Lingteng Pharmaceuticals conducts bispecific antibodies for global clinical phase 3 trials of gastric cancer.

On July !---- 15, Lingteng Pharmaceuticals announced that it had obtained a drug clinical trial license from the State Drug Administration (NMPA) for a drug clinical trial for gastric metastatic gastric cancer with peritonite metastatic gastric cancerCartoso bistatis is the world's first bispecific antibody drug, whose inventor, DrHorst Lindhofer, is the co-founder of Lingteng PharmaceuticalsCardoso bistatis is a bispecific antibody drug developed by Lindis Biotech's Triomab technology platformThe product can be combined with tumor-related antigen EpCAM (epithelial cell adhesion) and T-cell CD3, and through Fc? R recruits immune-dependent cells to kill tumor cells in collaboration with T cells, and, by binding to specific Fc?receptors, cardoso bi-deficient can induce long-term tumor vaccine effects, which have been proven in animal experimentsCartoso bistatis is the world's first listed T-cell-linked bi-anti-drug, approved by EMA in 2009 for the treatment of malignant ascitesFor commercial reasons, the product was delisted after several years on the marketThe drug was approved in China in a two-stage, multi-center, open-label, randomized, controlled registered clinical trial to assess the safety and efficacy of cartoso double-anti-abdominal perfusion administration in patients with peritonatransfer gastric cancer patients who are not suitable for systemic chemotherapyAt the same time, Ling Teng Pharmaceutical recently received approval from Taiwan's Ministry of Health and Welfare (MOHW) and the Korea Food and Drug Administration (MFDS) for phase 3 clinical trials of homologous diseaseChina is a big country with stomach cancerAccording to statistics, about 70% of the world's stomach cancer patients in China, more than 70% of Chinese stomach cancer patients at the time of diagnosis is terminal (phase 3 or 4)Perituma metastasis is a form of cancer metastasis caused by direct growth of gastric cancer primary cancer through the blood system, lymphatic system or peritoneal growth, and is also one of the main causes of death of advanced gastric cancerThe higher the degree of peritoneal metastasis, the shorter the patient's life, usually no more than one yearNon-removable, not suitable for systemic chemotherapy with the peritoneal metastatic gastric cancer patients currently do not have standard therapy, treatment is very limited"We are very excited about the resumption of clinical development of cardoso double resistance and are looking forward to further validating the potential broad-spectrum cancer capabilities of Cartoso Double Resistance," said DrJinze Lee, co-founder and CEO of Lingteng PharmaOur initial clinical development strategy is also based on the excellent therapeutic potential of cardoso difficile in the clinical use of advanced gastric cancer Gastric cancer is the sixth most high-risk tumor in the world, with about 70% of the world's gastric cancer patients in China Gastric cancer has a huge clinical need in China, and more than 70% of patients are diagnosed with advanced stages We are very pleased to open this clinical trial and hope to bring new hope to Chinese patients who are in desperate need of new treatments Dr Horst Lindhofer, co-founder and chief scientist of Lingteng Pharmaceuticals, said Ling Teng Pharma is a clinical, research-driven biopharmaceutical company dedicated to the development of innovative T-cell-linked bispecific antibody drugs that transform malignant tumors into controlled, curable diseases In partnership with Lindis Biotech, founded by Dr Horst Lindhofer, Lingteng Pharma will develop cardoso dual resistance in the Asia Pacific region Based on the clinically validated Cardoso dual-anti-drugs and their original research technology platform Triomab, Lingteng Pharma is developing Fleximab, a next-generation dual-resistant technology platform that will significantly improve The development of CMC and reduce immunogenicity In fact, as early as the 1990s, the German scientist Dr Horst Lindhofer invented Catumaxomab Antibody drugs were used in tumor therapy shortly after the onsto Dr Lindhofer believes that for a disease with a high degree of malignancy, it is not enough to simply mobilize the body fluid immunity in the body's immune system, and as the next generation of tumor immunotherapy products, it must be able to activate multiple pathways of the immune system Based on this, he designed three functional bispecific antibodies, and selected the epCAM epidermal adhesion factor, which is widely expressed in abdominal cavity tumors As a tumor target, this factor is not the main growth signaling pathway, and individual inhibition does not prevent tumor cell growth, so it is frequently blocked in the field of mono-resistance development Catumaxomab not only recognizes tumor surface targets, but also its other Fab arm recognizes specific CD3 molecular targets on T cells and binds specifically to CD32A of immune-dependent cells by using an engineered Fc arm Catumaxomab molecular action mechanism through the synergy of the three parties, Catumaxomab on the one hand to use body fluid immunity, on the one hand to activate cell immunity, but also through the immune subsidiary cells to provide a common activation signal, three-pronged, remove stubborn tumor cells, and let the human immune system produce a certain degree of immune memory, the effect of cancer vaccine, inhibit tumor metastasis and recurrence, become the first approved to effective lysa tumor therapy dual-immune therapy The invention of the Catumaxomab antibody molecule has been recognized by academia and industry In the after-trial pursuit, Dr Lindhofer founded Trion Pharma for preclinical development of the drug He abandoned financial investors who lacked industry resources, failed to accept investment proposals for multinational drug companies with a stronger drug development orientation, and eventually accepted equity investments from Fresenius, a European medical device company The two parties are jointly responsible for the clinical research of the product and the post-marketing sales Due to its advance in scientific design and the unique ness of the chosen indications, clinical development took only about 3 years to complete Catumaxomab was officially approved by EMA in 2009 to list in Europe, becoming the world's first bispecific antibody to go on the market Professor Heiss pointed out with great insight that The immune treatment of Catumaxomab has significant effects on EpCAM-positive tumors and is also beneficial for extending the total lifetime of some patients with good immune function A total of 258 patients with ovarian, gastrointestinal, breast metastasis, and advanced pancreatic cancer were enrolled in a group of 258 patients with ovarian, gastrointestinal, breast metastasis, and advanced pancreatic cancer, according to a key phase II/III randomized controlled clinical study he chaired Their tumours were surgically and chemotherapy- and had malignant ascites However, after the treatment of Catumaxmab celiac, their puncture-free survival was extended from 11 days to 46 days (HR-0.254, P13% of patients (20% to 30% of normal people) with an overall survival rate of 131 days in the treatment group and 41 days in the control group (HR-0.518, P-0.0072) The researchers were very cautious from the start, although none of the 2,000 patients treated with Catumaxomab had a drug-related death in 258 clinical trials (tumor subgroup) At the time, the industry's understanding of cancer immunity was much less than it is today, and they didn't know which patients would benefit from immunotherapy In clinical applications, it was observed that after the immune system was activated by the drug, patients experienced side effects including fever, nausea, vomiting, etc., which at first the researchers thought would affect the clinical treatment effect, and later reviewed and found that patients with side effects (such as fever) had good treatment results Also such as the HAMA reaction (human anti-rat antibody response, Catumaxomab is rat-derived antibodies), the phenomenon was considered an adverse reaction, and even some people thought Catumaxomab was delisted because of this adverse reaction and cytokine storm But from today," the ability of patients to produce anti-rat antibodies is proof that the body's immune system can still function and is not inhibited by multiple rounds of chemotherapy, so that it can be effectively activated by Catumaxomab and involved in tumor removal An after-the-fact analysis of key studies found that the prognosis of HAMA-positive patients was significantly better than in negative patients: a 64-day puncture-free survival rate v.s 27 days later, (HR-0.33), PHAMA response on patient survival impact at the 2011 annual meeting of the American Society of Clinical Oncology (ASCO), Dr Lindohfer also published two studies on Catumaxmab (Removab) The data, obtained by two separate research groups using Catumaxomab to treat malignant abdominal and stomach cancer, show that Catumaxomab can produce a long-term immune response Under his plan at the time, the next step was to establish a link between the immune response and the patient's survival, which unfortunately was ultimately not completed because the product was discontinued in 2013 2) Ascites to adapt: It is thought that the auxiliary drug Catumaxomab has also taken some detours in the choice of indications and treatment subjects One of the most obvious effects observed in early trials was the retreat of abdominal water in patients after administration In order to ensure the success rate, the research team chose this indication to declare the listing Professor Heiss had lamented that, although it was known at the time that malignant ascites were mostly associated with the metastasis of the primary tumor, in other words, asahylysis was likely to be a manifestation of celiac cancer The ascites subside is actually because celiac cancer is eliminated by the immune system, but given the budget and risks, they chose a conservative reporting strategy, with the lowest cost, the fastest speed to ensure that the product successfully launched Assaywater subsidies and celiac cancer are two indications that clinicians see as differences between the cure and the cure Asvely is one of the complications of patients with advanced cancer, it is often clinically used to directly intubate the drainage of these patients, because the drug treatment is already difficult to be effective Catumaxomab's ascites and immune activation responses often lead doctors who first come into contact with it for an auxiliary drug with obvious side effects Although the EMA-approved indications do not require the volume of ascites, most doctors consider using it when a large amount of asae appears, rather than in the early stages of abdominal tumor metastasis 3) Sales strategy: Dr Lindhofer, inventor of Cheng's also-Xiao-Ho Catumaxomab, worked at the Helmholtz Center Munich Research Center in the 1990s Here, he began the development of double resistance and patent applications In 1998, Dr Lindhofer started his business, and he founded Trion Pharma with his previous patent to continue developing double-drug drugs This was followed by contact with Fessenyus At the time, Fessenyus wanted to expand its marginal business and incorporate biopharmaceuticals into its own business, so the two sides were on the move Fessenius formed Fresenius Biotech to take a stake in Trion Pharma to support its drug development At the beginning of the partnership, Fessenius considered himself unfamiliar with the field of biomedicine, giving Dr Lindhofer great erasing research and development freedom and maintaining his minority shareholder status at Trion Pharm It was decided that Dr Lindhofer and his research and development team would be responsible for drug development, production and clinical trials, and that Fessenyus would be responsible for providing financial support and post-marketing promotion Early tacit cooperation between the two companies led to rapid drug development, and in the sixth year of the partnership, Catumaxomab was successfully approved for sale in Europe At this stage, Dr Lindhofer and his team were instrumental However, due to the strategic transformation of Fessenyus, after Catumaxomab went public, the company did not establish a professional sales team for the project, nor did it develop a reasonable price and marketing program for the innovative product, and did not fully promote the efficacy of the drug to prolong the patient's life, which directly led to the drug's commercial fiasco Due to the dismal sales of Catumaxmab, the project was unable to continue without a follow-on investment, and eventually Fessenyus and Dr Lindhofer chose to "break up" Fessenius sold Fresenius Biotech (renamed Neovii Biotech GmbH) to Israeli company Neopharm, exiting the game Dr Lindhofer, on the other hand, founded Lindis Biotech to take back assets, patents and production technologies associated with the Dual Anti-Drug Platform and Catumaxomab products Looking back at Catumaxmab's research and development launch process, it's a twist Today's startups often attribute success to the heroes of the times, and the birth of a company or product, one step earlier, a step late, or a strategic mistake, may face the fate of failure Once A catumaxmab was like a premature baby, hurried to the world, and then hurried away, too late to prove the value of his existence Conclusion: Dr Lindhofer, who recently visited Shenzhen, and Dr Lindhofer, who detailed the development process of Catumaxomab in his report, still have confidence in Catumaxmab "Now is the time for immunotherapy, and we are finally realizing the need to fully mobilize the immune system We have a new opportunity Professor Heiss said: "The indications of the product should be identified as celiac cancer, not malignant ascites, and the total survival of the patient should be identified as the end of clinical observation, while the role of immune mechanisms in improving the overall survival of patients is fully studied so that the effects of treatment and the mechanism of interpretation of the effects of the drug can be clearly reflected." If a new trial is designed, catumaxomab should be used early, even after surgical removal "The industry is also very positive about this, and in the Expert Consensus on Gastric Peritone almanathamic metastasis, published just last year, "Catumaxomab as an 'unlisted drug' is likely to benefit patients." Dr Lindhofer decided to partner with Chinese companies to put Catumaxomab on the bigger stage, given the excellent performance of Catumaxmab in advanced gastric cancer The product was launched last year at CMO in Germany and will launch a re-listing application and the development of new indications this year From the perspective of drug development, the failure to develop, the leading sales of heavy-duty drugs are not in the minority, Catumaxomab is a failure to see the subsequent clinical research, hope that this drug in the near future for more patients to bring good news References: 1 The trifunctional antibody catumaxomab for the treatment of malignant as.