Author丨Wei Xiao
Edit丨Sun Chaoyi
Picture Source丨TuChong
2012, the 6-year-old girl Emily Whitehead was in a life-and-death juncture when all kinds of therapies failed and no medicine was available. CAR-T treatment made the malignant leukemia cells in her body disappear. This special case made cell therapy the "focus" in the medical field and also promoted more companies to develop cell drugs. Dr. Zhang Jishuai, founder of
, pointed out that cellular drugs are a new generation of drugs, and their revolutionary significance lies in the ability to continue the lives of patients.
BCMA is a new target for CAR-T drugs and an ideal target for myeloma immunotherapy. It is worth noting that the market space of CAR-T products targeting BCMA is about US$20 billion, and there are currently many competitors in this field, and Prikin is one of them.
According to Qichacha information, Prikin has currently completed its B round of financing.
reduces CAR-T production costs by half
On October 18, Keji Pharmaceutical-B (2171.HK) announced that the China National Drug Administration (NMPA) has accepted the application for the launch of its new drug for the Zewaukee Olensey Injection, a CAR-T cell candidate product, which is intended to be used to treat relapsed/refractory multiple myeloma. If approved for marketing, Zewaukee Olensey Injection will become the third domestic CAR-T cell therapeutic drug and the first CAR-T product to target BCMA targets.
In February this year, the U.S. Food and Drug Administration (FDA) approved the CAR-T therapy Ciltacabtagene autoleucel ( Sida Keollense ) targeting BCMA, which was launched on the market for the treatment of recurrent/refractory multiple myeloma; since then, it was approved for the market in Europe and Japan in May and September this year.
However, Sida Keolunsey is not the world's first BCMA CAR-T therapy approved for marketing. Abecma, jointly developed by BMS and Bluebird Bio, was approved by the FDA in March 2021 for patients with multiple myeloma who have received 4-line treatment or more treatments.
It is reported that BCMA is a new target for CAR-T drugs. At present, most of my country's products are concentrated in CD19 targets, including Fosun Kate's Yikaida and WuXin Juan-B's Benoda.
BCMA is an ideal target for myeloma immunotherapy, is associated with myeloma cell proliferation, and is highly expressed on all multiple myeloma cells, but not in other normal tissues (except plasma cells ).
multiple myeloma (MM) mainly occurs in the elderly population over 65 years old. In recent years, the incidence of MM in China has continued to rise.
It is worth noting that the market space of CAR-T products targeting BCMA is about US$20 billion, with great potential. Abecma's first-year sales have reached US$164 million, with sales of US$156 million in the first half of this year, with increasing by 550% year-on-year; Cyda Keollensai's net sales in the third quarter were approximately US$55 million. This is an increase of 129.17% from 24 million in the second quarter. The market competition of
is also fierce, and there are many BCMA-targeted CAR-T therapies under development in China. In June this year, Reindeer Bio and Innovent Biologics jointly announced that the Ikylonsai injection jointly developed by both parties has the application for marketing authorization (NDA) for the treatment of relapsed/refractory multiple myeloma (R/R MM) (NDA) has been officially accepted by the China National Medical Products Administration (NMPA).
In addition, Genxi Biotechnology also announced at the European Hematology Association's annual meeting in June this year. Its dual-target autologous CAR-T candidate product GC012F is based on updated data from a multi-center clinical study on the treatment of relapsed/refractory multiple myeloma (RRMM).
It is worth noting that Prekin focuses on this field. Its BCMA CAR-T cell drug PRG1801, used to treat relapsed and refractory multiple myeloma, is the fastest-progressing cellular drug for chimeric humanized nano-antibody. It was approved by the China Drug Review Center in March 2020 and has now entered phase II clinical practice.
PRG1801 has significant efficacy and good safety. According to follow-up data of 34 patients receiving PRG1801, the ORR (objective response rate) was as high as 88%, and the OS (overall survival) at 18 months was 76.5%.The 15 subjects treated in the registered clinical trials had an ORR of up to 100%. More importantly, although CAR-T had relatively high neurotoxicity and AE mortality, no obvious safety problems were found in PRG1801 during follow-up.
Dr. Zhang Jishuai once explained that PRG1801 uses single-humanized VHH as its binding region. Single-humanized VHH has strong specificity and affinity for BCMA, which can reduce the risk of mismatch and has better killing effect than other types of extracellular binding regions. In addition, PRG1801CAR structure has higher safety and lower incidence of severe CRS and neurotoxicity.
In the future, with the increasing number of competitors, why can Prikin stand out? Zhang Jishuai said that his product advantages include: first, safety, effectiveness, and controllable quality; second, cost controllable, which can be reduced to 50% of other companies. "Because the complete set of CMC processes, including production processes, impurity research, quality research, etc., is developed by the company itself. Other companies are outsourcing through CDMOs, so the total cost can be greatly reduced and stable supply can be ensured."
has good safety and effectiveness and high quality standards, many well-known pharmaceutical companies at home and abroad are seeking to cooperate with Prikin to develop PRG1801. Among them, Nanjing Xiansheng Pharmaceutical obtained the development rights of the product in Greater China for hundreds of millions of yuan; Dr. Ruidi Laboratory Co., Ltd., the top three multinational pharmaceutical companies in India, obtained the development rights of the product in the Indian market for hundreds of millions of dollars; European and American markets have also reached product authorization cooperation with world-renowned pharmaceutical companies of about 1 billion euros .
mobilizes all forces to promote the "fast" listing
Shenzhen Puruijin Biopharmaceutical Co., Ltd. was established in 2012 and is deeply engaged in the field of cell drugs; the product pipeline includes CAR-T, TCR-T, CAR-NK, stem cell drugs, etc., and the indications cover hematologic tumors, solid tumors, , orthopedics and other fields.
Zhang Jishuai introduced that since he started his business in 2015, the company's positioning has always focused on cell drugs. Cell drugs are a brand new form of drug. Unlike traditional small-molecular or large-molecular drugs, the application scenarios are mainly two aspects, namely diseases that have clinical needs but no solutions, and diseases that have clinical solutions but not have good solutions.
"Take our PRG1801 as an example, traditional drugs have relapsed and are difficult to treat, but using cellular drugs can achieve good results. The greatest value lies in the ability to continue the patient's life."
In terms of technology platformization, Prikin has a small and pilot amplification system for new biological drugs such as the gene editing platform, a large-scale virus and cell preparation platform, and a nano-antibody screening platform.
Among them, the Protein-protein engineering platform can screen out high-affinity nano-antibodies for the research and development of CAR-T and other cellular drugs in enterprises. It is worth noting that the targeting domain of CAR-T cells is currently mainly based on single-chain antibodies, so nano-antibody may be more advantageous as targeting domains.
is one of the few companies at home and abroad that use nano-antibody to develop CAR-T cell drugs. Prekin's BCMA CAR-T cell drugs based on the characteristics of nano-antibody have the advantages of high affinity and non-polymerization. 19 patents have been applied for.
is different from traditional drugs. CAR-T is a personalized autologous cell product. T cells need to be collected from the patient's body, then transported to the factory for in vitro genetic engineering modification, and then returned to the patient, so that the T cells can recognize specific tumor antigens and activate autoimmune killing tumor cells. It is a single batch of individual production, with high costs, and patients need to wait for medication.
According to reports, the current price of CAR-T products on the market in China is one million yuan, and the manufacturing cost accounts for about two-thirds. Among the manufacturing costs, 30 to 40% are the cost of the raw material " lentivirus ".
In this regard, Prikin developed a vectoRs-vector development and production platform, and used a suspended serum-free cell culture system to produce lentiviruses on a large scale, which can greatly reduce costs.
generally believes that the production of "universal" cell therapy products is the future direction, and the cost is reduced while improving clinical accessibility. In response to this, Prekin plans to develop general-purpose cellular drugs, which are expected to be approved for clinical approval next year.In addition, as a "spot type" product, this cellular immunotherapy can be standardized and mass-produced, which can effectively reduce costs and is highly clinically popular.
In terms of developing TCR-T drugs that are more difficult to develop, Prekin uses computational chemistry to design the TCR sequence, which greatly shortens the screening and discovery time of TCR drugs, from a few years to less than one year. At present, its clinical trial of TCR-T cell drugs for solid tumors has been accepted.
In addition, Prekin also introduced the stem cell drug ALLOB, which is already in phase II clinical trials in Europe, for the treatment of non-union and delayed fracture healing. In terms of the international layout of
, Zhang Jishuai introduced that since 2015, Prikin has captured the future trend of cell therapy that must be developed according to drug standards from US regulatory requirements, and has carried out a series of quality management work in accordance with international standards, including product development, preclinical research, clinical research, and pharmaceutical process development.
This will also help enterprises gain recognition from international cooperative enterprises and promote internationalization. According to reports, Prekin currently has a series of pipelines in solid tumors, hematomas and other fields according to international standards, and has filed applications in China, the United States and India. In terms of commercialization strategy, Zhang Jishuai introduced that the business model of Prikin's choice of a development with partners can greatly reduce the pressure on R&D investment and mobilize the world's strength to help products go on the market as soon as possible.
Take PRG1801 as an example. China needs at least 1.5 million yuan for a patient's clinical trial cost, India needs nearly 200,000 US dollars, and the United States needs more than 1 million US dollars. Now we are conducting clinical trials simultaneously in China, India, Europe and the United States. It takes millions of US dollars to do one patient each, and more than 100 patients are required during the first and second phases of the clinical trials, and hundreds of millions or even more than one billion US dollars are required to promote clinical trials of this product worldwide.
Zhang Jishuai introduced that is of great significance to accelerate the launch of good products. On the one hand, it can benefit patients as soon as possible, and on the other hand, companies can obtain profits as soon as possible. In addition, after a large amount of cash flow, we can better invest in research and development, including breaking through hematoma, improving versatility, automation, etc., to obtain more cooperation opportunities with better technical products and form a virtuous cycle.
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This issue editor Li Yutong Intern Wu Ziying
