Fidasimtamab

SHANGHAI, China, March 29, 2024 (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 its financial results for the full year of 2023 and provided corporate updates. FINANCIAL HIGHLIGHTS Total revenue was approximately RMB1,503 million during 2023. The revenue from pharmaceutical products increased by approximately 58% compared to 2022. The sales revenue of TUOYI® (toripalimab) was approximately RMB919 million, representing an increase of approximately 25% compared to the previous year. Total research and development (“R&D”) expenses were approximately RMB1,937 million in 2023, representing a decrease of approximately 19% compared to 2022. The decrease in R&D expenses was mainly due to the strategic management of R&D investments in certain early-stage pipelines, while optimizing resource allocation and focusing on R&D pipelines with greater potential. Loss attributable to owners was RMB2,282 million in 2023, representing a decrease of RMB104 million compared to the previous year. BUSINESS HIGHLIGHTS During 2023, we continued to focus on “unmet medical needs” and have made original, innovative and breakthrough progress in discovery, R&D and commercialization of innovative therapies and novel drugs. Here are the notable achievements and milestones: Advancements in the pipeline: Junshi Biosciences’ innovative R&D field has expanded from monoclonal antibodies to the research and development of more drug modalities, including small molecules drugs, polypeptide drugs, antibody-drug conjugates (ADCs), bi-specific or multi-specific antibodies and nucleic acid drugs, as well as the exploration of next-generation innovative therapies including cancer and autoimmune diseases. The product pipelines cover five major therapeutic areas, including malignant tumors, autoimmune diseases, chronic metabolic diseases, neurologic diseases and infectious diseases. A total of three drugs (TUOYI®, JUNMAIKANG and MINDEWEI) are being commercialized, around 30 assets are undergoing clinical trials, and over 20 drug candidates are at the preclinical drug development stage. In January 2023, the marketing of MINDEWEI (Deuremidevir Hydrobromide Tablets, code: JT001/VV116), an oral nucleoside analog anti-SARS-CoV-2 Category 1 innovative drug, was conditionally approved by the National Medical Products Administration of China (the “NMPA”) for the treatment of adult patients with mild to moderate COVID-19. In February 2023, the United Kingdom’s Medicines and Healthcare products Regulatory Agency (the “MHRA”) accepted the the marketing authorization application (the “MAA”) for toripalimab combined with cisplatin and gemcitabine for the first-line treatment of patients with locally recurrent or metastatic nasopharyngeal carcinoma (“NPC”), as well as toripalimab combined with paclitaxel and cisplatin for the first-line treatment of patients with unresectable locally advanced/recurrent or metastatic esophageal squamous cell carcinoma (“ESCC”). In March 2023, the investigational new drug (“IND”) application for JS010 (a recombinant humanized anti-CGRP monoclonal antibody injection) was approved by the NMPA. In April 2023, the NMPA accepted the supplemental new drug application (“sNDA”) for TUOYI® in combination with chemotherapy as perioperative treatment and monotherapy as consolidation therapy after adjuvant therapy for the treatment of resectable stage III non-small cell lung cancer (“NSCLC”). This application was later approved for marketing in December 2023, marking the first and only approved perioperative therapy for lung cancer domestically. In April 2023, the new drug application (“NDA”) for ongericimab (a recombinant humanized anti-PCSK9 monoclonal antibody, code: JS002) was accepted by the NMPA. In April 2023, the IND application for JS401 (a small interfering RNA (“siRNA”) drug targeting angiopoietin-like protein 3 (“ANGPTL3”) messenger RNA (“mRNA”)) was approved by the NMPA. In May 2023, the NMPA accepted the sNDA for TUOYI® in combination with paclitaxel injection (albumin-bound) for the treatment of PD-L1 positive (CPS ≥ 1) untreated metastatic or recurrent metastatic triple-negative breast cancer. In June and August 2023, the IND application for a randomized, double-blind, placebo-controlled, international multi-center phase III clinical study of tifcemalimab (a recombinant humanized anti-BTLA monoclonal antibody, code: TAB004/JS004) in combination with toripalimab as consolidation therapy in patients with limited-stage small cell lung cancer (“LS-SCLC”) without disease progression following chemo-radiotherapy was approved by the U.S. Food and Drug Administration (the “FDA”) and the NMPA, respectively. In July 2023, the sNDA for TUOYI® in combination with axitinib for the first-line treatment of patients with unresectable or metastatic renal cell carcinoma (“RCC”) was accepted by the NMPA. In July 2023, the sNDA for TUOYI® in combination with etoposide plus platinum as the first-line treatment of extensive-stage small cell lung cancer (“ES-SCLC”) was accepted by the NMPA, which marked the tenth marketing application submitted for TUOYI® in China. In August 2023, the IND application for JS207 (a recombinant humanized anti-PD-1/VEGF bispecific antibody) was approved by the NMPA. In September 2023, the primary endpoint of progression free survival (“PFS”, based on independent radiological review) of a randomized, controlled, multi-center phase III clinical study (NCT03430297) of toripalimab versus dacarbazine for the first-line treatment of unresectable or metastatic melanoma had met the pre-defined efficacy boundary. In October 2023, the FDA approved the Biologics License Application (the “BLA”) for toripalimab (U.S. trade name: LOQTORZI™), in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced NPC, and as a single agent, for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy. Toripalimab is the first and only drug approved in the United States for the treatment of NPC, and is also the first innovative biological drug independently developed and manufactured in China that was approved for marketing by the FDA. In December 2023, the Therapeutic Goods Administration (the “TGA”) of the Australian Government’s Department of Health and Aged Care accepted the New Chemical Entity (the “NCE”) application for toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced NPC, and as a single agent, for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy. Additionally, the TGA also granted an orphan drug designation to toripalimab for the treatment of NPC. In December 2023, TUOYI® and MINDEWEI were successfully added to Category B of the National Drug List for Basic Medical Insurance, Work-Related Injury Insurance and Maternity Insurance (Year 2023) (the “NRDL”) upon negotiations. Notably, three new TUOYI® indications were added, bringing the total to six indications included in the NRDL. TUOYI® is the only anti-PD-1 monoclonal antibody included in the NRDL for the treatment of melanoma. The inclusion of the MINDEWEI indication for adult patients with mild to moderate COVID-19 marked its first official listing in the NRDL. Update on external collaborations In March 2023, the company entered into a shareholders agreement with Rxilient Biotech and its wholly-owned subsidiary, Excellmab. The company would subscribe to the newly issued shares of Excellmab by payment in kind to obtain 40% equity interest in Excellmab. Subject to the fulfillment of the conditions precedent as agreed under the Shareholders Agreement, the company would substantially perform its capital contribution obligations, and express its intention to enter into a license agreement with Excellmab in the form agreed upon by the parties at the time of entering into the Shareholders Agreement, thereby granting Excellmab an exclusive license and other relevant rights to develop and commercialize intravenous toripalimab in Thailand, Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines and Vietnam. According to the R&D progress of toripalimab and other matters, Junshi Biosciences may receive a milestone payment of up to approximately US$4.52 million, plus a percentage of royalties on the net sales. In May 2023, Junshi Biosciences entered into an exclusive license and commercialization agreement with Dr. Reddy’s, pursuant to which the company agreed to grant Dr. Reddy’s a license to develop and exclusively commercialize toripalimab injection in Brazil, Mexico, Colombia, Argentina, Peru, Chile, Panama, Uruguay, India and South Africa. Dr. Reddy elected to expand the scope of the license to cover Australia, New Zealand and nine other countries. 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. Four of the company’s innovations have already reached the Chinese or international markets, one of which is toripalimab, China’s first domestically produced and independently developed anti-PD-1 monoclonal antibody, approved in both China and the US. Additionally, more than 30 drugs are currently in clinical development. During the COVID-19 pandemic, Junshi Biosciences actively shouldered the social responsibilities of a Chinese pharmaceutical company through its involvement in developing etesevimab, MINDEWEI®, and other novel therapies for the prevention and treatment of COVID-19. With a mission of “providing patients with world-class, trustworthy, affordable, and innovative drugs,” Junshi Biosciences is “In China, For Global.” At present, the company boasts approximately 3,000 employees in the United States (San Francisco and Maryland) and China (Shanghai, Suzhou, Beijing, Guangzhou, etc). For more information, please visit: Junshi Biosciences Contact Information IR Team: Junshi Biosciences info@junshipharma.com + 86 021-6105 8800 PR Team: Junshi Biosciences Zhi Li zhi_li@junshipharma.com + 86 021-6105 8800

双特异性抗体早期研发表达困难、稳定性差、生产工艺复杂。其需要筛选大量的不同双特异性抗体分子后才确定了成药分子，研发成本明显高于单抗。因此，与单抗的全面开花不同，双抗目前获批产品数量远少于单抗。在双抗研发管线的数量上，全球拥有最多双抗研发管线的企业是罗氏、安进和强生，而国内企业则是信达。01 全球共获批上市12款双抗，1款提交了上市申请双抗通常指的是双特异性抗体（bsAb，Bispecific Antibody）拥有两种特异性抗原结合位点，可以同时与靶细胞与功能细胞相互作用，进而增强对靶细胞的杀伤。双特异性抗体在自然界并不存在，需要通过重组DNA技术或细胞融合技术人工制备。大部分双抗药物选择肿瘤作为适应症，肿瘤在适应症的占比高达90%，其中实体瘤适应症占比59%，血液肿瘤占比29%；其次是自身免疫疾病，占比约8%；剩下的适应症包括眼科疾病（AMD）、罕见病（血友病）等。据Nature Reviews Drug Discovery上曾发表的一篇名为《Bispecific antibodies in oncology》的文章预测，到2027年将会有多个治疗肿瘤的双特异抗体批准上市，到时其总体市场销售额将到达37亿美元。其中，血液瘤CD20/CD3双抗的销售额将会占据双抗市场25%的份额，但值得注意的是，其将面临已有CAR-T疗法的竞争。 图1：双抗全球销量预测 来源：Bispecific antibodies in oncology目前，全球共12款获批上市的双抗药物，其中有1款因经营问题已于2017年遗憾退市（Catumaxomab）。另外，杨森公司于2022年12月，向FDA完成递交了Talquetamab的生物制品许可申请(BLA)，用于治疗复发或难治性多发性骨髓瘤患者。Talquetamab是一款在研、皮下注射、潜在“first-in-class”的双特异性抗体，同时靶向GPRC5D与CD3分子。据Evaluate的报告显示，预计该药物将在今年下半年公布治疗复发或难治性多发性骨髓瘤的进一步结果。表1：全球12款获批上市的双抗药物+1款已递交BLA的双抗药物来源：药研网、生物制药进展杂评，药时空整理02 超40家国内药企布局双抗，信达的管线数量最多目前，国内有超40家企业涉足双抗药物的研发，如康方生物、信达生物、康宁杰瑞、百济神州、恒瑞医药、贝达药业等。其中，康方生物的卡度尼利是首款上市的国产双抗药物，也是全球首款PD-1/CTLA-4双抗。表2：国内部分双抗公司研发进展来源：国泰君安证券研究国内在研的双抗药物研发在临床阶段、治疗领域和靶点组合方面均呈现出了集中的特点：截止2022年底，国内双抗在研药物共145个，早期研究占比高达84.1%；从治疗领域看，国内双抗治疗领域的分布高度集中在肿瘤领域（占91.2%）；从靶点组合分析，在前十的靶点组合中，主要是CD3、PD-L1以及PD-1与其他靶点组合，其中排名前三的分别是CD3/CD20、PD-L1/TGFβ和PD-L1/CD137。值得注意的是，在布局双抗的企业中，信达生物是国内双抗布局最多的企业。据公开信息显示，信达此前已经有10款双抗进入到临床阶段。但是，将信达之前曾披露过的双抗管线信息和其2022年财报及官网在研产品一览相对比，我们可以发现以下两方面的变化：（1）有4款产品管线不见了。IBI-318、IBI-319、IBI-315和IBI-321这4款处于临床研究的双抗产品信息找不到了，它们均是信达与国外药企合作开发的产品，其中的IBI-318还是处于临床3期的产品。（2）重点布局眼科领域双抗产品。信达在研的6款双抗产品中，有一半都属眼科产品。表3：信达的10款双抗在研管线来源：生物制药小编03 信达未再披露的那4款在研双抗IBI-318：一款重组全人源IgG1抗PD-1/PD-L1双特异性抗体，它也是全球首个进入临床的PD1/PDL1双抗。该产品由信达和礼来共同研发，礼来负责其在实体瘤中的临床开发，信达负责血液瘤。据此前的公开信息披露，该产品已进入了临床3期，它也是信达临床研究最为靠前的双抗产品。但据CDE注册中心显示，该产品的三项临床已经主动终止了。IBI-319：全球首款PD-1/4-1BB（CD137）双抗，也是由信达生物和礼来共同研发。其具有靶点明确、药物稳定性好等特点，保留了PD-1的药效活性；并同时激活CD137的信号，协同增强药效。IBI-321：一款PD-1/TIGIT双抗，同样是信达和礼来合作开发。据临床前的各项研究显示，该药物保留了PD-1抑制剂的药效活性，并同时抑制TIGIT的信号，协同增强药效。IBI315：全球首个抗Her2/PD-1双特异性抗体，由信达与韩美制药共同研发。其可同时结合T细胞上的PD-1分子和肿瘤细胞上的HER2分子，起到免疫激活和抑制肿瘤细胞的作用。临床前研究显示IBI315还可以桥接T细胞和肿瘤细胞，促进杀伤肿瘤细胞。这4款双抗产品均是全球首款，但是目前其相关信息均已不再被披露，可见情况不太乐观。对信达而言，其后续只能将重点放在其他双抗产品上了。