This month, two major events occurred in the domestic innovative drug industry, one is the failure of the Cinda Biological PD-1 antibody Xindilizumab to the United States, which is the first time that the domestic PD-1 directly faces the ODAC (FDA Oncology Drug Expert Committee), which is considered by the market to be the vane of "Chinese drug internationalization"; the second is that the CAR-T product Xida Chiorense jointly developed by Nanjing LegendAry Biologics and Johnson & Johnson was approved in the United States, which is the first domestic CAR-T product approved by the FDA. It is known as a milestone for domestic innovative drugs to go to sea.
In less than 30 days, these two experiences of "ice and fire" have undoubtedly taught a profound lesson to domestic innovative pharmaceutical companies - domestic innovative drugs go global, the core orientation is to be able to solve the "unmet clinical needs", innovation is more important than price reduction.
In fact, this truth has long been understood by insiders, but the reality is more bone-chilling, and it is really difficult to innovate. In the past two years, many medical investors have been saying, "Resolutely do not invest in me-too, look for first-in-class companies." Recently, some investors have bluntly said, "In the domestic innovative drug market, me better is already very good, and the real first-in-class innovative drugs are too difficult to find." ”
It is in such an industry situation that Shanghai Stansai Biotechnology Co., Ltd. (hereinafter referred to as "Stansai"), which is expected to become the world's first domestic innovative pharmaceutical company to provide FIRST-in-class car-T products for the treatment of solid tumors, has entered the capital eye. It is reported that Sternsay is the world's first and currently the only company to use CAR-T technology to treat colorectal cancer with major clinical breakthroughs.
In August 2021, GCC19CAR-T, a solid tumor cell therapy product developed by Stancey based on the Coupled CAR technology platform, has successfully taken the first step in internationalization through the APPLICATION OF THE US FDA IND.
The target is unique and the platform technology is highly scalable
As a new precision targeted therapy for the treatment of tumors, in recent years, CAR-T research has become more and more popular in China, which has aroused the pursuit of many innovative pharmaceutical companies and investors. However, compared with the brilliance of CAR-T in the field of blood tumor treatment, CAR-T therapy has not made much substantial progress in the application of solid tumors.
It should be known that solid tumors account for about 90% of cancer incidence and blood tumors account for only 10%, which means that CAR-T therapy has a huge unmet clinical need in the field of solid tumors.
Stancer grasped the key to innovation, established a CollaborativeCAR technology platform specifically for solid tumors, and screened out a series of very specific targets, taking the lead in achieving a clinical breakthrough for colorectal cancer GCC targets.
According to reports, the clinical data of 35 patients with advanced colorectal cancer accumulated by Stancer in China, the orR of the medium dose group of the dose climbing test reached 50%, while the ORR of the current two three-line colorectal cancer drugs regofenib was only 1%, and the ORR of the other trifluorouridine/tilidazim was only 1.6%. Compared with the two, the ORR of the Stancey GCC19CART product has been significantly improved.
Through rapid IIT clinical trials and product validation, GCC19CART has been approved by the FDA and is currently advancing clinical Phase I trials.
It should be noted that unlike other popular targets, the colorectal cancer GCC target is the exclusive clinical target of Stancy, and there is currently no competition in this field, and the unmet clinical demand is also very large.
Figure/ Stansay took the lead in achieving a clinical breakthrough for the GCC target of colorectal cancer
Relevant data show that the number of new colorectal cancer cases in mainland China is about 400,000 per year, and the number of deaths is about 190,000, which is the second most morbid and the fourth most mortality. In the United States, about 150,000 new patients with colorectal cancer are added each year, and 54,000 patients die from colorectal cancer, the second most mortality rate after lung cancer. In contrast, for colorectal cancer patients after second-line treatment, there are few treatment options available, and the efficacy is even more limited. In addition, colorectal cancer also has a feature - cold tumors, that is, general immunotherapy, such as PD-1 antibody drugs, is ineffective against the vast majority of colorectal cancer.
It can be said that in addition to the global innovative CoupledCAR's own platform technology, Stancer is currently the only company in the world with good clinical data performance on the GCC target, and the target drug is expected to become the world's first approved CAR-T product for the treatment of colorectal cancer, truly achieving first-in-class.
What is even more valuable is that in addition to colorectal cancer, Stancer's CoupedCAR technology platform also has strong scalability, which can replace different targets to target different indications, such as ovarian cancer, prostate cancer, thyroid cancer, etc.
It is revealed that Stancer is also laying out the product line of multiple tumors, including prostate cancer, ovarian cancer, thyroid cancer, etc., and is committed to finding and screening out targets with tumor specific expression and safety to treat a variety of solid tumors.
Behind the global leadership of innovative technology, "internal strength accumulation" is the key
Playing iron also needs to be hard. As mentioned earlier, although many domestic innovative pharmaceutical companies call themselves "innovation", in fact, many pharmaceutical companies are doing secondary innovation and engaging in me-too, resulting in serious homogenization of targets, and truly original innovative drugs are extremely scarce.
The reason why Sternsay can achieve first-in-class and fill the gap in clinical needs is inseparable from the company's consistent product orientation to meet "unmet clinical needs" on the one hand, and on the other hand, the team's strong research and development capabilities and absolute innovation strength.
As Dr. Lei Xiao, founder of Stansay, understands, "Innovation is not only a strategy, but first and foremost an ability." ”
Photo/ Dr. Xiao Lei, founder of Stansay, believes that innovation is first and foremost a kind of ability
For innovative pharmaceutical companies, to a large extent, product innovation lies in the innovation of targets and technology platforms, and these need to be based on science. This requires the R&D team of innovative pharmaceutical companies to continuously collect new target information and improve platform technology, and exert excellent innovation ability, after scientific evaluation and experimental verification, and finally find safe and effective new targets and products.
Stansay has a mature research, clinical and management team, and the core members are all doctors of biology or doctors of medicine. Xiao Lei graduated from the Department of Biology of Wuhan University, received his Ph.D. from the University of Munich, and then completed his postdoctoral work at the Hopkins University Cancer Center. In 2005, Xiao Lei returned to China and served as the research team leader of the Shanghai Institute of Biochemical Cell Research of the Chinese Academy of Sciences, and later served as a professor and vice dean of the Translational Medical College at Zhejiang University, and in 2010, he won the National Outstanding Youth Fund, and has more than 20 years of experience in cell biology, cell therapy and gene editing. Xiao Lei is the co-founder of Stansay Biotech and has served as the company's CEO full-time since the beginning of 2016. Wu Zhao, president and co-founder of Stancer, is a Ph.D. from the Institute of Biochemistry and Cell Sciences of the Chinese Academy of Sciences, with 15 years of experience in stem cell and cell therapy research and industry. The other members of the team come from China and the United States and have extensive experience in CAR-T technology research, manufacturing, clinical trials and FDA regulatory approvals.
Among them, Dr. Xiaobin Lu, Senior Vice President of Stancer, is a former FDA senior review expert with more than 18 years of experience in product development and regulatory matters in the field of cell and gene therapy, and 10 years of EXPERIENCE in FDA cell and gene therapy review. In 2017, as the chairman of the conference, Lu Xiaobin organized the ODAC conference of novartis Kymriah, the world's first CAR-T drug, Kymriah, the world's first CAR-T cell product approved for marketing by the FDA. Dr. Lu Xiaobin joined Stensay in 2018 because of the latter's true global innovation.
In addition, the team includes Dr. Eugene Kennedy, Chief Medical Officer, Dr. Chris Ballas, Senior Vice President in charge of the production process, and Dr. Tian Le, who is in charge of intellectual property affairs. Eugene is primarily responsible for U.S. clinical trials, is an associate professor and director of pancreatic cholangiosurgery at Thomas Jefferson University, a surgeon oncology at Johns Hopkins University Hospital, a physician at Virginia School of Medicine, and has over 15 years of experience in Phase 1-3 clinical trials of oncology and tumor immune drugs, and has served as the former chief medical officer of publicly traded companies Lumos Pharma and NewLink Genetics Chris has 25 years of experience in cell and gene therapy, having served as former vice president of manufacturing at Rocket Pharmaceuticals and former senior director of the Advanced Therapies Division at Wuxi AppTec in Philadelphia; Dr. Tian Le holds a dual Ph.D. in biology and jurisprudence, as well as over 10 years of intellectual property experience in life sciences.
It is worth mentioning that at the beginning of its establishment, Stansay's main direction was actually to explore the development of induced pluripotent stem cell (iPS cell) technology, which is much more complex than CAR-T technology. In 2012, Stancey began to turn to CAR-T research and development, and this technical "dimensionality reduction strike" style of play began to show obvious advantages.
In just 3 years, that is, since 2015, cd19 CAR-T developed by Stancey for the treatment of advanced acute lymphoblastic leukemia has been conducted in 39 clinical trials in the hematology departments of more than 10 tertiary hospitals across the country, with a complete remission rate of 84.6% and an MRD negative rate of 80%. In 2019, STATCAR014, an innovative product for NHL, with a cd19 target and expression of Dominant Negative PD-1, also received FDA clinical trial approval from the US FDA.
It is also with the technical precipitation in iPS and hematology car-T in the past that Stancer is in the field of solid tumor CAR-T treatment in the world, and it is a surprise. It should be emphasized that Stancer's CAR-T cell therapy is a single-drug single-dose infusion without a combination of drugs.
CDH VGC continues to be blessed, and the "reference sample" of domestic innovative drugs going to sea
As a global leader in the domestic innovative drug track, Stance has also been favored by capital along the way. Since obtaining angel investment in 2009, Stansai has received a total of 4 rounds of financing, of which CDH has invested two rounds in a row, which is one of the earliest investors in Stansai and a long-term and firm runner.
In fact, the CDH VGC team, which has been deeply involved in medical investment for many years, has been committed to finding and paying attention to the "inflection point" of scientific research to industrial transformation, and adhering to the technology-oriented investment oriented to clinical value. The continuous blessing of Stancer requires forward-looking power for CDH VGC, but also has corresponding patience and courage. After all, St-in-class is made of first-in-class, and the products are not benchmarked at home and abroad.
It is reported that before making the decision, Cdhwast VGC senior partner Gao Jieliang and the team from the product mechanism, pre-clinical research, clinical trial data, production, registration to marketing and sales and other aspects of the product to do a comprehensive and in-depth investigation of Stancer's products, especially the in-depth study of the core product clinical trial data, and achieved very detailed due diligence results. Ultimately, these due diligence results point to the fact that "Stancer's CAR-T products are the most effective compared to the various existing therapies."
To a larger extent, to some extent, whether it is Stansai's breakthrough in CAR-T treatment of solid tumors or the product development model, it is undoubtedly a demonstration case for domestic innovative pharmaceutical companies.
As many people may know, in the past, due to the lack of improvement, the market often doubted the reliability of CAR-T cell treatment of solid tumors. The clinical results of the Stancy for the GCC target of colorectal cancer have verified the effectiveness of CAR-T in the treatment of solid tumors from scientific research to clinical practice, which can be said to break the spell of CAR-T in the treatment of solid tumors.
At the same time, the overseas mode of Stensey products also provides a breakthrough path for domestic innovative pharmaceutical companies, that is, "global innovation + Chinese research and development + international verification". Stancer is an efficient R&D in China, then using the international mature approval path to take the lead in clinical trials in the United States, and finally first commercialized and marketed in the United States.
"We have maintained close contact with the FDA since pre-IND, and for us, it is more important to ensure effective communication and keep the information constantly updated, and the trial design should follow the latest SOC and FDA regulations, follow strict standards, in the target market, under the supervision and guidance of the FDA." Dr. Lu Xiaobin said that for innovative drugs to "go to sea" smoothly, early communication is very important, and the FDA can give very valuable suggestions from their perspective for points that applicants may not have noticed.
Of course, all of this has a premise – to be truly globally innovative. The key to achieving this premise is nothing more than two points, one is to enhance the ability to innovate, and the other is to meet the "unmet clinical needs" as the orientation.
"Drug research and development is centered on patient needs and should be guided by clinical value. At present, China's innovative drugs still have to break through multiple difficulties, but if enterprises have breakthrough innovative drugs that meet the above two points, they naturally have the foundation to stand up and have the confidence and ability to knock on the door of the broader overseas market. Stansay said. (Text/Ma Mujie, Source/Cast China Network)