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Strong and strong!Dongyao Pharmaceutical and Hao Yuan Pharmaceutical reached a strategic cooperation
9On October 19, Dongyao Pharmaceutical Co., Ltd. reached a strategic cooperation with Shanghai Haoyuan Pharmaceutical Co., LTD。Combined with each other's advantages, the two sides will work closely to deepen the building of a one-stop CDMO quality service platform covering the whole process of ADC drugs from research and development to industrialization。
根据客户需求，Dongyao Pharmaceutical will provide monoclonal antibody production and ADC drug CMC process development, bulk solution and preparation production, filling services，And to provide GMP standards for pre-clinical research, clinical research and commercial-scale production services;Haoyuan Pharmaceutical can provide non-GMP to GMP Linker, Payload and Payload Linker and other intermediates research and development, process optimization, process verification, registration, GMP industrialization, etc。Based on the above advantages, the two parties will jointly provide customers with early process development of ADC products, intermediate scale-up and GMP production services through stronger technical synergy。双方也将组织联合服务团队，Support customers in commissioning ADC drug development and production，From early stage to late stage, small molecule intermediates are rapidly integrated into the coupling process development and production，获得更全面完善的体验，优化在以往中间体物料提供方面，额外切换供应所带来的成本与风险，实现开发提速、降本增效，共同打造可持续发展合作模式，Better enable customers to ADC new drug development and industrialization process。
（信息来源：药智新闻）
Takeda has partnered for more than $500 million to develop antisense oligonucleotide therapies
AcuraStemThe company announced that it has reached an agreement with Takeda for a total amount of 5.The $800 million licensing agreement will co-develop and commercialize the company's PikFYve-targeted therapies, including AS-202, an innovative antisense oligonucleotide (ASO) therapy for the treatment of amyotrophic lateral sclerosis (ALS)。
PIKFYVEIs a new therapeutic target for ALS and may also be applied to treat TDP-43 protein diseases such as frontotemporal dementia (FTD).。AcuraStem is focused on developing therapies that target PIKFYVE, primarily to address neurodegeneration by expelling toxic protein aggregates and protecting healthy neuron function。AcuraStem identified the clinical candidate therapy AS-202 through screening on its patient-based iNeuroRx technology platform。AS-202 is an intrathecal injection of ASO therapy that strongly inhibits PIKFYVE in the central nervous system。
Under the terms of the agreement, Takeda will receive an exclusive worldwide license to AcuraStem's PIKFYVE project。If all future clinical, regulatory and commercial milestones are achieved over the term of the agreement, AcuraStem will be eligible for a total of up to approximately 5.8亿美元的前期和里程碑付款。AcuraStem will be responsible for assisting in advancing AS-202 into clinical trials, while Takeda will be responsible for all other development activities, including clinical development, regulatory matters and global commercialization。
AcuraStemIt was co-founded in 2016 by Mr Sam Alworth, Dr Justin Ichida, Dr Paul August and Dr Qing Liu，Committed to the continuous improvement of its patient-based iNeuroRx technology platform，发现多种神经退行性疾病的有效疗法，并将其治疗项目快速推进至患者，These include its existing SYF2 and UNC13A programs for the treatment of ALS and FTD。
（信息来源：药明康德）
Roche and PeptiDream are once again working together to develop peptide-radio-coupling drugs
9PeptiDream today announced a new multi-target collaboration and licensing agreement with Roche's Genentech to discover and develop novel macrocyclic peptide-radioisotope (Peptide-RI) conjugated drugs。
Under the agreement, PeptiDream will use its proprietary Peptide Discovery Platform System (PDPS) technology to discover, optimize and develop macrocyclic peptide candidates for the development of peptide-RI coupled drugs against targets of interest to Genentech。PeptiDream will lead early preclinical development and then transition the peptide-RI coupling product resulting from the collaboration to Genentech for further development and commercialization。PeptiDream will retain the right to develop and commercialize such peptide-RI coupling products in Japan。
Under the terms of the agreement, PeptiDream will receive $40 million (5.9 billion yen, $1 =147) from Genentech.7 yen) in advance and eligible for potential payments of up to $1 billion (147.7 billion yen) based on the achievement of certain development, regulatory and commercial milestones。In addition, PeptiDream is eligible to receive tiered royalties on the net sales of any such products (excluding Japan) resulting from the collaboration。
The new collaboration and licensing agreement builds on the long-standing relationship between the two companies，The two parties signed a multi-target cooperation and licensing agreement in December 2015，Genentech then licensed PeptiDream's PDPS technology in 2016，并于2018年扩大了双方的合作。
（信息来源：医药魔方）
Roche and Orionis Biosciences enter into collaboration on molecular gel drug development
9Orionis Biosciences today announced a multi-year collaboration with Genentech, a unit of Roche, to jointly develop novel small molecule drugs against challenging targets in major disease areas, including oncology and neurodegenerative diseases。
Orionis的Allo-Glue™The platform utilizes a variety of unique approaches to discover drug classes for disease targets that are still difficult to capture with traditional drug discovery methods.drug-like）小分子。The platform integrates a proprietary suite of chemical biology technologies, including bioanalysis, computational analysis, chemical libraries, and automated processes for high-throughput discovery, rational design, and optimization of small molecules that promote or induce protein interactions in living cells。
These also include molecular gels, which either facilitate interactions that lead to degradation of the target (through almost any ligase) or regulate the function of the target through direct or allosteric regulatory mechanisms。Orionis' holistic approach to molecular gel discovery synergies both target-centric and ligase-driven models of drug discovery。
Under the terms of the agreement, Orionis will be responsible for discovering and optimizing molecular gels for Genentech's designated targets, while Genentech will be responsible for subsequent preclinical, clinical development, regulatory filings and commercialization of these small molecules。Orionis will receive an upfront payment of $47 million and be eligible for development milestone payments, as well as commercial and net sales milestone payments that could exceed $2 billion, as well as tiered royalties on sales of collaborative products。
（信息来源：医药魔方）
Genting Xinyao has entered into a collaboration and licensing agreement with Kezar to develop and commercialize Zetomipzomib in Greater China and other Asian markets
Genting Xinyao is a biopharmaceutical company focused on the development, manufacturing and commercialization of innovative drugs and vaccines，On September 21, it announced a collaboration and licensing agreement with Kezar Life Sciences，To develop and commercialize Kezar's first clinical-stage candidate, zetomipzomib, in Greater China, South Korea and selected Southeast Asian countries，This is the first selective immunoproteasome inhibitor of its kind，It is used to treat a range of autoimmune diseases including lupus nephritis (LN)。
Luo Wing-ching, CEO of Genting Xinyao, said, "We are delighted to enter into this partnership with Kezar，Co-develop and commercialize zetomipzomib，This will further enrich our existing product pipeline for renal diseases and autoimmune diseases，And help consolidate Genting Xinyao's leading position in the field of kidney disease and autoimmune diseases in Asia。Nephropathy and autoimmune diseases are key therapeutic areas of Genting Xinyao's strategic focus, and we look forward to working closely with our partners in clinical development and other areas to leverage Genting Xinyao's strengths in clinical development and registration to market to bring this important innovative therapy to the Asian region as soon as possible.。”
Dr. Zhengying Zhu, Chief Medical Officer of Genting Xinyao Internal Medicine, said, "Lupus nephritis is the most common secondary immune glomerular disease, which can gradually lead to renal failure as the disease progresses。It is estimated that there are 1 million patients with systemic lupus erythematosus (SLE) in China alone, and 40% to 60% of SLE patients have the disease involving the kidneys, known as lupus nephritis。Unlike traditional direct immunosuppressant effects, zetomipzomib regulates innate and acquired immune responses, thereby reducing organ damage caused by inflammation。This property gives it the potential to treat a variety of autoimmune diseases, including lupus nephritis and systemic lupus erythematosus。”
KezarJohn Fowler, co-founder and CEO, said: "Kezar's collaboration with Genting Xinyao is an important milestone in the development of zetomipzomib。Genting Xinyao stands out for its focus on the nephrology sector and its talented team with deep global pharmaceutical experience, making it the ideal partner for Kezar in Asia。Genting fully understands the broad potential of zetomipzomib and their team will work closely with us to advance the enrollment of PALIZADE in the global clinical trial for lupus nephritis。It is well known that the prevalence of many autoimmune diseases, including lupus nephritis and systemic lupus erythematosus, is higher in Asia, and we are excited to bring zetomipzomib to more patients with urgent clinical needs through this collaboration.。”
Under the terms of the agreement, Kezar is entitled to an upfront payment of $7 million and up to $1.$25.5 billion in clinical and commercial milestone payments and tiered royalties available from product net sales in the single to low ten digits。云顶新耀将有权进行本地化制造。
Genting Xinyao and Kezar will jointly advance the global Phase 2b PALIZADE clinical study to evaluate the efficacy and safety of zetomipzomib at two dose levels in patients with active lupus nephritis。The PALIZADE global study has been launched in mid-2023 with the goal of enrolling 279 patients。Preliminary clinical trial data showed that zetomipzomib demonstrated good safety and tolerability in the treatment of lupus nephritis, and patients with lupus nephritis showed clinically meaningful overall renal treatment results after 6 months of treatment with zetomipzomib。In addition to lupus nephritis, Genting Xinyao and Kezar also have the opportunity to collaborate on clinical trials and indications for other autoimmune diseases such as systemic lupus erythematosus to continue the development of zetomipzomib。
In Genting Xinyao's nephrology product pipeline, Fukang is the first therapy for the treatment of primary IgA nephropathy®The New Drug Marketing Application (NDA) has received priority review from the China National Medical Products Administration and is expected to be approved in the second half of this year。In addition, EVER001, a next-generation covalent reversible Bruton tyrosine kinase (BTK) inhibitor, is in clinical development for the treatment of glomerular disease。The company also has a preclinical self-development program, with one of the most advanced drug candidates in the renal field expected to submit to an IND next year。In the field of autoimmune diseases, Genting Xinyao has completed patient recruitment for the Asian multi-center Phase 3 clinical trial of etrasimod for the treatment of moderate to severe active ulcerative colitis, and will strive to submit NDA in the Asian interest area as soon as possible。
Zetomipzomib(KZR-616) is a novel, first-of-its-kind, selective immunoproteasome inhibitor with broad therapeutic potential in a variety of autoimmune diseases。Preclinical studies have shown that selective immunoproteasome suppression produces a broad anti-inflammatory response in animal models of multiple autoimmune diseases while avoiding immunosuppressive effects。Data from Phase 1 and 2 clinical trials strongly demonstrate that zetomipzomib has a good safety and tolerability profile for the treatment of severe, chronic autoimmune diseases。
PALIZADEThis is a global, placebo-controlled, randomized, double-blind Phase 2b clinical trial designed to evaluate the efficacy and safety of zetomipzomib at two dose levels in patients with active lupus nephritis。The target enrollment was 279 patients who were randomly assigned (1:1:1) to receive 30mg zetomipzomib, 60 mg zetomipzomib, or placebo subcutaneously once a week for 52 weeks in addition to standard care。Background therapy may include standard induction therapy (optional)。During the first 16 weeks, a gradual reduction of corticosteroids to 5 mg/ day or less will be mandatory。治疗结束评估将在第53周进行。The primary efficacy endpoint was the proportion of patients who achieved complete renal response (CRR) at week 37, which includes urinary protein creatinine ratio (UPCR) less than or equal to 0 in the absence of salvage or contraindosed drugs.5。
Genting Xinyao is a biopharmaceutical company focused on the development, manufacturing and commercialization of innovative drugs and vaccines to meet the unmet medical needs of the Asian market。Genting Xinyao's management team has deep expertise and extensive experience in high quality clinical development, pharmaceutical administration affairs, chemical manufacturing and control (CMC), business development and operations in leading pharmaceutical companies in China and globally。Genting Xinyao has built a number of drug combinations that have the potential to become the world's first or best in class, most of which are already in advanced stages of clinical trials。The company's therapeutic areas include renal diseases, infectious and infectious diseases, mRNA platforms, and autoimmune diseases。
Kezar Life SciencesIt is a clinical-stage biopharmaceutical company dedicated to the discovery and development of breakthrough treatments for immune-mediated and oncological diseases。The company is pioneering first-of-its-kind small-molecule therapies that harness the primary regulator of cell function to inhibit multiple disease drivers through a single, powerful target。Its lead drug candidate, zetomipzomib, is a selective immunoproteasome inhibitor that also has the potential to address multiple chronic immune-mediated diseases。
（信息来源：美通社）
Plop Pharmaceutical announced that PLOP Industrial Investment intends to increase the capital of Hopson Technology by 30 million yuan
9On October 26, PLo Pharmaceutical announced that Dongyang Plo Equity Investment Fund Partnership (Limited Partnership)(" PLO Property Investment ") is an industrial investment fund established by the company and Hengdian Capital Management Co., LTD。Ptic recently signed the "Capital Increase Agreement on Wuhan Hopson Technology Co., LTD." with Wuhan Hopson Technology Co., LTD., Liu Tiangang, Wuhan University Asset Management Investment Management Co., LTD., Shanghai Hillhouse Chenjun Equity Investment Partnership (Limited Partnership) and other Hopson Technology shareholders.，To increase the capital of Hopson Technology by 30 million yuan through currency with its own funds，After the completion of the capital increase, PLOI holds Hopson Technology 5.6604%股权。
According to the company's strategic layout, the company actively explores development opportunities in the field of synthetic biology。Hopson Technology, the target company of the foreign investment of PLOC, has strong research and development strength in the field of synthetic biology, and can form industrial synergies with the company, which helps the company's business layout in the field of synthetic biology, promotes the long-term development of the company's business, and conforms to the company's overall development strategy。
（信息来源：智通财经）
Anaerobic biology completed strategic financing, exclusive investment of Wanze shares
9On October 26, Anaerobic Biology announced the successful completion of strategic financing。This round of financing is exclusively invested by Wanze Industrial Co., LTD., with Huaxing Capital acting as the exclusive financial advisor。This round of financing will be mainly used for live bacterial drug clinical trials, candidate drug pipeline development and bacterial drug production platform construction。
厌氧生物成立于2019年，位于成都天府国际生物城，It is a high-tech enterprise engaged in the research and development of innovative drugs for human microflora，By scientists who have long worked on anaerobic microbes，Relying on national anaerobic microbiology research institutions (Chengdu Biogas Research Institute, Ministry of Agriculture and Rural Affairs)，通过科技成果转化的方式创立。
At present, anaerobic biology is mainly committed to the research and development of innovative drugs for formula bacteria, and some of its pipelines have made important progress。Among them, the formulations for bacterial vaginosis (BV) have completed phase II enrollment, and most of the formulations for postmenopausal atrophic vaginitis (PAV) have also completed enrollment.And the related pipeline for intestinal diseases has submitted IND application。
KAL-001, the first class I innovative drug independently developed by anaerobic biology, is the world's first multi-combination vaginal formula bacterial drug，It is also the first multibioactive drug to enter clinical research in China，主要针对育龄女性的阴道炎症疾病，已完成II期临床入组，It is also the first domestic treatment of postmenopausal atrophic vaginitis of live bacteria drugs，即将完成II期临床入组。At the same time, anaerobic biology has laid out a number of indications for intestinal diseases, and the IND application for intestinal live bacteria innovative drugs will be formally submitted within the year。
After the completion of this financing, the team will continue to maximize the value of the platform and pipeline of source innovation, with the goal of rebuilding the micro-ecological balance, deepening the field of disease treatment, and extending and expanding the research and development of health consumer products。
Mr. CAI Yongfeng, Deputy general manager and Secretary of the Board of Directors of Wanze Shares, said: "Sichuan Anaerobic Biology relies on the former Key open Laboratory of anaerobic Microorganisms of the Ministry of Agriculture，Founder Dr. Cheng Lei has been engaged in research on anaerobic microbial resources and utilization for nearly 20 years，It has built a technological platform for the research and development of living biological new drugs with independent intellectual property rights，具备从“菌”到“药”的研发能力。Wanze Shares and anaerobic biology have a high degree of business complementarity in the research and development, production and marketing of new products in the field of micro-ecology。As an industrial investor, Wanze Shares will enable the development of anaerobic biological product pipelines, and work together to promote the development of China's micro-ecological industry for the benefit of the people。”
Dr. Cheng Lei, founder of Anaerobic Biology, said, "I am very grateful to Wanze for its support and trust in Anaerobic Biology。As a pioneer in the formulation of microflora drugs in China, anaerobic biology insists on starting from the unmet clinical needs, focusing on the development platform construction from microflora to drugs, and laying out a forward-looking and differentiated R&D pipeline。We hope that together with Wanze, we can give full play to our respective advantages, accelerate the clinical and commercial promotion of microbial drugs, and make unremitting efforts to realize the vision of "harmony of human bacteria and health for everyone"。”
Ms. Jia Jia Jiang, Managing Director of China Renaissance Capital's Medical and Life Technology Business Division, said: "The field of microecological therapy is a direction we continue to pay close attention to, and this blue ocean market has reached the eve of the outbreak。Anaerobic biology as the head of the field of innovative companies has built a complete chain of technology platform, and highly differentiated product pipeline and comprehensive talent team。As a partner of anaerobic biology, Huaxing Capital will continue to contribute to help the company create good results and achieve breakthroughs。”
（信息来源：投资界）
Novo Nordisk raises $2.7 billion 'AI+ Pharma'
Novo Nordisk said in a statement on September 25 that it has entered into a partnership agreement with U.S. technology company Valo Health to seek to use human data and artificial intelligence to discover and develop new therapies for cardiometabolic disease (CMD)。
Under the terms of the agreement, Valo will receive upfront payments and potential near-term milestone payments totaling $60 million and be eligible to receive milestone payments for up to 11 projects totaling up to $2.7 billion, plus funding for research and development expenses and potential royalties。
In recent years, cooperation cases between pharmaceutical companies and technology companies have been frequent, and the advantages of AI pharmaceuticals have gradually emerged。Industry insiders believe that the use of AI technology can shorten the new drug research and development cycle, save costs, and significantly improve the efficiency of drug research and development and enterprise competitiveness。Artificial intelligence technology is gradually penetrating the biopharmaceutical field from many aspects, and has the opportunity to bring major changes to the industry。At the same time, there are also a number of domestic pharmaceutical companies to join hands with AI technology companies to accelerate innovation and transformation, with the continuous injection of capital, pharmaceutical research and development efforts have gradually increased, and the iteration speed of AI pharmaceutical related technologies has also significantly accelerated。In the context of the hot global AI pharmaceutical market, AI pharmaceutical has also ushered in a development opportunity in China, which is expected to become a new opportunity to change the biopharmaceutical industry。
China's AI pharmaceutical development ushered in a good opportunity, and Internet giants have entered
At present, the competitors in China's AI New Drug research and development (AIDD) industry are mainly divided into three categories, Internet giants, traditional pharmaceutical companies and start-ups。Among them, Internet companies cooperate with traditional pharmaceutical companies, colleges and start-ups to build software and platforms, and invest in start-ups to enter the industry。Start-ups provide relevant services for traditional pharmaceutical companies and CRO companies through self-developed software and platforms。
As early as 2015 and 2018, Tencent participated in the series A and B financing of Jingtai Technology, one of the leading AI pharmaceutical companies in China。In 2020, it will focus on creating "cloud deep intelligent medicine", and officially include AI drug research and development in the enterprise map。
Huawei has laid out Huawei Cloud EIHealth in the medical field, and plans to further expand its layout in the field of AI drug research and development in 2021。
Alibaba's Alibaba Cloud has partnered with the Global Health Drug Research and Development Center to develop AI drug research and development and big data platforms, as well as data mining for drug research and development for coronaviruses such as SARS/MERS。
In September 2020, Baidu established BTU to enter the field of AI pharmaceuticals。Its LinearFold algorithm shortens the genome-wide secondary structure prediction of the novel coronavirus from 55 minutes to 27 seconds，提速120倍，Bytedance has set up an Aurora division dedicated to big health，AI Lab's teams in Beijing, Shanghai and the United States have also officially begun to recruit AI pharmaceutical talents。
China AI New Drug Research and development (AIDD) industry regional layout
At present, China's AI new drug research and development (AIDD) enterprises are mainly concentrated in Beijing, Guangdong, Shanghai, Jiangsu and Zhejiang。Among them, the proportion of companies located in Beijing reached 29 percent.2 percent, followed by Guangdong and Shanghai, each reached 20 percent.8%。
Southwest Securities said that domestic AI pharmaceuticals started relatively late, but the market heat has risen sharply in recent years。Compared with traditional new drug research and development, the application of AI technology to drug research and development can significantly shorten the research and development cycle, reduce research and development costs, and improve the research and development success rate and return on investment。With the rapid development of AI technology, its application areas are more extensive and can participate in multiple stages of the drug development process。
Sinolink Securities pointed out in its research report that AI technology has penetrated into many aspects of drug research and development, including target discovery, compound synthesis and screening, crystal type prediction, mechanism exploration, selection of subject populations, pharmacovigilance and so on。At present, a number of domestic pharmaceutical companies have laid out AI+ new drug research and development related fields。With the continuous maturity and landing of relevant applications, it is expected to significantly improve the efficiency of drug research and development and corporate competitiveness。
Soochow Securities believes that the three elements of AI new drug research and development are data, computing power and algorithms，Software providers build on their strengths in algorithms，It is expected to achieve the opening of business models by providing software products;Platform R & D enterprises have great advantages in data accumulation，It is expected to generate CRO companies that develop new AI drugs，Provide support for enterprises that do not have the front-end development capability of AI new drugs。
（信息来源：前瞻网）
Lingke Pharmaceutical completed the C2 round of financing, the overall financing amount of the C round 3.22亿人民币
9Linke Pharmaceutical (Hangzhou) Co., LTD., an innovative drug research and development company, officially announced the completion of C2 round of financing。This round of financing is jointly participated by Shaoxing Binhai New Area biomedical Industry Equity Investment Fund, Haibang Investment and Good Buy Fund, and the old shareholders Lianxin Capital and Eli Lilly Asia Fund continue to increase their bets。This is a new round of financing obtained by the company after the C1 round of financing on May 31, and the total financing amount of the C round to date is 3.22亿元人民币。Haoyue Capital acted as the exclusive financial advisor for this round of financing。
Founded in 2018, Linke Pharmaceutical is a leader in the research and development of FIC and BIC drugs in the fields of autoimmune diseases, inflammation and oncology。Based on the core team's deep background in pharmaceutical chemistry, biology, clinical development and commercial development, with an average of more than 20 years of new drug research and development experience, Linke Pharmaceutical's pipeline layout focuses on innovation and differentiation。The core pipeline focuses on the development of second-generation highly selective and third-generation tissue-specific JAK inhibitors, while exploring the possibility of drug conversion of innovative targets。
Since its establishment, efficient execution continues to drive Lingke Pharmaceutical to accelerate its development。In the past 3 months, the Phase II clinical trial data of LNK01001 in rheumatoid arthritis, atopic dermatitis and ankylosing spondylitis have been published successively, and the results all show significant therapeutic effect and high safety, fully reflecting the characteristics of fast acting and good efficacy of small molecule JAK1 inhibitor。The company has recently submitted a number of Phase II clinical trial end/Phase III clinical trial pre-launch conference applications;Several pipelines are about to enter Phase III clinical trials, aiming to reach as many patients as possible。At the same time, LNK01004 Phase Ib clinical study for psoriasis and atopic dermatitis has also achieved the first patient enrollment;The early clinical trial data of the company's LNK01002 and LNK01003 pipelines are positive, and the preclinical pipeline research and development is also advancing rapidly。
Lingke Pharmaceutical's innovative R&D and clinical development capabilities continue to be verified and enhanced, and it is at a critical stage of rapid value explosion。According to Frost and Sullivan, the JAK1 inhibitor market alone will be as high as $30.5 billion in 2030, and the future market is broad。The company relies on the huge market in the field of autoimmune diseases and oncology, and the future commercialization potential is expected。
Dr. Wan Zhaokui, Chairman and Chief Executive Officer of Linke Pharmaceutical, said, "I would like to thank Shaoxing Binhai New Area Bio-Pharmaceutical Industry Equity Investment Fund, Union New Capital, Haibang Investment, Haomai Fund and Eli Lilly Asia Fund for their support and trust，At the same time, I would like to thank the C1 investment institutions Tailong Investment and Liandong Investment，共同助力我们顺利完成C轮融资。Linke Pharmaceutical is a company focusing on the field of autoimmune diseases and cancer treatment, developing globally competitive FIC/BIC innovative drugs, and is committed to benefiting patients around the world with differentiated innovative therapies。We are very pleased to see that even in the current situation of biomedical capital winter, Lingke Pharmaceutical continues to gain the support of new and old shareholders, fully demonstrating the capital market's recognition of the team。Now Linke Pharmaceutical is in a stage of rapid development, we will further integrate multi-party resources, continue to increase investment in clinical development, research and development team and technology platform, and strive to make more safe and effective innovative drugs benefit more patients as soon as possible。Haoyue Capital acted as exclusive financial advisor to this financing and we are grateful for their professionalism and support。”
Mr. Ding Yameng, founding Managing Partner and Chief Operating Officer of Haoyue Capital, said, "We are honored to continue to assist Lingke Pharmaceutical in completing this round of financing。The types of diseases in the field of autoimmunity are diverse and complex, and there is still a lot of unmet clinical needs and differentiated innovation opportunities。Lingke Pharmaceutical has an internationally competitive innovation pipeline, which is continuously verified and recognized by the market。We look forward to Linke's multiple significantly differentiated pipelines showing breakthrough potential in subsequent clinical validation, and believe that under the leadership of a team full of execution and sense of mission, Linke Pharmaceutical will continue to steadily cross the cycle, embrace the vast blue ocean market, and provide patients with better choices as soon as possible。”
（信息来源：咸宁网）
Facing the challenge of commercialization and "internal volume", where is the breaking point of the sky-high "net celebrity" CAR-T？
近日，Shanghai Municipal Science and Technology Commission issued the "Shanghai 2023" Science and Technology Innovation Action Plan "Cell and Gene therapy special Project Application Guide Notice"，Research on new targets and mechanisms of cell (gene) therapy，关键核心技术研究，研究者发起的临床研究，The construction of clinical medical research center has given directional support to four thematic directions。Among them, the funding limit for the research on new targets and new mechanisms of cell (gene) therapy and the development of new CAR-T technology can reach up to 500,000 yuan and 1.5 million yuan respectively。
As the cell gene therapy market continues to heat up, a variety of support policies have also followed, helping enterprises to seize development space。据Frost&Sullivan predicts that the global CAR-T market size in terms of sales value has grown from 0.$100 million increased to $1.1 billion in 2020, and the global CAR T cell therapy market sales value is expected to reach $21.8 billion by 2030, with a compound annual growth rate of 34 percent from 2021 to 2030.8%。
At present, CAR T therapies that have been listed in China include Fosun Kite Yikaida, pharmaceutical giant Norbinoda and reindeer biofosu。Brokerage pharmaceutical industry analysts to the 21st Century Business Herald said，“中国一方面作为癌症高发大国，每年大约有400万左右的新增病例，There is an urgent need for CAR-T technology in clinical treatment，产生庞大的市场需求；另一方面，As the commercialization value of CAR-T is verified, the heat rises，越来越多国内企业涌入该赛道，有望推动CAR-T产品价格下调。”
加速CAR-T落地临床
Cell gene therapy is a new generation of precision therapy after small molecule and large molecule targeted therapy, and its huge market potential is attracting Chinese and foreign enterprises to compete for layout。
According to the clinical stage of cell gene therapy trials, about 39% of the world's clinical trials are in clinical phase I, 28% are in clinical phase I-II, 25% are in clinical phase II-III, and 6% are in clinical phase III。According to the FDA, from 2020 to 2025, cell gene therapy drugs will usher in the harvest period, there will be 10-20 drugs approved for market every year, and more than 50 cell gene products will be listed globally by 2025。
At present, the domestic CAR-T therapy market process is also accelerating。According to the 21st Century Business Herald reporter, from the perspective of CAR-T research and development optimization, the three CAR-T products that have been listed in China are divided into mouse source, alpaca source, and full human source according to antibody sources。Among them, the latest approved in July this year, Iquiolencel injection (trade name "Fokosu") is a full-human CAR-T product, which can reduce immunogenicity and has positive significance in enhancing the safety and efficacy of CAR-T products。
According to the relevant person in charge of the Shanghai Drug Evaluation and Verification Center, at present, the global cell therapy products have begun to enter the industrialization stage。Nine CAR T cell therapy products have been approved worldwide，其中，The FDA has approved six CAR-T therapies，They are Novartis' Kymriah, Gilead's Yescarta and Tecartus, Bristol-Myers Squibb's Breyanzi, Bristol-Myers Squibb's Abecma and Bluebird Bio's Abecma，And Johnson and Carvykti from Legendary Creatures。
"Cell gene therapy products have gone through the stage where the industry has questioned them, and after safety and effectiveness have been improved, the number of cell gene therapy products approved has increased in recent years。”上述负责人介绍。
China is a country with a high incidence of cancer in the world, and there is an urgent demand for CAR-T technology in clinical treatment, and the market demand is huge。随着CAR-T商业化价值被验证后，越来越多国内企业涌入该赛道，In addition to joint ventures with large overseas pharmaceutical companies for the introduction of mature products and localized production of enterprises such as Fosun Kat and Pharmed Juno，更多的是走自主研发路线的本土企业，Such as reindeer biology, Shanghai Cell Group, Keji Biology, Genxi biology and so on。
The Smart Bud research report shows that worldwide patent applications in the field of CAR-T cell immunotherapy are currently about 2.1万件。Among them, the United States in the field of CAR T cell therapy is in a leading position in technology, China is significantly ahead of Europe and Japan to closely follow the United States, it is not difficult to see that China's CAR T market competition tends to be white-hot。
Analysts said that from the perspective of research and development pipeline, about 13% of pipeline products belong to cell gene therapy, but the number of existing listed products is less than 1%, the industry is still in a rapid growth stage, which is a trans-era big category after small molecules and large molecules。However, we also need to note that if CAR-T products want to be bigger, there are many links that need to be further broken through。
“天价药”商业化难
Behind the booming market and technology, CAR T cell therapy still faces many challenges - side effect control, solid tumor efficacy, etc., in addition, the "sky-high" treatment cost is still the commercialization challenge to be overcome by the industry。
The most expensive product on the market is Kate's Kymriah, which is 47.5万美元/针。In addition, CAR-T product prices are also gradually rising, Bristol-Myers Squibb Abecma unit price from 41.95万美元/针上涨至43.8万美元/针。
According to a Nature Reviews Drug Discovery survey, 65% of patients said that the high price was the biggest barrier to receiving cell therapy, more than meeting the indications and disease progression。
In this connection, the relevant person in charge of reindeer biology told the 21st Century Economic Herald that the United States has been approved CAR-T products priced between $370,000 and $470,000, and the domestic two introduced CD19 CAR-T prices are 1.2 million and 1.29 million yuan, Fukosu®It is the first approved myeloma CAR-T in China, taking into account the specific situation of domestic patients in pricing, and the price is about 1/3 of the price of the two approved similar products abroad, which is also lower than the previous two introduced CAR-T products。
"In order to improve the accessibility of CAR-T therapy, enterprises also need to actively explore multiple accessibility enhancement programs, including innovative payment models such as commercial insurance and urban welfare insurance.。At the same time, it also provides an innovative solution for patients who have difficulty paying in stages and installments。We will also actively explore the feasibility of entering medical insurance。Reindeer Biology said that CAR-T product pricing is mainly based on value, efficacy, cost, operation and patient accessibility and other factors, will also take into account the high early research and development investment。The personalized customization of CAR-T determines the high production cost and production management cost, in addition, from the perspective of efficacy, "one shot effect" this feature is also one of the reasons for the high pricing of all approved CAR-T。具体而言：
On the one hand, from the cost side, the cost of the CAR-T production process is mainly composed of three aspects: equipment, raw materials and labor。The equipment mainly relies on imports;The three parts of the production process of the plasmid, viral vector and cell in the raw material are complex, and a strict quality control system is in place, and product safety, purity, efficacy and uniformity need to be strictly controlled。On the other hand, from the artificial side, CAR T cell products are very different from traditional cancer drugs。CAR-T is a "live" drug, which belongs to a fully personalized customized therapy, and each patient is a single production batch, which cannot be mass-produced。Each step of production is "fine work", time-consuming and labor-intensive, difficult to expand, laboratory staff must also go through a long period of training to take up the post, the overall personnel operating costs far exceed the production of traditional drugs。
In addition, the CAR T cell therapy industry also has the most complex supply chain system, requiring more stable production and rapid delivery。As a fully customized product, CAR-T therapy has relatively high requirements for hospitals and doctors。
"Therefore, CAR-T layout companies currently choose to do qualification certification in the country's strong third-class hospitals.。Medical institutions must pass the qualification certification of the company before the use of Focosur。The qualification certification process mainly includes product related content training, quality audit, simulation exercise, etc., to clarify the management norms of patient single blood collection and product transfusion, so that the whole process from cell collection to product transfusion can be controlled, and finally ensure the drug safety of patients。”驯鹿生物方面表示。
破局多维度“内卷”
Although CAR-T faces commercial penetration problems, it does not affect the enthusiasm of many enterprises。
At present, many people in the industry believe that CAR-T will face PD-1 type "internal volume".。As early as three years ago, there were consulting agency statistics, the global CAR T cell therapy clinical trial registration projects more than 600, and among them, China with 357 clinical trials ranked first in the world。CD19 is the most common target for CAR-T in hematoma, with 175 trials involving this target。
In this trend, enterprises need to face not only commercialization problems, but also increasingly fierce market competition。Especially pipeline target concentration, product homogenization serious dilemma how to break？
In response to problems such as the clustering of new drug targets in China, CDE issued the "Guiding Principles for Clinical Value-Oriented Clinical Research and Development of Anti-tumor Drugs" in November 2021, which will strive to promote original innovation and reduce the approval of homogenized products。On the CAR-T circuit, the few products that will eventually be approved for market must be those with excellent efficacy and guaranteed safety。At the same time, the layout company has realized that it needs to avoid homogenization competition from its own research and development perspective as far as possible, create differentiated advantages of the company in terms of products, efficacy, safety, and external strategic cooperation, and achieve high-quality development。
In addition, executives of pharmaceutical companies told the 21st Century Business Herald that CAR T therapy is currently mainly concentrated in the field of blood tumors, but in malignant tumors, blood tumors account for only 10%, and the remaining 90% are solid tumors。This also fully shows that solid tumors have better commercial prospects than hematoma。In the many layout of CAR-T treatment solid tumor companies, Keji Pharmaceutical, Stansai, Boshengji, Legendary Biology and other companies have or are entering the clinical trial stage。
"In vivo generation of CAR-T direction, universal CAR-T direction, CAR-NK and solid tumor direction may become breakthrough points, but there are great technical difficulties, such as the efficacy and survival of allogeneic cell therapy, and the safety of CAR-T in vivo.。Companies need to move forward through self-research or joint development with other companies。”驯鹿生物相关负责人指出。
As for the direction of CAR-T treatment, the expansion of autoimmune diseases and solid tumors is the two major trends, in addition, accelerating CAR-T products to the sea has become the trend of industry development。
In the view of reindeer biology, domestic CAR-T therapy needs to overcome some difficulties to successfully go to sea, including the verification of the technical level, the accumulation of clinical data, the satisfaction of international regulatory compliance, etc., but also to face the competition in the international market。At the same time, compared with the Chinese market, there are certain differences in the overseas pricing system, payment ability and payment environment。At present, CAR-T drugs are in short supply overseas。The payment system of "commercial insurance + medical insurance" in Europe and the United States is relatively perfect, and the insurance coverage is wide, which makes it easier for patients to accept CAR-T, an innovative drug with relatively high price but excellent curative effect。
"For the more mature overseas CAR-T market that is in short supply, the necessity and opportunity for domestic CAR-T to go to sea are also more prominent.。Expanding global market share and cooperating with more multinational groups in the pharmaceutical industry will help enhance the innovation capacity and international competitiveness of the domestic biomedical industry。The relevant person in charge of reindeer biology said that CAR T cell therapy as a cutting-edge treatment technology has great potential for development。In the future, with the continuous innovation and breakthrough of research and development, as well as the continuous improvement of the domestic multi-level health insurance system and the establishment and promotion of many innovative commercial insurance payment systems, domestic CAR-T products will accelerate the rise and benefit more patients。
（信息来源：21经济网）
10After the annual investment of 350 billion, how much is the gap between China and Japan's pharmaceutical industry
With the value rotation of China's innovative pharmaceutical industry from imitation to innovation, pharmaceutical companies' attention to innovation is also deepening, and more and more domestic pharmaceutical companies begin to look for differentiated competitive advantages。
To this end, domestic pharmaceutical companies have invested a lot of research and development costs。According to the incomplete statistics of the listed innovative drug companies, in the past decade, China's innovative drug research and development has invested about 348 billion yuan。In fact, this is only the data of listed companies, plus non-listed companies, domestic pharmaceutical research and development investment will be far more than this figure。
So after investing a huge amount of money, how far has the transformation of China's innovative drug industry come？On this point, we may wish to take Japan as a reference to find out。
After all, whether from the perspective of population background, culture, or development trajectory, the Japanese pharmaceutical market and the Chinese pharmaceutical market have similarities。
From the perspective of market capitalization, the total revenue of Japan's top 10 pharmaceutical companies last year was 1.7万亿元，国内则为1.01万亿元，二者相差1.Seven times is not a huge difference.However, from the revenue point of view, the gap between domestic pharmaceutical companies and Japanese pharmaceutical companies is obvious, and the revenue of Japan's top ten pharmaceutical companies is three times that of China。
It seems that even though China's innovative drug industry has developed rapidly in recent years, the gap between it and Japanese pharmaceutical companies is still not small。And the income gap may be difficult to close in the short term。
因为，从产品管线布局来看，There are many FIC drugs with great potential in the pipeline of Japanese pharmaceutical companies，The areas targeted range from digestive disorders to rare diseases to neurological disorders，药企各有所长；而国内，目前的情况则是管线同质化严重，Most pharmaceutical companies are still clustered in hot targets in the oncology field。
客观来讲，这种差距的存在是必然的。After all, the domestic innovative drug industry started only ten years ago, in contrast to Japan, Daiichi Sankyo, Astellas, Takeda Pharmaceutical and other pharmaceutical companies have decades or even hundreds of years of historical accumulation。
Give Chinese drug companies a little more time, and the gap between the Chinese and Japanese pharmaceutical industries may not be closed。
01、中日TOP10药企：市值相差1.7倍，营收相差3倍
Japan is the leader of the pharmaceutical industry in Asia, and Asia has entered the top 10 pharmaceutical companies in the global pharmaceutical list, and only Takeda Pharmaceutical, a major Japanese pharmaceutical company, is one。
Of course, the strength of the Japanese pharmaceutical industry goes beyond owning Takeda。
从市值上来看，The TOP10 pharmaceutical companies in Japan are Daiichi Sankyo, Takeda Pharmaceutical, Sino-Foreign Pharmaceutical, Astellas, Otsuka Holdings, Eisai, Shiono Yoshii, Tanabe Mitsubishi, Sumitomo Pharmaceutical, and Ono Kanichi，The largest, Daiichi Sankyo, has a market value of 388.6 billion yuan，The market value of Ono Pharmaceutical, ranked 10th, is only 7.4 billion yuan。Taken together, Japan's top ten pharmaceutical companies have a market capitalisation of 1.79万亿元。
In China, the top ten pharmaceutical companies in terms of market value are Hengrui Pharmaceutical, Beigene, Legendary Biological, Fosun Pharmaceutical, East China Pharmaceutical, Stone Pharmaceutical Group, Xinda Biological, Hanson Pharmaceutical, China Biopharmaceutical, Changchun High-tech。这十家药企的总市值为1.01 trillion yuan, accounting for 60% of the total market value of large pharmaceutical companies in Japan。
However, although the total market value of the top ten pharmaceutical companies in Japan is high, the value differentiation of these ten pharmaceutical companies is more obvious, which is reflected in the concentration of the head pharmaceutical companies and the fault of the waist pharmaceutical companies。
Specifically, the top five pharmaceutical companies in Japan have a market value of more than 100 billion yuan, while the ninth and tenth pharmaceutical companies have a market value of 10.8 billion yuan and 7.4 billion yuan。
In China, there are fewer drug companies in the head and more drug companies in the waist。At present, only Hengrui Pharmaceutical and Beigene two pharmaceutical companies have a market value of more than 100 billion yuan, and the remaining eight pharmaceutical companies have a market value of about tens of billions of yuan。
Compared with the gap in market value, the revenue gap between domestic pharmaceutical companies and Japanese pharmaceutical companies is even greater, reaching 3 times。
Japan's top 10 pharmaceutical companies have a combined revenue of 671.7 billion yuan。Among them, Takeda Pharmaceutical, which ranks second in market value, had revenue of 218.9 billion yuan, crushing all other pharmaceutical companies in the top 10 with absolute advantages。
In China, the total revenue of ten pharmaceutical companies is only 199.1 billion yuan, less than the revenue of Takeda Pharmaceutical。其中，营收超过百亿的仅有6家。The top 10 pharmaceutical companies in Japan have revenues of more than 20 billion yuan。
In general, the domestic head pharmaceutical companies compared with the Japanese big pharmaceutical companies, whether in market value or revenue level, there is still a large gap。
02、FIC还是BIC？来自日本的他山之石
Of course, with the continuous development of the young Chinese innovative drug industry, there will be a number of pharmaceutical companies in China in the future, among the world's top pharmaceutical companies。
But it promises to be a long and bumpy process。In this process, if you feel Japan this stone across the river, may be able to let domestic pharmaceutical companies take some detours。
After analyzing the product pipelines of the top ten pharmaceutical companies in Japan, we found that compared with FIC, the rise of the vast majority of Japanese pharmaceutical companies relied on me better or BIC drugs。
Take the largest market value of the first Sangong, in the past two years, this drug company with the ADC big killer drug DS-8201 suddenly rose to become the most competitive player in the global ADC drug field。But even as powerful as DS-8201, it is not an FIC drug, but an upgraded BIC drug based on the second generation of HER2 ADC drugs。
The rise of Takeda, Japan's second-largest pharmaceutical company by market capitalisation, has also relied heavily on BIC drugs。
Takeda has made the fastest shift to me better of any Japanese drug company。After Japan's medical reform, Takeda Pharmaceutical relied on the foundation laid by generic drugs, and shifted the focus of drug research and development from generic drugs to me too and then to BIC。The four blockbuster products that have contributed greatly to Takeda Pharmaceutical's revenue, leprerelin microspheres, Lansoprazole, Candesartan, and pioglitazone, are BIC drugs that have been improved and innovated。
In addition, Astellas' blockbuster product Enzalutamide and Otsuka Pharmaceutical's blockbuster product aripiprazole are BIC products。
Back in the country, after me too drugs fell into extreme internal volume in the past, me too strategy became the target of public criticism, and FIC began to become the most important evaluation criteria for innovative drugs。Even at its peak, an FIC pipeline, even if it is still in an uncertain clinical stage, will receive a high valuation。
Although in the cold winter of biopharmaceutical, investors are not as enthusiastic as before for FIC pipeline, but there are still many investors for FIC pipeline with its own filter。
Returning to the actual situation of China's innovative drugs, in the absence of original capital accumulation and lack of basic research, domestic innovative drug companies want to directly enter FIC is more like a false proposition。
And like Japanese pharmaceutical companies accumulate original capital through me too, and then gradually turn to BIC drugs, and wait until their own strength is sufficient to challenge FIC drugs, it seems more feasible。
03、正视BD，不可或缺的外部引擎
So, where do these BIC drugs from big Japanese pharmaceutical companies come from？外部引进是重要的渠道。
License inThe conventional practice of mergers and acquisitions of Japanese big pharmaceutical companies to expand the pipeline is also these drugs from outside, providing sufficient impetus for the development of Japanese pharmaceutical companies。
Take Takeda Pharmaceutical, for example, it has also spent a lot of thought on self-developed drugs, but because self-developed drugs have repeatedly hit a wall, Takeda Pharmaceutical began to look at the path of mergers and acquisitions。
2008Takeda acquired US innovative drug company Millennium for $8.8 billion。Through this acquisition, Takeda acquired drugs such as Bortezomib, Esaszomib, osteosarcoma drug rice wood peptide and leukemia drug Adcetris。Among them, bortezomib alone brought more than $3 billion in sales for Takeda Pharmaceutical in 2014。
2019In January, Takeda Pharmaceuticals acquired rare disease company Shire for $62 billion, marking the largest acquisition ever by a Japanese pharmaceutical company。It is also because of the proceeds brought by this transaction that Takeda Pharmaceutical has become the first and only Asian company to be ranked in the top 10 global pharmaceutical companies。
Another example is Astellas, in its revenue main product matrix, in addition to the blockbuster products Enzalutamide, Xospata, Padcev, etc. come from cooperation with other pharmaceutical companies。
in fact, not only in Japan, but also globally, acquisitions and licenses are important ways for pharmaceutical companies to find cash cows。Of the 323 new drugs approved by the FDA between 2015 and 2021, only 28 percent were invented in-house, with the rest coming from external or collaborative discoveries。
Back in China, biotech is no stranger to the license in strategy, even quite familiar。However, in the past, due to the "patchwork" pipeline listing of some innovative pharmaceutical companies through the license in strategy, the license in China was once full of controversy。
For many domestic traditional big pharmaceutical companies, they have been used to working behind closed doors。Typical as Ge Hengrui Medicine, historically more independent research and development, until the past two years began to gradually sporadic BD action。
However, in fact, from the rise of Japanese pharmaceutical companies, it is not difficult to find that the license in model is an essential means for pharmaceutical companies to continue to expand their scale。This also requires domestic pharmaceutical companies to face up to the license in the past after the brutal expansion, leverage the license in, and return to the track of exploring their own better development。
04、不执着于肿瘤，多领域百花齐放
Cancer has always been a battleground for pharmaceutical companies, and domestic pharmaceutical companies are keen to cluster here。However, from the perspective of the core pipeline focus, the choice of Japanese pharmaceutical companies is quite diversified。
For example, Takeda Pharmaceutical's five core areas are digestion, rare diseases, plasma products, oncology and neuroscience, among which the digestive field is its traditional advantage field, the birth of Lansoprazole, vitolizumab, fumarate Wonazan and other blockbuster drugs。
Astellas' pipeline covers transplantation, immunology, infectious diseases, urology, oncology, neuroscience, complications of diabetes and metabolic diseases and many other therapeutic areas, especially in the field of organ transplantation and urology, Astellas has the world's leading therapeutic drugs and technologies。
Recently, because of the continuous breakthrough in the field of Alzheimer's disease, the reputation of Eisai Pharmaceutical is also the head pharmaceutical company in Japan, different from the extensive layout of the above-mentioned big pharmaceutical companies, Eisai Pharmaceutical has been focused on neurological diseases, but also in the field of Alzheimer's disease for many years, and finally in return for "return".。
In July this year, Eisai/Bojian targeted Lecanemab finally received full FDA approval, becoming the first fully approved new drug for Alzheimer's disease since 2003。
Back in the country, most of the domestic pharmaceutical companies to cancer as the main field of exploration, cancer seems to have become a major pharmaceutical companies research and development layout must choose。
For example, half of the innovative drugs approved by Hengrui Pharmaceutical are around cancer drugs;Forty percent of Fosun's revenue in 2022 will come from tumor-as-immunomodulatory products。
Of course, there is nothing wrong with the layout around the field of cancer, after all, there is a huge clinical unmet need in the field of cancer。However, the speed of drug update iteration in the field of cancer is extremely fast, and there are many players, and this field has become one of the most competitive fields。
There is also a huge clinical unmet need in areas other than oncology。By contrast, these areas may not have received much attention, and digging deeper in these areas may be able to avoid internal volume and meet clinical needs while reaping rich rewards。
05、总结
At present, although there is still a big gap between Chinese innovative pharmaceutical companies and Japanese pharmaceutical companies。However, compared with the development of Japan for a hundred years, China's innovative drug industry is still quite young, and the full count is only ten years, and the gap is naturally reasonable。
In the future, Chinese innovative pharmaceutical companies will continue to forge ahead along with the experience of Japan and the efforts of China's innovative pharmaceutical industry, and the gap between China and Japan's innovative pharmaceutical industry is bound to continue to narrow。
（信息来源：氨基观察）
When there is no license in the era, only the license in the era is available
When innovative drug companies received a clear signal from the depressed market: reduce costs and increase efficiency, and stop all money-burning behaviors, the costly license in China also cooled rapidly。
数据最为直观。According to the data of the Pharmaceutical Rubik's Cube, as of July 5, there were only 10 domestic innovative drug license in (authorized introduction) cooperation, and the number of transactions declined significantly。At the same time, transaction amounts also continued to decline, with the potential total amount of innovative drug licenses in the first half of 2023 at 12.That's $800 million, just 30 percent of last year's total。
in the first half of the year, there were 17 innovative drug projects going to sea, with a total amount of $14.3 billion disclosed, more than three times that of the same period last year, among which, the total amount of cooperation between Brisiscom and Eisai on her2 ADC alone reached $2 billion, exceeding the total amount of license in the first half of the year。
When drug companies are becoming more cautious, there are more and more pessimistic voices about the license in。
in fact, license in and out are two sides of the same body, in out transactions become the mainstream at the same time, the importance of license in will not disappear。Because it is a shortcut for the licensor to obtain cash flow in the early stage of commercialization, it is also a way for the importer to fill the short board of the pipeline。
However, the simple license in the past is, after all, a consumable model, and today, it is no longer suitable for the development model of China's innovative pharmaceutical companies。
When there is no license in the era, only the license in the era is available。
01Step on the license in Time dividend
所谓红利，就是短暂的供需失衡。供需失衡，就意味着机会。
Perhaps the biggest supply-demand imbalance our generation has experienced is the Internet dividend。In the innovative drug industry, the biggest imbalance between supply and demand is the lack of innovative drugs from scratch to stage, and the huge clinical unmet demand。
Just like the rise of e-commerce in the Internet dividend, when the network just rose, there were more buyers and fewer sellers, and there was an imbalance between supply and demand。As long as the business goes in, it will give support and traffic, and it will make money。Many people succeed, is to eat this wave of "flow dividend", intentionally or unintentionally step on the tuyere。
With the dividend of the upgrading and development of the innovative drug industry, license in this way has become popular。At that time, the license in order to meet the clinical needs of patients, but also to give full play to the advantages of domestic pharmaceutical companies in clinical resources and market channels and other fields, accelerate the overseas innovative drugs in the domestic market access。
in the past few years, innovative pharmaceutical companies with prophetic foresight have effectively seized the window period and become beneficiaries by relying on licenses in China。典型如再鼎医药。
2014年，杜莹创办了再鼎医药。According to public information, after getting the first round of financing after the establishment, Zai Ding Medicine introduced 5 overseas top drugs in more than a year, and the number of introduced transactions after 2015 was as high as 14。
In addition to keen vision, again Ding medicine life coincides with the flourishing times。In 2015, Bi Jingquan took office as the head of the food and drug administration system, initiating a series of drastic reforms。The adjustment of industrial policy has paved a new road for the development of innovative drugs in China。
The success of Re Ding Medicine has also made many traditional pharmaceutical companies in China know that innovative drugs are not only "one billion dollars in ten years", which is a road to drug research and development。
At that time, the number of license-in users began to increase。According to Mabar Health, the number of license in China has continued to increase every year since 2016, and the number of license in 2021 has reached a record high of 133 cases。
But the players seem to be ignoring one fact。Innovative pharmaceutical companies represented by Zaiding Pharmaceutical can rely on the license in model to start, not only because of their own efforts, but also because at that time, China's innovative drugs are in a transition period from scratch。
2014When Zai Ding was established, China's new drug approval environment is very different from today, a product may take 5 to 7 years to be approved for listing, and at that time, with the license in, we can quickly seize the time difference window for the listing of innovative drugs in China and the United States。
But for most players who arrived late, the imagination of the license in model has long since waned。In 2017, China officially joined ICH, and the global mutual recognition of clinical trial data reviewed and approved at home and abroad directly accelerated the entry of imported innovative drugs into the Chinese market, and the "window period" for domestic pharmaceutical companies to quickly follow up also ceased to exist。
in the case of many drug companies flocked into the situation, the price of license in the rising ship。The price of the same drug four or five years ago and the current price are three or four times different。Against this backdrop, investors are no longer impressed by the license in story。
At the same time, the capital winter is cold, innovative pharmaceutical companies are Mired in financing difficulties, IPO obstacles and other problems, and license in transactions will naturally be more cautious。
02、当红利消失
现在，电商红利已经基本没有了。Because as long as there is a dividend, sellers will quickly gather and rob buyers until supply and demand balance and the dividend disappears。
Innovative drugs have also come to this stage, and the internal volume has also come from this。
License in模式在现实中也遭遇了重重挑战。First of all, the tightening of IPO policy has made the license in China no longer popular, and some license in overseas clinical projects have failed to achieve the expected effect, which continues to test the patience of the market。
When the dividend could no longer be sustained, things started to look bad for license in。
In the past, innovative drug companies introduced projects from overseas, and the commercial terms often defined the Greater China interests first。Won foreign clinical stage projects, and then prepared to basically copy overseas research indications and clinical programs in China, occasionally modified, but also for streamlining clinical and accelerate market consideration。
To put it bluntly, spending money to introduce projects and get domestic rights and interests is more for pharmaceutical companies to "gather together" pipelines。But this "regular" license in the country is becoming less and less operational。
On the one hand, this is because the time gap window will never return, and on the other hand, because the country is also becoming the birthplace of innovation。This can be seen from the license out data in the first half of the year。
in the first half of the year, there were 17 innovative drug projects going to sea, with a total disclosed amount of 14.3 billion US dollars, more than three times that of the same period last year, among which, the total cooperation between Brisiscom and Eisai on her2 ADC alone reached 2 billion US dollars, exceeding the total license in the first half of the year。
The current fire ADC drugs have become the main camp of license out of domestic innovative drugs, and overseas pharmaceutical companies have come to sweep goods in China。in this case, the license in mode is naturally difficult to make a difference in the ADC field。
Dividends are always short-lived, but the importance of licenses in today's innovative drug industry will not disappear when they are out of the mainstream。Because it is a shortcut for the licensor to obtain cash flow in the early stage of commercialization, it is also a way for the importer to fill the short board of the pipeline。
只不过模式正在发生改变。
Pharmaceutical companies are also more concerned about "operation" at the license level, in addition to targeting unmet clinical needs, considering how to avoid the crazy internal volume of the same target in China, and more specifically, pharmaceutical companies are beginning to target the global rights and interests of some projects。For example, when introducing the new generation of DLL3 ADC (YL212) from Yilian Biology this year, it signed a global exclusive license agreement, and it obtained the global development and commercialization rights of YL212。
Another example is Genting Xinyao, which has entered into a cooperation and licensing agreement with Kezar to develop, manufacture and commercialize zetomipzomib, a self-immunizing drug for Kezar, in Greater China, South Korea and certain Southeast Asian countries。
Of course, from China's rights and interests to the global market, this puts forward higher requirements for the comprehensive ability of pharmaceutical companies, whether it is capital or research and development, clinical, and commercialization。
License inHow effective it will be remains to be seen, but this sends a big signal that the license in model will not stop。
03、创新药的面子和里子
It seems that the controversy about license in China has not been interrupted for a long time。
But in fact, the global biotechnology industry has been developing for decades, and the license in different types of companies is not uncommon, and it has always been an important strategy for multinational pharmaceutical companies on the other side of the ocean to expand the pipeline。
License in模式本身并没有问题。License in mode itself is neutral, and there is no right or wrong, the key is, what is the starting point of using this mode, and how to land。
If you carefully observe the license in overseas pharmaceutical companies, you will find that compared with the innovative varieties license in domestic pharmaceutical companies, overseas big pharmaceutical companies or biotech, it is more common to develop a new development path after obtaining pipeline authorization。
Horizon Therapeutics, for example，Development of Teprotumumab, a monoclonal antibody targeting IGF-1R，The drug was first developed by Roche as a popular anti-tumor target，后权益几经辗转，Horizon获得权益，Start with thyroophthalmia (TED) as a direction。
This project was approved as the first TED drug to be marketed, with net sales reaching 8.8% in 2020 alone.$200 million, making it one of the most commercially successful rare disease drugs。
Behind this, pharmaceutical companies are not only required to make up for the gaps in the preliminary research (CMC, safety) of the introduced projects, but also to re-select clinical indications and design schemes from their own strategies。
这涉及了创新药研发的全流程。所谓研发，英文是R&D，即Research研究&Development开发。This is actually two types of complementary but not quite the same work, research is to design a drug, development is clinical development, including clinical indication route, design, promotion。
in the past, it was believed that license in could help domestic pharmaceutical companies smoothly go through the relatively weak R link and accelerate the drug market。But actually, a more meaningful license in practice might be the overseas model。Even if the project has reached the middle and late clinical stage, there is still a lot of research work that can be carried out, which is why Horizon and other overseas pharmaceutical companies will reshape the research and development path based on their own research results after obtaining the corresponding project rights。
Research and development and introduction, one is the inside of innovative drugs, one is the face, the inside determines the face。
The key to innovation is to break the logic of yesterday, and this is also true of the license in。
（信息来源：氨基观察）
The first subject was enrolled in the phase 3 clinical study of meiglutide biosimilar drug of East China Medicine
9Huadong Pharmaceutical announced that the Phase 3 clinical trial of Simeiglutidine injection biosimilar jointly conducted by its wholly-owned subsidiary ZhongAmerican Huadong and Chongqing Paijin Biological completed the first subject enrollment and administration。This is a multicenter, randomized, open, and parallel controlled Phase 3 clinical study to demonstrate the equivalence of the investigational drug Semaglutide injection with the original drug for glycemic control after 32 weeks of treatment in patients with type 2 diabetes with poor glycemic control after metformin treatment。
Semaglutide is a long-acting human glucagon-like peptide-1 (GLP-1) analogue with 94% homology to the amino acid sequence of natural GLP-1, and can act as a GLP-1 receptor agonist。Semaglutide, developed by Novo Nordisk, has been approved overseas for the treatment of type 2 diabetes and for the control of general obesity or overweight, and in China for the treatment of type 2 diabetes。
Public information shows that semiglutide reduces blood sugar by stimulating insulin secretion and reducing glucagon secretion。The mechanism by which the drug lowers blood sugar also involves a slight delay in early gastric emptying after a meal。Semaglutide also reduces appetite, reduces food intake, induces weight loss, and significantly reduces the risk of major cardiovascular events in patients with type 2 diabetes。
Simaglutide injection is a biosimilar drug, which is a highly effective and highly selective GLP-1 receptor agonist, and is intended to be used in the clinical treatment of adult type 2 diabetes。In October 2020, Sino-American Huadong and Chongqing Paijin signed a product cooperation development agreement to cooperate in the development and commercialization of Simeiglutide injection on a global scale。Chongqing Paijin is responsible for the completion of the preclinical research of Simaglutide injection to meet the IND declaration standard in China;Central America East China is responsible for the subsequent global development, registration and commercialization of the product。
According to a press release from Huadong Medicine, the completed Phase 1 clinical trial has demonstrated pharmacokinetic similarity between the company's Semaglutide injection and the original product in healthy people。This Phase 3 study is planned to be carried out in more than 50 clinical research centers in China, enrolling no less than 496 adult subjects with type 2 diabetes, and is expected to complete the enrollment of all subjects in the first half of 2024。
（信息来源：医药观澜）
The bridge study of Rongchang Biotecitacept injection and Tecitacept injection dosage form was approved
9Rongchang Biophamaceutical (Yantai) Co., Ltd. announced that a dosage form bridging study trial of Taitacept injection (pre-filled) and Taitacept injection (freeze-dried powder injection) was approved by the Center for Drug Evaluation (CDE) of the State Drug Administration。
Taitacept injection (pre-filled) will provide patients with a more convenient way to administer the drug。Compared with the traditional packaging, this type of injection not only simplifies the preparation and management of medication, but also improves the accuracy of the dosage, and patients can take the medicine home after training to inject themselves, which is not only more convenient to use and reduce the risk of medication errors。
此前，2020年1月，Based on the significant efficacy and safety of Taitacept for injection for systemic lupus erythematosus (SLE) in phase Ⅱb in China，The U.S. Food and Drug Administration (FDA) has approved the international Phase III study of Taitacept in patients with SLE directly in the United States，The study used the liquid form of Taitacept (pre-filled injection).。
泰它西普（商品名：泰爱®It is an innovative double-target fusion protein drug independently developed by Rongchang Biology, which can effectively block the proliferation of B lymphocytes and the maturation of T lymphocytes by simultaneously inhibiting the overexpression of BLyS and APRIL cytokines, and treat a variety of autoimmune diseases mediated by B cells。In March 2021, the first indication of Taitacept was conditionally approved by the State Food and Drug Administration, becoming the world's first dual-target biological new drug for the treatment of systemic lupus erythematosus。除SLE外，The marketing application for the treatment of rheumatoid arthritis has been accepted by the CDE，Phase III clinical studies are underway for the treatment of IgA nephropathy, optic neuromyelitis spectrum disease, primary Sjogren's syndrome, myasthenia gravis and multiple sclerosis，I/II clinical trials are underway for a number of other indications。
（信息来源：药智新闻）
艾伯维SKYRIZI®Good news!All primary and secondary study endpoints were met in a head-to-head study with ustekinumab in Crohn's disease
近日，艾伯维宣布SKYRIZI®(risankizumab）对比Stelara®The Phase 3 SEQUENCE study of ustekinumab in moderate-to-severe Crohn's disease met all primary and secondary endpoints。
SEQUENCEThe clinical trial evaluated risankizumab versus ustekinumab in adults with moderate to severe Crohn's disease with a history of failure of one or more anti-tumor necrosis factor (TNF) treatments over a 48-week period。The Risankizumab group was given an intravenous induction dose of 600mg at weeks 0, 4, and 8，Subcutaneous injection of 360mg every 8 weeks from week 12 onwards;ustekinumab group，第0周静脉给药，之后每8周皮下注射90mg，The two groups were compared by week 48 in patients with moderately to severely active Crohn's disease who had failed one or more anti-TNF treatments。
研究结果达到了首个主要研究终点，Clinical remission at week 24 (according to the Crohn's Disease Activity Index [CDAI])，定义为CDAI<150），risankizumab was not inferior to ustekinumab (non-inferiority threshold was 10%);The response rate in the risankizumab group was 59 percent，The ustekinumab group was 40%。
Results met the second primary endpoint, endoscopic response at week 48 (SES-CD≤4, at least 2 points lower than baseline, and no sub-score greater than 1 point).。Risankizumab优效于ustekinumab；risankizumab组的缓解率为32%，ustekinumab组的缓解率为16%（p<0.0001）。
In the SEQUENCE study, the safety profile of risankizumab was consistent with the known safety profile of risankizumab, and no new safety risks were observed。In the Risankizumab group, the most common adverse events included COVID-19, headache, and Crohn's disease.In the ustekinumab group, the most common adverse events included COVID-19, Crohn's disease, and joint pain。
SEQUENCEThe full results of the study will be presented at a future medical meeting and submitted to a peer-reviewed journal for publication。
RisankizumabSKYRIZI is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading the development and commercialization of Skyrizi worldwide。
（信息来源：药智新闻）
Fosun Pharmaceutical: Its holding subsidiary, Fukesue, was approved for clinical trials
Fosun Pharmaceutical announced on the evening of September 22 that the company's subsidiary Shanghai Fosun Pharmaceutical Industry Development Co., Ltd. recently received CDE approval for clinical trials of its licensed product anti-human T cell rabbit immunoglobulin for the prevention of graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation。The drug is a listed therapeutic biological product. As of August 2023, the cumulative R&D investment of the Group at this stage for the drug is about 30.65 million yuan (unaudited).。
同日复星医药公告，The company's holding subsidiary Fuhong Hanlin Biotechnology Co., Ltd. and its holding subsidiaries independently developed Hans-like (namely, Srulizumab injection) combined with fluorouracil and platinum drugs for the first-line treatment of PD-L1-positive unresectable locally advanced/recurrent or metastatic esophageal squamous cell carcinoma (ESCC), the listing registration application was recently approved by the national drug supervisionAuthority approval。
The announcement shows that Hans-like (that is, Srulizumab injection) is an innovative anti-PD-1 monoclonal antibody independently developed by the Group, which is mainly used for the treatment of a variety of solid tumors。As of August 2023, the Group's cumulative R&D investment for this drug (single drug and various combination chemotherapy) at this stage is about 23.01亿元（未经审计）。
（信息来源：中证网）
The Daiichi Sankyo/Astrazeneca TROP2 ADC is the first Stage III clinical success in breast cancer
9月22日，第一三共与阿斯利康共同宣布，TROP2 ADC Dato-DXd（DS-1062）针对既往接受过内分泌治疗和至少一种全身治疗的不可切除或转移性HR阳性、HER2低表达或阴性（IHC 0、IHC 1+或IHC 2+/ISH-）乳腺癌的III期临床试验TROPION-Breast01研究达到PFS主要终点。
Compared to the investigator-selected chemotherapy regimen, Dato-DXd showed a statistically significant and clinically significant improvement in progression-free survival (PFS)。At the same time, an improvement trend in both primary endpoints of OS was observed. The data was not yet mature at the time of interim analysis, and OS will continue to be evaluated as planned。
This is the first phase III clinical trial of Dato-DXd in breast cancer to publish results, and with the positive results of the trial, the two companies intend to submit the corresponding marketing application to global regulatory authorities。In the field of breast cancer, the drug has two other phase III clinical trials underway: TROPION Breast02 for the first-line treatment of triple-negative breast cancer and TROPION Breast03 for the adjuvant treatment of triple-negative breast cancer。
值得一提的是，在今年7月，Dato-DXd has just received its first positive Phase III clinical results，TROPION Lung01 for advanced NSCLC also met the primary endpoint of PFS，There are also two phase III clinical trials, TROPION Lung07 and TROPION Lung08, covering first-line NSCLC，These two studies explored the combination regimen of Dato-DXd with the K drug Pabolizumab，值得期待。
Dato-DXdThe TROP2 ADC, jointly developed by Daiichi Sankyo and Astrazeneca, is loaded with a topoisomerase-1 inhibitor and is linked by a tumor-specific lyolytic linker with a DAR value of ~ 4。
Breast cancer is, of course, another key area of distribution, and through the Dato-DXd approach to breast cancer, Daiichi Sankyo will consolidate the advantages established by Enhertu and broaden the comprehensive coverage of breast cancer across all lines。
（信息来源：生物制品圈）
ADCPhase 3 combination therapy trial achieved double primary endpoints!First-line treatment for patients with advanced bladder cancer
9月23日，Astellas and Seagen announced，The drug Padcev (enfortumab vedotin) combined with the PD-1 inhibitor Keytruda (pembrolizumab) achieved dual primary endpoints in a Phase 3 EV-302 clinical trial in patients with initially treated locally advanced or metastatic uroepithelial carcinoma (la/mUC) versus chemotherapy。The EV-302 trial is intended to serve as a confirmatory trial for accelerated FDA approval of the combination therapy and as a basis for filing a global regulatory application。
Bladder cancer is the 10th most common cancer worldwide, with more than 57 new cases diagnosed each year.3万例。Urothelial cancers most often originate in cells inside the bladder and account for about 90% of bladder cancer cases。In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and the renal pelvis。Most patients with urothelial cancer are diagnosed at an early stage, but about 50% of patients who undergo surgery experience disease progression and recurrence within 2-3 years after surgery。In addition, about 20%-25% of patients with urothelial carcinoma develop metastatic disease。
PadcevIs an antibody-coupled drug (ADC) that targets Nectin-4, a protein that sits on the cell surface and is highly expressed in bladder cancer。Non-clinical data suggest that the anticancer activity of this drug is due to the fact that it binds to cells expressing Nectin-4 and then internalizes and releases the anti-tumor drug MMAE into the cells, causing the cells to no longer proliferate (cell cycle arrest) and programmed cell death (apoptosis) to occur.。Pembrolizumab is a PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, to activate T lymphocytes for anti-tumor efficacy。In April 2023, based on the results of the EV-103 trial, the US FDA accelerated approval of Padcev in combination with Keytruda for la/mUC adult patients who are not suitable for cisplatin-containing chemotherapy。
EV-302The KEYMATE-A39 trial is an open-label, randomized controlled phase 3 study evaluating the efficacy and safety of Padcev versus Keytruda in previously untreated la/mUC patients。In the study, patients were randomly treated with combination therapy or chemotherapy。The double primary endpoint of this trial was blinded Independent Center Review (BICR) according to RECIST 1.Overall survival (OS) and progression-free survival (PFS) assessed in Version 1。
The analysis showed that the combination therapy met the dual primary endpoints of OS and PFS compared to chemotherapy。The Independent Data Monitoring Board determined at the time of the interim analysis that OS exceeded a predetermined efficacy threshold。The safety results of the combination were consistent with those previously reported in patients with la/mUC who were not eligible for cisplatin therapy。
（信息来源：药明康德）
China's first new drug for lung cancer EGFR20ins is listed
Recently, the State Medical Products Administration conditionally approved the 1 type of innovative drug Suvotinib tablet (trade name: Suvotinib) declared by Dizhe (Jiangsu) Pharmaceutical Co., LTD。The drug is suitable for disease progression during or after prior treatment with platinum-containing chemotherapy，或不耐受含铂化疗，Locally advanced or metastatic non-small cell lung cancer with epidermal growth factor receptor exon insertion mutations (EGFR20ins) was confirmed by testing，NSCLC）的成人患者，This provides a new treatment option for patients with locally advanced or metastatic NSCLC with EGFR20ins。
For adult patients with locally advanced or metastatic non-small cell lung cancer with suvotinib adapted epidermal growth factor receptor exon 20 insertion mutations, the EGFR20ins gene test is available。In addition, other site mutations common to EGFR, such as exon 19 deletion mutation, exon 21 point mutation, exon 18 point mutation, can also be detected。
With the identification of a series of oncogenic driver genes in lung cancer, a number of domestic and international studies have shown that targeted therapeutic drugs have greatly improved and prolonged the prognosis and survival of patients with non-small cell lung cancer carrying corresponding driver genes。There are many common mutations of EGFR gene in non-small cell lung cancer. EGFR 20ins has an incidence of about 2-3% in non-small cell lung cancer and is the most common mutation type among rare EGFR mutations, accounting for about 30-40% of rare EGFR mutations。Studies have reported that EGFR 20ins account for 4 of all EGFR mutations in Western populations.8-12% EGFR 20ins in Chinese population accounted for 3-4% EGFR mutations。China's first "Chinese expert Consensus on Standardized Diagnosis and Treatment of EGFR 20 Exon Insertion Mutation non-small cell Lung Cancer (2023 edition)" was published in the lung cancer journal "Chinese Journal of Lung Cancer"，It is hoped that patients with EGFR20ins, a rare target in this type of lung cancer that once had a poor prognosis, will have more treatment options。
EGFREpidermal Growth Factor Receptor, or epidermal growth factor receptor, is normally embedded in the cell membrane on the surface of cells. It is a membrane protein that plays an important role in the proliferation, growth, repair and survival of tumor cells。The EGFR gene is located in the 7p12-14 region of the short arm of human chromosome 7 and consists of 28 exons, of which exons 18-24 comprise the tyrosine kinase domain encoding the gene。研究发现，There are many mutations in the tyrosine kinase region of EGFR gene，These mutations are mainly concentrated in exon 18-21，The deletion mutation of exon 19 and the mutation of exon 21 L858R are the most common，All were sensitive mutations of EGFR-TKI.Exon 18 G719X, exon 20 S768I and exon 21 L861Q are also sensitive mutations.T790M mutation in exon 20 is associated with EGFR-TKI acquired resistance，The positive rate of EGFR gene sensitive mutation in Asian and Chinese lung adenocarcinoma patients is 40-50%。Clinical studies have found that these mutations can well predict the effect of targeted drugs in the treatment of non-small cell lung cancer, and provide guidance for tumor drug use。
EGFR-TKIsIt is mainly targeted at lung adenocarcinoma patients with EGFR gene mutation，多项临床试验已证实，Egfr-tkis for EGFR targets，Such as ohitinib, erlotinib, gefitinib, etc，Patients with non-small cell lung cancer who carry EGFR mutations can benefit significantly from EGFR-Tkis treatment。According to statistics, in NSCLC patients, oral targeted drugs are 70% effective for EGFR mutation population, but less than 1% effective for EGFR non-mutation population。Therefore, detection of EGFR mutations is the basis for judging whether some targeted drugs are effective。Common testing methods for EGFR include single-gene testing and second-generation sequencing。Single gene testing is for a certain or several genes to detect, its process mainly includes collecting samples, extracting DNA(deoxyribonucleic acid), computer detection and analysis of gene mutations。
（信息来源：转化医学网）
Kelun Pharmaceutical "progesterone gel" listing application accepted, "the first imitation" will flower who？
9On October 20, the latest publicity of CDE showed that the listing application of four generic drugs progesterone vaginal slow-release gel submitted by Sichuan Kelun Pharmaceutical company was accepted on September 19, and only the original drug was approved for listing in China。Previously, Fairy Ju Pharmaceutical, Hebei Xinzhang Pharmaceutical/Hebei Yadong Pharmaceutical, Zhejiang Aisheng Pharmaceutical has submitted the generic drug listing application of this variety of dosage form and was accepted。
Progesterone, also known as progesterone hormone, progesterone, is the main biologically active progesterone secreted by the ovary, which can protect the female endometrium, provide support and protection for the early growth and development of the fetus during female pregnancy, and can play a certain calming effect on the uterus。Clinically, progesterone is used in the clinical diagnosis of amenorrhea or amenorrhea causes such as threatened abortion and habitual abortion。
Progesterone vaginal slow-release gel was first developed by Columbia Laboratories under the brand name Crinone。Through targeted administration, the drug improves endometrial receptivity, promotes embryo implantation and reduces the risk of miscarriage as a complementary treatment for assisted reproductive technology in women who are infertile due to progesterone deficiency。The original drug adopted Columbia's unique patented bioadhesive delivery drug release technology, and used hypoallergenic polycarpofil as the matrix to minimize the leakage of progesterone gel in the vagina, which was the mainstream recommended dosage form for assisted reproduction。
ColumbiaProgesterone vaginal sustained-release gel has been approved in several countries, and it is licensed for sale outside the United States to Merck Serono, all for progesterone supplementation in assisted reproduction。In 2008, the original research drug was approved for import registration in China for the first time, the specification is 8% (90mg), the trade name "Snow", has not yet entered the medical insurance。
In recent years, the patient base and prevalence rate of infertility in China have continued to rise。According to Frost & Sullivan data, the number of infertile couples in China is increasing year by year, and the number will reach 50.5 million in 2020。Pharmaceutical Rongyun data show that in recent years, the sales of progesterone vaginal sustained-release gel in hospitals have continued to rise。另据米内网数据显示，In 2021, terminal progesterone sales in China's urban public hospitals, county-level public hospitals, urban community centers and township health centers (referred to as China's public medical institutions) exceeded 1.7 billion yuan;among，Progesterone vaginal sustained release gel is the "leader" in the market of this product，2021年销售额突破7亿元，同比增长29.6%, ranked second in the TOP20 progesterone products。
As a common drug for assisted reproduction, progesterone vaginal slow-release gel has a bright prospect, and has also attracted a number of domestic enterprises to lay out generic drugs。新京报记者查询CDE受理品种目录，2022年8月，Fairy Ju Pharmaceutical first mentioned progesterone vaginal sustained release gel marketing application and accepted;November of the same year，Hebei Xinzhang Pharmaceutical/Hebei Yadong Pharmaceutical also submitted the listing application of the variety and was accepted;Zhejiang Aisheng Pharmaceutical and Kelun Pharmaceutical respectively declared the variety on the market in June and September this year，均在受理中。
In addition, there are many listed pharmaceutical companies such as Sentient Pharmaceutical, Shutai Shen, Baicheng Pharmaceutical, Jiangsu Wuzhong, Enhua Pharmaceutical, and Taienkang in the layout。
（信息来源：新京报）
Astrazeneca Ohitinib new indication filed for listing in China
9On October 21, CDE's official website showed that Astrazeneca's application for the marketing of ocitinib for a new indication was accepted。Ocitinib is an irreversible third representative epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) with clinical activity against CNS metastasis。该产品已有3项适应症在中国上市，They are: 1) for disease progression during or after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI)，And adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR T790M mutation positive were confirmed by testing;2) For first-line treatment of NSCLC patients with EGFR exon 19 deletion or exon 21 (L858R) replacement mutations;3) Adjuvant therapy for adult patients with EGFR-sensitive mutated NSCLC after tumor resection。
Since its launch in 2015, the Ocitinib market has been performing well。The product began with full-year sales of more than $5 billion in 2021 and was as high as 29 percent in the first half of this year.$1.5 billion, mainly due to the expansion of its indications for adjuvant treatment of early lung cancer。
In May, Astrazeneca announced positive results from the Phase III Flaura2 study of ocitinib in combination with chemotherapy in EGFR-mutated NSCLC, with statistically significant and clinically significant improvements in PFS, data that were presented at the 2023 World Congress on Lung Cancer (WCLC)。Compared with ocittinib monotherapy, the investigator-evaluated combination of ocittinib extended the median PFS by 8 percent.At 8 months, the median PFS in the oxitinib combined chemotherapy group evaluated by the Blind Independent Center Review Committee (BICR) was 9 months longer.5个月。
（信息来源：医药魔方）
Blockbuster migraine drug!Novartis receives marketing approval for irenaiumab in China
9Novartis' Erenumab injection was approved in China to prevent migraines in adults only once a month。
ErenumabAmgen and Novartis co-developed a fully human monoclonal antibody to prevent migraine by blocking the activity of calcitonin gene-related peptide (CGRP)。In May 2018, Erenumab was approved by the FDA, becoming the world's first approved antibody drug targeting CGRP receptor.Launched in the EU in July 2018。According to the company's financial report, Erenumab's sales revenue in 2022 was 6.32亿美元。
2021In March, Novartis announced positive results from the DRAGON Phase III study, which met its primary endpoint。This is a randomized, double-blind, multicenter, placebo-controlled Phase III clinical trial designed to evaluate the efficacy and safety of Erenumab for the prophylactic treatment of chronic migraine in adults。A total of 557 patients were enrolled in the study, mainly in Asian and Chinese populations。
The results showed that the Erenumab 70mg group was significantly better than the placebo group on the end point (primary endpoint) of reduced migraine days per month (MMD) compared to baseline during the last 4 weeks of the 12-week double-blind treatment period。In addition, the response rate in the Erenumab 70mg group was significantly higher than that in the placebo group with a reduction of more than 50% in the number of migraine days per month from baseline。At the same time, the safety tolerability profile of Erenumab was similar to that of placebo, and no new safety concerns were identified。
Migraine is a common chronic neurovascular disease, its condition is characterized by repeated attacks, one or both sides of the pulsating severe headache and mostly in the side of the head, accompanied by nausea, vomiting and sensitivity to light, sound and smell, about 1/3 of the patients before the onset of the nervous system aura symptoms。It is defined by the World Health Organization as one of the most disabling chronic diseases。中国偏头痛患病率为9.3%，约有超过1.With 300 million sufferers, it is the country with the highest number of migraine sufferers in the world。Through the standard preventive treatment can effectively improve the effect of acute phase of treatment, reduce the frequency and degree of attacks, reduce the impact on work and life。
（信息来源：医药魔方）
Kangrun Biological freeze-dried rabies vaccine for human use was approved for market
9On October 22, the NMPA official website announced that the listing application of freeze-dried human rabies vaccine (Vero cells) submitted by Jiangsu Kangrun Biotechnology Co., Ltd. has been approved。Public information shows that this vaccine is suitable for the prevention of rabies。
Rabies virus is a ribonucleotide type rhabdovirus, which is highly virulent in mammals such as dogs and cats。Infection with the virus can cause rabies, which is an acute infectious disease of humans and animals. Clinical manifestations are unique fear of water, wind, pharyngeal muscle spasm, progressive paralysis, etc. Once symptoms appear, the fatality rate is close to 100%。At present, there is a lack of effective clinical treatment for rabies, so post-exposure prophylaxis is crucial, mainly through vaccination of human rabies vaccine and injection of passive immune agents。
According to the official website of Kangrun Biology, its freeze-dried human rabies vaccine (Vero cells) is inoculated with a fixed strain of rabies virus into Vero cells, which is cultured, harvested, concentrated, inactivated, and freeze-dried to prevent rabies。
According to China Drug clinical trial registration and information publicity platform，Conrun Bio is conducting two Phase 3 clinical trials of freeze-dried human rabies vaccine (Vero cells)，One was a randomized, blind, controlled trial of the same type of vaccine to evaluate the safety and immunogenicity of the vaccine in healthy people aged 10 to 50 years，The other is a randomized, open, parallel controlled Phase 3 clinical supplement study to evaluate the immune persistence of the 5-dose immunization program and the 4-dose immunization program (2 doses of the first dose) in healthy people aged 10 to 50 years。
（信息来源：医药观澜）
Merck's "first-in-class" therapy is eligible for priority review by the FDA for the treatment of advanced cancer patients
9月20日，默沙东（MSD）宣布，The FDA has accepted a Supplemental New Drug Application (sNDA) for Welireg (belzutifan), its "first-in-class" hypoxia-inducible Factor-2α (HIF-2α) inhibitor.，并授予优先审评资格，For the treatment of adult patients with advanced renal cell carcinoma (RCC)，These patients developed disease progression after receiving immune checkpoint and anti-angiogenic therapy。The FDA intends to complete the review by January 17, 2024。
Renal cell carcinoma is the most common type of kidney cancer, and about 9 out of 10 cases of kidney cancer diagnosed are renal cell carcinoma。肾细胞癌男性约为女性的2倍。Most cases are found by chance during imaging tests for other abdominal diseases。About 15% of kidney cancer patients are diagnosed at an advanced stage。
WeliregIt is the first HIF-2α inhibitor to receive accelerated FDA approval，It has been approved in the United States, the United Kingdom, Canada and several other countries and regions，Objective response rate (ORR) and duration of response (DOR) data from the Phase 2 LITESPARK-004 trial，For the treatment of adult patients with von Hippel-Lindau (VHL) disease who are associated with renal cell carcinoma, central nervous system hemangioblastoma, or pancreatic neuroendocrine tumors and do not require immediate surgery。
The sNDA application is based on data from the LITESPARK-005 trial，Based on a scheduled interim analysis conducted by the Independent Data Monitoring Board，In patients with advanced RCC who developed disease progression after treatment with PD-1/PD-L1 checkpoint inhibitors and vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKI)，Compared to everolimus，Patients in the Welireg group had a statistically significant and clinically significant improvement in progression-free survival (PFS)。The trial's key secondary endpoint, objective response rate (ORR), also showed statistically significant improvement。
（信息来源：药明康德）
KThe new indication of the drug was declared and listed to treat the newly diagnosed cervical cancer
9Merck announced that the Supplemental Biologics License Application (sBLA) for Palizumab (Keytruda, K drug) has been approved by the FDA for priority review for the treatment of newly diagnosed high-risk locally advanced cervical cancer patients in combination with concurrent chemoradiotherapy。The PDUFA date is January 20, 2024。If approved, drug K would be the first immunotherapy for this population。
The sBLA is based on the positive results of the Phase III KEYNOTE-A18 study。The study was a randomized, double-blind, parallel-controlled Phase III clinical trial，A total of 1060 patients with locally advanced cervical cancer with node-positive stage IB2-IIB or III-IVA who had not received any treatment were enrolled，To evaluate the efficacy and safety of K drug combined with concurrent chemoradiotherapy compared with concurrent chemoradiotherapy。The primary endpoints were progression-free survival (PFS) and overall survival (OS).。
Patients in the experimental group were treated with 20 doses of K (first 5 doses of Q3W, then 15 doses of Q6W) and concurrent chemoradiotherapy, plus external beam radiotherapy (EBRT), followed by concurrent chemoradiotherapy。The control group received placebo and concurrent chemoradiation plus EBRT followed by concurrent chemoradiation。
The results showed that the study met the primary endpoint of PFS。In addition, overall survival (OS) is also trending longer, although the data is not yet mature。
Previously, K drug has been approved in cervical cancer indications ① monotherapy for PD-L1-positive recurrent or metastatic cervical cancer that has progressed after chemotherapy ② Combined with bevacizumab and platinum chemotherapy for persistent, recurrent or metastatic PD-L1-positive cervical cancer。
Cervical cancer is the fourth most common cancer in women worldwide and is mainly caused by persistent infection with high-risk types of human papillomavirus (HPV)。据估计，2023年美国约1.40,000 new cases of cervical cancer and 4,000 deaths。In 2020, there will be about 110,000 new cases of cervical cancer in China, and about 60,000 deaths。
HPV vaccination is currently the most effective way to prevent HPV infection, however, although there are four HPV vaccines on the market worldwide, there are still many women of appropriate age who do not have the opportunity to vaccinate。However, there are only 6 clinically available cervical cancer treatment drugs, namely K drug, cardonilizumab, cimiprilizumab, bevacizumab, tisotumab vedotin and sepalizumab。Among them, only pabolizumab and bevacizumab can be used for first-line treatment of cervical cancer。
In the domestic phase III drugs under research, Kangfang Biologic Cardonilizumab, Hengrui SH-1701, stone drug Enlangsubezumab, Qilu Pharmaceutical PSB205, Yuheng Biologic Cepalizumab and Bokang prolgolimab are in the first-line treatment of cervical cancer phase III clinical。
（信息来源：医药魔方）
恩格列净新适应症获FDA批准上市，治疗慢性肾病
9月22日，Eli Lilly/Boehringer Ingelheim announces FDA approval of SGLT2 inhibitor Jardiance (empagliflozin)，Englipzin tablets are indicated for the treatment of adult patients with chronic kidney disease (CKD) who are at risk of progression，To reduce their estimated risk of sustained decline in glomerular filtration rate (eGFR), end-stage renal disease, cardiovascular death, and hospitalization。
This approval is based on the positive results of the EMPA-KIDNEY study。The study included more than 6,600 adults with CDK with or without type 2 diabetes。The results showed that compared with placebo, Jardiance reduced the relative risk of kidney disease progression or cardiovascular death in the composite primary endpoint by 28 percent (3 percent absolute risk reduction per patient-year) over standard care.6%，HR=0.72；95% CI：0.64-0.82；P<0.0001）。The event rate for the Jardiance group was 13.1% (432/3304) versus 16 in the placebo group.9%（558/3305）。
In addition, compared with placebo, Jardiance significantly reduced the risk of first and recurrent hospitalization (predetermined key secondary endpoints) by up to 14% (HR=0).86；95% CI：0.78-0.95；p=0.0025）。A total of 1,611 hospitalizations occurred in 960 patients in the Jardiance group (24.8起事件/100患者年）。In the placebo group, 1,895 hospitalizations occurred out of 1,035 patients (29.2例事件/100患者年）。EMPA-KIDNEY is the first study in which an SGLT2 inhibitor significantly reduced the risk of first and recurrent hospitalization in patients with CKD。
Englizine is a once-daily, highly selective oral SGLT2 inhibitor。To date, the drug has been approved by the FDA for the treatment of type 2 diabetes, heart failure with reduced ejection fraction/retention, cardiovascular risk, and chronic kidney disease in five indications。In addition, so far, Nglaglizin has also been approved in China for 3 indications, including type 2 diabetes and heart failure with reduced ejection fraction/retention。
（信息来源：医药魔方）
The star Alzheimer's drug Leqembi has been approved for sale in Japan
9Eisai and Bojian jointly announced that Leqembi injection (200 mg, 500 mg, lecanemab) has been approved in Japan for slowing the progression of mild cognitive impairment (MCI) and mild dementia caused by Alzheimer's disease (AD)。
LeqembiIt is A humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody against aggregated soluble fibril and insoluble forms of Aβ。Leqembi targets beta-amyloid, the main component of amyloid plaques that define the disease in the brains of Alzheimer's patients。Clinical trials have clearly shown that removing amyloid from the brain has measurable, meaningful benefits for people with early Alzheimer's disease。
LeqembiIs the first and only conventionally approved treatment to alter the underlying course of Alzheimer's disease by selectively binding to and eliminating the most toxic Aβ aggregates (fibrils) that cause neurotoxicity in AD, reducing the rate of disease progression and slowing cognitive and functional decline。
2020Bojian has submitted a Japanese New Drug Application (J-NDA) for Leqembi to the Japanese Ministry of Health, Labour and Welfare (MHLW) and has submitted a marketing authorization application for Leqembi, which is eligible for priority review in January 2023。Japan is the second country to receive traditional ratification after the United States in July 2023。
LeqembiThe approval in Japan is based on data from Eisai's large global Phase 3 clinical trial, Clarity AD, in which Leqembi met the primary endpoint and all key secondary endpoints with statistically significant results and confirmed the clinical benefit of Leqembi。The primary endpoints were the Global Cognitive and Functional Scale and the Clinical Dementia Rating Scale (CDR-SB).。
In Eisai's confirmative phase III study, Clarity AD, Leqembi demonstrated consistency across cognitive and functional scales and subgroups (race, ethnicity, comorbidivities)。As assessed by CDR, Leqembi treatment reduced the risk of progressing to the next stage of the disease by 31% (hazard ratio: 0.69）。
Slope analysis based on observed data and extrapolation to 30 months of CDR-SB showed that Leqembi treatment was 25.Five months was equivalent to a placebo at 18 months, suggesting that Leqembi could delay disease progression by up to 7 percent.5个月。A simulation model based on Phase II trial data suggests that Leqembi may slow the rate of disease progression 2.5～3.1 year, helping patients stay in the early stages of AD for longer。In addition, Leqembi maintains patients' health-related quality of life and reduces caregiver burden (23-56% reduction in score deterioration).。
Evidence on cognition and function, disease progression, health-related quality of life, and caregiver burden collectively suggests that Leqembi therapy provides positive benefits for patients, caregivers, clinicians, and society。
Eisai will conduct a post-marketing special use outcome survey (whole-case surveillance) for all patients receiving Leqembi in accordance with the approval conditions stipulated by the Japanese Ministry of Health, Labour and Welfare until data on a certain number of patients is accumulated after marketing。In addition, the appropriate use of Leqembi will be promoted in accordance with the packaging instructions, and training materials will be developed for healthcare professionals to assist in the management and monitoring of amyloid-associated imaging abnormalities (ARIA).。
Eisai is the leader in the development and global regulatory filing of Leqembi. Eisai and Bojian jointly commercialize and promote Leqembi, and Eisai has the final decision-making rights。In Japan, Eisai and Bojian will jointly promote Leqembi, with Eisai distributing the product as the marketing authorization holder。BioArctic has the right to commercialize lecanemab in the Nordic region, where Eisai and BioArctic are currently preparing for joint commercialization。
（信息来源：药智新闻）
亳州市场9月27日快讯
新青葙子：The price is 45-50 yuan /kg, and the price of old goods is still high。
巴戟天：Affected by the rainy weather in the origin, the amount of new goods on the market is reduced, the inventory is weak, and the price is rising. At present, the market is 125-130 yuan /kg for large meat, 110 yuan /kg for medium meat, and 105 yuan /kg for small meat。
金樱子：Production new into the middle and late period, there are businesses concerned, this year more new production, the price is low, the current Jiangxi unified goods market price of about 13 yuan /kg。
辽细辛：With the increase of goods in the market, the market price holds a high price shock, the demand is not large for the time being, and the market is adjusted slightly。At present, the market price of asarum root goods 250-260 yuan /kg, washed root goods 275-280 yuan /kg, to the end of the selection of goods priced from 400-450 yuan /kg。
白及：The supply is not moving fast, the new production is gradually approaching, the purchase and sales are generally, and the market is temporarily stable。At present, the market price of white and unified goods is 170-180 yuan /kg, and the price of selected goods is 190-200 yuan /kg。
葛根：Normal purchase and sale, small batch purchase and sale, the current market Kudzu Chai Ding unified goods price 12-13 yuan /kg, powder Kudzu unified goods price 15-18 yuan /kg range。
高良姜：Generally, the market supply is temporarily sufficient, the price is high, the concern is not much, the market is temporarily stable。At present, the market price of galangal unified goods is 49-50 yuan /kg。
薏苡仁：The purchase and sale are not fast, the market supply inventory is large, and the market fluctuates slightly。At present, the market coix seed large grain price is about 10 yuan /kg, and the price of Coix barley in Guizhou is 11.5-12元/kg。
槐米：Goods to increase, weak demand, recent consultation concerns not many businesses, the market stabilized。At present, the general unified goods of sopacia rice on the market 32-35 yuan /kg, and the price of green series is 38-40 yuan /kg。
葛花：Recently, there is little demand, and the supply of goods is mainly based on actual purchase and sales, and the market is relatively stable。At present, the market price of caraway unified goods 21-22 yuan /kg, floret asking 25-26 yuan /kg。
母丁香：Recently, there are not many consulting businesses, small batch purchase and sales, the market is running smoothly。At present, the market price of mother cloves is 12-13 yuan /kg。
（信息来源：康美中药网）
安国市场9月27日快讯
全蝎：At present, the new production is over, the production is gradually clear, the early market has a small adjustment, but the space is not large, the market is now small clean water prices at 2250 yuan, salt water prices at 1000 yuan, continue to pay attention to the late supply of goods sales。
山柰：Recently affected by the cost of goods to rise, the supply of bulk sales smooth, the overall market has risen, the market now the price of imported small pieces of apple between 35-36 yuan, the price of large goods at 40 yuan。
小茴香：The early market rose, and then the normal purchase and sale of goods, the recent business attention to the general, the market is now imported cumin green goods price at 20 yuan, continue to pay attention to the late source of goods sales。
高良姜：The supply of goods is in a normal state of purchase and sale, and the business attention is less than the previous stage, and the market price of galangal is between 47-48 yuan, and the price of pieces is between 40-50 yuan。
蒲公英：Recent supply trading smooth, the overall market is slightly higher than the previous period, the market wild dandelion due to the quality of different prices between 12-15 yuan, the product this year's supply production is relatively small, continue to pay attention to the late supply of sales。
青葙子：At present, the output of new goods, the supply of goods has a quantity, the market has declined significantly compared with the previous period, but the price of high cost suppliers is still high, and the net price of the new cockscomb seed in the market is 45 yuan。
朱砂：Affected by the small amount of goods, the holders have the psychology of reluctant to sell, and the Shouting price is significantly higher than the previous period, and the market is now priced at 900 yuan for vermilion natural goods, and the price of water flying goods is 850 yuan。
延胡索：The market is running at a high level, buyers are buying according to demand, the recent market performance is strong, and the general goods of Yanhu in the market are Shouting at 145 yuan, and the price of the full inspection goods is about 155 yuan。
三七：The recent supply of goods is in a normal state of purchase and sale, the business attention is general, the market has no change with the previous period, the current market price of 37 standard 120 goods is between 130 yuan, the price of standard 80 goods is between 135-140 yuan, and the price of standard 60 goods is between 145-150 yuan。
黄草石斛：For Thailand imports, the recent market has been strong, businesses shout higher prices, now the market yellow grass Dendrobium bar goods more shout price at 48 yuan。
玫瑰花：Most of the recent supply is normal purchase and sale, the market has no change with the previous period, and the external business attention is generally, and the current market of Shandong rose goods is between 60-65 yuan。
沙苑子：Recent business attention is general, the supply of goods is in a normal state of purchase and sale, the market is running in the firm, and the market price of flatstock is about 300 yuan, and the price of package inspection is about 380 yuan。
（信息来源：中药材天地网）
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