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    Home > Active Ingredient News > Drugs Articles > Revealing the deep logic behind Yasheng/Xinda’s 1.6 billion yuan-level cooperation in the era of "integration, vertical and horizontal" in the pharmaceutical industry

    Revealing the deep logic behind Yasheng/Xinda’s 1.6 billion yuan-level cooperation in the era of "integration, vertical and horizontal" in the pharmaceutical industry

    • Last Update: 2021-07-30
    • Source: Internet
    • Author: User
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    In the past few days, Asia Sheng Pharmaceutical-B (06855.
    HK) and Cinda Bio (01801.
    HK) reached a blockbuster cooperation of 1.
    6 billion yuan in the medical circle
    .

    In recent years, China's pharmaceutical industry is entering a new era of large-scale cooperation.
    The "integration" between different companies is no longer new.
    Among them, innovative pharmaceutical companies are more common in cooperation with multinational giants going overseas, alliances with traditional pharmaceutical companies, etc.
    Form of cooperation
    .

    However, two fast-growing innovative pharmaceutical companies such as Yasheng Pharmaceutical and Cinda Biopharmaceuticals will conduct a comprehensive, multi-level and in-depth approach from the three major aspects of "joint commercial promotion of core products", "joint clinical development of core products", and "equity investment".
    The binding cooperation case is indeed a pioneering work among local innovative pharmaceutical companies
    .

    In this regard, Yang Dajun, Chairman and CEO of Yasheng Pharmaceutical, said that if such cooperation is done well, it can achieve 1+1>10 results, which shows its deep expectations and confidence
    .

    As the saying goes: dreams and distance are important, but who you walk with is more important
    .

    Why the two companies can work together tacitly, Sina Pharmaceuticals returns to the cooperation project itself, in-depth discussion of the logic behind the cooperation between the two parties
    .

    Specifically, the cooperation projects between Yasheng Pharmaceutical and Cinda Bio include:

    1) Jointly develop and commercialize the third-generation BCR-ABL inhibitor HQP1351, the core product of Yasheng Pharmaceutical;

    2) Ascent Pharmaceuticals small molecule innovative drug APG-2575 and Cinda Bio's CD20 monoclonal antibody and CD47 monoclonal antibody have developed clinical cooperation respectively;

    3) Cinda Bio will subscribe for US$50 million worth of ordinary shares of Yasheng Pharmaceutical at HK$44.
    0 per share and obtain warrants for the purchase of US$50 million
    .

    Next, we will elaborate on these three aspects one by one:

    Commercialization of HQP1351, the first shot of Yasheng's new drug on the market



    Yasheng HQP1351 R & D and listing progress, the picture comes from the official website

    HQP1351 is an original class 1 new drug under research by Yasheng Pharmaceutical.


    It is an oral third-generation BCR-ABL inhibitor and has outstanding effects on BCR-ABL and a variety of BCR-ABL mutants including the T315I mutation


    As the first core product of Yasheng Pharmaceutical to apply for the listing of a new drug, HQP1351 is currently undergoing rapid development and marketing in the United States and China:

    In July 2019, HQP1351 was approved by the US FDA for clinical trials and directly entered phase Ib clinical studies
    .

    In May 2020, HQP1351 successively obtained the orphan drug qualification and the fast-track qualification for review granted by the US FDA
    .

    In October 2020, HQP1351 submitted a new drug marketing application (NDA) in China, and it has been included in the priority review and breakthrough therapy category by CDE
    .

    It is reported that HQP1351 is expected to obtain a conditional marketing license for the treatment of T315I mutation-resistant CML patients in the second half of 2021, and will then become China’s first third-generation BCR-ABL targeted drug-resistant chronic myelogenous leukemia (CML) Therapeutic drugs
    .

    For patients, this will undoubtedly be a great boon
    .



    CML, also known as chronic myeloid leukemia, is a rare malignant hematological disease
    .


    Before the birth of the first-generation BCR-ABL inhibitor-Imatinib (Gleevec) in 2001, the five-year survival rate of CML patients was less than 30%


    Imatinib created the era of CML targeted therapy, but the emergence of imatinib resistance has caused another difficult medical problem.


    Many patients need to take nilotinib and dasa after drug resistance.
    Second-generation BCR-ABL inhibitors such as tinib and bosutinib, but after a period of time they will develop resistance


    Note: BCR-ABL kinase region mutation is one of the important mechanisms of acquired drug resistance.


    T315I mutation is one of the common types of drug resistance mutations, and the incidence rate in drug-resistant CML is as high as about 25%


    However, currently there is only one third-generation drug Pranatinib on the market, and it has not yet been approved in China
    .


    Many Chinese CML patients who are resistant to the first and second-generation BCR-ABL inhibitors are still drug-free, and the survival time is often only a few months


    As the first domestically produced third-generation BCR-ABL inhibitor, Yasheng Pharmaceutical’s HQP1351 is approaching to market, it will undoubtedly accelerate the change of the situation that there is no cure for CML patients who are ineffective in China's existing drug treatments
    .

    In addition, it is worth noting that, as the only third-generation BCR-ABL inhibitor currently on the market in the world, Pranatinib has been requested by the FDA to suspend its sales due to the risks related to "life-threatening thrombosis and severe vascular stenosis".
    Since the drug was the only option for patients with T315I gene mutant CML, the FDA approved it again under safety monitoring by restricting indications and adding black boxes to warn about the risks of arterial thrombosis and liver toxicity related to treatment
    .

    It can be seen that if Yasheng Pharmaceutical HQP1351 can achieve better clinical data performance in the future, the global market prospects will also be infinitely broad
    .

    As for a unique innovative drug like HQP1351, how Yasheng Pharmaceutical will use it to make the first shot of the new drug on the market is undoubtedly the key move
    .

    Nowadays, as many domestically produced new drugs have gradually matured, "commercialization capability" and "average return on investment of new drugs" have become another high ground for innovative pharmaceutical companies to fight for pipelines and post-market speed.
    At the same time, "commercialization capabilities" have also become An increasingly critical factor affecting market investment logic
    .

    Yasheng Pharmaceutical was established in 2009 and has been well-known for its R&D >
    .


    HQP1351's listing pace is approaching, which means that it will soon usher in the "commercialization test


    In order to deliver a beautiful market answer sheet, Yasheng Pharmaceutical began to form its own commercialization team at the end of last year, and on this basis, it chose to form an alliance with Cinda Bio to increase its commercialization layout
    .

    The two parties reached an agreement on HQP1351: 50%:50% of the profits from the joint promotion will be shared, and Yasheng Pharmaceutical will receive a down payment of 30 million U.
    S.
    dollars and be eligible for the agreement terms of a milestone payment of no more than 115 million U.
    S.
    dollars
    .

    As the leader of local innovative pharmaceutical companies, Cinda Bio has accumulated outstanding performance in the number of research pipelines, production capacity and sales capacity in recent years, leading the industry
    .

    Choosing such a partner and cooperation method, Yang Dajun, Chairman of Yasheng Pharmaceutical, emphasized the following two important reasons:

    1) The aim is to further tap the value of HQP1351 products and promote the rapid expansion of its new indications
    .


    In this regard, Cinda Bio, which is also an innovative pharmaceutical company, undoubtedly has more support potential in terms of R&D concepts and R&D strength


    2) The aim is to work together to build an excellent hematology oncology team in China, and help HQP1351 quickly complete multi-level coverage in hospitals and pharmacies at all levels after the listing
    .


    Today, Cinda Bio has a sales team of more than 2,000 people, and its scale is far ahead among local innovative pharmaceutical companies, and it has certain experience and advantages in the field of hematology and tumors.


    In addition, some professionals also pointed out that through such cooperation, Yasheng Pharmaceutical can also replenish cash flow in a timely manner, and quickly provide ammunition for its large-scale clinical investment worldwide
    .

    For Cinda Bio, adding an exclusive innovative product HQP1351 that is approaching the commercialization stage based on its original R&D and sales advantages is also a multiplier task.
    It not only enhances its R&D layout, but also further commercializes it.
    The advantages are brought into play
    .
    Prior to this, Cinda Bio has reached a commercialization support cooperation with Baoyuan Pharmaceutical
    .
    It can be seen that Cinda Bio is building a stronger business map through an extended cooperation path
    .

    Bcl-2 is being developed at the time, a strong combination of large and small molecule drugs

    In the product strategy of Yasheng Pharmaceutical, if HQP1351 is the first bullet, then the development of a series of inhibitors for the treatment of cancer against the Bcl-2 target is another blockbuster weapon with high hopes
    .

    B lymphocyte tumor-2 gene (Bcl-2) is one of the most important oncogenes in apoptosis research
    .
    According to statistics, a total of 5 Bcl-2 inhibitors entered the clinical research phase from 2010 to 2019, namely Oblimersen, Navitoclax (ABT-263), Venetoclax (ABT-199), Obatoclax mesylate (GX15-070), AT-101 Among them, only AbbVie’s Venetoclax was approved for listing in the United States in 2016
    .

    In the development of Bcl-2 for more than 20 years, the Bcl-2 protein has experienced many twists and turns, including the identification of small molecule lead compounds, druggability, and target selectivity, from the proof-of-concept of drug targets to the listing of Venetoclax, before it was finally effectively transformed.

    .

    Nowadays, companies in the Bcl-2 field in China include Yasheng Pharmaceutical, BeiGene, and Fosun Pharma
    .
    Among them, Yasheng Pharmaceutical is a leader in the field of apoptosis in China and even in the world
    .

    According to Yasheng Pharmaceutical's official website, the company's research pipeline includes three targeted Bcl-2 inhibitor drugs, namely:

    APG-1252(BCL-2/BCL-xL);

    APG-2575(Bcl-2);

    AT-101(Bcl-2/Bcl-xL/Mcl-1)
    .

    Among them, AT-101 is currently in clinical stage Ⅱ/Ⅲ, and both APG-1252 and APG-2575 are in clinical stage Ⅰb/Ⅱ
    .

    This time, Yasheng Pharmaceutical will cooperate with Innovent Bio/Eli Lilly's anti-CD20 monoclonal antibody, Dabohua, and Innovent Bio's anti-CD47 monoclonal antibody letaplimab (IBI188), respectively, for APG-2575
    .

    APG-2575 is a new type of oral Bcl-2 small molecule inhibitor, which restores the apoptosis mechanism of tumor cells by selectively inhibiting Bcl-2 protein, thereby killing tumors
    .
    Data show that in preclinical studies, APG-2575 used alone, and combined with BTK inhibitors, CD20 mAbs, PI3K inhibitors, and Ascent Pharmaceuticals' own MDM2-p53 inhibitors, is effective against a variety of B-cell malignancies.
    Has good anti-tumor activity
    .

    APG-2575 is currently the second Bcl-2 inhibitor in the world and the first domestic Bcl-2 inhibitor with a clear curative effect and best-in-class potential
    .
    At this year’s American Society of Clinical Oncology (ASCO) annual meeting, APG-2575 was used for the first time in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) and other hematological malignancies.
    The test data is published in the form of an oral report
    .
    Its objective response rate (ORR) in the treatment of R/R CLL/SLL patients reached 80.
    0%, and it was well tolerated, with controllable adverse events.
    Dose limiting toxicity (DLT) was not observed at the highest dose of 1200 mg, and the maximum resistance was still not reached.
    There is no clinical or laboratory tumor lysis syndrome (TLS) report
    .

    This time, regarding the combination of APG-2575 and Innovent’s CD20 monoclonal antibody and CD47 monoclonal antibody, the industry believes that it is expected to further enhance the anti-tumor activity of the drug and reduce the company’s R&D costs and risks.
    After all, AbbVie’s Venetoclax The combined use of CD20 monoclonal antibody rituximab and other cases have been successfully demonstrated
    .



    In 2018, AbbVie announced that the FDA had approved Venetoclax and rituximab (CD20) for the second-line treatment of CLL/SLL
    .
    The clinical results showed that Venetoclax combined with Rituxan achieved 94.
    9% PFS and 26.
    8% CR at 24 months
    .

    In March 2020, the European Commission approved Venetoclax and Gazyvaro (Obinutuzumab, CD20 mAb) as the first-line treatment of chronic lymphocytic leukemia (CLL) in adult patients
    .
    This approval is based on the pivotal phase III CLL14 study, and the results show that Venetoclax and Gazyvaro have an ORR of 85%, a CR of 50%, a bone marrow MRD negative rate of 57%, and a peripheral blood MRD negative rate of 76%
    .
    Compared with SOC, combination therapy can significantly reduce the risk of disease progression and death
    .

    In December 2020, Venetoclax was approved for marketing in China.
    The indication is combined with azacitidine, decitabine or low-dose cytarabine (LDAC) for the treatment of newly diagnosed patients aged 75 years or older or failure due to complications Acute myeloid leukemia (AML) patients receiving strong induction chemotherapy
    .
    The test results showed that compared with azacitidine+placebo, Venetoclax+azacitidine has a complete response rate (CR) of 37%, CR+CRh (complete remission with partial hematological recovery) up to 65%, and placebo The CR of the group was only 18%, CR+CRh was only 23%; the OS of the treatment group was 14.
    7m, and the placebo group was only 9.
    6 months
    .

    It can be seen that by virtue of the different mechanism of action, Bcl-2 inhibitors have the potential advantages of combined treatment with multiple drugs to enhance anti-tumor activity, and the combination of Bcl-2 and CD20 monoclonal antibody is also becoming Bcl-2 An important development direction for inhibitors in the future
    .

    As the current popular target track for CD47 monoclonal antibody drugs, it is regarded as the next PD-1 by the industry and has high expectations
    .
    The blood toxicity of CD47 monoclonal antibody also makes combination therapy a consensus
    .

    As a result, the industry has paid more attention to the two collaborations between APG-2575 and Innovent Bio/Eli Lilly's anti-CD20 monoclonal antibody Dabohua and Innovent Bio's anti-CD47 monoclonal antibody letaplimab (IBI188)
    .
    The Yasheng/Cinda partners also expressed their expectations for such a "strong combination of large and small molecules"
    .

    Equity investment, welcoming new opportunities for innovation

    If the first two cooperations are Cinda Biotech’s commercialization of Yasheng Pharmaceutical’s core products and the potential of its R&D pipeline, then the third equity investment further demonstrates Cinda Bio’s confidence in Yasheng Pharmaceutical
    .

    In terms of equity investment, the agreement reached between Cinda Bio and Yasheng Pharmaceutical this time is:

    1) Cinda Bio will subscribe for US$50 million ordinary shares of Yasheng Pharmaceutical at HK$44.
    0 per share;

    2) Cinda Biotech has obtained the equity subscription warrant of Yasheng Pharmaceutical, and has the right to subscribe for the ordinary shares of Yasheng Pharmaceutical worth 50 million US dollars at a price of 57.
    2 Hong Kong dollars per share
    .
    If Cinda Biotech has not exercised the subscription rights within 6 months at a share price of 57.
    2 Hong Kong dollars or more per share of Yasheng Pharmaceutical, Yasheng has the right to redeem this part of the equity subscription warrants
    .

    Some people in the industry pointed out that equity investment is actually a manifestation of a genuine desire to share the results of corporate innovation, which means the determination to grow together
    .

    As of July 26, 2021, Yasheng Pharmaceutical-B (06885.
    HK) closed at HK$48.
    7 per share, an increase of about 42.
    4% from the issue price of HK$34.
    2 per share
    .
    Cinda Bio (01801.
    HK) closed at HK$76.
    25/share, which was an increase of over 445% from the issue price of HK$13.
    98/share, and was far ahead of the pharmaceutical companies listed in Hong Kong after the Hong Kong Stocks New Deal
    .

    In this regard, Sina Pharmaceuticals has reviewed the performance of unprofitable biopharmaceutical companies listed in Hong Kong after the Hong Kong Stocks New Deal.
    Although the Hong Kong Stocks New Deal has lowered the entry barrier for pharmaceutical companies, the capital’s requirements for pharmaceutical companies themselves have not been lowered.
    In addition to the potential of its own R&D pipeline, pharmaceutical companies that have successfully commercialized their products and quickly achieved profitability are obviously more sought after by capital
    .

    Today, Yasheng Pharmaceutical’s first hit product-HQP1351 is about to be released, and the core heavy product APG-2575 has also found new growth space through Hexinda Bio’s CD20 and CD47.
    Will Yasheng Pharmaceutical be like Xinda Bio in the future? , The performance of the Hong Kong stock market is so strong, we will wait and see
    .
    And what kind of changes will be brought to the competitive landscape of China's pharmaceutical industry by the pioneering in-depth cooperation between Yasheng Pharmaceuticals and Cinda Biotech? Sina Pharmaceuticals will continue to pay attention
    .

    Reference materials: "Yang Dajun, Chairman of Yasheng Pharmaceutical: To solve unmet clinical needs, the first new drug has been applied for listing"

    Reference materials: "Yang Dajun, Chairman of Yasheng Pharmaceutical: To solve unmet clinical needs, the first new drug has been applied for listing"
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