Tifcemalimab

Shanghai Junshi Biosciences Co., Ltd (“Junshi Biosciences,” HKEX: 1877; SSE: 688180), a leading innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies, announced that the U.S. Food and Drug Administration (“FDA”) has recently agreed a randomized, double-blind, placebo-controlled, multi-regional phase 3 clinical study of tifcemalimab (product code: TAB004/JS004), an anti-BTLA monoclonal antibody used in combination with toripalimab, an anti-PD-1 monoclonal antibody, as consolidation therapy for patients with limited-stage small cell lung cancer without disease progression following chemoradiotherapy may proceed. Junshi Biosciences will officially initiate the phase 3 clinical study in the near future. According to GLOBOCAN 2020, lung cancer is a form of malignant tumor with the highest incidence rate and mortality in China. Lung cancer can be broadly categorized into non-small cell lung cancer (“NSCLC”) and small cell lung cancer (“SCLC”), based on cell type. Specifically, small cell lung cancer is the most invasive subtype of lung cancer, accounting for about 15%-20% of all lung cancer cases with characteristics such as rapid progression, early metastasis, and poor prognosis. Small cell lung cancer includes limited-stage small cell lung cancer (“LS-SCLC”) and extensive-stage small cell lung cancer, and LS-SCLC accounts for about one-third of all small cell lung cancer cases. For LS-SCLC patients who are unable to undergo surgery or refuse it, chemo-radiotherapy (CRT) is the standard of care (SOC). However, even after standard cardiac resynchronization therapy, the prognosis remains poor, with a median progression-free survival (mPFS) of approximately 13.5 months, a median overall survival (mOS) of 16-24 months, and a 5-year survival rate of only 15%-26%. There is still a huge unmet medical need for the treatment of LS-SCLC, and there is an urgent need to explore more effective and well-tolerated therapeutic approaches in clinical practice. There are currently no globally approved immune checkpoint inhibitors specifically for LS-SCLC. The study to be initiated by Junshi Biosciences is a randomized, double-blind, placebo-controlled, multi-regional phase 3 clinical study aimed to evaluate the efficacy and safety of tifcemalimab in combination with toripalimab, toripalimab alone, or placebo as consolidation therapy for LS-SCLC patients without disease progression following CRT. This study serves as the first confirmatory trial of BTLA-targeted drugs, and the principal investigator will be academician Jinming YU, President of Shandong Cancer Hospital & Institute. The study plans to enroll 756 patients from China, the United States, Europe, and other regions across the world. “In recent years, immune-oncology (I-O) therapy has made rapid advancements, particularly in the field of lung cancer, where it has emerged as the standard of care for first-line treatment of advanced NSCLC,” said Dr. Jianjun ZOU, the Global Research and Development President of Junshi Biosciences. “Regarding more aggressive SCLC, however, the progress in I-O therapy has been relatively slow. To date, no immune checkpoint inhibitor has received approval for the treatment of LS-SCLC. Tifcemalimab is Junshi Biosciences’ first independently developed ‘first-in-class’ product, and it bears the potential to be combined with our cornerstone antibody, toripalimab, and enhance patient response to I-O therapy, increase the number of patients who can benefit from I-O therapy, and introduce new breakthroughs in the treatment of LS-SCLC patients!” About Tifcemalimab (JS004/TAB004) Independently developed by Junshi Biosciences, tifcemalimab is the world’s first-in-human recombinant humanized anti-BTLA (B- and T-lymphocyte attenuator) monoclonal antibody against cancer. Tifcemalimab has been agreed to enter phase 3 clinical study, and several phase 1b/2 clinical trials of tifcemalimab in combination with toripalimab in patients with different types of tumors are currently underway in China and the United States. The B and T lymphocyte attenuator (BTLA), the target of tifcemalimab, was discovered in 2003. BTLA is a member of the CD28 receptor family and possesses a single IgSF V extracellular domain. Its sequence is similar to other molecules within the CD28 family (such as PD-1 and CTLA-4). BTLA is expressed in the T lymphocyte, B lymphocyte, and dendritic cell subpopulations. In 2005, the interaction between BTLA and its ligand, Herpes virus entry mediator (HVEM), was discovered. HVEM, a TNF receptor, is extensively expressed in the hematopoietic system and has been confirmed as the ligand of BTLA. BTLA is an immunoglobulin-associated membrane protein; its protein structure is similar to that of the transmembrane receptors (CTLA-4 and PD-1). Under normal physiological conditions, after BTLA binds with its ligand HVEM, it inhibits the over-activation of lymphocytes in the human body, thus preventing autoimmune injuries. By binding with BTLA, tifcemalimab blocks the HVEM-BTLA interaction, thereby obstructing the BTLA-mediated inhibitory signal pathways and activating the tumor-specific lymphocytes. About Toripalimab Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 promotes the immune system’s ability to attack and kill tumor cells. More than forty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally by Junshi Biosciences, including in China, the United States, Southeast Asia, and Europe. Ongoing or completed pivotal clinical trials evaluating the safety and efficacy of toripalimab cover a broad range of tumor types, including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney, and skin. In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI®). Currently, there are six approved indications for toripalimab in China: unresectable or metastatic melanoma after failure of standard systemic therapy; recurrent or metastatic nasopharyngeal carcinoma (“NPC”) after failure of at least two lines of prior systemic therapy; locally advanced or metastatic urothelial carcinoma that failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy; in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic NPC; in combination with paclitaxel and cisplatin in first-line treatment of patients with unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma ("ESCC"); in combination with pemetrexed and platinum as the first-line treatment in EGFR mutation-negative and ALK mutation-negative, unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). The first three indications have been included in the National Reimbursement Drug List (NRDL) (2022 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for the treatment of melanoma. In the United States, the Biologics License Application (BLA) for toripalimab in combination with gemcitabine/cisplatin for the first-line treatment of patients with advanced recurrent or metastatic NPC and toripalimab monotherapy for the second-line or later treatment of recurrent or metastatic NPC after platinum-containing chemotherapy is under review by the U.S. Food and Drug Administration (“FDA”). The FDA has granted Breakthrough Therapy designations for toripalimab in combination with chemotherapy for the first-line treatment of recurrent or metastatic NPC as well as for toripalimab monotherapy in the second or third-line treatment of recurrent or metastatic NPC. Additionally, the FDA has granted Fast Track designation for toripalimab for the treatment of mucosal melanoma and Orphan Drug designations for the treatment of esophageal cancer, NPC, mucosal melanoma, soft tissue sarcoma, and small cell lung cancer (SCLC). In Europe, marketing authorization applications (MAA) were accepted by the European Medicines Agency (EMA) and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) for 1) toripalimab combined with cisplatin and gemcitabine for the first-line treatment of patients with locally recurrent or metastatic NPC and 2) toripalimab combined with paclitaxel and cisplatin for the first-line treatment of patients with unresectable locally advanced/recurrent or metastatic ESCC, in December 2022 and February 2023. About Junshi Biosciences Founded in December 2012, Junshi Biosciences (HKEX: 1877; SSE: 688180) is an innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of innovative therapeutics. The company has established a diversified R&D pipeline comprising over 50 drug candidates, with five therapeutic focus areas covering cancer, autoimmune, metabolic, neurological, and infectious diseases. Junshi Biosciences was the first Chinese pharmaceutical company that obtained marketing approval for an anti-PD-1 monoclonal antibody in China. Its first-in-human anti-BTLA monoclonal antibody for the treatment of various cancers was the first in the world to be approved for clinical trials by the FDA and NMPA and has since entered Phase Ib/II trials in both China and the US. Its anti-PCSK9 monoclonal antibody was the first in China to be approved for clinical trials by the NMPA. In the face of the pandemic, Junshi Biosciences’ response was strong and immediate, joining forces with Chinese and international scientific research institutions and enterprises to develop an arsenal of drug candidates to combat COVID-19, taking the initiative to shoulder the social responsibility of Chinese pharmaceutical companies by prioritizing and accelerating COVID-19 R&D. In 2021, JS016 (etesevimab), China’s first neutralizing fully human monoclonal antibody against SARS-CoV-2 administered with bamlanivimab, was granted Emergency Use Authorizations (EUA) in over 15 countries and regions worldwide. Meanwhile, VV116 (deuremidevir hydrobromide), a novel oral nucleoside analog anti-SARS-CoV-2 drug designed to hinder virus replication, has been approved for marketing in China and Uzbekistan. The JS016 and VV116 programs are a part of the company’s continuous efforts towards innovation for disease control and prevention of the global pandemic. Junshi Biosciences has about 3,000 employees in the United States (San Francisco and Maryland) and China (Shanghai, Suzhou, Beijing, Guangzhou, etc.). For more information, please visit: http://junshipharma.com. The content above comes from the network. if any infringement, please contact us to modify.

-- Preliminary study results show that tifcemalimab is well-tolerated at all administered doses. The observed clinical activity of tifcemalimab in combination with toripalimab in lymphoma patients refractory to checkpoint inhibitors warrants further evaluation. Combination dose expansion is under way. -- Among the 28 evaluable patients who received the combination regimen, while 85.7% of the patients progressed upon prior anti-PD-1, 39.3% achieved ORR, and median DoR has not yet been reached. SHANGHAI, China, Dec. 10, 2022 (GLOBE NEWSWIRE) -- Shanghai Junshi Biosciences Co., Ltd (“Junshi Biosciences”, HKEX: 1877; SSE: 688180), a leading innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies, announced today that the updated preliminary data from a Phase I study of tifcemalimab as a single agent or in combination with toripalimab in relapsed/refractory lymphomas in a poster at the 64th American Society of Hematology (ASH) Annual Meeting. Tifcemalimab is the world’s first-in-human anti-tumor anti-BTLA monoclonal antibody independently developed by the company. “Nowadays, PD-1 inhibitors are widely used in the treatment of lymphomas, particularly relapsed or refractory classical Hodgkin’s lymphoma (R/R cHL),” said Dr. Yuqin Song of Peking University Cancer Hospital and Institute. “However, if PD-1 inhibitors fail, there is no standard treatment to resort to, thus new treatment methods are urgently needed in clinical practice. Through research, we have discovered that these types of patients can expect to benefit once again when treated with tifcemalimab and toripalimab combined. We’ve also observed a similar advantage in this treatment method as well as other immune checkpoint inhibitors—both may bring long-term survival benefits to patients. As the clinical trials continue, we look forward to observing tifcemalimab’s performance and the new treatment options it can bring to more lymphoma patients.” “The first of its kind in the entire world, tifcemalimab exhibits promising safety and efficacy in early clinical trials,” said Dr. Jianjun Zou, Global Research and Development President at Junshi Biosciences. “In particular, the updated research data released at the ASH Annual Meeting highlights that the tifcemalimab-toripalimab dual immunotherapy is promising for patients with relapsed/refractory lymphoma resistant to anti-PD-1 monoclonal antibodies, and is worth further evaluation. Apart from that, we’ve also seen its outstanding safety and efficacy in patients with solid tumors, and are eager for further verification in subsequent research.” The study is a single-arm, open-label, multicenter, dose-escalation phase I study (NCT0447772) evaluating the safety and efficacy of tifcemalimab as a single agent or in combination with toripalimab in relapsed/refractory lymphomas. This is the very first time an anti-BTLA antibody was evaluated for safety and efficacy in the treatment of lymphomas. Earlier this year in June, tifcemalimab made its debut with preliminary data from the clinical trials at the American Society of Clinical Oncology (ASCO) annual meeting, creating a milestone for all BTLA-targeting drugs in the field of cancer. Now, updated results from the clinical trial for lymphomas have been presented at the ASH annual meeting. The leading PI of this study include Dr. Jun Ma from Harbin Institute of Hematology and Oncology and Dr. Jun Zhu from Peking University Cancer Hospital and Institute, with Dr. Yuqin Song as the presenting author. By the cutoff date of October 26, 2022, a total of 63 patients with relapsed/refractory lymphoma were enrolled in the study, including 43 patients with Hodgkin's lymphoma (HL) and 20 with non-Hodgkin's lymphoma (NHL). Among the 25 evaluable patients who received monotherapy, 9 received monotherapy dose escalation and 16 received monotherapy dose expansion; among the 38 patients who received combination treatment, 6 received combination dose escalation and 32 received combination dose expansion. Patients were heavily treated with median 4 prior lines of therapy. 46 patients (73.0%) received prior anti-PD-1/L1 therapy. In terms of safety and tolerability, as of October 26, 2022, no dose-limiting toxicity (DLT) was observed in either monotherapy or combination dose escalation. Additionally, the immune related adverse event (irAE) profile of the combination was consistent with toripalimab monotherapy, and no novel safety signals were identified in the combination cohorts. Regarding clinical anti-tumor activity, as of October 26, 2022, the median follow-up was 29.1 weeks, 1 case of partial remission (PR) and 7 cases of stable disease (SD) were observed among the 25 evaluable patients receiving monotherapy. Among the 28 evaluable patients receiving the combination regimen, 24 (85.7%) patients progressed upon prior anti-PD-1, and 1 complete response (CR), 10 PR, and 13 SD were observed. The objective response rate (ORR) reached 39.3% and the disease control rate (DCR) reached 85.7%. All patients with CR/PR responses in the combination groups are ongoing by the cutoff date and the median duration of response (DoR) is not yet reached. About Tifcemalimab (JS004/TAB004)Tifcemalimab is the world’s first-in-human recombinant humanized anti-BTLA (B- and T-lymphocyte attenuator) monoclonal antibody independently developed by Junshi Biosciences. So far, tifcemalimab has entered phase Ib/II study, and several trials of tifcemalimab in combination with toripalimab in patients with different types of tumors are ongoing in China and the United States. In 2003, B and T lymphocyte attenuator (BTLA), the target of tifcemalimab was discovered. It is a member of the CD28 receptor family. It has a single IgSF V extracellular domain; its sequence is similar to other molecules of the CD28 family (such as PD-1 and CTLA-4). BTLA is expressed in the T lymphocyte, B lymphocyte and dendritic cell subpopulations. In 2005, the interaction between BTLA and its ligand, Herpes virus entry mediator (HVEM) was discovered. HVEM is a TNF receptor extensively expressed in the hematopoietic system and is confirmed as the ligand of BTLA. BTLA is an immunoglobulin associated membrane protein; its protein structure is similar to that of the transmembrane receptors (CTLA-4 and PD-1). Under normal physiological conditions, after BTLA binds with its ligand HVEM, the over-activation of lymphocytes in the human body is inhibited, thus avoiding autoimmune injuries. By binding with BTLA, tifcemalimab blocks the HVEM-BTLA interaction, thereby obstructing the BTLA-mediated inhibitory signal pathways and activating the tumor specific lymphocytes. Tifcemalimab interferes with the HVEM-BTLA interaction by binding to BTLA, thus blocking the inhibitory signal pathway mediated by BTLA and resulting in the activation of tumor-specific lymphocytes. About Junshi BiosciencesFounded in December 2012, Junshi Biosciences (HKEX: 1877; SSE: 688180) is an innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of innovative therapeutics. The company has established a diversified R&D pipeline comprising over 50 drug candidates, with five therapeutic focus areas covering cancer, autoimmune, metabolic, neurological, and infectious diseases. Junshi Biosciences was the first Chinese pharmaceutical company that obtained marketing approval for anti-PD-1 monoclonal antibody in China. Its first-in-human anti-BTLA monoclonal antibody for the treatment of various cancers was the first in the world to be approved for clinical trials by the FDA and NMPA and has since entered Phase Ib/II trials in both China and the US. Its anti-PCSK9 monoclonal antibody was the first in China to be approved for clinical trials by the NMPA. In the face of the pandemic, Junshi Biosciences’ response was strong and immediate, joining forces with Chinese and international scientific research institutions and enterprises to develop an arsenal of drug candidates to combat COVID-19, taking the initiative to shoulder the social responsibility of Chinese pharmaceutical companies by prioritizing and accelerating COVID-19 R&D. Among the many drug candidates is JS016 (etesevimab), China’s first neutralizing fully human monoclonal antibody against SARS-CoV-2 and the result of the combined efforts of Junshi Biosciences, the Institute of Microbiology of the Chinese Academy of Science and Lilly. JS016 administered with bamlanivimab has been granted Emergency Use Authorizations (EUA) in over 15 countries and regions worldwide. Meanwhile, VV116, a new oral nucleoside analog anti-SARS-CoV-2 drug designed to hinder virus replication, is in global Phase III clinical trials. The JS016 and VV116 programs are a part of the company’s continuous innovation for disease control and prevention of the global pandemic. Junshi Biosciences has more than 3,100 employees in the United States (San Francisco and Maryland) and China (Shanghai, Suzhou, Beijing and Guangzhou). For more information, please visit: http://junshipharma.com. Junshi Biosciences Contact InformationIR Team:Junshi Biosciencesinfo@junshipharma.com+ 86 021-6105 8800 PR Team:Junshi BiosciencesZhi Lizhi_li@junshipharma.com+ 86 021-6105 8800