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    Home > Medical News > Latest Medical News > Wang Jianyi: A new possibility to inhibit the immune excitability strategy of tumor outside the path.

    Wang Jianyi: A new possibility to inhibit the immune excitability strategy of tumor outside the path.

    • Last Update: 2020-09-24
    • Source: Internet
    • Author: User
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    Guide read: "Played a one-year time difference, just for us in the United States to accumulate data, and then return to the domestic declaration, so that next year can achieve china and the United States simultaneously do adaptive expansion test."
    just a few weeks ago, a clinical trial application for the next-generation CD137/4-1BB agonist antibody LVGN6051 submitted by Reedin Bio was accepted by CDE.
    line layout alone, the LVGN6051 is already one of its two products entering the clinic.
    another product, LVGN3616, which was developed by Anke Bio less than half a year after rejin Bio was established, belongs to PD-1 inhibitor antibodies.
    the deal, which exceeded 50 million yuan, made the company famous, but in the interview, Wang said more about the former.
    June this year, Lijin Bio announced a clinical research partnership with Mercedon to evaluate the effectiveness of LVGN6051 in combining with Mercadon's PD-1 inhibitor Corinthian to treat patients with lung cancer, melanoma, gastrointestinal cancer and lymphoma.
    "We demonstrated some of our agonist antibody innovations and preclinical data for our products, which were quickly endorsed by Mercadon."
    " Wang added that multinational companies usually choose projects that focus more on differentiation, and that this exclusive partnership of 4-1BB targets is an important endorsement of Lijin's bio-research and development ideas.
    in his expectations, "the road ahead should be more interesting."
    with the clinical value of LVGN6051 gradually appearing, Wang's envisaged tumor immuno-excited antibody strategy is a step closer to industrialization.
    , from Abbott to Lijin bio: thick thin hair, entrepreneurship is at that time, although into the entrepreneurial circle, Wang Qiyi still has some kind of scientist temperament.
    this feeling is not hollow wind, in fact, throughout the study career, he has made clear from the beginning to study abroad, in the forefront of the subject of the goal.
    1980, Wang Entered Shanghai Medical University, "studying pharmacology."
    the profession was not established for a long time at the time, somewhere between medicine and pharmacy, but Wang Wasi enjoyed it.
    graduated from college because he "found it interesting to do research", he went on to become a graduate student in biochemistry at the university, followed by a doctoral student.
    " finally didn't finish reading, and went out in 1989 (at the State University of New York at Stony Brook) to read on.
    ", Wang recalls, "on the eve of graduation in 1994, he was invited by Abbott at a conference, and then went to the company to continue his laboratory research.
    ", perhaps even Wang didn't expect to be in Abbott, or the subsequent division of AbbVie for more than two decades.
    and this employment experience, but also let it constantly adjust the direction of special research, expand the field of research, and ultimately lead to the birth of the recidrine creatures.
    the 1990s, Abbott had not had much of a name for him in drug development.
    ", there will be some antibiotics and antiviral programs.
    I was in a transition period and started trying to lay out the anti-tumor field, so I was one of the first scientists in the company to enter the field of cancer research and development, and I am very familiar with and understand the whole process of cancer-targeted drugs.
    " Wang said that at that time by Folkman's "tumor growth depends on new angiogenesis" view, the industry has conducted a lot of research on the role of anti-tumor new angiogenesis in the treatment of malignant tumors.
    project, led by Wang Qiyi, is also related to new angiogenesis.
    a natural protease, MetAP2, was discovered in a Harvard laboratory at the time to inhibit the production of new blood vessels in tumors.
    Sece the relevant articles, Wang Zhiyi as a new target to study, from its functional cell distribution, to inhibition of the effects on cell growth behind the mechanism of all explore clearly, proving that it can make angiogenesis cells and some tumor cells do not multiplies the role.
    team of chemists to invent the world's leading small molecule inhibitor.
    he became an authority in the field of MetAP2, publishing several important papers and patents.
    , the project ultimately failed to pass clinical and commercial team reviews due to internal need for layer-by-layer assessment.
    also reflects the great difficulty of being a fully innovative target.
    After Abbott acquired Knoll of BASF in 2000, he acquired the technology and team for the development of polymer drugs, which wang used to shift his focus from small molecules to large molecules, leading c-Met antibodies, antibody coupled drugs (ADCs) and bisysoid antibodies, which were later advanced to the clinical stage.
    " take the double resistance, now the field is very popular, but the technical level is not simple, the workload is much more than twice the amount of a single anti-drug.
    is more important, how does the double resistance play the effect of 1 plus 2? "Wang Jianyi believes that research and development companies, including Lijin Bio, which are to be laid out in the field of dual resistance, should fully consider and answer this, "Although we all say that there are their own double resistance, but only from the perspective of the platform to say 'can do', the distance can really make medicine, there is still a lot of room.
    2016, Wang returned to Shanghai to start his own entrepreneurial career.
    A build-up in Abbott, according to his own account, gives him both depth and breadth of awareness of the entire process of drug development, "to a certain extent, always felt that if he had independent executive power, he would be able to fully lay out a project, he would certainly do better." After more than
    years of considering waiting and preparing, Wang Qiyi balanced the family factor, while on the other side seized on the positive trend of China's innovation environment: "From a capital perspective, someone can support you and invest in you to make new drugs;
    " II, from inhibitors to agitants: cross-link antibody platform of the new breakthrough Lijin biological how to choose the direction of research and development? This is a problem that Wang Qiyi had to consider at the beginning of his business.
    " so to speak, Lijin and many companies should not be the layout and strategy of the same.
    what kind of project are we doing? me too or something that no one else has a drug for, that is, those potential first in class? Over the years, we can see that What Lijin is doing is innovation with more valuable needs.
    "During Abbott's time, I did a full range of research on tumor immune targets, which led to the company now using irritating targets as one of the breakthroughs," Wang explained, referring to Lijin Bio's business.
    market space, the general direction of tumor immunity has been recognized by many biopharmaceutical companies.
    in the choice of market segments, however, the industry mainly focuses on PD-1/L1 and other inhibitory targets, especially at home, has almost become a competitive "Red Sea".
    opposite agonists, theoretical research has been gradually enriched, but no mature drugs have yet been developed.
    Wang explains the difference: "Inhibitory targets are like 'brakes', inhibitors are meant to remove the effects of 'brakes' and allow the immune system to return to normal 'driving', while irritating targets are seen as 'throttles', and we activate these positive functions to more directly increase the immune system's lethal effect on tumors."
    " however, getting preclinical data support is only the beginning, and agonists and inhibitors are not only different in mechanism, but also difficult to develop.
    simple understanding, inhibitors to achieve good enough affinity and selectivity, the suppression path of the target blocking, can achieve tumor immunity effect.
    therefore, the products made by each family will not be much different.
    and agonists directly combined with the target will produce biological effects, in other words, each molecule will be a different situation, involving the molecular binding capacity is how much, where the binding point is, how much impact after the combination and other factors.
    " you will find that it is closely related to the structure of each molecule, especially with antibodies as an asticicant.
    " Wang Jiayi further added that the body's immunoglobulin antibodies in addition to specific binding with antigens, there is also a constant region Fc end, the latter in the antibody function plays an important regulatory role.
    , the Fc end can affect the agitation (Fab end) effect of the entire antibody by being linked to different subjects, even in vitro and in vivo tests.
    of antibody astridestics, the key to restricting the development of antibody astrists is how to balance their activity with toxicity.
    Wang said: "The study of astrists is no less than inhibitors, there are some products in the international clinical stage, the existing results show that each astrist is still very different, some very strong activity, some activity in general."
    those highly active anthicants are often limited by safe doses and do not fully function, while weak activity is guaranteed in terms of toxicity, but the regulatory function is not sufficient.
    so it's a pain point, and according to our understanding, it's where Lijin can make a breakthrough.
    " use of natural immunoglobulin to achieve dual anti-function, to achieve the choice of tumor environment, which is the strategy of recidive biology.
    , the team created an "exciting intercourse antibody platform."
    On the one hand, when the Fc end of the antibody binds to the unique subject Fc-RIIB, because the latter is expressed on the surface of a variety of immune cells, the agitants work using the tumor microencourse, and on the other hand, the Fab end binds to the appropriate point of the immune target to make the agitation more selective.
    , thanks to the body's normal immunoglobulin foundation, the incision of the organism has a high degree of pharmacy.
    this is an advantage over some bi-anti-molecular astrologists, although the latter is also a select agitated based on the tumor microenvironent.
    III, from Biotech to Big Pharma: Zhiji Evergreen, just as standing on the shoulders of its foremans to do the development of 4-1BB agonists, Wang said, for PD-1/L1, a popular and more mature target layout, is still a strategy.
    "The discovery of PD-1 has changed the way we think about anti-tumor in the past," Wang explained.
    as the 'cornerstone' of immunotherapy, such a product is needed in the pipeline.
    " According to the plan, LVGN3616 will enter Clinical Phase I in 2019 and is expected to enter Clinical Phase II in 2021, with the earliest expected listing in 2024.
    but PD-1 inhibitors are more likely to be "business".
    with the relevant cooperation authorization, Lijin Bio and then obtain ongoing funding, back-feeding agitants and other core pipelines.
    addition to 4-1BB, Regency Biology selects a second target CD40 from a scientific and clinical point of view for a thriller breakthrough.
    " distribution is not the same as PD-1, 4-1BB, mainly in the early stages of immune start-up.
    role of CD40 is how antigens are recognized by the immune system and then presented to T cells.
    , activating CD40 can turn a 'cold tumor' into a 'hot tumor', increasing the effectiveness of immunotherapy and greatly expanding the adaptive disorder.
    ," Wang said.
    At present, the LVGN7409 target CD40 has completed preclinical validation, and its design concept is consistent with the LVGN6051 project, combining the presence of Fc-RIIB in the tumor microenviron environment, drug activity and toxicity to maintain a reasonable balance.
    Wang Jianyi envisions that the development of the main immunomodulation targets, such as PD-1, 4-1BB and CD40, especially for the latest two astrists and drug combinations, will be a predictable value point for recidive organisms.
    "Of course we're going to work toward Big Pharma," he said.
    " Wang said further, "Lijin Bio's company is named Lyvgen Biopharma, and it is in the hope of making Lijin a comprehensive and innovative biopharmaceutical company."
    ", but before that, Wang Qiyi was more important to steady play.
    asked if he would start to lay out the factory, Wang replied, "That's the next stage of financing."
    unlike some biotech companies, The concept of Reed Bio is project-oriented.
    whether it is talent or department, only when the company's projects enter the corresponding stage, Lijin bio will consider a corresponding expansion.
    " first the clinical early stage research and development team continues to expand, then involves CMC, GMP production links, and then to clinical Phase III samples and commercial production.
    CDMO, but their own production is also necessary to ensure that the technology of an innovative core and effective management of CDMO.
    ," Wang said at the end.
    as for the company's IPO, Wang Also appears to be methodical, still return to the product as the core.
    from an investor's point of view, Lijin Bio could go public as early as 2022 with the help of reforms in China's capital markets.
    experts: Wang Jianyi, chairman and CEO of Lijin Bio (Shanghai).
    Ph.D., Stony Brook University, New York, USA, Specialist in Oncology Immunology and New Drug Research and Development, and Senior Chief Scientist at Abbott and AbbVie, has led the development of a variety of drugs for clinical trials in cancer treatment, including monoclonal antibodies, dual-specific antibodies, and antibody drug consonants (ADCs).
    has 26 years of experience in new drug development, specializing in drug target discovery verification, drug design function screening evaluation, and clinical development strategies.
    Created by Lijin Bio, an innovative pharmaceutical company focused on the development of tumor immuno-excited antibodies and cancer treatment, with the team's in-depth understanding of tumor immunity and antibody engineering, with a global innovative cross-link antibody functional technology platform, to create a highly competitive new immuno-excited antibody drug, the development of the world's leading cancer immunological combination therapy.
    .
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