused concern outside the world about how they obtained written consent from anonymous participants and patients.

At present, the company cooperates with the Moores Cancer Center. If all patients in the center do not expressly withdraw, they agree to have HumanLongevity sequence the genome for themselves, as well as 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, the company has become destined to become the center of genetic research, and Venter decided to establish a case file for each sequencer, even if it does not consider the combination of microbial and metabolic data There should also be the business value he mentioned, that is, I don't know (we can only hope) that the clinical value is not so late.

The negative report on "Next-Generation Sequencing" is seen as a temporary report of any subversion, and between "out of control", there are always some "document risks".

Just on the eve of the Christmas shopping season last year, FDA sent a letter prohibiting 23andMe from selling $99 of genetic testing products to consumers. Currently 500,000 consumers have chosen this product. With a cotton swab, you can learn more about your ancestors and 248 genetic characteristics (such as a particular health risk, a certain drug reaction) and Health information.

However, from Wired Magazine, January 2014 Comments: The 23andMe gene test was stopped and the battle with the FDA was lost, not the entire genetic testing war.

In the FDA's allegation, 23andMe was classified as a medical device (which means the most rigorous regulation). Since it is considered to be used as a diagnosis, it must be approved by the FDA after providing comprehensive research data as support. Can be recommended to consumers. The letter points 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 medicine for themselves. The FDA has determined that the cost of the abuse of genetic information is greater than the potential benefits to consumers.

Some reports show that when a patient consults his doctor with genetic data, the doctor either does not understand it or does not want to, or simply resists it because the doctor is part of an existing interest group and will face a doctor-patient relationship. With their subversive changes, they must struggle. Various existing interest groups ran to the regulators to complain (previously, Uber, Lyft, Sidecar, Airbnb), but this time it was 23andMe.

The company has softened the FDA and promised to no longer provide information other than genetic data. Perhaps in the future, the company will reach a certain settlement with the FDA. If it is difficult to extinguish the FDA anger, the value of this new company and the technology may end. The market is not only 23andMe, but has emerged a number of monitoring, testing, sensing equipment, allowing consumers to wait for their own health, sleep, food intake and other lifestyle is correct. Perhaps regulators in the future will be pressured by consumers (great demand) and industry players (new opportunities bring reshuffle).

The value of massive amounts of genetic data lies not only in improving health, reducing costs, but also in bringing medical research on the right track. This may be the biggest change in health care after the discovery of antibiotics in the early 20th century. The possibility of testing less than $100 in the future is not just a matter of millions of genetic data, but all. Regardless of 23andMe's ultimate fate, the loser will be the one who thinks he can win the future by blocking the trend.

With Illumina, the representative of Next-Generation Genome Sequencing (NGS), which has drastically lowered the price threshold and dramatically increased the sequencing speed, scientists now study genes that really stand on the basis of the open hypothesis, not just the same as in the past. Focus on the "hot" place of the genome to find some of the key mutations. The popular metaphor is that you find the key in the dark, and the probability of success with a floodlight is greater than with a flashlight.

We believe that the first beneficiaries of NGS are pharmaceutical companies, especially drug companies for cancer drugs. Previously, we used lesions to define cancers, such as lung cancer, breast cancer, prostate cancer, etc. More and more studies have shown that we should start with the gene pathways and mutations that cause lesions. The lesioned body parts are only “byproducts”. . Many first-line treatments are not only ineffective, but can even cause side effects. With the development of NGS, the efficiency of R&D projects for pharmaceutical companies will be greatly enhanced in the future, and patients' drug costs will also be reduced.

What is the bottleneck? Two. Bioinformatics and regulation. First of all, let everyone have a concept of the speed of development of the industry, as of the end of 2013, a total of 50K genome sequencing, and through Illumina's latest HiSeqXTen equipment, only one group (10 units) to complete the 18K genome. The main parties involved will be Broad Labs (Harvard and MIT co-host), drug companies (Regeneron, Amgen already represented), and new commercial laboratories (Human Longevity, just established by CraigVenter).

The massive amount of genetic data brought by new technologies is the first thing to face is the lack of a unified industry standard, how to define the format, quality, which will constitute obstacles for the subsequent large-scale commercial application. So we have seen 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 a Global Alliance (Global Alliance for Genomics and Health) to help shape industry standards in the field of genetics. In the absence of standards at the moment, in order to obtain genetic data and speed up the development of new therapeutic methods (mainly in the field of oncology), drug companies are also trying every trick. Some have joined forces with laboratory and clinical diagnostic companies (Foundation Medicine, FMI), others have introduced external resources through mergers and acquisitions, and established internal company laboratories (such as Amgen and deCODE Genetics).

The second major bottleneck in clinical application of NGS is regulatory uncertainty (hysteresis). After Illumina's MiSeqDx has received FDA approval for clinical use, the institution that uses this device for clinical diagnostic testing still needs to choose whether to obtain an FDA approval or to take “shortcuts”—a lab-developed-test. , LDT), abandon CLIA-waived approval, and is not regulated by the FDA.

The latter has become a desirable solution for reproductive health and tumor gene sequencing. But the problem has also emerged, although it is not obvious but there is a deepening trend, that is, LDT brings competitive pressure to companion diagnostics (CDx). The concomitant diagnosis is to cooperate with drug companies and improve the efficiency of drug development. The market for CDx is currently focused on individual gene mutations. With the development of NGS, mutations that span different gene pathways will become the next potential market for CDx.

Although the CDx has been officially recognized, the FDA has not given a clear regulatory line, so the advantage of competition with the apparently looser regulation of LDT is not obvious. On the one hand, the enthusiasm for diagnosing the company's investment will decrease with the important strength of the diagnosis. On the other hand, insurance The company is unwilling to support the face of uncertainty, so that the diagnosis of the company's investment is likely to be unable to recover.

In addition, as mentioned earlier, the future new drugs will be based on gene pathways, and the existing FDA approvals are still mainly based on the mutation sites, so future studies may find that the corresponding drugs may not have FDA approval. This has already been reflected in the FMI (Foundation Medicine). Treatment of patients is critical, and doctors may be forced to prescribe drugs without FDA labeling, and patients will increasingly face such awkward choices.