Peri-Seme Squibb introduces cancer immunotherapy research and development strategies and key early-stage research and development projects.

DrRupert Vessey, President of bmS Research and Early Development, said bmS's drug development philosophy is patient-centered and has accumulated a large patient database of patients through the company's own clinical trials and interactions with partnersUsing modern molecular biology techniques to analyze the molecular biology characteristics of a patient's disease can redefine disease from a molecular biology perspectiveCombined with machine learning, patient databases can help identify new targets for treating diseasesBMS can then use the company's existing multi-drug discovery platform to develop innovative treatments for these new targetsusing molecular biology characteristics to segment patients can also help identify the best group of patients for innovative therapies, accelerating the proof-of-concept and further clinical development of innovative therapies at the clinical development stageexample of blood cancer, the company's patient database includes more than 2,500 samples of myeloma patients and more than 3,500 samples of lymphoma patientsThe analysis of the molecular biology characteristics of these samples not only verified 10 potential innovative myeloma targets, but also divided a class of high-risk myeloma patients based on genomic characteristicsThese patients may need more aggressive treatment optionsconcept used in the company's drug discovery and development of other diseasesAmong other things, the use of human population genetics technology to analyze patient databases can help identify potential targets that have been validated by human geneticsThese targets tend to have a higher success rate in research and developmentAn example cited by Dr Vessey is the TYK-2 protein, which plays an important role in mediating inflammatory responses and has been proven in human geneticsTHE BMS USED ITS DRUG DISCOVERY PLATFORM TO DISCOVER A TYK-2 DECONSTRUCTANT INHIBITOR CALLED BMS-986165It may become a "best-in-class" TYK-2 inhibitorUsing the same philosophy, BMS has developed innovative therapies that target coagulation factors Xia, JNK-1 and BTK protein degradation therapy: "Reverse" drug development reflects the usual drug development sequence is from the disease, first to identify the target, and then to develop the target of innovative therapies The development sequence of the celMoD molecules of the protein degradation therapy developed by BMS is reversed, and these candidate therapies are developed by first having target-targeted compounds, and then discovering their degraded protein targets, and finally identifying diseases associated with these targets new compounds developed by the CELMoD molecule samine-based polymyeloma therapy pomalidomide and lenalidomide The researchers found that one of the mechanisms by which pomadoamine and reinamine treat multiple myeloma are that they can be combined with the E3 ubiquitin-linked enzyme CRBN, altering CRBN's ability to label ubiquitins to different protein targets Proteins labeled with ubiquitin are sent to the protease in the cell to degrade As a result, CELMoD molecules with similar functions to pomadoamines and reinadoamines can improve the degradation of different target proteins by binding to CRBN BMS researchers have developed a library containing a variety of CELMoD compounds, and based on structural studies to find the structural characteristics of the target protein for this protein degradation mechanism Combined with proteomics, the researchers found a variety of protein targets that can be effectively degraded by CELMoD molecules by comparing with existing literature and research, the researchers found that some of these targets could be used immediately for drug development for specific diseases For proteins that do not appear to have a clear biological function, researchers can also use machine learning to compare them with potential targets and signaling pathways obtained from molecular biology analysis in patient databases to identify potential disease biological mechanisms that correspond to them based on this research and development strategy, BMS has developed innovative molecules for the treatment of polymyeloma, iberdomide and CC-92480, based on pomadoamines and reinamine Moreover, the application of CELMoD compounds is no longer limited to multiple myeloma, other molecules can be used to treat acute myeloid leukemia, chronic lymphocytic leukemia and other diseases Among them, the innovative protein degradation agent CC-90009, which targets GSPT1, has shown promising anti-leukemia activity in clinical trials in addition, one end of the targeted protein degradation molecule called Ligand Directed Degraders can bind to CRBN and the other end to the protein target This targeted protein degradation molecule can further expand the use of CRBN-mediated protein degradation systems Cc-94676, developed under this strategy, is an androgen receptor degradation agent that has launched Phase 1 clinical trials to treat patients with despotic prostate cancer Dr Vessey also said that advances in protein engineering technology have allowed researchers to improve biologics to develop biological agents that are more effective and target innovative targets In the investor event, he mentioned two therapeutic therapies that target B-cell maturation antigens (BCMA), of which CC-93269 is a T cell interface (T cell engager) that targets BCMA It has two BCMA binding domains and a CD3 receptor binding domain, and the modification of the fc end of the bispecific antibody can further improve the stability of biological products and targeting BCMA's antibody conjugate therapy CC-99712, which can coconnect cytotoxic drugs at specific sites of antibodies, thus controlling the drug antibody ratio (DAR) to 4 Control of DAR helps control the safety and efficacy of therapy Cancer Immunotherapy: Treating Early Cancer Patients and Exploring a New Generation of Cancer Immunotherapy Dr Samit Hirawat, Chief Medical Officer of BMS, presented BMS's development plan for oncology immunotherapy In the field of oncology immunotherapy, BMS's PD-1 inhibitorOpdivo and CTLA-4 inhibitor Yervoy are undoubtedly among the focus of research and development In addition to further expanding the indications of these two immunocheckpoint inhibitors, one of the focuses of BMS research and development is to explore the effectiveness of cancer immunotherapy in treating early-stage cancer patients this is because the use of cancer immunotherapy in early cancer patients who have not yet metastasized is expected to be combined with surgery or other therapies to cure the disease And with a better immune system in early cancer patients, immunocheckpoint inhibitors may play a greater role in this situation In the treatment of melanoma, cancer immunotherapy has been shown good results as an auxiliary post-surgery therapy (adjuvant) BMS has initiated a number of clinical trials to explore the effectiveness of cancer immunotherapy in different early cancer types In the case of lung cancer, the company has initiated clinical trials using cancer immunotherapy as a new complementary therapy (Neo-Ajuvant, pre-surgery), assistive therapy (post-surgery), and epithelial therapy (Peri-Adjuvant, pre- and post-surgery) to treat patients with early-stage lung cancer another important direction for the company's cancer immunotherapy is the development of a new generation of immunotherapy In this direction, Dr Hirawat introduced the company's LAG-3 antibody, the relatlimab The activation of LAG-3 may be related to T-cell depletion The combination of the relatlimab with PD-1 inhibitors may further stimulate the anti-cancer immune response of T cells Phase 2/3 clinical trials on metastatic melanoma are expected to produce results by the end of this year/early next year the IL-2 signalpath activator bempegaldesleukin, developed jointly by the company in conjunction with NEKTAR Therapeutics, is also currently tested in five registered clinical studies BMS will also conduct two online investor events this week to further introduce the company's research and development pipelines and strategies in the areas of hematology, immunology and cardiovascular disease The potion Kant Content team will also introduce its highlights, so stay tuned.