Sym-021

结直肠癌（CRC）是全球第三大常见恶性肿瘤，仅次于乳腺癌与肺癌。免疫检查点抑制剂（ICI）在晚期或转移性结直肠癌（mCRC）治疗中展现出巨大潜力，尤其对有错配修复缺陷（dMMR）和微卫星不稳定性高（MSI-H）的患者疗效显著；但对于错配修复功能良好（pMMR）、微卫星稳定（MSS）或微卫星不稳定性低（MSI-L）的患者，ICI响应率极低。因此，为这类患者寻找新的治疗策略迫在眉睫。 多项研究提示，肠道菌群调节或可改善CRC患者对ICI的耐药问题。在此基础上，我国研究人员取得突破性进展——《Cureus》期刊报道了全球首例“替雷利珠单抗+贝伐珠单抗+FMT胶囊”联合治疗IV期pMMR/MSS转移性结直肠癌的病例，该方案成功将肿瘤缩小至可根治性手术范围，最终实现病理完全缓解（pCR）！ 全球首例！粪菌移植联合替雷利珠单抗+贝伐珠单抗三管齐下，助晚期结直肠癌患者病灶全缩小，肿瘤标志物骤降 该患者是一位57岁中国男性，确诊为升结肠错配修复充分（pMMR）晚期转移性结直肠癌（mCRC），伴继发性肝脏恶性肿瘤，近半个月来反复出现腹痛、大便性状异常等症状。基因检测显示KRAS/NRAS/BRAF均为野生型，临床分期为cT4bN2M1b Ⅳb期。 患者先后接受三次治疗：首次入组Ⅱ期临床试验，采用CPGJ602+mFOLFOX6（奥沙利铂+氟尿嘧啶+亚叶酸钙）方案，疗效不佳；随后改为贝伐单抗联合FOLFOXIRI（奥沙利铂+伊立替康+亚叶酸钙）方案，完成3个周期后CT评估达部分缓解（PR），但因高强度化疗引发消化道反应、骨髓抑制等严重副作用，患者拒绝继续该方案，且病情暂不适合根治性手术，最终接受第三次治疗——口服肠道菌群胶囊联合替雷利珠单抗+贝伐单抗。治疗后疗效显著，结果显示如下： 1、 肿瘤标志物大幅下降 ： 癌胚抗原（CEA）从入院时的30.1μg/L骤降至4.3μg/L，CA19-9从62.64kU/L降至23.97kU/L 。 2、 病灶全面缩小并达PR ：相较于第二次治疗后“结肠及淋巴结病灶缩小、肝转移灶无变化”的情况，此次所有病灶均明显缩小——CT显示 结肠肿瘤从3.7cm×3.1cm缩小至2.1cm×1.7cm，腹膜后淋巴结转移灶从5.2cm×4.3cm缩小至2.3cm×1.4cm，肝脏肿瘤从3.9cm×3.2cm缩小至2.9cm×2.3cm （详见下图）。肿瘤缩小至可手术切除的程度。术后， 患者获得病理完全缓解（pCR） 。 ▼该患者第二次治疗后，腹部轴向CT图像 ▲图源“Cureus”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 ▼该患者第三次治疗后，腹部轴向CT图像 ▲图源“Cureus”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 益生菌的前世今生，开启全新抗癌模式 肠道中的天然菌群大部分由益生菌构成，其中乳酸菌较为常见，此外还涵盖肠球菌、迷走球菌、魏斯氏菌、明乳球菌、链球菌、四联球菌、双歧杆菌、肉杆菌、酒球菌、片球菌、乳杆菌、大肠杆菌以及酵母菌等。需要注意的是，同一物种的细菌并非都具备相同特性，且可能会对生物体产生不同影响，而且并非所有菌株都属于益生菌范畴。 益生菌是一类“活的、非病原性微生物”，在适量摄入的情况下，可为宿主提供多种有益影响。早在益生菌被明确认知之前，奶酪、面包、葡萄酒、啤酒等发酵产品就因其具备营养和治疗功效而被广泛应用。 早期对于益生菌的研究，主要聚焦于其作为食品或膳食补充剂时所发挥的营养作用。然而，近期的研究重点则转向了益生菌在医学和治疗领域的功能，其中在癌症领域的作用尤为突出。益生菌在癌症防治方面的作用广泛，其抗癌作用主要体现在以下三个方面： 1、多项研究显示，益生菌能够提高机体免疫功能，对改善肝癌、肺癌、肾癌、结直肠癌等多种癌种的预后具有积极意义，有望成为癌症和免疫治疗领域的热门研究方向之一。 2、微生物群可参与多种癌症的致癌进程，妇科癌症便是其中之一。以宫颈癌为例，菌群失调已被证实会通过影响人乳头瘤病毒（HPV）的感染、清除及持续状态，进而影响HPV感染情况，同时还会通过改变TGFβ1等免疫系统蛋白的水平，对宿主免疫反应产生影响。 3、益生菌还可用作辅助药剂，以增强或调节其他诊断和治疗手段的效果。例如，全身化疗常引发腹泻这一副作用。研究表明，益生菌丁酸梭菌能够减轻肺癌患者因化疗导致的腹泻症状，同时缓解全身炎症反应。 小编寄语 在癌症治疗的漫漫征程中，积极调节肠道菌群已然强势崛起，成为继癌症疫苗、免疫细胞疗法之后的又一“抗癌新星”。肠道菌群作为人体内部生态的关键“守护者”，与癌症防治紧密交织，恰似为抗癌之战精心构筑的一道 “隐形防线”。通过科学有效的调节举措，不仅能为患者的整体健康状况筑牢根基、添砖加瓦，更能显著提升抗癌及免疫治疗的 “战斗力”，巧妙化解手术与放化疗带来的诸多副作用 “难题”，宛如在荆棘满布的抗癌路上，铺就一条更为平坦、顺遂的通途，小编也希望未来能实现“无痛抗癌”的美好愿景。 但全球肿瘤医生网小编温馨提示，癌症患者由于疾病的高度复杂性，建议在专业营养师或有执照的医疗保健人员的指导下，选择私人订制版个体化益生菌，这类益生菌是根据不同病种筛选出的特定菌种组成，可针对患者的自身病情，辅助肠道建立优势菌种架构，并能排除毒素和有害菌、重整肠道环境，从而促进疾病显著改善，以达到预期的应答水平。《柳叶刀》也曾指出“个体化益生菌群可能是未来癌症免疫治疗的策略”。想了解益生菌更多内容的患者，就将治疗经历、近期检查结果等提交至通过 全球肿瘤医生网医学部 ，初步评估营养状况。 参考资料 [1]Cheng X,et al.Shen T. Successful Treatment of pMMR MSS IVB Colorectal Cancer Using Anti-VEGF and Anti-PD-1 Therapy in Combination of Gut Microbiota Transplantation: A Case Report. Cureus. 2023 Jul 24;15(7):e42347. https://pmc.ncbi.nlm.nih.gov/articles/PMC10445052/ 本文为全球肿瘤医生网原创，未经授权严禁转载

Boan Biotech (6955.HK) today announced its 2025 half-year results and latest developments. During the reporting period, the company's total revenue was RMB 393 million, up 8% YoY, and the contribution to this from product sales was RMB 385 million, up 16% YoY. The company has maintained profitability for three consecutive half-year reporting periods and currently holds over RMB 1 billion in cash reserves. The strong cash position and healthy cash flow laid a solid foundation for Boan Biotech to accelerate innovation going forward.  Building momentum for growth by expanding the product portfolio Boan Biotech has four products approved for marketing. Three of them generated a combined sales growth of 16% in the first half of this year. The solid growth was driven by the company’s sophisticated commercial operation system, including a nationwide sales network covering 3,000-plus hospitals and other healthcare organizations, an experienced in-house sales & marketing team, and various strategic partners. Boyounuo® Boyoubei® Boluojia® Boyouping® In oncology, the company took advantage of its own sales & marketing team to promote and sell Boyounuo® (bevacizumab injection) and Boluojia® (denosumab injection 120 mg), resulting in the continued expansion of the two products’ coverage in the marketplace. In areas other than oncology, the company worked with Qingdao Conson Pharmaceutical to extend the reach of Boyoubei® (denosumab injection 60 mg). In August 2025, Boyouping® (Dulaglutide Injection), the 4th product of Boan Biotech, was approved for marketing in China. This was also China’s first locally developed dulaglutide injection approved for marketing in the country. The company granted Shanghai Pharmaceutical Co., Ltd. (Shaphar) the exclusive right to commercialize this product in the Chinese mainland, taking advantage of the latter’s integrated sales & marketing expertise across channels and extensive distribution network to accelerate the ramp-up time for the product. In addition, the company’s pipeline also includes several investigational drugs that will be made commercially available soon. For example, BA9101 (aflibercept injection) is under review for its Biologics License Application (BLA) in China, and Boyoubei (denosumab injection 60 mg) and Boluojia (denosumab injection 120 mg) will complete their Phase 3 clinical trials in Europe, the U.S., and Japan soon. The launch of these drugs will further fuel the company’s high-speed growth.  Doubling down on innovation to build a competitive edge Boan Biotech’s pipeline currently includes 2 drug candidates with their BLA under review, and 10-plus drug candidates in the clinical or preclinical development stage. With the first cohort of drug candidates being commercialized one after another, the company is able to generate a sustainable cash flow, which can be used to speed up new drug development on an ongoing basis. The company has built a pipeline of innovative drugs standing out from the competition. It pursues an “IO + ADC” strategy for new drug development, with a focus on developing IO 2.0 therapies as well as the next-generation bispecific and dual-toxin antibody-drug conjugates (ADCs). Here are some examples: ● BA1106 (a non-IL-2 blocking anti-CD25 antibody): This is the first innovative anti-CD25 antibody in China to undergo clinical trials for the treatment of solid tumors. A Phase 1 clinical trial of BA1106 as a monotherapy has been completed. A dose-escalation clinical trial of BA1106 in combination with BA1104 (nivolumab injection), a PD-1 inhibitor developed by the company, also began to enroll patients in June 2025. In April 2025, the early results of the Phase 1 clinical trial of BA1106 were presented at the annual meeting of the American Association for Cancer Research (AACR). In the trial, BA1106 was shown to have the potential for treating multiple types of solid tumor and a pharmacodynamic (PD) profile matching its intended mechanism of action. It was shown to be safe and well-tolerated as well. Besides, BA1106 demonstrated a good pharmacokinetics (PK) profile with low immunogenicity, and all of its anti-drug antibody (ADA) assays were negative. ● BA1302 (an anti-CD228 ADC): This is China’s first innovative anti-CD228 ADC under clinical development. A dose-escalation part of Phase-1 clinical trial is currently going on in China using it as a monotherapy. It was granted an Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) for treating squamous non-small cell lung cancer (sqNSCLC) and pancreatic cancer, and was cleared by the FDA for clinical trials as well. ● BA1301 (an anti-Claudin18.2 ADC): It is undergoing a dose-expansion part of Phase 1 clinical trial as a monotherapy in China. This drug candidate was also granted an ODD in the U.S. for the treatment of gastric cancer and pancreatic cancer. Furthermore, the company is also accelerating the development of other innovative biologics in the pre-clinical phase, including:   ● PR201 (an antibody-cytokine fusion protein targeting PD-1 and IL-2): Developed in house, PR201 was shown to be a potent anticancer agent in multiple tumor models where anti-PD-1/PD-L1 antibodies were ineffective or had a low efficacy. ● PR203 (a bispecific antibody targeting TL1A and IL23): Its targeted indications include inflammatory bowel disease (IBD), psoriasis (PS), and psoriatic arthritis (PSA).  ● BA1304 (a bispecific ADC targeting EGFR and B7-H3): Based on site-specific glycan conjugation, it is intended to treat lung cancer, colon cancer, bladder cancer, kidney cancer, esophageal cancer, and other types of cancer. The company is talking with several partners including multinational pharmaceutical companies to speed up the development of the aforementioned high-potential candidates globally. Maximizing the synergy for BD through collaboration across the value chain Boan Biotech is among a small number of Chinese biopharmaceutical companies operating an integrated system to develop, manufacture and sell products on its own. This system enables seamless collaboration across the value chain, which can be translated into powerful productivity and exceptional efficiency. At the same time, the company is actively deepening external operations by building an ecosystem of partners across the realms of development, production, and commercialization. Its aim is to work with exceptional partners around the world to maximize the synergy and achieve win-win results. Empowering new drug development Previous examples of collaboration include granting Joincare the exclusive rights to develop and commercialize BA2101 (a long-acting anti-IL-4Rα monoclonal antibody) for the treatment of respiratory diseases in the Chinese mainland; conducting a Phase 3 clinical trial of BA9101 in China with Ocumension and granting the latter the exclusive right to commercialize this drug in the Chinese mainland; granting Zencore Biologics the non-exclusive right to use Boan Biotech's proprietary BA-HIEXcell® platform to develop stable cell lines in the Chinese mainland; and collaborating with the Hong Kong University of Science and Technology in several frontiers of biomedicine. Increasing productivity Previous examples of collaboration include working closely with Haier Biomedical for digital, automation and AI endeavors, to improve its digital capabilities for manufacturing and quality management. Speeding up global commercialization Previous examples of collaboration include granting Shaphar the right to commercialize Boyouping in the Chinese mainland; granting Qingdao Conson Pharmaceutical the right to commercialize Boyoubei in the Chinese mainland; granting Kexing Biopharm the right to commercialize Boyoubei and Boluojia in Hong Kong and Macao, as well as the right to commercialize BA9101 in markets other than the Chinese mainland, the EU, the U.K., the U.S., and Japan; and joining hands with overseas partners to commercialize Boyounuo, Boyoubei, and Boluojia in Brazil. In addition, Boan Biotech is also talking with partners for the development and commercialization of multiple drugs in different regions abroad.  Increasing capacity through smart manufacturing Boan Biotech already has a production capacity that is enough to address the growing demand driven by new product launch and business development. It also leverages smart manufacturing to optimize production processes and upgrade digital production systems. The company has put into place a quality management system conforming to Chinese, American, European, and Japanese standards. The system has been certified by four major internationally recognized standards: ISO 9001, ISO 14001, ISO 45001, and ISO 50001. In addition, its manufacturing facility has passed the GMP inspection by Brazil’s ANVISA resulting in a “no observation” result and the QP audit of the EU. Boan Biotech was on the “List of Provincial Quality Management Examples” in Shandong, and its digital facility was named one of the “Provincial Digital Facilities of the Year in Shandong” for 2024, all in recognition of the company’s outstanding practices in quality management and digital transformation. Driving high-speed growth by achieving multiple milestones In the second half of 2025, Boan Biotech is expected to achieve multiple milestones, including completing clinical trials at different phases for several innovative biologics and achieving breakthroughs for several biosimilars in China and abroad. Here are some examples: ● The dose-escalation part of Phase 1 trial for the combination therapy of BA1106 (a non-IL-2 blocking anti-CD25 antibody) and BA1104 (nivolumab injection) to be completed this year; ● The dose-expansion part of Phase 1 trial of BA1301 (an anti-Claudin18.2 ADC) as a monotherapy to be completed this year. The phased clinical data will be presented at this year’s annual meeting of the European Society for Medical Oncology (ESMO);  ● The dose-escalation part of Phase 1 trial of BA1302 (an anti-CD228 ADC) as a monotherapy to be completed this year; ● BA9101 (aflibercept injection), under review for its BLA in China, to be approved for marketing this year; ● Boyounuo (bevacizumab injection), under review for its BLA in Brazil, to be approved for marketing this year; ● The international multicenter Phase 3 clinical trials of Boluojia (denosumab injection 120 mg) and Boyoubei (denosumab injection 60 mg) to be completed in Europe, the U.S., and Japan, with their BLAs to be submitted in the U.K. this year and in the U.S. next year; ● Patient enrollment to be completed for the Phase 3 clinical trial of BA1104 (nivolumab injection) in China this year, with permission from the FDA already granted to waive the need for a Phase 3 clinical trial of it in the U.S. Jiang Hua, Chairlady and Chief Executive Officer of Boan Biotech, said:  “The first half of 2025 was our third consecutive half-year reporting period of being in the black. This made us one of a small number of biotech companies to achieve sustained profitability through product sales thanks to our efficient commercialization efforts and our strategy for building a differentiated portfolio.  In the future, we will continue to pursue the goal of becoming a leading biopharmaceutical company in the world with a focus on four fronts: the first is to extend the reach of our four existing products, Boyouping in particular, by enhancing our commercial capabilities; the second is to expedite the approval of several core products for launch in China and abroad to drive revenue growth; the third is to ramp up the development of innovative drugs and build a value-added pipeline; and the fourth is to cash in on our innovation and speed up the development of high-potential candidates overseas by building partnerships. We are confident that we will maintain the high-speed growth over the next three years, to deliver better products for our patients and better results for our shareholders.”   About Boan Biotech Boan Biotech is a fully-integrated biopharmaceutical company developing, manufacturing, and marketing biologics, with a focus on oncology, autoimmune diseases, ophthalmology, and metabolic diseases. The company's drug discovery activities revolve around multiple platforms: Human Antibody Transgenic Mouse and Phage Display Technology Platform, Bispecific T-cell Engager Technology Platform, ADC Technology Platform and Cell Therapy Platform. Boan Biotech operates across the entire value chain of the industry covering antibody discovery, cell line development, upstream and downstream process development, analytical and bio-analytical method development, technology transfer, non-clinical research, clinical research, regulatory affairs and registration, and commercial production. In the cell therapy field, Boan Biotech focuses on a new generation of enhanced and regulated CAR-T technology, developing safer, more effective, and affordable treatments for patients. Boan Biotech’s portfolio includes four products approved for marketing. Its pipeline includes one investigational drug under review for its marketing application, multiple novel biologics as drug candidates protected for their international intellectual property rights, and biosimilar candidates. In addition to China, the company is also developing biopharmaceutical products in overseas markets, including the U.S., the EU, and Japan. With a differentiated portfolio and well-established commercial capabilities, Boan Biotech operates across the industry’s value chain from research and development to manufacturing and commercialization, laying a solid foundation for long-term, high-quality growth in the future.