LCK

On July 29, Boehringer Ingelheim announced a major acquisition, with plans to buy Nerio Therapeutics for $1.3 billion. Nerio Therapeutics, a pharmaceutical company focused on phosphatase research, has successfully developed highly selective phosphatase PTPN2/N1 inhibitors for an innovative regimen of tumor immunotherapy. With a leading position in the global oncology market, Boehringer Ingelheim has continuously strengthened its strategic presence in oncology in recent years. According to preliminary statistics, the company has established cooperative relationships with a number of well-known pharmaceutical companies in recent years to accelerate the construction of tumor research and development pipelines: In December 2020, Boehringer Ingelheim acquired NBE Therapeutics for 1.18 billion euros to acquire novel antibody-coupled drugs to address the challenge of refractory solid tumors. In the same month, Boehringer Ingelheim acquired Labor Dr. Merk & Kollegen to increase its research and development and clinical manufacturing capabilities to support its next generation cancer immune drug development program. In January 2021, the company entered into a strategic partnership with Enara Bio to develop innovative cancer immunotherapies using its Dark Antigen™ platform. In September 2021, Boehringer Ingelheim acquired Abexxa Biologics to gain expertise in targeting cancer-specific proteins within cells, expanding the range of potential cancer antigen targets. In June 2022, the company entered into A global licensing agreement with the Agency for Science, Technology and Research of Singapore (A*STAR) to acquire the development and commercialization rights for A*STAR's series of innovative tumor-specific antibodies. In January 2023, Boehringer Ingelheim and 3T Biosciences entered into a strategic collaboration and licensing agreement to jointly explore and develop the next generation of cancer therapies. In March 2023, the company partnered with Covant Therapeutics to develop a covalent drug candidate for the ADAR1 cancer target. In November 2023, Boehringer Ingelheim acquired T3 Pharmaceuticals for CHF 450 million (approximately $508 million), which specializes in innovative therapeutic platforms that enhance immunotherapy with live bacteria. In the same month, Boehringer Ingelheim established a strategic collaboration and licensing agreement with Phenomic AI to jointly discover key targets in rich stromal cancers. In February 2024, Boehringer Ingelheim and CBmed entered into a long-term strategic partnership to accelerate the development of first-of-its-kind oncology drugs using translational medicine to improve the lives of patients. In May 2024, Boehringer Ingelheim and OSE expanded their collaboration to jointly develop first-of-its-kind therapies for tumor and cardio-renal metabolic diseases, including the anti-SIRRP α tumor Immunity program and the cis targeted anti-PD1 / cytokine platform. While Boehringer Ingelheim does not yet have a significant oncology product in the market, its oncology pipeline includes several promising candidates, such as Zongertinib(Phase 1), Brigimadlin (Phase two-thirds) and BI-764532 (Phase 2). Zongertinib is an innovative covalently bound, orally effective and selective HER2 small molecule inhibitor. It covalently binds to the tyrosine kinase domain (TKD) of both wild-type and mutant HER2 receptors, including exon 20 mutations, while preserving the wild-type signal of EGFR, thereby demonstrating good tolerability and safety while ensuring efficacy. Data from the Phase 1a/1b clinical study of Zongertinib monotherapy for HER2-variant advanced solid tumors (NCT04886804), presented at the ASCO meeting in 2024, showed that Zongertinib demonstrated superior efficacy and was well tolerated in patients with HER2-mutation-positive advanced NSCLC. Brigimadlin is a mouse dual microhomologous gene 2 (MDM2) -p53 antagonist targeting MDM2-amplified tumors such as biliary adenocarcinoma, non-small cell lung cancer, and pancreatic cancer. Currently, Brigimadlin's first-line treatment of dedifferentiated liposarcoma (DDLPS) has entered phase 2/3 of clinical trials. New results from the Phase 1a/1b study (NCT03449381) presented at the ASCO Meeting in 2024 show that Brigimadlin induces proteomic changes in DDLPS that may serve as potential biomarkers for predicting treatment response and adverse events. BI 764532 is a first-in-class T cell-mediated bisspecific antibody developed at Boehringer Ingelheim that induces a patient's own T cells to attack cancer cells expressing DLL3. BI 764532 has received fast track approval from the FDA for the treatment of advanced SCLC and advanced or metastatic extrapulmonary neuroendocrine carcinoma. In both DLL3-positive cell and xenograft models, BI 764532 showed potential preclinical antitumor activity. PTPN2 and PTPN1 (also known as PTP-1B) are phosphatases that negatively regulate multiple cytokine signaling pathways and T cell receptor (TCR) signaling pathways. They inhibit inflammation by dephosphorylation of JAK and STAT family members, and reduce T-cell sensitivity to antigens by phosphorylation of LCK and FYN. PTPN2 deletion was found to increase the number of activated cytotoxic CD8+T cells in the tumor, improve antigen presentation and sensitivity to IFNγ, and thus enhance tumor sensitivity to CD8+T cells. Given the critical role of PTPN2/N1 in tumor and immune cells and its highly conserved active sites, researchers are developing PTPN2/N1 inhibitors. Currently, there are several PTPN2/N1 inhibitors, such as ABBV-CLS-579 and ABBV-CLS-484 (AC484). AC484 is an oral PTPN2/N1 active site inhibitor that enhances the response to interferon and promotes the activation and function of immune cell subsets. In a PD-1-resistant mouse model, AC484 monotherapy showed significant antitumor effects. Currently, a Phase 1 clinical trial of AC484 is underway to evaluate its efficacy alone or in combination with PD-1 inhibitors or VEGFR tyrosine kinase inhibitors (TKI) in the treatment of advanced or metastatic solid tumors. In addition, using Chemistry42, its generating-AI platform, Insili has also developed a novel PTPN2/N1 inhibitor that has drug-like properties, good oral bioavailability in vivo, and strong in vivo anti-tumor activity, demonstrating nanoscale inhibitory efficacy.

The prevalence of soft tissue sarcoma has been rising over the past few years, which prompts the growing demand for treatment options. The increasing prevalence of soft tissue sarcoma and the growing research and development activities to develop novel therapies to treat soft tissue sarcoma to drive the market. The companies developing the potential therapies in the last stage of development include Advenchen Laboratories, Philogen, Nanobiotix, and several others. LAS VEGAS, May 10, 2023 /PRNewswire/ -- DelveInsight's ' Soft Tissue Sarcoma Pipeline Insight – 2023 ' report provides comprehensive global coverage of available, marketed, and pipeline soft tissue sarcoma therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the soft tissue sarcoma pipeline domain. Key Takeaways from the Soft Tissue Sarcoma Pipeline Report DelveInsight's soft tissue sarcoma pipeline report depicts a robust space with 125+ active players working to develop 130+ pipeline therapies for soft tissue sarcoma treatment. Key soft tissue sarcoma companies such as Advenchen Laboratories, Philogen, Gradalis, Epizyme, Chugai Pharma France, CytRx, Taiho Pharmaceuticals, KaryoPharm Therapeutics, Nanobiotix, Apexigen, Lytix Biopharma, Incyte Corporation, Iovance Biotherapeutics, Aadi Bioscience, Inc., AVEO Pharmaceuticals, Bayer, VasGene Therapeutics, Mirati Therapeutics, Novartis Pharmaceuticals, Incyte Corporation, Tracon Pharmaceuticals, Jiangsu Hengrui Medicine, Exelixis, Qbiotics, AstraZeneca, Loxo Oncology, ImmunityBio, Monopar Therapeutics, Chipscreen Biosciences, Ltd., Agenus, C4 Therapeutics, Inc., Noxopharm Limited, Moleculin Biotech, Inc., Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd., Tracon Pharmaceuticals Inc., Guangdong Xiangxue Precision Medical Technology Co., Ltd., Cornerstone Pharmaceuticals, Takara Bio Inc., Jazz Pharmaceuticals, Lyell Immunopharma, Telix Pharmaceuticals, and others are evaluating new soft tissue sarcoma drugs to improve the treatment landscape. Promising soft tissue sarcoma pipeline therapies in various stages of development include AL-3818, Onfekafusp alfa, Vigil, Tazemetostat, Aldoxorubicin, TAS-116, Selinexor, NBTXR3, APX005M, GPX-150, LTX-315, Lenvatinib, Chiauranib, Zalifrelimab, INCB081776, LN-145-S1, ABI-009, Tivozanib, LOXO-101, sEphB4-HSA, Sitravatinib, Envafolimab, Camrelizumab, Tigilanol Tiglate, Durvalumab, Tremelimumab, CFT8634, NOX66, Liposomal Annamycin, 609A, YH001, TAEST16001, CPI-613+Hydroxychloroquine, TBI-1301, Lurbinectedin, LYL132, and others. In October 2022, LIXTE Biotechnology Holdings, Inc. announced that the Spanish Agency for Medicines and Health Products (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) had authorized a Phase 1b/randomized Phase 2 study of LB-100, the Company's lead clinical compound, plus doxorubicin versus doxorubicin alone, the global standard for initial treatment of advanced soft tissue sarcomas (ASTS). In September 2022, Immutep Limited was pleased to announce it has signed a Material Transfer Agreement ("Agreement") with the Maria Skłodowska-Curie National Research Institute of Oncology in Warsaw, Poland, to enable an investigator-initiated open-label Phase II clinical trial. The trial will evaluate Immutep's lead product candidate, efti in combination with pembrolizumab and radiotherapy in the neoadjuvant setting (prior to surgery) in up to 40 patients with select soft tissue sarcoma (STS). In September 2022, TRACON Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted fast-track designation for the development of envafolimab (KN035) for patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) who have progressed on one or two prior lines of chemotherapy. In September 2022, Avacta Group plc announced that the US Food and Drug Administration (FDA) had granted Orphan Drug Designation (ODD) to the company's lead pre|CISION drug candidate, AVA6000, for treatment of soft tissue sarcoma.AVA6000 is a form of the generic chemotherapy doxorubicin that has been modified using the pre|CISION technology so that it is activated predominantly in the tumor with the aim of sparing healthy tissue from exposure and improving the safety, tolerability, and efficacy of the drug. In May 2022, Immix Biopharma, Inc., announced positive interim study data showing that after one cycle of treatment, ImmixBio's lead candidate IMX-110 produced 75% survival vs. 0% survival for Trabectedin (sold as YONDELIS ® by Janssen, a Johnson & Johnson Company, a U.S. FDA approved drug) in a connective tissue cancer Soft Tissue Sarcoma (STS) mice study. In this study, IMX-110 was compared against approved drugs used to treat STS. Trabectedin was dosed according to Meco et al., 2003 (trabectedin monotherapy treatment arm), and IMX-110 was administered at 2.0 mg/kg. In April 2022, Telix Pharmaceuticals Limited announced that it has entered into a license agreement with Eli Lilly and Company ("Lilly") under which Telix is granted exclusive worldwide rights to develop and commercialize radiolabelled forms of Lilly's olaratumab antibody for the diagnosis and treatment of human cancers. Telix's initial development focus will be on a rare type of cancer known as soft tissue sarcoma (STS). Request a sample and discover the recent advances in soft tissue sarcoma drug treatment @ Soft Tissue Sarcoma Pipeline Report The soft tissue sarcoma pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage soft tissue sarcoma drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the soft tissue sarcoma clinical trial landscape. Soft Tissue Sarcoma Overview Soft-tissue sarcomas (STS) are rare neoplasms that can develop in supporting or connective tissue, such as muscle, nerves, tendons, blood vessels, and fatty and fibrous tissues. They commonly affect the arms, legs, and trunk. They can also be found in the stomach and intestines (GIST), behind the abdomen (retroperitoneal sarcomas), and in the female reproductive system (gynecological sarcomas). Soft tissue sarcomas are classified based on the cell type involved, the nature of the malignancy, and the clinical course of the disease. The signs and soft tissue sarcoma symptoms differ greatly between patients depending on the type of soft tissue sarcoma. It is not associated with any obvious symptoms early in the course of the disease, but affected individuals may notice a slow-growing, painless mass in the affected area. Find out more about drugs for soft tissue sarcoma @ New Soft Tissue Sarcoma Drugs A snapshot of the Soft Tissue Sarcoma Pipeline Drugs mentioned in the report: Learn more about the emerging soft tissue sarcoma pipeline therapies @ Soft Tissue Sarcoma Clinical Trials Soft Tissue Sarcoma Therapeutics Assessment The soft tissue sarcoma pipeline report proffers an integral view of soft tissue sarcoma emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Soft Tissue Sarcoma 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: Infusion, Intra-arterial, Intradermal, Intralesional, Intratumoral, Intravenous, Oral, Parenteral, Subcutaneous Therapeutics Assessment By Molecule Type: Antibody, Antibody-drug conjugate, Cell therapy, Gene therapy, Immunotherapy, Nanoparticle, Peptide, Recombinant fusion protein, Small molecule Therapeutics Assessment By Mechanism of Action: Fibroblast growth factor receptor antagonists, Platelet-derived growth factor beta receptor antagonists, Proto oncogene protein c-kit inhibitors, Vascular endothelial growth factor receptor 3 antagonists, Vascular endothelial growth factor receptor-1 antagonists, Vascular endothelial growth factor receptor-2 antagonists, Immunostimulants, Free radical stimulants, DNA intercalators, Type II DNA topoisomerase inhibitors, Cell membrane structure modulators, Antibody-dependent cell cytotoxicity, Programmed cell death-1 receptor antagonists, T lymphocyte stimulants, Type 1 fibroblast growth factor receptor antagonists, Type 3 fibroblast growth factor receptor antagonists, Type 4 fibroblast growth factor receptor antagonists, Type-2 fibroblast growth factor receptor antagonists, Fms-like tyrosine kinase 3 inhibitors, Lymphocyte specific protein tyrosine kinase p56(lck) inhibitors; Lyn protein-tyrosine kinase inhibitors, Src-Family kinase inhibitors Key Soft Tissue Sarcoma Companies: Advenchen Laboratories, Philogen, Gradalis, Epizyme, Chugai Pharma France, CytRx, Taiho Pharmaceuticals, KaryoPharm Therapeutics, Nanobiotix, Apexigen, Lytix Biopharma, Incyte Corporation, Iovance Biotherapeutics, Aadi Bioscience, Inc., AVEO Pharmaceuticals, Bayer, VasGene Therapeutics, Mirati Therapeutics, Novartis Pharmaceuticals, Incyte Corporation, Tracon Pharmaceuticals, Jiangsu Hengrui Medicine, Exelixis, Qbiotics, AstraZeneca, Loxo Oncology, ImmunityBio, Monopar Therapeutics, Chipscreen Biosciences, Ltd., Agenus, C4 Therapeutics, Inc., Noxopharm Limited, Moleculin Biotech, Inc., Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd., Tracon Pharmaceuticals Inc., Guangdong Xiangxue Precision Medical Technology Co., Ltd., Cornerstone Pharmaceuticals, Takara Bio Inc., Jazz Pharmaceuticals, Lyell Immunopharma, Telix Pharmaceuticals, and others. Key Soft Tissue Sarcoma Pipeline Therapies: AL-3818, Onfekafusp alfa, Vigil, Tazemetostat, Aldoxorubicin, TAS-116, Selinexor, NBTXR3, APX005M, GPX-150, LTX-315, Lenvatinib, Chiauranib, Zalifrelimab, INCB081776, LN-145-S1, ABI-009, Tivozanib, LOXO-101, sEphB4-HSA, Sitravatinib, Envafolimab, Camrelizumab, Tigilanol Tiglate, Durvalumab, Tremelimumab, CFT8634, NOX66, Liposomal Annamycin, 609A, YH001, TAEST16001, CPI-613+Hydroxychloroquine, TBI-1301, Lurbinectedin, LYL132, and others. Dive deep into rich insights for new drugs for soft tissue sarcoma treatment; visit @ Soft Tissue Sarcoma Medications Table of Contents For further information on the soft tissue sarcoma pipeline therapeutics, reach out @ Soft Tissue Sarcoma Drug Treatment Related Reports Soft Tissue Sarcoma Market Soft Tissue Sarcoma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key soft tissue sarcoma companies, including Gem Pharmaceuticals, Lytix Biopharma, Incyte Corporation, Daiichi Sankyo, NantPharma, Iovance Biotherapeutics, Agenus, Eli Lilly and Company, Adaptimmune, Aadi, AVEO Pharmaceuticals, Amgen, among others. Soft Tissue Sarcoma Epidemiology Forecast Soft Tissue Sarcoma Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the soft tissue sarcoma epidemiology trends. Clear Cell Sarcoma Pipeline Clear Cell Sarcoma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products and the key clear cell sarcoma companies, including Tesaro, NantPharma, Rafael Pharmaceuticals, Pfizer, among others. Ewing Sarcoma Pipeline Ewing Sarcoma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key Ewing sarcoma companies, including Gradalis, Inc., Shanghai Pharmaceuticals Holding Co., Ltd, Tyme, Inc, Pfizer, Hutchison Medipharma Limited, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

Scientists have performed the largest study yet examining drug sensitivity in childhood acute lymphoblastic leukemia across genomic subtypes and its association with treatment response. Scientists at St. Jude Children's Research Hospital are reporting the most comprehensive study to date describing the variations in drug response across different genetic subtypes of acute lymphoblastic leukemia (ALL). The findings provide a blueprint for precision medicine to further individualize therapy. The study was published today in Nature Medicine. ALL, a cancer of lymphocytes (a type of white blood cells), is the most common childhood cancer. About 98% of children with ALL go into remission within weeks after starting treatment, and about 90% of those children will eventually be cured. Modern treatment for ALL is risk-adapted, meaning chemotherapy is tailored based on clinical features, leukemia genomics and the degree of minimal residual disease (MRD), which is the presence of microscopic levels of cancer cells that remain after initial treatment. Pharmacogenomics is the study of how genetic attributes affect drug response. St. Jude scientists have now comprehensively studied the pharmacogenomics of ALL by examining how the cancer cells respond to different therapeutics in the context of their cancer genomics. The results, from more than 800 patients, revealed wide variability across ALL, as well as distinct patterns of drug sensitivity by subtype. "Compared to traditional cancer genomics research, our pharmacogenomics work starts with defining the drug response phenotype of each patient, after which we look into genomics to search for the biological basis for the inter-patient variability in leukemia drug sensitivity," said corresponding author Jun J. Yang, Ph.D., St. Jude Department of Pharmacy and Pharmaceutical Sciences. "This approach sheds light on the therapeutic implications of specific genomic alterations, which may help clinicians alter care through a better understanding of how and why patients respond to treatment." "This work has yielded a wealth of new insights into the effectiveness of different medications used to treat childhood leukemia," said William Evans, PharmD, an emeritus faculty member and former St. Jude president and CEO, who co-led the study with Yang. "This work is the product of decades of collaborative research at St. Jude and across the pediatric cancer community. St. Jude may be the only place that can deploy technologies to generate discoveries at this scale across such a large number of children with cancer." The researchers found that ALL subtypes with the most favorable prognosis are closely tied to sensitivity to the chemotherapeutic drugs asparaginase and glucocorticoids. Surprisingly, some subtypes are similar in their genomics but have different patterns of drug sensitivities. The team also found that patients could be divided into distinct groups based on their drug sensitivity profiles which was associated with prognosis even after accounting for known risk factors. This highlights the importance of understanding these groups, ALL pharmacotypes, for survival outcomes. ALL from a functional perspective The researchers studied children with newly-diagnosed ALL, spanning different St. Jude flagship Total Therapy ALL clinical trials. The trials cover a period of over 20 years, generating a large and unique cohort of patient data. The scientists determined the sensitivity of leukemia cells to 18 different chemotherapy drugs in patients representing 23 molecular subtypes defined by leukemia genomics. The findings add a functional understanding to previous studies that identified high-risk or favorable subtypes. For example, ETV6-RUNX1 ALL has a favorable prognosis while BCR-ABL1-like ALL has a poor prognosis. These pharmacogenomics findings provided insight into why individuals with those subtypes had certain types of prognoses. Another potential application of these data is to discover biological pathways underlying drug sensitivity, which could pave the way for novel therapeutic development. For example, pharmacogenomics work by the Yang lab previously revealed that LCK activation underlies sensitivity to the drug dasatinib in T-ALL, making it an important target in some leukemias and spurring the development of several ongoing clinical trials to test the concept. For this study, the researchers analyzed hundreds of thousands of individual data-points. The work thus provides an important resource for the scientific community. "We hope our data will lead to more discoveries and new targets to drive a new generation of ALL trials in the near future," said first-author Shawn Lee, M.B.B.S., formerly of St. Jude and now of Khoo Teck Puat-National University Children's Medical Institute, National University Hospital Singapore. Results that matter for patients everywhere "ALL is actually a very heterogenous disease -- there are a lot of differences between genomic subtypes, such as presenting features and prognosis," Lee said. "Now, we have shown how drug sensitivity also varies between subtypes." The researchers would like to expand the findings with added population diversity. Such efforts to capture a more comprehensive picture of pediatric ALL pharmacogenomics around the globe would bring a biologically informed approach to future treatments. "This work is a big step in the right direction to individualize ALL therapy to spare children the side effects of drugs that will not work against their cancer, as well as to steer them to the novel therapies against which their cancer will likely respond," Yang said. "It is functional precision medicine, it's not just about the genetics and the targets but also about using the right drugs for the right patients." Authors and funding The study's other authors are Gary Rosner, Sidney Kimmel Comprehensive Cancer Center; and Wenjian Yang, Yoshihiro Gocho, August John, Lauren Rowland, Brandon Smart, Hannah Williams, Dylan Maxwell, Jeremy Hunt, Wentao Yang, Kristine Crews, Kathryn Roberts, Sima Jeha, Cheng Cheng, Seth Karol, Mary Relling, Hiroto Inaba, Charles Mullighan and Ching-Hon Pui of St. Jude. The study was supported by grants from the National Institutes of Health (GM115279, GM141947, CA26487, CA264610, CA021765), a Singapore NMRC Research Training Fellowship and ALSAC, the fundraising and awareness organization of St. Jude.