SHR-1501

On April 22, 2024, ImmunityBio announced that the FDA has approved Anktiva (N-803) in combination with Bacillus Calmette-Guérin (BCG) for the treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors. The drug is expected to be available in the United States by mid-May 2024. Nogapendekin alfa inbakicept-pmln(N-803)N-803 (nogapendekin alfa inbakicept-pmln) is an interleukin-15 (IL-15) superagonist complex composed of a mutated variant of IL-15 (IL-15N72D) fused with the IL-15Rα sushi domain and an IgG1 Fc fusion protein. The IL-15Rα sushi domain allows for activation of downstream signaling pathways without the requirement for trans-presentation, as is necessary for natural IL-15, while the IgG1-Fc fragment significantly extends the drug's half-life. Previously, the FDA granted N-803 Fast Track designation and Breakthrough Therapy designation, and in October 2023, accepted the resubmission of the Biologics License Application (BLA) for N-803 in combination with BCG. In a single-arm, multi-center Phase 2 trial, 77 patients with high-risk non-muscle invasive bladder cancer (NMIBC) who were unresponsive to BCG and who had undergone transurethral resection with or without Ta/T1 papillary lesions were enrolled; patients received N-803 induction followed by intravesical instillation of Bacillus Calmette-Guérin (BCG), with maintenance therapy lasting up to 37 months. For up to 2 years, tumor status was evaluated every three months via cystoscopy and urinary cytology, with biopsies performed (randomly or under cystoscopic guidance) within the first 6 months after treatment initiation. The primary efficacy endpoints were the complete response (CR) at any time and the duration of complete response (DOR). CR is defined as a negative cystoscopy (with TURBT/biopsy where applicable) and negative urinary cytology. The results showed a CR rate of 62% (95 CI: 51, 73); 58% of patients with CR had a DOR of ≥12 months, and 40% had a DOR of ≥24 months. The most common adverse reactions (≥15%) included laboratory abnormalities such as increased creatinine, dysuria, hematuria, urinary frequency, urinary urgency, urinary tract infections, elevated potassium, musculoskeletal pain, chills, and fever. Beyond non-muscle-invasive bladder cancer (NMIBC), N-803 has also shown promising therapeutic potential in pancreatic cancer. At the 2022 ASCO GI, Immunity Bio revealed phase II data for N-803 combined with standard-of-care chemotherapy, albumin-bound paclitaxel, and PD-L1 t-haNK as a third-line treatment for pancreatic cancer. The results indicated a median overall survival (mOS) of 6.3 months, doubling compared to historical data. Regarding safety, grade 3 or higher adverse events mainly included anemia, neutropenia, and thrombocytopenia. Additionally, preclinical data published in the journal Science suggested that in combination with broadly neutralizing antibodies, N-803 might enable the immune system to control human immunodeficiency virus (HIV) without the need for antiretroviral therapy. IL-15IL-15, as a T cell growth factor, is mainly produced by monocytes and macrophages. It binds to the IL-15 receptor (IL-15R) on responsive cells, mediating the proliferation and activation of T cells, NK cells, and B cells, and inducing the generation of cytotoxic T lymphocytes (CTLs). IL-15 principally employs two distinct mechanisms for signal delivery: cis-presentation and trans-presentation. In cis-presentation, IL-15 binds to the transmembrane or soluble forms of IL-15Rα before associating with IL-15Rβγ. In trans-presentation, IL-15Rα is expressed on the surface of IL-15 producing cells, such as dendritic cells and macrophages, delivering IL-15 in a trans manner to responder cells carrying the IL-15Rβ/γc receptor, such as NK or memory CD8+ T cells. This may play a key role in coordinating the innate and adaptive branches of the immune system. The specific binding of IL-15 to its receptor IL-5R can activate the JAK-STAT5 signal transduction molecule, which then leads to the cascade activation of multiple signaling pathways including PI3K/Akt and Ras/Raf/MAPK, ultimately exerting its biological effects. Additionally, IL-15Rα can also shed from the membrane and exist in a free form after binding to IL-15, activating the IL-15Rβ/γc receptor at a distance. Due to IL-15’s ability to promote the activation and proliferation of immune cells, it plays a very important role in immunotherapy. IL-15 does not induce apoptosis in activated T cells and can maintain the survival of memory T cells, thereby achieving the goal of long-term treatment. However, the application of IL-15 in immunotherapy also faces some challenges. For example, excessive secretion of IL-15 may lead to an over-activation of the immune system, which can induce inflammatory responses, autoimmune diseases, infectious diseases, and tumors. Because the IL-15 signaling pathway requires the sushi domain of IL-15Rα, it is limited by the expression level of IL-15Rα within the body. Moreover, the short half-life of IL-15 (less than 1 hour in humans) and strict post-transcriptional regulation significantly limit IL-15's clinical applications. The most common strategies to address this include increasing the molecular size to reduce renal elimination, or fusion with the neonatal Fc receptor (FcRn). Additionally, considering IL-15's unique ability to maintain the homeostasis and proliferation of memory CD8+ T cells, applying it in CAR-T engineering also promises to achieve stronger antitumor efficacy. According to incomplete statistics, there are currently only approximately 200 IL-15 drugs under research globally, with about 90 having entered the clinical stage. Apart from N-803, other drugs worth paying attention to include SOT101, a subcutaneous formulation developed by SOTIO, SHR-1501 by Jiangsu Hengrui Pharmaceuticals, ASKG315 by Aosaikang Pharmaceutical, and BJ-001 by BJ Bioscience. Regarding Non-Muscle Invasive Bladder CancerBladder Urothelial Carcinoma (UC) is the 13th most common cancer worldwide by incidence and is divided into two main categories: non-muscle invasive bladder cancer (NMIBC), which accounts for 70%, and muscle-invasive bladder cancer (MIBC), which accounts for 30%. The peak incidence age of this disease is between 50 and 70 years old, with the incidence rate of urothelial carcinoma in men being 3 to 4 times that in women. In 2020, there were 516,000 cases of urothelial carcinoma globally, and it is projected to reach 586,000 by 2025 and 663,000 by 2030. In China, there were about 77,000 new cases of urothelial carcinoma in 2020, and the number is expected to rise to 91,000 by 2025 and to reach 106,000 by 2030. NMIBC refers to bladder malignancies that are confined to the mucosal layer (Ta) and lamina propria (T1), with no invasion into the muscular layer. This includes Ta, T1, and Tis stages, with Ta accounting for 70%, T1 representing 20%, and Tis making up 10%. Based on the different risks of recurrence and prognosis, NMIBC is divided into low-risk NMIBC, intermediate-risk NMIBC, high-risk NMIBC, and very high-risk NMIBC. Treatment options, intravesical instillation, and follow-up plans are chosen according to the grouping of risk levels. The standard treatment for NMIBC is transurethral resection of bladder tumor (TURBT). Due to the high recurrence rate of NMIBC postoperatively, adjuvant intravesical instillation therapy is recommended for all NMIBC patients. Commonly used chemotherapeutic agents for instillation include mitomycin, gemcitabine, and epirubicin, and there is no evidence that maintenance instillation schemes using different chemotherapy drugs significantly differ in effectiveness. Despite guidelines recommending chemotherapy instillation and BCG intravesical therapy, about 50% of patients still experience tumor recurrence within five years. The standard treatment for patients after tumor recurrence is radical cystectomy, which makes patients lose their normal urine storage and voiding functions, severely affecting their quality of life and psychological health. Therefore, the development of new drugs is crucial for NMIBC patients who do not respond to chemotherapy and BCG. Representative drugs approved in recent years include: In January 2020, the FDA approved pembrolizumab ("Drug K") as a monotherapy for treating BCG-unresponsive, high-risk NMIBC patients with CIS, with or without papillary tumors, who are ineligible for or have elected not to undergo cystectomy. In December 2022, the FDA approved Ferring's gene therapy, nadofaragene firadenovec-vncg (commercial name Adstiladrin), for treating high-risk NMIBC patients unresponsive to BCG therapy, with CIS, with or without papillary tumors. ImmunityBioImmunityBio is a clinical-stage immunotherapy company headquartered in California, United States, dedicated to the development of a new generation of treatments that harness immunogenic mechanisms for the treatment of cancer and infectious diseases. In January 2024, Oberland Capital provided ImmunityBio with up to $320 million in royalty monetization and equity financing, with total proceeds of $210 million due on December 29, 2023. This additional financing provides the company with significant financial resources to accelerate its commercialization efforts, in anticipation of regulatory approval, and to expand its product line in the broader field of urologic oncology. The raised funds will also support ongoing business operations and clinical trials, extending the indications of N-803 to multiple solid tumors.

DelveInsight's bladder cancer pipeline report depicts a robust space with 100+ active players working to develop 100+ pipeline therapies for bladder cancer treatment. LAS VEGAS, Aug. 23, 2022 /PRNewswire/ -- DelveInsight's ' Bladder Cancer Pipeline Insight 2022 ' report provides comprehensive global coverage of available, marketed, and pipeline bladder cancer therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the bladder cancer pipeline domain. Key Takeaways from the Bladder Cancer Pipeline Report DelveInsight's bladder cancer pipeline report depicts a robust space with 100+ active players working to develop 100+ pipeline therapies for bladder cancer treatment. Leading bladder cancer companies such as CG Oncology, FKD Therapies, Bristol-Myers Squibb, LintonPharm Co., Ltd., ImmunityBio, Inc., Hamlet Pharma AB, Asieris Pharmaceuticals, Pfizer, Taizhou Hanzhong biomedical co. LTD, Protara Therapeutics, CicloMed LLC, enGene, Inc., Emtora Biosciences, Theralase Inc., Vaxiion Therapeutics, Janssen Research & Development, LLC, Astellas Pharma, RemeGen Co., Ltd., UroGen Pharma Ltd., Flame Biosciences, Aura Biosciences, BeiGene, Incyte Corporation, QED Therapeutics, G1 Therapeutics, AN0025, Kyowa Kirin, Inc., Infinity Pharmaceuticals, Shanghai Hengrui Pharmaceutical Co., Ltd., HiberCell, Inc., Ikena Oncology, Genentech, Fusion Pharmaceuticals, GI Innovation,SOTIO Biotech AG, Celon Pharma SA, 4D Pharma PLC, Keythera Pharmaceuticals, Quadriga Biosciences, Inc., NeoTX Therapeutics Ltd., Mirati Therapeutics, NGM Biopharmaceuticals, TransThera Biosciences, Ocellaris Pharma, Palleon Pharmaceuticals, Medicenna Therapeutics, Klus Pharma, Novartis, Toray Industries, Carisma Therapeutics, Avacta Life Sciences Ltd, Seagen Inc., Elevation Oncology, Corvus Pharmaceuticals, ADC Therapeutics S.A., IO Biotech, Byondis B.V., Takara Bio, Seven and Eight Biopharmaceuticals, Dragonfly Therapeutics, InnoCare Pharma, and others are evaluating novel bladder cancer drugs candidate to improve the treatment landscape. Key bladder cancer pipeline therapies in various stages of development include CG0070, ADSTILADRIN, Nivolumab, Catumaxomab, N-803, alpha1H, APL-1202, PF-07225570, HX008, TARA-002, CPX-POM, EG-70, eRapa, TLD-1433, VAX014, Erdafitinib, Enfortumab vedotin, RC48-ADC, TAS 102, UGN-102, FL-101, AU-011, Tislelizumab, Pemigatinib, Infigratinib, Trilaciclib, AN0025, KHK2455, IPI-549, SHR-1501, HC-7366, IK-175, ado-trastuzumab emtansine, FPI-1966, GI-101, SO-C101, CPL304110, MRx0518, KF-0210, QBS10072S, Naptumomab Estafenatox, Sitravatinib, NGM120, TT-00420, OC-001, E-602, MDNA11, A166, Spartalizumab, TRK-950, CT-0508, AVA6000, SEA-TGT, Seribantumab, CPI-006, ADCT-301, IO 102, SYD985, TBI-1301, BDB001, DF1001, ICP-192, and others. In July 2022, The FDA accepted for review a Biologics License Application (BLA) from ImmunityBio, Inc. (NASDAQ: IBRX), for its antibody cytokine fusion protein as a treatment for patients with BCG-unresponsive non-muscle-invasive bladder cancer carcinoma in situ (CIS) with or without Ta or T1 disease. ImmunityBio, a leading clinical-stage immunotherapy company, filed the BLA based on positive results from a series of studies of the investigational treatment, including the ongoing QUILT 3.032 trial. The Prescription Drug User Fee Act (PDUFA) target action date is May 23, 2023. In June 2022, CG Oncology announced the interim data on two ongoing clinical studies to be presented at The American Society of Clinical Oncology (ASCO) 2022 Annual Meeting.The first poster presentation reports on efficacy and safety data from a global Phase 2 study (CORE1) of CG0070 in combination with Merck's anti-PD-1 therapy KEYTRUDA® (pembrolizumab), for the treatment of patients with Non-Muscle-Invasive Bladder Cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG). The second poster presentation centers on a Phase 1b/2 study (CORE2) of CG0070 in combination with OPDIVO®(nivolumab), as a neoadjuvant immunotherapy for Muscle-Invasive Bladder Cancer (MIBC) in cisplatin-ineligible patients. In May 2022, Asieris Pharmaceuticals announced that the ANTICIPATE Study will be presented at the 2022 American Society of Clinical Oncology (ASCO) annual meeting on June 3-7, 2022, in Chicago. This is a study of taking oral APL-1202 in combination with BeiGene's tislelizumab compared to just taking tislelizumab alone as neoadjuvant therapy (NAC) in patients with muscle invasive bladder cancer (MIBC). In March 2022, Protara Therapeutics, Inc. announced that the Company had dosed the first patient in ADVANCED-1, its Phase 1 clinical trial evaluating TARA-002, an investigational cell-based immunopotentiator, for the treatment of non-muscle invasive bladder cancer (NMIBC). In January 2022, Vaxiion Therapeutics, announced the U.S. Food and Drug Administration had cleared the company's Investigational New Drug application (IND) for VAX014 for investigational use in the intralesional treatment of solid tumors refractory to standard treatment options. VAX014 is a first-in-class recombinant bacterial minicell-based oncolytic immunotherapy. In December 2021, LintonPharm Co., Ltd., announced that the first patient had been dosed in the Company's Phase 1/2 clinical trial program for catumaxomab (clinicaltrials.gov: NCT04799847), a monoclonal bispecific antibody being studied for the treatment of Non-Muscle-Invasive Bladder Cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG). Request a sample and discover the recent advances in bladder cancer treatment @ Bladder Cancer Pipeline Report The bladder cancer pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage bladder cancer drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the bladder cancer pipeline landscape. Bladder Cancer Overview Bladder cancer usually starts in the cells that line the inside of the bladder. It typically affects adults over the age of 70 and is more common in men. Bladder cancer is the fifth most prevalent type of cancer in the general population and the fourth most common in males. When detected early, bladder cancer usually responds well to bladder cancer treatment. Smoking is among the most common bladder cancer causes. Blood in the urine is usually the first sign of bladder cancer. Other bladder cancer symptoms may include urine pain or burning, as well as a change in urinary habits. This can include frequent urination or the need to urinate but being unable to do so. The tests used for bladder cancer diagnosis include biopsy, cystoscopy, urine cytology, imaging tests, and others. Find out more about bladder cancer drugs in development @ Bladder Cancer Drugs A snapshot of the Bladder Cancer Pipeline Drugs mentioned in the report: Learn more about the novel and emerging bladder cancer pipeline therapies @ Bladder Cancer Clinical Trials Bladder Cancer Therapeutics Assessment The bladder cancer pipeline report proffers an integral view of the bladder cancer emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Bladder 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: Inhalation, Intranasal, Parenteral, Oral, Intravenous, Subcutaneous, Intramuscular Therapeutics Assessment By Molecule Type: Antibody, Antisense oligonucleotides, Immunotherapy, Monoclonal antibody, Peptides, Protein, Recombinant protein, Small molecule, Stem cell, Vaccine Therapeutics Assessment By Mechanism of Action: Cell death stimulants, Granulocyte macrophage colony stimulating factor agonists, Interleukin-15 receptor agonists, DNA synthesis inhibitors, Cyclin-dependent kinase 4 inhibitors, Cyclin-dependent kinase 6 inhibitors, Gene transference, IFNA2B expression stimulants, Antibody-dependent cell cytotoxicity, Programmed cell death-1 receptor antagonists, T lymphocyte stimulants Key Bladder Cancer Companies: CG Oncology, FKD Therapies, Bristol-Myers Squibb, LintonPharm Co.,Ltd., ImmunityBio, Inc., Hamlet Pharma AB, Asieris Pharmaceuticals, Pfizer, Taizhou Hanzhong biomedical co. LTD, Protara Therapeutics, CicloMed LLC, enGene, Inc., Emtora Biosciences, Theralase Inc., Vaxiion Therapeutics, Janssen Research & Development, LLC, Astellas Pharma, RemeGen Co., Ltd., UroGen Pharma Ltd., Flame Biosciences, Aura Biosciences, BeiGene, Incyte Corporation, QED Therapeutics, G1 Therapeutics, AN0025, Kyowa Kirin, Inc., Infinity Pharmaceuticals, Shanghai Hengrui Pharmaceutical Co., Ltd., HiberCell, Inc., Ikena Oncology, Genentech, Fusion Pharmaceuticals, GI Innovation,SOTIO Biotech AG, Celon Pharma SA, 4D Pharma PLC, Keythera Pharmaceuticals, Quadriga Biosciences, Inc., NeoTX Therapeutics Ltd., Mirati Therapeutics, NGM Biopharmaceuticals, TransThera Biosciences, Ocellaris Pharma, Palleon Pharmaceuticals, Medicenna Therapeutics, Klus Pharma, Novartis, Toray Industries, Carisma Therapeutics, Avacta Life Sciences Ltd, Seagen Inc., Elevation Oncology, Corvus Pharmaceuticals, ADC Therapeutics S.A., IO Biotech, Byondis B.V., Takara Bio, Seven and Eight Biopharmaceuticals, Dragonfly Therapeutics, InnoCare Pharma, and others Key Bladder Cancer Pipeline Therapies: CG0070, ADSTILADRIN, Nivolumab, Catumaxomab, N-803, alpha1H, APL-1202, PF-07225570, HX008, TARA-002, CPX-POM, EG-70, eRapa, TLD-1433, VAX014, Erdafitinib, Enfortumab vedotin, RC48-ADC, TAS 102, UGN-102, FL-101, AU-011, Tislelizumab, Pemigatinib, Infigratinib, Trilaciclib, AN0025, KHK2455, IPI-549, SHR-1501, HC-7366, IK-175, ado-trastuzumab emtansine, FPI-1966, GI-101, SO-C101, CPL304110, MRx0518, KF-0210, QBS10072S, Naptumomab Estafenatox, Sitravatinib, NGM120, TT-00420, OC-001, E-602, MDNA11, A166, Spartalizumab, TRK-950, CT-0508, AVA6000, SEA-TGT, Seribantumab, CPI-006, ADCT-301, IO 102, SYD985, TBI-1301, BDB001, DF1001, ICP-192, and others. Dive deep into rich insights for bladder cancer drugs, visit @ Bladder Cancer Treatment Table of Contents For further information on the bladder cancer pipeline therapeutics, reach out @ New Drug for Bladder Cancer Treatment Related Reports Bladder Cancer Market Bladder 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 bladder cancer companies including RemeGen Co., Ltd., Taiho Oncology, Inc., Xennials Therapeutics, Flame Biosciences, among others. Bladder Cancer Epidemiology Forecast Bladder Cancer Epidemiology Forecast to 2032 report delivers an in-depth understanding of the disease, historical and forecasted bladder cancer epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Muscle Invasive Bladder Cancer Pipeline Muscle Invasive Bladder Cancer Pipeline Insight, 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key muscle invasive bladder cancer companies, including SOTIO a.s., Celon Pharma SA, Shanghai PerHum Therapeutics Co., Ltd., 4D Pharma PLC, among others. Muscle Invasive Bladder Cancer Market Muscle Invasive Bladder 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 muscle invasive bladder cancer companies including SOTIO a.s., Celon Pharma SA, Shanghai PerHum Therapeutics Co., Ltd., 4D Pharma PLC, among others. Non Muscle Invasive Bladder Cancer Pipeline Non Muscle Invasive Bladder Cancer Pipeline Insight, 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key non muscle invasive bladder cancer companies, including Theralase Inc., Vaxiion Therapeutics, Janssen Research & Development, LLC, Seagen Inc., among others. Non Muscle Invasive Bladder Cancer Market Non Muscle Invasive Bladder 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 non muscle invasive bladder cancer companies including Theralase Inc., Vaxiion Therapeutics, Janssen Research & Development, LLC, Seagen Inc., among others. 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