Interferon Beta-1b

Gastric Cancer (GC), also known simply as GC, is one of the most lethal malignancies worldwide, with over one hundred million new cases reported in 2022, leading to the death of 783,000 individuals. Globally, the incidence and mortality rates of gastric cancer have been on the decline in most regions over the past few decades. This considerable change is largely attributed to economic development and improved practices in food preservation associated with refrigeration technology during food transport and storage. In 2020, it was estimated that there were 1.1 million cases of stomach cancer diagnosed globally, with 720,000 in males and 370,000 in females. Stomach cancer ranks among the top three most common cancers in 19 countries worldwide and is the most common cancer in four countries: Bhutan, Kyrgyzstan, Cape Verde, and Tajikistan. Sixty percent of all stomach cancer cases occur in East Asia, with China alone accounting for 43.9% of cases. The incidence of stomach cancer is higher in males, with 66% of all cases occurring in men. There are significant differences in the incidence rates across different regions; in several African countries, the incidence rate is less than 5 cases per 100,000 person-years in males, whereas in East Asian countries, it exceeds 30 cases per 100,000 person-years. This indicates that factors such as gender, region, and level of economic development have a significant impact on the incidence of stomach cancer. Moreover, in high-incidence areas such as East Asia, especially China, the prevention and control of stomach cancer represent a considerable challenge. In 2020, it was estimated that there were 1.1 million cases of stomach cancer diagnosed globally, with 720,000 in males and 370,000 in females. Stomach cancer ranks among the top three most common cancers in 19 countries worldwide and is the most common cancer in four countries: Bhutan, Kyrgyzstan, Cape Verde, and Tajikistan. Sixty percent of all stomach cancer cases occur in East Asia, with China alone accounting for 43.9% of cases. The incidence of stomach cancer is higher in males, with 66% of all cases occurring in men. There are significant differences in the incidence rates across different regions; in several African countries, the incidence rate is less than 5 cases per 100,000 person-years in males, whereas in East Asian countries, it exceeds 30 cases per 100,000 person-years. This indicates that factors such as gender, region, and level of economic development have a significant impact on the incidence of stomach cancer. Moreover, in high-incidence areas such as East Asia, especially China, the prevention and control of stomach cancer represent a considerable challenge. From: DOI: 10.1016/j.eclinm.2022.101404However, unlike the previously reported continuous decline in the overall incidence rate across all age groups, recent reports indicate an increase in the incidence of gastric cancer among young adults (under the age of 50), particularly a noticeable growth in the incidence of non-cardia tumors among the more affluent population. Gastric cancer can be roughly divided into two major anatomical sub-sites: although the majority of gastric cancers occur in the distal part of the stomach (non-cardia), globally, about 18% of gastric cancers originate in the cardia, which is the region adjacent to the gastroesophageal junction. Both anatomical locations of gastric cancer have overlapping risk factors, such as smoking, heavy alcohol consumption, and consumption of pickled foods; however, they also have their distinct etiologies. Cardia gastric cancer is often associated with gastroesophageal reflux disease and obesity, while approximately 90% of non-cardia gastric cancers can be attributed to Helicobacter pylori (H. pylori) infection. This implies that prevention and treatment strategies for different types of gastric cancer may need to be distinct, especially considering the rising incidence rates in young populations and the etiological differences between cardia and non-cardia gastric cancers. From: DOI: 10.1016/ S0140-6736(16)30354-3Timeline of Significant Discoveries and Key Advances in the Treatment of Gastric Cancer: In recent years, targeted therapies against specific molecular targets have been introduced into clinical practice, such as the anti-HER2 antibody trastuzumab and the anti-VEGFR-2 antibody ramucirumab. Claudin 18.2 is also a significant target for gastric cancer treatment, as the gene is associated with specific molecular subtypes involved in the development and progression of gastric cancer. This gene and its interaction pathways serve as potential targets for the development of new personalized treatment strategies. The G protein-coupled receptor (GPCR) signaling pathway is one of those pathways. Abnormal activation of GPCRs and G proteins can promote the progression of gastric cancer. Activated GPCRs/G proteins may serve as effective biomarkers for early diagnosis, prognostic prediction, and clinical therapeutic targets. This indicates that through the detection and intervention of these receptors and their aberrant activation states, it is possible to achieve early detection, accurate prognostic assessment, and targeted treatment of gastric cancer, thereby improving patient survival rates and quality of life. GPCR and Gastric CancerAs early as 1986, a study by Young et al. was the first to link G protein-coupled receptors (GPCRs) with tumorigenic activity. They demonstrated through experiments that the Mas proto-oncogene could confer tumorigenicity to NIH 3T3 cells in vivo in nude mice. Mas encodes a typical GPCR and, unlike most oncogenes, does not carry activating oncogenic mutations. Instead, tumorigenicity is caused by its overexpression and the abundance of ligands in the circulation system or locally produced ligands. There is now a substantial body of evidence suggesting that various wild-type GPCRs, acting under the influence of excessive circulating agonists or agonists produced within the tumor microenvironment, can induce oncogenic transformation and drive tumor progression. Specific neuropeptides, particularly neurotransmitters and intestinal hormones, play an autocrine and paracrine role in various cancers. These neuropeptides include Gastrin-Releasing Peptide (GRP), Endothelin, Bradykinin, Neuromedin B, Neuropeptide Y, Gastrin, Cholecystokinin, Arginine Vasopressin, and Angiotensin II, among others. Each, upon binding to their respective GPCRs, triggers sustained activation, thereby stimulating proliferation in a variety of cell types and playing a crucial role in many malignant human cancers, such as small cell lung carcinoma, pancreatic cancer, head and neck squamous cell carcinoma, prostate cancer, and gastric cancer. From: DOI: 10.3390/cancers15030736Progress in the development of new drugs for gastric cancer targeting GPCR-class receptorsAccording to statistics from the Synapse database, there are currently nearly 1000 research and development pipelines for gastric cancer globally, of which 38 are GPCR (G protein-coupled receptor) type target pipelines. Popular pipeline targets include SSTR, EP2R, EP4R, CCR8, CCKR, SMO, NTSR1, A2bR, CCR7, among others. The leading indications related to gastric cancer include gastric cancer, gastro-enteropancreatic neuroendocrine tumors, gastroesophageal junction tumors, and Her2-negative gastric cancer, among others. The principal types of therapeutic agents include radiopharmaceuticals, peptide conjugates, radionuclide-conjugated drugs, synthetic peptides, monoclonal antibodies, and fusion proteins. In the field of clinical research, the major regions for clinical studies on gastric medications are the United States, China, Japan, Europe, Australia, and others. Several drugs are currently in the late stages of clinical trials (Phase 2, Phase 2/3, Phase 3, etc.). Representative investigational drugs include: Representative Pipeline: (177Lu) Lutetium-DOTATATE and SSTRs ReceptorLutetium-177 Dotatate (LU-177 Lutetium Dotatate, also known as Lutathera) is a radiopharmaceutical developed by Advanced Accelerator Applications. It is primarily used for the treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This medicinal product is formed by the conjugation of the somatostatin analogue Dotatate with the radioactive isotope Lutetium-177. Dotatate is a compound that can specifically bind to somatostatin receptors (SSTRs) that are overexpressed on neuroendocrine tumor cells. Lutetium-177 is a beta-emitting radioisotope. When combined with Dotatate, the resultant Lutetium-177 Dotatate can accurately target and accumulate within tumor cells that express high levels of somatostatin receptors. The radioactive decay of Lutetium-177 releases beta radiation, which destroys the cancer cells, thereby achieving a localized radiation therapy effect. Somatostatin is a peptide hormone composed of 14 amino acid residues and features a single disulfide bond. This hormone is capable of inhibiting the secretion of growth hormone, insulin, glucagon, gastrin, cholecystokinin, and thyrotropin, but due to its extremely short half-life in the body (less than 3 minutes), its value in therapy is limited. Research has identified the β-turn pharmacophore of somatostatin, which has become the lead sequence for the development of analogs with greater biological stability and potency. Based on this, octreotide was developed and approved for the treatment of acromegaly, adenomas, and pancreatic, breast, and prostate tumors. Subsequent research has spurred the development of selective receptor antagonists, such as lanreotide, vapreotide, and pasireotide, and has introduced the fields of peptide imaging and peptide receptor radionuclide therapy. In these radionuclide therapies, radioactive elements such as ^111In, ^90Y, ^68Ga, or ^99mTc are linked to selective somatostatin analogs through chelating groups, leading to approved radiopharmaceutical formulations. These drugs can be used for tumor detection. In 2001, a preclinical animal model study on Lutetium Dotatate LU-177 was published in the International Journal of Cancer. It reported on the investigation of the biologic distribution of the drug in a rat model of pancreatic tumors, and these data were used to estimate the absorbed doses in normal human tissue. A 2004 study on the treatment effectiveness in patients with metastatic gastroenteropancreatic tumors positive for the somatostatin receptor revealed that, out of 50 patients treated with Lutetium Dotatate LU-177, disease stabilization was achieved in 24 patients, 19 patients experienced stable disease, the condition of 6 patients progressed, and 1 patient's disease status could not be assessed. The therapy significantly improved their overall health condition, quality of life, and scores for various functions and symptoms. In 2005, a clinical study on the use of Lutetium Dotatate LU-177 in 131 patients with metastatic or inoperable somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors was announced. After treatment with a maximum cumulative dose of 600 to 800 mCi of Lutetium Dotatate LU-177, 3 patients (2%) achieved complete remission, 32 patients (26%) had partial remission, 24 patients (19%) showed a minor response (tumor size reduction of 25% to 50%), 44 patients (35%) had stable disease, whereas 22 patients (18%) experienced disease progression. A high remission rate correlated positively with high uptake shown on pre-treatment somatostatin receptor imaging and fewer liver metastases. In contrast, patients with lower performance scores and extensive disease distribution had a significantly higher frequency of disease progression. Severe side effects were very rare, and the median time to disease progression was comparable to that with chemotherapy, with better effectiveness in patients with a limited tumor burden. An expanded clinical study published in 2008 further validated the safety and efficacy of Lutetium Dotatate LU-177. In a study involving 310 patients with gastroenteropancreatic neuroendocrine tumors, complete and partial tumor response rates were observed at 2% and 28%, respectively, with minor response rates (tumor size reduction of over 25% but less than 50%) at 16%. Compared with historical controls, this treatment method provided a survival benefit of 40 to 72 months from the point of diagnosis. From: DOI: 10.1200/JCO.2007.15.2553In 2017, results from a Phase 3 clinical study published in The New England Journal of Medicine indicated that, in a randomized, controlled trial involving 210 patients with gastroenteropancreatic neuroendocrine tumors, the experimental group (116 patients) receiving intravenous injections of 7.4 GBq dose of Lutetium Lu 177 Dotatate every 8 weeks for a total of four times, along with a concurrent intramuscular injection of 30 mg of long-acting octreotide every 4 weeks, had a significantly higher estimated progression-free survival rate at 20 months (65.2%) compared to the control group (10.8%), which consisted of 113 patients treated only with intramuscular injections of 60 mg of long-acting octreotide every 4 weeks. Additionally, the response rate for the Lutetium Lu 177 Dotatate group was 18%, markedly higher than the 3% observed in the control group. From: DOI: 10.1056/NEJMoa1607427Based on this, at the end of 2017, the U.S. FDA approved Lutetium Dotatate LU-177 for the treatment of patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Due to its targeted nature and relatively low systemic toxicity, this therapy has received widespread attention and application in the field of precision medicine. In October 2017, Novartis acquired the French innovative pharmaceutical company Advanced Accelerator Applications for $3.9 billion to build and expand its radioligand therapy platform. In 2018, Novartis invested an additional $2.1 billion to acquire the biopharmaceutical company Endocyte, securing several more radiopharmaceutical candidates. Through these acquisitions, Novartis has established and extended its radioligand therapy platform, comprising multiple marketed products: Lutathera (177Lu-DOTATATE) and 68Ga-Edotreotide, as well as several products in development: 177Lu-PSMA-617, 177Lu-PSMA-R2, 177Lu-NeoB, 177Lu-FF58, 225Ac-PSMA-617, etc. Furthermore, Lanreotide Acetate is a non-selective somatostatin receptor (SSTRs) antagonist that was first approved for marketing in 2002 for the treatment of acromegaly. Its investigational indications include gastroenteropancreatic neuroendocrine tumors. 68Ga-Edotreotide is a non-selective SSTRs antagonist product developed by Advanced Accelerator Applications. It is a radioactive diagnostic agent used in PET scans to detect somatostatin receptor-positive neuroendocrine tumors in both adult and pediatric patients. Other related R&D pipelinesMisoprostol is a medication primarily used to reduce the risk of stomach ulcers in users of non-steroidal anti-inflammatory drugs (NSAIDs). Its mechanism of action involves stimulating prostaglandin receptors in the stomach, enhancing gastric protection against acidic substances, and reducing gastric acid secretion, thereby protecting the gastric mucosa from damage. Additionally, Misoprostol is used for various medical applications: in the field of gynecology, it can be used to manage early miscarriage, prevent postpartum hemorrhage, and perform abortion surgery during early pregnancy. When Misoprostol acts on prostaglandin receptors in the uterus and cervix, it increases the strength and frequency of uterine contractions and decreases cervical tension, thus playing a key role in the management of miscarriage. ONO-4578, developed by Ono Pharmaceutical, is a highly selective antagonist of the EP4 receptor and is currently being studied for its safety and efficacy as monotherapy and in combination with nivolumab in patients with advanced or metastatic solid tumors, including gastric cancer. Based on the results of a Phase 1 clinical study, ONO-4578 has demonstrated good tolerability and certain antitumor activity. YY-001 and HTL-0039732 are selective EP4 receptor antagonists developed by Shanghai Yu Yao and Sosei Group, respectively, and are currently involved in clinical studies for various solid tumors, including gastric cancer. BMS-986340 is an IgG1 subtype monoclonal antibody product targeting CCR8, originally researched and developed by BMS. This drug possesses enhanced non-fucosylated (NF) Fc region features. As the CCR8 receptor is a chemokine receptor expressed on the surface of regulatory T cells (Tregs) and participates in the regulation of the immune system, BMS-986340 has been engineered to specifically bind CCR8. Due to its non-fucosylated Fc segment, it enhances effector functions against target cells. This optimization enables BMS-986340 to effectively deplete regulatory T cells (Tregs), which may modulate the immune response for treating diseases associated with excessive immunosuppression or dysfunctional Tregs. Currently, clinical trials for various solid tumors, including gastric cancer, are underway involving BMS-986340. FPI-2059 is a small molecule radiopharmaceutical that targets the Neurotensin Receptor 1 (NTSR1). This receptor is overexpressed in a variety of solid tumors, including pancreatic ductal adenocarcinoma, colorectal cancer, head and neck squamous cell carcinoma, gastric cancer, Ewing sarcoma, and neuroendocrine-differentiated prostate cancer. FPI-2059 is developed based on compounds previously known as IPN-1087 and 3BP-227. These compounds have been studied as beta-emitting radiopharmaceuticals in researcher-initiated studies and phase I clinical trials. In 2021, Fusion Pharmaceuticals acquired this asset and transformed it into an alpha-emitting radiopharmaceutical, labeled with Actinium-225. Concurrently, FPI-2058 is a diagnostic analog of FPI-2059, replacing Actinium-225 with Indium-111 as the radioactive isotope for medical imaging and diagnostic purposes. This targeted radiopharmaceutical design aims to achieve precise targeted therapy and diagnosis for the aforementioned types of tumors. TT-4 is a selective A2B receptor antagonist developed by Tarus Therapeutics that is currently in phase 1/2 clinical development. The trial aims to evaluate its therapeutic effect in patients with various advanced solid tumors, including gastric cancer. 177Lu-PP-F11N is a radioactive drug complex that combines PP-F11N (a gastrin analog) with the beta-emitting radioactive isotope Lutetium-177. This drug exhibits potential antitumor activity and may be used as an agent for single-photon emission computerized tomography (SPECT) imaging. After intravenous injection, PP-F11N specifically binds to the Cholecystokinin-2 Receptor (CCK2R). This allows visualization of the tumor cells expressing the CCK-2 receptor using nuclear medicine imaging techniques. Additionally, the Lutetium-177 radioactive isotope delivers cytotoxic doses of beta-radiation to the tumor cells expressing the CCK-2 receptor, providing targeted destruction of these cells. As the CCK-2 receptor is widely expressed in various types of tumor cells, 177Lu-PP-F11N has the potential for the treatment of these specific types of tumors and offers targeted imaging for personalized, precise cancer diagnosis and therapy.

2019年初夏，一位中航基金经理，被蝴蝶的翅膀拍了一下，发生风格偏移，把药明康德买成军民融合基金的重仓，最终卷入一场风暴。药明康德，一家被美国人控制的企业，现在却受到美国的制裁威胁。意外性造成的荒诞感，在地缘关系的阴影中被放大。你可能不再记得这是药明系第几次带崩生物医药板块，但谁也不能肯定是最后一次。2024年是美国大选之年，来自政客的jump scare绝不会是最后一次。无论制裁提议能否变成法律，每次恐吓都会对市场带来实质性影响。需要直面的问题是，为何我们的生物科技产业如此脆弱，任何口头脱钩都能引发雪崩？01 谁是最大受损者？跨国药企是全球化受益者，在中国创新药领域占有主导地位。2022年，8家跨国药企（阿斯利康、默沙东、拜耳、赛诺菲、罗氏、诺华、诺和诺德、礼来）制药业务中国市场合计收入约289亿美元。据青桥阳光统计，56家通过18A通道上市的港股未盈利生物科技公司（剔除康希诺）的合计产品营收，2022年为254亿人民币，2023年超过400亿人民币，仍不及外资零头。2款率先直接在美国销售的国产创新药泽布替尼、西达基奥仑赛，预计2023年美国市场合计收入约15亿美元，在美国创新药（2021年销售额4565亿美元）中可谓沧海一粟。跨国药企才是全面脱钩的最大直接受损者。中国成为阿斯利康第二大市场，2023H1阿斯利康中国区营收30.43亿美元，同比增长7%，占比全球业绩14%。中国成为默沙东第三大市场，2023H1中国区销售额35.81亿美元，约为同期恒瑞医药销售额2.5倍，同比增长45%。中国成为赛诺菲第二大市场，2023Q3中国市场销售额7.28亿欧元。诺华、武田制药都把中国纳入第二大目标市场。截至2023H1，中国有7家CDMO海外收入占比超过75%，主要发展逻辑是承接海外药企研发生产外包订单的转移，其行业平均薪酬是海外同行一半左右，这也使得国内服务的收费仅为发达国家30%-60%。如果CDMO供应链全面脱钩，跨国药企在控制成本上将受到第二波损害。全世界新增小分子CDMO产能主要集中在中国，既能获得美国FDA和欧盟EMA多个产品GMP认证，又是成本洼地的产能并不多，跨国药企可选择余地不大。从另一组数据可以看到，中国西药类产品出口以低附加值的原料为主（占比80%），呈现量增价减态势，为全球制药业提供高质低价的精细化学及中间体，对平抑药价有关键作用。据中国医药保健品进出口商会统计，2023年前三季度，中国西药类产品出口额388.5亿美元，进口额403.6亿美元，其中西药原料出口额311.4亿美元，进口额74.1亿美元，西成药出口额47.4亿美元，进口额191.7亿美元，生化药出口额29.7亿美元，进口额137.9亿美元。中国在西成药、生化药上严重依赖进口，存在触目惊心的贸易逆差，这与上述跨国药企在中国创新药领域的主导地位是一致的。02 无法简单切割全球医药产业链的深度融合和相互依存，已经超出民粹主义的认知，无法进行简单切割。高性价比常用药断供，后果严重，已构成全球性挑战。美国持续出现药荒，2023年，美国短缺化疗药物顺铂注射液，紧急向齐鲁制药采购，连中文包装盒都没来得及换。据美国国家癌症研究所的数据，高达20%的癌症患者依赖铂类化疗药物进行治疗。这次药物短缺与供应顺铂材料的印度工厂因质量问题停产有关。占美国90%处方量的仿制药主要来源是印度，这种对单一供应商的依赖存在较大风险。2022年，WHO和各国卫生部门将印度止咳糖浆与冈比亚、乌兹别克斯坦和喀麦隆的至少141名儿童死亡关联起来。2023年，印度生产的两款眼药水没消毒，造成美国3人死亡，4人眼球被摘除。全美药品短缺的另一个原因是，制药公司停止生产许多挽救生命的非专利药物，因为利润太低，造成约300种基本药物都常年供不应求。长春新碱是一种治疗儿童白血病的低利润基本药物，每剂成本仅为约5美元，2019年美国仅有两家制造商，Teva在放弃生产长春新碱后，辉瑞表示无法跟上市场需求量。跨国药企一个小涟漪，可能造成供应链大波澜，甚至掀起患者群体生命中的大海啸。跨国药企在配置全球产能时，立足于经济效益，人道主义不是考量重点，如果产药无利可图，有时会以客观因素为由牺牲掉别国市场。在国内创新药大发展前夕，2016年新华社曾经发文发问：专利药受制于人，中国如何摆脱“进口药物依赖”？背景是拜耳两款药物在中国市场面临断货，先是治疗肺动脉高压的特效药物“万他维”，后是中国市场上唯一可降低多发性硬化症发作频率的药物“倍泰龙”。2015年12月10日，一封由1400余名患者、医生、人大代表联名签署的公开信，发送到拜耳医药总部，请求留下“万他维”。这封信指出，在美国并未出现“万他维”退市的情况，中国患者对其在中国市场的退出行为感到难以接受，并尖锐提问：难道中国患者的生命比不上美国患者的生命吗？2016年两会期间，针对国内缺乏进口专利药品的替代品，导致部分进口专利药品不仅价格高，而且形成“药物依赖”的危险局面，有全国人代表忧心忡忡：我们不能被跨国药企卡住脖子。据《中国震颤患者白皮书》，2019年中国帕金森病患者约284万人，数量居全球首位。米内网数据显示，2021年上半年，国内公立医院帕金森进口原研药占据90.97%，国产药份额不到10%。默沙东的帕金森神药息宁（卡左双多巴缓释片）发生过3次断货。息宁在国外生产，国内进行分包装，2016年第一次大范围断货，默沙东解释为生产因素所致，2019年第二次断货，默沙东再次表示为生产工厂原因，2021年第三次断货的原因默沙东未公布，医院内息宁单盒价格只需要50元，供应紧张后，网上药店标准装价格暴涨到799元~996元。阿糖胞苷作为血液肿瘤常用药，因为辉瑞决定对意大利生产工厂进行停产检修, 导致2019年1月起在全球范围内出现供货不足的情况。辉瑞占据阿糖胞苷市场份额97%以上，直到2022年12月，才有首家国产阿糖胞苷仿制药通过一致性评价。03 在外部冲击中成长固定的用药习惯，以及对原研药或进口药的固化信任，也是造成供应链失衡的原因之一。辉瑞阿糖胞苷断供期间，患者及家属焦虑不安，其实有5家国产药企持有注射用盐酸阿糖胞苷的批准文号。本土制药需要更多信任。2015年1月，毕井泉执掌国家食药监局，中国进入创新药元年，成长至今不足10年，源头创新能力和商业化体量仍然弱小，抗风险能力差，面对外部冲击，难免泥沙俱下。而创新药定价机制、入院限制、融资困境，又意味着国际化才能打开更高的天花板。中国药企的适应能力超强，在海外非美市场、长尾市场提前布局。国产PD-1、生物类似药以性价比优势，将在出海史上写下浓重一笔。复宏汉霖汉曲优在海外获批上市时间其实比国内还早半个月，成为首个登陆欧盟的国产曲妥珠单抗，2022年海外销售和BD收入约2.04亿元，目前在超过30个国家和地区成功获批上市。2023年底PD-1单抗H药（汉斯状）在印度尼西亚获批用于治疗广泛期小细胞肺癌，成为首个在东南亚国家上市的国产PD-1。这也是H药首次在海外市场获批，今年1月H药完成首批海外发货。未来复宏汉霖将继续携手合作伙伴KGbio推动H药在东南亚、中东、北非等“一带一路”市场的商业化。目前H药对外授权已达70多个国家和地区，全面覆盖欧美主流法规市场和新兴市场。君实生物PD-1特瑞普利单抗通过对外授权已覆盖50多个国家和地区，包括鼻咽癌高发的东南亚。科兴制药的商业模式比较独特，一边在国内捡18A公司的漏，另一边卖给海外下沉市场。商业逻辑完美闭环，但这家公司的经营能力有待验证。科兴制药经过20多年的海外积淀，在海外产品注册、海外开拓和营销、海外GMP合规审计方面有着丰富资源与商业化经验，已通过40个国家和地区的市场准入并实现销售，销售网络已100%覆盖人口过亿的新兴国家市场。公司从2021年开始通过引进产品的方式快速扩充产品池，已获得10款生物类似药、化学药在欧盟及海外新兴市场国家的销售权益，在60多个国家及地区提交80多份引进产品的注册申请，其中从挣扎在生死线上的东曜药业、迈博药业低价（首付款分别为3000万、5000万）引进贝伐珠单抗、英夫利西单抗。进度上，埃及药监局对英夫利西单抗和贝伐珠单抗完成了现场GMP审计，巴西药监局对英夫利昔单抗的现场GMP审计于2024年1月中旬完成。若海外注册顺利推进，引进产品将于2024年陆续在海外实现商业化。地缘风险的阴影投射到每家创新药企的厂牌上，2024年注定不平静，但中国生物医药产业已经深度融入全球产业链。据医药魔方统计，截至2024年1月18日，跨国药企在中国投资Biotech多达132起，涉及123家医药企业。处于生命周期早期的中国创新药企，将在与世界的博弈和共振中成长壮大。