TNO-155

From the perspective of therapeutic interventions, proteins involved in tyrosine phosphorylation in signal transduction pathways are considered potential targets in drug development, as these proteins transmit various growth factor signals during the occurrence and development of tumors. PTPN11 is the first confirmed oncogene in the tyrosine phosphatase family, playing a crucial role in signal transduction downstream of growth factor receptors. The Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2), encoded by the PTPN11 gene, is the only confirmed oncogenic protein. Increased expression or mutations of SHP2 can lead to various solid tumors, such as leukemia, breast cancer, colon cancer, and melanoma. Since SHP2 is a regulator of proliferative signaling pathways (e.g., Ras/MAPK, PI3K/Akt), dysregulation of these pathways may lead to tumorigenesis. Research shows that 35% of Juvenile Myelomonocytic Leukemia (JMML) carries PTPN11 mutations, mainly located in the N-SH2 and PTP domains, which may impair the self-inhibition function of SHP2, leading to persistent activation of SHP2 protein. Expression of activated mutant forms of SHP2, such as D61Y and E76K, in hematopoietic cells promotes cell cycle progression and survival of hematopoietic progenitor cells, and results in sustained activation of PI3K/Akt and Ras/MAPK. In addition to JMML, SHP2 mutants have also been found in myeloid tumors, such as Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndromes, Acute Lymphoblastic Leukemia, primarily among children, and are rarely found in adults. The expression of SHP2 is upregulated to 70% in ductal invasive breast cancer, and the SHP2-binding protein GAB2 is also overexpressed in 10-15% of human breast cancers. Downregulation of the SHP2 gene can significantly inhibit the proliferation of breast tumor initiating cells and block the maintenance and progression of breast cancer. SHP2 levels are also often elevated in melanoma, with higher levels of expression closely related to poorer prognosis and a metastatic phenotype. Moreover, inhibiting SHP2 can suppress the growth of RTK-driven cancer cells, such as EGFR-L858R-driven lung adenocarcinoma, BRAF-mutated colon cancer, and KRAS-mutated breast cancer. In addition, in KRAS-mutated non-small cell lung cancer (NSCLC), inhibiting SHP2 can promote tumor aging, thereby triggering the immune system to eliminate cancer cells. Furthermore, analysis of tumor samples from advanced EGFR mutation-positive NSCLC patients revealed that those with higher SHP2 and ILK expression benefitted less from EGFR-TKI treatment than those with lower levels. As a multifunctional protein, SHP2 plays a critical role in the regulation of Ras/MAPK and PI3K/Akt signaling pathways and in maintaining body homeostasis. SHP2 also has some non-signaling functions such as mitochondrial activity and epigenetic regulation. Corresponding to its multifunctionality, mutants of SHP2 can cause a range of diseases, among which the specific molecular mechanisms are still to be studied and many problems remain to be solved. SHP2 Competitive LandscapeAccording to the data provided by Patsnap Synapse-Global Drug Intelligence Database: the following figure shows that as of 25 Sep 2023, there are a total of 34 SHP2 drugs worldwide, from 54 organizations, covering 30 indications, and conducting 67 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. In conclusion, the target SHP2 has attracted the attention of several pharmaceutical companies, including Jacobio Pharmaceuticals Group Co., Ltd., Novartis AG, and Revolution Medicines, Inc. These companies are actively involved in the research and development of drugs targeting SHP2, with a focus on indications such as Non-Small Cell Lung Cancer, Solid Tumors, and Squamous Cell Carcinoma of Head and Neck. The development of SHP2-targeting therapies is primarily driven by small molecule drugs and PROTACs. Small molecule drugs have shown significant progress in Phase 2, Preclinical, and Inactive stages, indicating their potential as innovative treatments. PROTACs, a novel drug class, are also gaining attention in the development of SHP2 inhibitors. The United States, China, and Australia are leading the development of SHP2-targeting therapies, with notable progress in each country. China, in particular, has made significant strides with 2 drugs in Phase 2 and 6 drugs in Preclinical stages, showcasing its growing capabilities in the pharmaceutical industry. Overall, the current competitive landscape of target SHP2 is characterized by active research and development efforts from various companies and countries. The future development of SHP2-targeting therapies holds promise, especially in the areas of small molecule drugs, PROTACs, and the contributions of China to the field. SHP2 inhibitors that have entered Phase II clinical trials: TNO-155TNO-155 is a small molecule drug that targets SHP2, a protein involved in various cellular processes. It has shown potential therapeutic benefits in several therapeutic areas including neoplasms, digestive system disorders, skin and musculoskeletal diseases, and respiratory diseases. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. In terms of specific indications, TNO-155 has demonstrated activity against colorectal cancer, non-small cell lung cancer, gastrointestinal stromal tumors, EGFR-mutated non-small cell lung cancer, esophageal squamous cell carcinoma, KRAS G12C mutant non-small cell lung cancer, melanoma, squamous cell carcinoma of the head and neck, solid tumors, and neoplasms. This wide range of indications suggests that TNO-155 may have a broad spectrum of activity against different types of cancers and other diseases. TNO-155 is developed by Novartis Pharma AG, a renowned pharmaceutical company known for its expertise in developing innovative drugs. As of the latest available information, TNO-155 has reached Phase 2 of clinical development globally. In China, it has progressed to Phase 1, indicating that it is still in the early stages of clinical testing in this region. In summary, TNO-155 is a small molecule drug targeting SHP2, with potential therapeutic applications in neoplasms, digestive system disorders, skin and musculoskeletal diseases, and respiratory diseases. It has shown activity against various indications, including colorectal cancer, non-small cell lung cancer, and melanoma. Developed by Novartis Pharma AG, TNO-155 has reached Phase 2 globally and Phase 1 in China, indicating ongoing clinical development and potential future advancements in its therapeutic use. SHP2 inhibitors that have entered Phase I clinical trials: PF-07284892The drug PF-07284892 is a small molecule drug that targets SHP2, a protein involved in cell signaling pathways. It is being developed for the treatment of neoplasms, specifically solid tumors. The drug is being developed by Pfizer Inc., a leading pharmaceutical company. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Currently, PF-07284892 is in Phase 1 of clinical development. Phase 1 trials are the first stage of testing in humans and are primarily focused on evaluating the safety and dosage of the drug. This suggests that PF-07284892 is still in the early stages of development and has not yet been tested extensively in patients. It is worth noting that the information provided does not specify the specific indications or types of solid tumors that PF-07284892 is being evaluated for. Therefore, it is unclear whether the drug is being developed for a broad range of solid tumors or if it is targeting a specific subtype. In terms of regulatory progress, PF-07284892 has received IND (Investigational New Drug) approval in China. IND approval is a significant milestone in the drug development process as it allows for the initiation of clinical trials in the country. This suggests that Pfizer Inc. has obtained the necessary regulatory clearance to conduct clinical trials with PF-07284892 in China. Overall, based on the information provided, PF-07284892 is a small molecule drug being developed by Pfizer Inc. for the treatment of solid tumors. It is currently in Phase 1 of clinical development and has received IND approval in China. However, further information is needed to fully understand the potential of PF-07284892 in treating neoplasms and its specific indications within the solid tumor category.

The prevalence of esophageal cancer has been rising since the past few years, which prompts the growing demand for the treatment options. The market is driven by the increasing prevalence of cancer and the increase in research & development. The Companies developing the potential therapies in the last stage of development include Celgene,Jiangsu HengRui Medicine Co., Seagen, and several others. LAS VEGAS, Oct. 11, 2022 /PRNewswire/ -- DelveInsight's ' Esophageal Cancer Pipeline Insight – 2022 ' report provides comprehensive global coverage of available, marketed, and pipeline esophageal cancer therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the esophageal cancer pipeline domain. Key Takeaways from the Esophageal Cancer Pipeline Report DelveInsight's esophageal cancer pipeline report depicts a robust space with 80+ active players working to develop 90+ pipeline therapies for esophageal cancer treatment. Leading esophageal cancer companies such as Shanghai Henlius Biotech, CStone Pharmaceuticals, Jiangsu HengRui Medicine Co., Ltd., AstraZeneca, Symphogen, Hoffmann-La Roche, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Sinocelltech Ltd., Eli Lilly and Company, Ipsen, Jacobio Pharmaceuticals Co., Ltd., Shire, GlaxoSmithKline, Keythera Pharmaceuticals (Australia) Pty Ltd, Sunshine Lake Pharma Co., Ltd., Novartis Pharmaceuticals, Sanofi, Seagen Inc., Rapa Therapeutics LLC, Incyte Corporation, Atreca, Inc., Exelixis, Bayer, BeiGene, Lyell Immunopharma, Sichuan Baili Pharmaceutical, AP Biosciences.,Leap Therapeutics, Inc., Adlai Nortye Biopharma Co., Ltd., Athenex, Inc., Pfizer, Genentech, Hangzhou Neoantigen Therapeutics, Janssen Pharmaceutical, Curis, Inc.,Merck KGaA, Apexigen, Inc,Shenzhen Hornetcorn Bio-technology Company, LTD, MacroGenics, Bristol-Myers Squibb, Integral Molecular, CARTEXELL, EMD Serono, and others are evaluating new drugs for esophageal cancer treatment. Key esophageal cancer pipeline therapies in various stages of development include Serplulimab, CS1001, Camrelizumab, Durvalumab, Sym021, Spartalizumab, Sym022, Sym023, Regorafenib, S095033, INCB099318, RO7121661, XB002, LGK974, Abemaciclib, ladiratuzumab vedotin, ATRC-101, SGN-PDL1V, RO7247669, THOR-707, Letetresgene Autoleucel, TNO155, Anlotinib Hydrochloride, Larotinib, SCT-I10A, KF-0210, SCT200, Ramucirumab, Cabozantinib, JAB-3068, Onivyde, JAB-3312, SGN-B6A, RAPA-201,Ociperlimab, SI B001,Apatinib, AP 203, QEQ278, JAB-3312, DKN-01, AN0025, HR 070803,Oraxol, Sunitinib malate, Tiragolumab, iNeo Vac P01, Amivantamab, CA-4948, M1231, APX005M, DC-CIK, Margetuximab, Temozolomide, and others. In September 2022, Daiichi Sankyo and Sarah Cannon Research Institute (SCRI) announced that extended follow-up data from a phase I/II trial of DS-7300, continued to show promising durable tumor response in patients with several types of heavily pretreated cancers including lung, prostate or esophageal cancer.A response rate of 32% (95% CI: 24-41) was observed with 38 responses (33 confirmed; 28%; 95% CI: 20-37) in 118 patients with various solid tumors including small cell lung cancer (SCLC), squamous non-small cell lung cancer (NSCLC), metastatic castration-resistant prostate cancer (CRPC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC) or endometrial cancer receiving doses of DS-7300 ranging from 4.8 mg/kg to 16.0 mg/kg. In September 2022, Integral Molecular, has licensed a panel of monoclonal antibodies (MAbs) to CARTEXELL, enabling CARTEXELL to develop CAR-T cell therapies using Integral Molecular's Claudin 18.2 (CLDN18.2) MAbs. Under the terms of the agreement, Integral Molecular will provide an exclusive worldwide license to CARTEXELL to use the panel of high-affinity, high-specificity, and fully humanized CLND18.2 MAbs for the development of CAR-T cell therapies against solid tumors including gastric, lung, pancreatic and esophageal cancers. CARTEXELL will be solely responsible for all research, development, and commercial activities. In August 2022, BeiGene announced that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted a supplemental biologics license application (sBLA) for tislelizumab in combination with chemotherapy as first-line treatment in patients with unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC). In May 2022, Shanghai Junshi Biosciences Co., Ltd, announced that the China National Medical Products Administration (NMPA) has approved the supplemental new drug application (sNDA) for toripalimab in combination with paclitaxel and cisplatin in the first-line treatment of patients with unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma (ESCC). The sNDA was accepted by the NMPA in July 2021. This is the fifth indication approved for toripalimab in China and will benefit Chinese patients with advanced ESCC. In May 2022, Bristol Myers Squibb, announced that the U.S. Food and Drug Administration (FDA) has approved both Opdivo (nivolumab) (injection for intravenous use) in combination with fluoropyrimidine- and platinum-containing chemotherapy and Opdivo plus Yervoy (ipilimumab) as a first-line treatment for adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) regardless of PD-L1 status. The approvals are based on the Phase III CheckMate -648 trial, which evaluated Opdivo in combination with chemotherapy (n=321) and Opdivo plus Yervoy (n=325) each compared to chemotherapy alone (n=324), and was the largest Phase III trial of immunotherapy in first-line ESCC. In January 2022, Lyell Immunopharma, Inc., announced that the U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application to initiate a Phase I clinical trial for LYL132, an investigational T-cell receptor (TCR) therapy for patients with solid tumors expressing New York esophageal squamous cell carcinoma 1 (NY-ESO-1) that the company is developing in collaboration with GSK. Request a sample and discover the recent advances in esophageal cancer treatment @ Esophageal Cancer Pipeline Report The esophageal cancer pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage esophageal cancer drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the esophageal cancer pipeline landscape. Esophageal Cancer Overview Esophageal cancer grows in the esophagus, the tube that connects the throat to the stomach. Tumors develop in the mucosa, the inner lining of the esophagus. Esophageal cancer is classified into two types, each with its own set of risk factors: Adenocarcinoma -Adenocarcinomas are cancers that begin in gland cells at the bottom of the esophagus. This is the most common type of esophageal cancer. It usually happens near the stomach. The exact esophageal cancer causes are not known. Most esophageal cancer symptoms do not appear until cancer has progressed to an advanced stage, when it may be challenging to treat. Other, more common conditions can cause esophageal cancer symptoms. The most common esophageal cancer symptom is difficulty swallowing, particularly a sensation of food stuck in the chest. There are several tests used for esophageal cancer diagnosis. The most common include endoscopy with biopsy and endoscopic ultrasonography. Find out more about esophageal cancer drugs in development @ New Treatment for Esophageal Cancer A snapshot of the Esophageal Cancer Pipeline Drugs mentioned in the report: Learn more about the emerging esophageal cancer pipeline therapies @ Esophageal Cancer Clinical Trials Esophageal Cancer Therapeutics Assessment The esophageal cancer pipeline report proffers an integral view of esophageal cancer emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Esophageal Cancer Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Intra-articular, Intraocular, Intrathecal, Intravenous, Ophthalmic, Oral, Parenteral, Subcutaneous, Topical, Transdermal Therapeutics Assessment By Molecule Type: Oligonucleotide, Peptide, Small molecule Therapeutics Assessment By Mechanism of Action: Prostaglandin E EP4 receptor antagonists, ERBB 2 receptor antagonists, Phosphorylation inhibitors, Antibody-dependent cell cytotoxicity, Apoptosis stimulants, CD40 antigen stimulants, Immunostimulants, Programmed cell death-1 receptor antagonists, T lymphocyte stimulants, Programmed cell death-1 ligand-1 inhibitors, Epidermal growth factor receptor antagonists. Key Esophageal Cancer Companies: Shanghai Henlius Biotech, CStone Pharmaceuticals, Jiangsu HengRui Medicine Co., Ltd., AstraZeneca, Symphogen, Hoffmann-La Roche, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Sinocelltech Ltd., Eli Lilly and Company, Ipsen, Jacobio Pharmaceuticals Co., Ltd., Shire, GlaxoSmithKline, Keythera Pharmaceuticals (Australia) Pty Ltd, Sunshine Lake Pharma Co., Ltd., Novartis Pharmaceuticals, Sanofi, Seagen Inc., Rapa Therapeutics LLC, Incyte Corporation, Atreca, Inc., Exelixis, Bayer, BeiGene, Lyell Immunopharma, Sichuan Baili Pharmaceutical, AP Biosciences.,Leap Therapeutics, Inc., Adlai Nortye Biopharma Co., Ltd., Athenex, Inc., Pfizer, Genentech, Hangzhou Neoantigen Therapeutics, Janssen Pharmaceutical, Curis, Inc.,Merck KGaA, Apexigen, Inc,Shenzhen Hornetcorn Bio-technology Company, LTD, MacroGenics, Bristol-Myers Squibb, Integral Molecular, CARTEXELL and others Key Esophageal Cancer Pipeline Therapies: Serplulimab, CS1001, Camrelizumab, Durvalumab, Sym021, Spartalizumab, Sym022, Sym023, Regorafenib, S095033, INCB099318, RO7121661, XB002, LGK974, Abemaciclib, ladiratuzumab vedotin, ATRC-101, SGN-PDL1V, RO7247669, THOR-707, Letetresgene Autoleucel, TNO155, Anlotinib Hydrochloride, Larotinib, SCT-I10A, KF-0210, SCT200, Ramucirumab, Cabozantinib, JAB-3068, Onivyde, JAB-3312, SGN-B6A, RAPA-201,Ociperlimab, SI B001,Apatinib, AP 203, QEQ278, JAB-3312, DKN-01, AN0025, HR 070803,Oraxol, Sunitinib malate, Tiragolumab, iNeo Vac P01, Amivantamab, CA-4948, M1231, APX005M, DC-CIK, Margetuximab, Temozolomide and others. Dive deep into rich insights for esophageal cancer drugs, visit @ Chemo Drugs for Esophageal Cancer Treatment Table of Contents For further information on the esophageal cancer pipeline therapeutics, reach out @ New Drug for Esophageal Cancer Treatment Related Reports Esophageal Cancer Market Esophageal Cancer Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key esophageal cancer companies including Merck KGaA, Shenzhen Hornetcorn Biotechnology, Apexigen, Inc., Highlight Therapeutics, among others. Esophageal Cancer Epidemiology Forecast Esophageal Cancer Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted esophageal cancer epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Esophageal Squamous Cell Carcinoma Pipeline Esophageal Squamous Cell Carcinoma Pipeline Insight – 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key esophageal squamous cell carcinoma companies, including BeiGene, AstraZeneca, Ipsen, Shire, Sanofi, Seagen, among others. Esophageal Squamous Carcinoma Market Esophageal Squamous Carcinoma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key esophageal squamous carcinoma companies, including BeiGene, AstraZeneca, Ipsen, Shire, Sanofi, Seagen, among others. Esophageal Squamous Cell Carcinoma Epidemiology Esophageal Squamous Cell Carcinoma Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted esophageal squamous cell carcinoma epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. 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