Oncology NGS industry opens a second curve, MRD recurrence monitoring leads the industry to drastic changes

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Tumor recurrence is essentially due to residual microscopic lesions (MRD) that still exist at the location of the lesion after the patient has received standard treatment
.

MRD is not a new concept that has just emerged in the past two years, but because the methodology of ctDNA detection of MRD in the past is not mature, clinical research data is not perfect, and the industry has not formed a relatively uniform standard, it has not become a hot topic for industry development
.

As an application scenario juxtaposed with early screening and companion diagnosis, the status of recurrence monitoring in the oncology NGS industry has not received enough attention
.

From a formal point of view, the application of recurrence monitoring is similar to that of early screening.

The market space of recurrence monitoring is closer to that of companion diagnosis
.

For recurrence monitoring, the market size corresponds to the survival of tumor patients after surgery
.

The United States can accumulate such a high stock market, and a very important point is the high survival rate brought about by its huge medical investment
.

According to the latest statistics for 2020 released by the International Agency for Research on Cancer (IARC) of the World Health Organization, there will be 4.

There is no doubt about the clinical significance of recurrence monitoring.

Products have been approved worldwide, and the coverage has expanded from hematomas to solid tumors

In terms of insights into new directions, foreign countries always seem to be one step ahead of domestic ones
.
Both the European Union and the US FDA have approved the listing of some MRD recurrence monitoring products, including products from domestic companies
.
 

The progress of foreign companies related to MRD

Industrial progress abroad has focused on two companies, Adaptive Biotechnologies and Guardant Health
.

The core of Adaptive Biotechnologies is an immunotherapy research company whose business lines include drug discovery, life science research based on TCR antigens, and clinical diagnosis based on MRD detection
.

Adaptive's ClonoSEQ is the only liquid biopsy product approved by the FDA for MRD testing.
It was first approved in 2018 and then expanded in 2020
.
Since early screening cannot be carried out by imaging methods, MRD detection is extremely important for hematomas
.
Therefore, clinical guidelines related to hematoma, especially in acute lymphoblastic leukemia (ALL) and multiple myeloma (MM), all mention that MRD status is a reliable indicator of clinical outcome and response to treatment
.
Therefore, the market value of ClonoSEQ is prominent
.

So far, the coverage of ClonoSEQ has been limited to hematological tumors and has not expanded to solid tumors
.
But after all, the base of hematoma patients is small, and there is a huge gap with solid tumors.
From a long-term perspective, solid tumors still have more market space
.

For breakthroughs in solid tumors, we have to mention Guardant Health, which received a small-scale approval in New York as soon as the product was launched recently
.

In February 2021, Guardant Health launched its own MRD detection product Guardant Reveal, and soon obtained the New York State Department of Health's Clinical Laboratory Evaluation Program (CLEP, Clinical Laboratory Evaluation Program) two months later, through the analysis of patients MRD (Residual Minimal Lesions) to monitor the long-term recurrence of patients after colon cancer surgery
.

Compared to Grail, which was acquired by Illumina for US$8 billion, or Foundation Medicine, which was acquired by Roche for US$2.
4 billion in 2018
.
Guardant Health may be less well-known in the country
.
But in fact, this star company has been reliant on its stock price to maintain a high level since its listing in 2018.
The current market value has exceeded 10 billion U.
S.
dollars.
It is one of the most valuable oncology NGS companies in the world
.

Guardant Reveal is a liquid biopsy test based on NGS
.
When Guardant Health was first launched in 2018, Guardant Reveal (the project was code-named LUNAR-1 at the time) had already demonstrated its clinical value
.
In a collaboration with MD Anderson Cancer Center, Guardant Health evaluated specimens from colorectal cancer patients who had undergone radical surgery and had five years of follow-up data
.
Guardant Reveal found indications of residual tumor in 48% of patients, and according to the patient's clinical records, these patients, without exception, had tumor recurrence within 18 months after surgery
.

Subsequently, Guardant Health conducted a prospective clinical study
.
The 84 patients included in the major milestone analysis all had blood samples collected approximately one month after completing the final treatment
.
During the follow-up period of more than 1 year, all patients who had signs of recurrence in the initial test had tumor recurrence
.
If only the analysis conclusions given by the samples collected one month after the operation are considered, the sensitivity and specificity of Guardant Reveal can reach 55.
6% and 100% respectively, which means that there is no misdiagnosis, but more frequent missed detections have occurred
.
However, if periodic monitoring is introduced, the sensitivity can be significantly improved by 36%, eventually exceeding 90%
.

Based on this series of excellent clinical results, Guardant Health launched its own products and won the favor of some regulatory authorities
.

The progress of MRD cooperation abroad

Based on products that have entered the approval process, foreign companies that provide MRD testing have always maintained close cooperative relations with pharmaceutical companies
.
Adaptive Biotechnologies, which won the first approved product, has been working with companies such as Amgen and Genentech to promote cooperation on hematoma very early.
Other companies that have entered this field, such as ArcherDX, Natera, Genetron Health, etc.
, have also adopted The way pharmaceutical companies cooperate, share their own product research and development investment, and obtain a richer clinical research data set
.

In January 2021, GRAIL, the primary market of the early screening track, also announced that it will enter the MRD early screening track through the cooperation of pharmaceutical companies
.
This early to carry out a giant screen prospective cohort and hear the name of the world of business, finally broke their comfort zone, began to enter new areas, and is the first release Amgen, AstraZeneca, BMS three while working
.
The entry of the early screening giants further demonstrates the gold content of the MRD detection track.
I don't know if Grail will continue to call on the new track
.

Looking at the overall trend of foreign countries, MRD recurrence monitoring seems to be about to break through its own bottleneck for many years
.
The products of leading companies have begun to impact the application for listing, and the cooperation with pharmaceutical companies has become closer
.
And this state of rain and rain has attracted more companies to concentrate on this field, and the entire industry has shown a very obvious upward trend
.

All domestic large and small enterprises have entered the market, and new developments are emerging one after another

At this time, we will look back to the country
.
The domestic genetic testing industry is one of the few biological industries that can keep pace with the world
.
In the specific scenario of MRD detection, domestic companies don't let it go
.

Progress of domestic guidelines and consensus on MRD

While the industry is developing, domestic guidelines and clinical consensus have begun to follow up quickly
.
In the field of scientific research, the clinical consensus on solid tumors has been the first breakthrough in the field of lung cancer
.
At the regulatory level, CDE has already begun to formulate guidelines for the related applications of hematoma
.

Domestic industrial development is basically consistent with that of foreign countries on the timeline, and many companies have begun to deploy from a very early stage
.
However, from the second half of 2020, concentrated information disclosure began to emerge, and new products, new collaborations, and new scientific research progress emerged one after another
.

Recent domestic related disclosures about MRD

The domestic MRD testing is getting hot, and it will start from October 2020
.
Two domestic oncology NGS listed companies have successively released new news about MRD
.
Genetron Biotech has reached an exclusive license agreement with a Hangzhou start-up company, Aimu Anh , has obtained the global exclusive license for the company's hematological minimal residual disease (Seq-MRD) product, and will accelerate product development and commercialization; Burning Rock Medicine At the first International Liquid Biopsy Conference, he published his own multi-omics MRD test results, which provided important reference for the further precision of lung cancer diagnosis and treatment
.

Immediately in November 2020, Zhenhe Technology also announced its own MRD testing products on the market
.
In May 2021, on the occasion of the publication of the first quarterly report of 2021, Genetron Health, through the mouth of its CEO Wang Sizhen, announced the official release of the hematoma detection product Seq-MRD, which was previously cooperated in the form of LDT, and said in the field of solid tumors, " Thanks to the Mutation Capsule technology, the MRD detection project for liver cancer and colorectal cancer solid tumors has obtained excellent preliminary results, and plans to shift to larger multi-center research
.
" Almost at the same time, the world, and gene and Zhongshan University , Fudan University, prospective studies of colorectal cancer MRD research institutions together to complete the country's first multi-center, in the "Journal of Hematology & Oncolology" was published
.

Four tumor NGS leading companies have successively announced their entry into MRD testing, and this scenario may hardly not become a hot spot in the industry
.

Then in the beginning of 2021, Tongshu Gene, Huidu Medical, etc.
have successively released their own MRD detection products; Genesis Medicine's hematological tumor MRD detection products have obtained the European Union's CE access qualification and broke into overseas markets
.

Large companies competing layout, small businesses quickly follow, MRD detection at the circle in the fire up
.
As one of the leading companies in the domestic oncology NGS industry, Shihe Gene has also made relevant arrangements in the MRD field, and used a solid clinical research result to interpret the clinical value of MRD detection and show its progress in the MRD field
.

Combining companion diagnosis and recurrence monitoring to form a solution for the entire treatment cycle

The fire of early screening and the explosion of MRD detection actually point to the same conclusion-the maturity of companion diagnostic technology is driving the expansion of the genetic testing industry
.

The companion diagnostic technology has basically developed and matured.
According to different needs, patients can flexibly choose among single-cancer small panels, pan-cancer large panels, and full exome sequencing
.
Market education in most areas of the country has been relatively complete.
Doctors have a clear understanding of the clinical value of companion diagnosis, and patients can also understand the importance of companion diagnosis to their treatment process
.
At present, domestic oncology NGS companies have basically completed market exploration, and it will become more and more difficult to continue to rely on companion diagnostic services to maintain a high revenue growth rate
.

Therefore, oncology NGS companies began to promote their own second-curve growth at this stage
.
Many companies have foreseen this in advance, and have already made arrangements in advance before the companion diagnostics market is saturated
.
Taking companion diagnosis as the starting point, corporate business moves forward and backward along the path of tumor diagnosis and treatment
.
Moving forward is the early screening of tumors, so that more healthy people can be free from tumors; moving backward is the recurrence monitoring, so that more postoperative tumor patients can be free from recurrence
.
This is why early screening and MRD monitoring will become industry hotspots in the near future
.

So what will be the end of the oncology NGS industry? At present, the services provided by enterprises are still dotted.
Early screening is early screening, companion diagnosis is companion diagnosis, and recurrence monitoring is recurrence monitoring
.
In the future, with the maturity of early screening and recurrence monitoring technologies, oncology NGS will inevitably move toward a one-stop service that is more adapted to consumers’ habits, from early screening of tumors to the formulation of adjuvant diagnostic treatment plans, and then to post-treatment treatment.
Recurrence monitoring provides people with tumor solutions for the entire life cycle
.

But judging from the current situation, it seems too early to include early screening in this system
.
The current application scenarios of early screening are still concentrated in several major cancer types, especially colorectal cancer.
Market education is also still going on, and there is still a long way to go before it is fully rolled out
.
Recurrence monitoring is a rigid demand application scenario, and patients are more willing to pay.
Enterprises can also provide services through the LDT model, instead of emphasizing the importance of obtaining certificates like early screening
.

So it may be too early to talk about the "full life cycle" solution, but perhaps we may be able to see it soon
.
The formation of this new model may become the core driving force for the next phase of growth in the oncology NGS industry, so that more cancer patients will not regenerate under the shadow of tumor recurrence
.