A Phase 1, Open-label Study to Evaluate the Safety and Tolerability of BMC128 in Combination With Nivolumab in Patients With Non-small Cell Lung Cancer (NSCLC), Melanoma or Renal Cell Carcinoma (RCC)

The purpose of this study is to assess the safety and tolerability of BMC128 in combination with nivolumab (a known immunotherapy) in order to investigate if administration of select elements of the intestinal microbiome may serve as a novel and effective means of improving the efficacy of anti-cancer immunotherapies.

开始日期2022-05-01

申办/合作机构

Biomica Ltd.初创企业

100 项与 BMC-128 相关的临床结果

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100 项与 BMC-128 相关的转化医学

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100 项与 BMC-128 相关的专利（医药）

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项与 BMC-128 相关的新闻（医药）

2024-11-26

·今日头条

90%的癌症患者死于癌症！这五大长生存“秘籍”快收藏

“手术很成功，肿瘤已被完全切除了。” 王先生还清晰的记得半年前自己的主刀医生说的话。然而，令王先生和家人万万没想到的是，刚过了半年，复查就发现自己的肠癌手术部位又出现了病灶，并且已经转移到肝脏。这并不是个别的案例，有很多癌症患者的手术很成功，但最后却死在了复发和转移。据统计：90%的癌症死于复发转移!【1】所有的癌症患者治疗后都在担心一件事： “肿瘤真的被完全清除了吗？” 再完美的治疗方案，都会因复发而功亏一篑！导致肿瘤复发的四大元凶癌症复发的原因很多，主要是以下四点：一、局部治疗不彻底比如初次手术时，切缘为阳性，也就是说肿瘤没有切干净，或者该清扫的淋巴结没有清扫，造成术后发生快速的复发转移。二、治疗方案的选择在肿瘤的治疗中，手术、放疗和化疗的三大中流砥柱地位无人能撼动，但目前为止，没有任何一种单一的手段能完全清除体内的癌细胞。同时，放化疗等造成了患者免疫力下降，也就为肿瘤的复发和转移埋下了隐患。因此，临床中经常出现即便初次治疗很成功，还是会出现复发的情况。三、缺少巩固治疗常规治疗后，许多患者认为就可以高枕无忧了，尤其是早期的肿瘤患者，很多患者都是初次手术时，肿瘤切干净了，扫描也显示没有癌症迹象，实际上一些癌细胞也可能已经通过淋巴或血液系统扩散到身体的其他部位。这些无法检测到的细胞被称为微转移，会在一定时间内形成转移灶。因此既使在康复期, 复发和转移率仍然很高。四、癌细胞休眠目前已有研究证实癌细胞似乎具有 “隐藏”或休眠很长时间的能力。如20% 到 45% 的雌激素受体阳性乳腺癌复发发生在癌症成功治疗数年甚至数十年后。要知道，残存的几个癌细胞也有可能再次无限增殖，最终出现数百万个癌细胞共同形成一个肿瘤，这些病灶在初期极难被目前的检测手段发现。因此不管是早期还是晚期肿瘤患者，手术及化疗后千万不可掉以轻心。肿瘤本身的特异性差别很大，每个患者肿瘤的恶性程度、生长速度都不同，但总体来说，只要病人免疫力低下，那么不管肿瘤是早期还是晚期，在治疗后复发和转移的危险性都存在。癌症复发的两大高峰时间在首次治疗后的1~3年，是癌症复发转移的高危时期，其中约90%的患者发生在此期。癌症复发存在两个高峰：半年是复发的第一个高峰两年是复发的第二个高峰随时间的延长复发的机率越低。WHO人为规定5年不复发作为治愈的标准，是因为5年以后癌症又复发的几率较低。警惕！肿瘤复发的五大征兆癌症复发和转移并不总是会引起症状。当确实出现症状时，其性质和频率将取决于复发和转移肿瘤的大小和位置。 1.原有的症状与体征又出现（比如，肿瘤原来的部位出现新的肿瘤）; 2.体重明显下降; 3.原有的异常指标经治疗已恢复正常后又重新异常，如：肿瘤标志物正常后又升高; 4.淋巴结肿大或任何部位新发现占位性病变; 5.出现远处转移则出现相应部位的症状与体征。如：当癌症扩散到骨骼时，疼痛和骨折癌症扩散到大脑时出现头痛，癫痫发作或头晕癌症扩散到肺部时呼吸急促，咳嗽当癌症扩散到肝脏时，黄疸或腹部肿胀注：不同的癌症转移的规律不同，如：肺癌－脑、骨、肝等。乳癌－骨、肺、脑。前列腺癌－骨，脑瘤－颅内转移。五大调节方式，远离癌症复发和转移对于肿瘤患者和家属来说，从确诊到治疗再到康复过程中的每一步都至关重要。除了接受临床正规的治疗，如手术、放疗、化疗等，这是抗击癌症的主力军，作为一个聪明的患者，还应该通过五大调节方式“自救”，我们才能在这场与癌症的较量中大获全胜！ 01 心理调节正如一位癌症病友就自己的亲身感受所说：“在癌症面前，谁能树起必胜的信念，遵循科学的防治原则，与经治医生密切配合，努力适应新环境，对周围事物培养兴趣和爱好，坚韧不拔地与病魔抗争，谁就能获得生存与康复的希望”。的确，在临床上我们也可以看到，在同样的医疗条件下，一些病人思想开朗，有着与疾病抗争的顽强意志，比那些因患癌症而思前想后、精神陷入极度苦闷的人治疗效果要好得多。如果精神完全被摧垮，即使再好的疗法也收不到理想的效果。乐观的心态可以使人体处于一个最佳的状态，帮助大家更好维持自身免疫力。如果心理压力太大，会导致对免疫系统有抑制作用的荷尔蒙成分增多，从而降低免疫功能。当你在病床上还能够不忘开玩笑、找乐子，你的病就已经好了一大半。 02 营养调节 “饮食均衡，医生归田；饮食不好，仙丹无效。”由此可见：吃饭多少、营养状况好坏对于每个癌症患者，家属以及临床医生都是很重要的问题，甚至等同于治疗的重要性！很多“聪明”的患者通过饮食调理，改善了自身的营养状况，提高了免疫力。吃对了，吃健康了，免疫力自然就提高了，对抗癌症的力量就更壮大了！自身对抗癌症的能力增强了，生存期也会大大延长！专家建议,肿瘤患者应适当多摄入富含蛋白质的食物,适量多吃蔬菜、水果和其它植物性食物,吃富含矿物质和维生素的食物,限制精制糖摄入。总体的原则是：首先，多吃植物性食物。其次，要选择低脂饮食。第三，摄入精益蛋白质。最后，限制糖，酒精，加工肉三大致癌物摄入。而在制订癌症患者食谱时，由于每个患者的具体情况均有所不同，因此食谱的编制更应强调个性化，并依病人罹患肿瘤的种类来选择适当的食品，例如: 乳腺癌：忌油腻及生冷等难消化的食物，如肥肉、奶油等；宜食海带、紫菜、牡蛎、芦笋、弥猴桃等化痰软坚功能的食品。肺癌：早期应及时补充各种营养，使机体能够耐受以后的治疗，可多增加些蛋白质等高能量物质、维生素和矿物质；肺癌放、化疗时，应给予补充气血的食品，如香菜鲫鱼汤、燕窝、香菇、木耳等。胃癌：应注意多选用开胃降逆的清淡食物，如果汁、杏仁露、粥、山楂糕、大枣等，切忌辣椒、烟酒，以及土豆、红薯等含淀粉较多的食品，忌食油腻、生冷和粗硬难消化的食物。肠癌：宜多吃些黑木耳、茄子、丝瓜、胡萝卜和各种绿色蔬菜，忌食大油大肉等食品。此外，全球肿瘤医生网医学部给大家列出目前经证实的一些具有防癌抗癌或提升免疫功能的食用类物质研究，供大家参考。 1.胸腺肽胸腺肽属于免疫调节疗法，已经被广泛用作一种辅助性的治疗手段，一些观点认为其能够有效改善患者的长期预后一项研究表明，接受胸腺肽Tα1治疗的肺癌患者，5年无病生存率为77.3%；而未接受Tα1治疗的患者，整体的5年无病生存率为57.9%！【2】 2.西兰花提取物对几十年研究的全面回顾得出结论，十字花科蔬菜是一大类，每种都含有大量的维生素，矿物质和植物化学物质等，这在实验室中一些研究支持免疫系统保护细胞。3.舞蓉多糖舞茸，在我国因较早以“灰树花”之名收录于《中国的真菌》，所以国内习惯叫“灰树花”。原产于日本北部山区，味道佳口感好且有传承药效，日本科学界多年研究证实，舞茸是最有价值的食药两用菇类。根据日本的国际癌症研究中心提供的数据显示，对比香菇、灵芝提取物，舞茸提取物在提高机体的免疫应答能力上，显现出最强大和最持久的特性。 4.人参皂苷人参皂苷Rh2能够通过多种途径调节和增强机体免疫功能，对免疫系统具有保护作用。人参皂苷Rh2可显著提高IL-2（白介素-2）活性，提高巨噬细胞的吞噬功能和NK细胞的杀伤活性，从而发挥抗病毒抗肿瘤作用。 5.破壁灵芝孢子粉破壁灵芝孢子粉中含有灵芝多糖，三萜类灵芝酸等活性成分，具有促进T淋巴细胞增殖和T细胞介导的免疫反应，增强NK细胞活性等作用。 03 免疫调节众所周知，肿瘤患者的免疫功能本身处于失常状态，而手术，放疗，化疗会对人体的免疫功能造成一定损伤，在临床治疗后，尽快调整免疫功能，重建免疫防御系统，才能增强自身对抗肿瘤的能力，达到持久防护。肿瘤患者要时刻注意自己的免疫状况。通常可以自测，凭自己感觉，如是否容易感冒、发热、特别容易感染等，当然可以做一些免疫力的检查。相关阅读：为什么癌症患者都需要做免疫功能实时监测？对于免疫功能低下或异常的患者，临床医生会建议注射胸腺肽类的药物、干扰素，恢复免疫试别功能和恢复免疫杀伤功能的细胞免疫回输等等。过继性免疫细胞治疗技术是通过采集人体自身免疫细胞，经过体外培养，使其数量扩增成千倍增多，靶向性杀伤功能增强，然后再回输到患者体内，从而来杀灭血液及组织中的病原体、癌细胞、突变的细胞。如免疫细胞NK，DC,T细胞的临床辅助治疗已经过了大量的临床研究。晚期直肠癌肝转移的M先生肠部病灶手术后每3周接受一次用自己的免疫细胞培养的自体CIK细胞或自体NK细胞静脉回输，同时联合化疗。非常幸运的是，治疗后CT检查显示肝脏病灶竟然缩小了47%，达到了部分缓解（PR）。2020年底，M先生成功的进行了肝转移瘤切除术，术后为了清除身体里面残存的癌细胞，又接受了4个周期自体CIK/NK细胞联合6个周期化疗方案，让M先生万分惊喜的是，肿瘤标志物癌胚抗原均恢复正常范围内，治疗后生活质量改善，随访及增强CT检查未见肿瘤转移及复发！M先生激动地说，“2020年，我达到了NED状态——没有疾病迹象，并且已持续长达40个月！”目前M先生已经从癌症晚期重新回到了正常生活！需要注意的是，目前NK细胞疗法在全球范围包括中国、美国、英国在内的许多国家正在进行临床研究，暂未上市。想接受联合方案且经济条件允许的患者，可以提交病历至全球肿瘤医生网医学部进行评估。 04 肠道菌群调节我们的肠道非常重要，研究人员称其为人类的‘第二’大脑。因为在肠道中存在数量约为100万亿的庞大细菌群！这些微生物的种类非常多，有2,000种不同的细菌菌株或物种，编码超过 300 万个基因，产生数千种代谢物，共同调节人类宿主的许多功能，比如营养代谢、异生物质和药物代谢、维持肠道粘膜屏障的结构完整性、免疫调节和抵御病原体等等，功能非常强大！最令医学届惊喜的是，近五年，众多里程碑式的研究进一步表明，肠道菌群可能是改善癌症治疗的关键，也让基于肠道微生物的疗法可以帮助更多患者对免疫疗法做出更好的响应，这成为几十年来癌症治疗的最大突破之一，也成为全球癌症领域的研究热点。比如，国际上已经有众多“特定”菌株联合免疫疗法的研究： 1.BMC128是一种经过“精准设计的微生物群”口服型胶囊。作为一种活细菌产品，包含了4种独特的细菌菌株，这些微生物可以帮助恢复患者微生物群落的多样性和特定功能，从而提高他们对免疫疗法的反应。正在与纳武单抗联合用于非小细胞肺癌 (NSCLC)、黑色素瘤和肾癌患者验证联合治疗的效果。 2.Vedanta Biosciences 开发了 VE800，这是一种11 种细菌菌株的纯化、冷冻干燥混合物，可以激活产生干扰素-γ 的细胞毒性 T 细胞。它正在与 CPI 纳武单抗联合用于晚期结直肠癌、胃癌和黑色素瘤患者的测试。 3.美国马萨诸塞州剑桥的Seres Therapeutics正在测试另一种细菌联合候选药物 SER-401，用于与 nivolumab 联合治疗转移性黑色素瘤患者。SER-401 包含从健康的人类供体粪便中分离和纯化的菌株，将在 8 周内每天给予，从 CPI 开始之前开始并继续进行。 4.中国的研究人员对至少二线系统治疗失败的微卫星稳定型（MSS）晚期结直肠癌患者进行了创新性治疗，通过“三联疗法”（肠道菌群移植 + PD-1单抗 + 靶向药）有效延长难治型结直肠癌患者的生存期，疾病控制率高达95%！大家可以提交病历至全球肿瘤医生网医学部了解更多肠菌调节方式。为了增强肠道中的有益菌群，有些人选择服用益生菌补品。这些在保健食品商店，药店和网上都能购买到。值得注意的是，益生菌的具体菌株千差万别，不同的益生菌菌株和药物的相互作用又各不相同，尤其是对于肿瘤患者来说，有些可以协同增强治疗效果，有些则会阻碍药效发挥。所以大家切不可胡乱服用益生菌，要听主治医生指导或咨询全球肿瘤医生网医学部做肠道菌群状态的检测之后在判断需要补充哪类菌株。此外，还有国内外已研发出针对肿瘤患者的个性化定制肠菌胶囊，与临床上的各种治疗方案联合用于晚期结直肠癌、胃癌和黑色素瘤患者的测试。 05 运动调节研究显示，坚持规律、不过分剧烈的运动，体内免疫细胞的数量会有所增加。除此之外，经常锻炼还能促进血液循环，使免疫系统细胞的工作效率更高。事实上，很多癌症患者在患癌前都是不爱运动的，然而，不管中医、西医还是自然疗法医生都告诉我们，运动无比重要。有氧运动不仅可以促进脂肪燃烧而达到减肥的效果，还能促进癌细胞凋亡，也是活化自然杀手细胞的良方。人类的免疫系统才是世界上最好的“医生”，全天24小时不停歇的工作，保护我们不受入侵者的伤害，因此请大家在任何治疗期间都不要掉以轻心，时刻防范癌症卷土重来，做好以上五点点，保证我们自身的免疫功能处于健康状态，才能在与癌症这场较量中大获全胜！最后希望大家都能找到适合自己的抗癌方式，早日康复！参考文献：【1】Tarin D. Cell and tissue interactions in carcinogenesis and metastasis and their clinical significance. Sem Cancer Biol. 2011;21(2):72–82. [PubMed] [Google Scholar] 【2】Impact of thymosin α1 as an immunomodulatory therapy on long-term survival of non-small cell lung cancer patients after R0 resection: a propensity score-matched analysis. 本文为全球肿瘤医生网原创，未经授权严禁转载

放射疗法

2024-08-22

·PRNewswire

Evogene Reports Second Quarter 2024 Financial Results

Conference call and webcast: today, August 22, 2024, 9:00 am ET Financial and Business Highlights: H1 2024 revenues $5.1M, up from $1.3M in H1 2023; Q2 2024 revenues $914K, up from $654K in Q2 2023. Anticipated continued revenue growth in the second half of 2024 compared to the same period in the previous year, primarily driven by Casterra's initiation of supplying existing seed orders, which began in August 2024 and total over $8.0 million. H1 2024 loss $9.8M, down from $14.8M in H1 2023; Q2 2024 loss $6.0M, down from $7.8M in Q2 2023. Projected 2024 cash usage (excl. Biomica & Lavie Bio) $8.0M, down 36% from $12.5M in 2023. Implemented a 10:1 reverse stock split during July 2024. Casterra: Received a $440K order for castor seeds from an existing customer for a new African country. Completed a successful castor seed season in Brazil, with shipments planned for Q3 2024. Seeds produced in Brazil and Africa in 2024, are anticipated to meet existing orders totaling approximately $8.4M. Biomica: Promising Phase 1 results for BMC128 with nivolumab in RCC, NSCLC, and melanoma, presented at ASCO 2024. Lavie Bio: A significant milestone achieved in ICL collaboration, developing yield-increasing bio-stimulants for row crops under extreme weather conditions by leveraging AI to identify over a dozen novel microbial candidates. Announced commercial expansion of Yalos™ bio-inoculant to winter wheat. REHOVOT, Israel, Aug. 22, 2024 /PRNewswire/ -- Evogene Ltd. (Nasdaq: EVGN) (TASE: EVGN), a leading computational biology company aiming to revolutionize the development of life-science-based products, today announced its financial results for the second quarter period ended June 30, 2024. Mr. Ofer Haviv, Evogene's President and CEO, stated: "In our vision, we see Evogene as a pioneering company for creating groundbreaking life-science products, to improve life quality and longevity. During the past years we developed three innovative AI tech-engines addressing the main development challenges of products rooted in microbes, small molecules and genomics. Our AI tech-engines were structured to be compatible with the tremendous potential of various market segments and not limited to only one specific segment. "In order to capture the value of our AI tech-engines, our business strategy is to establish diverse collaborative partnerships through licensing or collaboration, with expert partners in specific fields that complement our technology. Together, we'll develop novel products, aiming for full or partial ownership upon project completion. This approach maximizes the potential of our AI tech-engines, while aiming to reduce financial and development risks. Today, Evogene has 4 subsidiaries, each focusing on a different market segment, and in addition, Evogene has diverse engagements with leading companies in additional market segments, not covered by our subsidiaries. "I am very pleased to share with you the main achievements made by Evogene's subsidiaries from the last report of our financial results." Casterra Ag Ltd. – focuses on developing an integrated solution to enable large-scale commercial cultivation of castor to address the global demand for stable castor oil supply, mainly for the biodiesel industry. Casterra is utilizing Evogene's GeneRator AI tech engine to direct and accelerate the development of its unique elite castor seed varieties. On June 25, Casterra announced receiving a $440K purchase order to supply castor seeds to a new African country in 2024. This order from an existing customer expands Casterra's operations and strengthens its position in the bio-fuel market. On July 31, Casterra announced the successful completion of its castor seed growing and harvesting season in Brazil, with shipments planned for the third quarter of 2024. Additionally, the castor harvest season in Africa has begun as scheduled. Castor seeds produced in 2024 in both Brazilian and African territories are expected to enable Casterra to meet all its existing orders, amounting to approximately $8.4M, with completion anticipated by the end of this year. Lavie Bio Ltd. – a leading ag-biologicals company that develops microbiome-based, computational-driven novel bio-stimulant and bio-pesticide products, utilizing Evogene's MicroBoost AI tech-engine. On July 2, Lavie Bio announced the commercial expansion of its bio-inoculant Yalos™ to winter wheat following successful trials, with sales starting across the US for the 2024-2025 season, effectively doubling its market potential. On July 22, 2024, Lavie Bio announced a milestone in its collaboration with ICL in developing bio-stimulant solutions for row crops facing extreme weather conditions by leveraging AI to identify over a dozen novel microbes within 12 months. Lavie Bio's pipeline is advancing according to plan, with field trials initiated in Q2 in most of the company's programs, following successful optimization processes. Results are expected during Q4. Biomica Ltd. – a clinical-stage biopharmaceutical company developing innovative microbiome-based therapeutics, utilizing Evogene's MicroBoost AI tech-engine. On May 23, positive safety and tolerability data for BMC128 was published. 72% of the patients treated have exhibited clinical benefits. 55% of patients showed sustained clinical benefit, with notable durations of effect (more than 24 months). These clinical results were presented at the prestigious 2024 ASCO annual conference in June. We look forward to continuing to evaluate BMC128's beneficial activity in subsequent phases of clinical development. Financial Highlights: Cash Position: As of June 30, 2024, Evogene held consolidated cash, cash equivalents, and short-term bank deposits of approximately $20.9 million. This amount does not include $8.4 million of expected payments for the open purchase orders of Casterra. The consolidated cash usage during the second quarter of 2024 was approximately $5.7 million. Excluding Lavie Bio and Biomica, Evogene and its other subsidiaries used approximately $2.7 million in cash during the second quarter of 2024. Projected cash usage for 2024, excluding Lavie Bio and Biomica, is expected to be around $8.0 million, marking a notable 36% decrease from approximately $12.5 million in 2023. Revenue: Revenues for the first half of 2024 were approximately $5.1 million, a significant increase from $1.3 million in the same period the previous year. This growth was primarily driven by revenues recognized from Lavie Bio's licensing agreement with Corteva and AgPlenus's new collaboration with Bayer. Revenues for the second quarter of 2024 were approximately $0.9 million, compared to approximately $0.7 million in the same period the previous year. The increase was mainly attributable to increased revenue in Lavie Bio. Evogene anticipates continued revenue growth in the second half of 2024 compared to the previous year, mainly based on Casterra's forecast for seed-order supply. R&D Expenses: Research and development expenses, net of non-refundable grants, for the first half of 2024 were approximately $8.8 million, a decrease from $10.2 million in the first half of 2023. The decrease in expenses is mainly due to the cease of Canonic's activities and a decrease in certain development expenses in Biomica as compared to the same period the previous year. Research and development expenses, net of non-refundable grants, for the second quarter of 2024 were approximately $4.0 million, and decreased significantly as compared to approximately $5.4 million in the same period in the previous year. The decrease is mainly attributable to decreased expenses in Canonic and Biomica, as mentioned above. Sales and Marketing Expenses: Sales and Marketing expenses for the first half of 2024 were approximately $1.9 million, a slight increase from approximately $1.7 million in the same period in the previous year. The increase is mainly attributable to increased sales and marketing activities in Casterra during the first half of 2024 as compared to the same period in 2023. Sales and Marketing expenses for the second quarter of 2024 were approximately $0.9 million and remained stable as compared to approximately $0.9 million in the same period in the previous year. General and Administrative Expenses: General and administrative expenses for the first half of 2024 decreased slightly to approximately $3.2 million from approximately $3.3 million in the same period last year. General and administrative expenses for the second quarter of 2024 decreased to approximately $1.5 million compared to approximately $1.8 million in the same period of the previous year, mainly due to decreased non-cash compensation and salary related expenses in Lavie Bio and Biomica, respectively, in the second quarter of 2024. Other Expenses: The decision to cease Canonic's operations in the first half of 2024 resulted in other expenses of approximately $0.5 million, mainly due to impairment of fixed assets in the first quarter of 2024. Operating Loss: The operating loss for the first half of 2024 was approximately $10.2 million, a significant decrease from approximately $14.7 million in the same period of the previous year, mainly due to increased revenues as mentioned above. The operating loss for the second quarter of 2024 was approximately $6.1 million, a decrease from $7.9 million in the same period of the previous year, mainly due to decreased operating expenses as mentioned above. Financing Income: Financing income, net for the first half of 2024 was $379 thousand, compared to financing expenses, net of $86 thousand in the same period of the previous year. This increase was primarily due to increased interest income and a revaluation of convertible SAFE. Financing income, net for the second quarter of 2024 was $138 thousand, compared to financing income, net of $144 thousand in the same period of the previous year. Net Loss: The net loss for the first half of 2024 was approximately $9.8 million, compared to approximately $14.8 million in the same period last year. The $5.0 million decrease in net loss was primarily due to increased revenues, decreased operating expenses, partially offset by the one-time $0.5 million of other expenses, related to ceasing Canonic's operations and an increase in financial income. The net loss for the second quarter of 2024 was approximately $6.0 million, compared to approximately $7.8 million in the same period last year. The $1.8 million decrease in net loss was primarily due to decreased operating expenses as mentioned above. For the financial tables click here. Conference Call & Webcast Details: Thursday, August 22, 2024 . 9 :00 AM EST 4:00 PM IDT To join the Zoom conference, please register in advance here. Or join via audio Or, dial from the US: +15642172000, from Israel: +972 3 978 6688 Webinar ID: 842 8320 2980 More International numbers Webcast & Presentation link available at: About Evogene Ltd. Evogene Ltd. (Nasdaq: EVGN, TASE: EVGN) is a computational biology company leveraging big data and artificial intelligence, aiming to revolutionize the development of life-science based products by utilizing cutting-edge technologies to increase the probability of success while reducing development time and cost. Evogene established three unique tech-engines – MicroBoost AI, ChemPass AI and GeneRator AI. Each tech-engine is focused on the discovery and development of products based on one of the following core components: microbes (MicroBoost AI), small molecules (ChemPass AI), and genetic elements (GeneRator AI). Evogene uses its tech-engines to develop products through strategic partnerships and collaborations, and its four subsidiaries including: Biomica Ltd. () – developing and advancing novel microbiome-based therapeutics to treat human disorders powered by MicroBoost AI; Lavie Bio () – developing and commercially advancing, microbiome based ag-biologicals powered by MicroBoost AI; AgPlenus Ltd. () – developing next generation ag-chemicals for effective and sustainable crop protection powered by ChemPass AI; Casterra Ag () – developing and marketing superior castor seed varieties producing high yield and high-grade oil content, on an industrial scale for the biofuel and other industries powered by GeneRator AI. For more information, please visit: . Forward-Looking Statements This press release contains "forward-looking statements" relating to future events. These statements may be identified by words such as "may", "could", "expects", "hopes" "intends", "anticipates", "plans", "believes", "scheduled", "estimates", "demonstrates" or words of similar meaning. For example, Evogene and its subsidiaries are using forward-looking statements in this press release when they discuss Evogene's strategy, Evogene's ability to develop novel products, that Evogene's strategy will result groundbreaking innovations and significant financial gains for Evogene, Casterra's ability to supply all existing purchase orders by the end of 2024, Lavie Bio's market potential, Lavie Bio's pipeline advancement, Biomica's BMC128's future beneficial activity, and Evogene's projected cash usage for 2024 and Evogene anticipated continued revenue growth in the second half of 2024. Such statements are based on current expectations, estimates, projections and assumptions, describe opinions about future events, involve certain risks and uncertainties which are difficult to predict and are not guarantees of future performance. Therefore, actual future results, performance, or achievements of Evogene and its subsidiaries may differ materially from what is expressed or implied by such forward-looking statements due to a variety of factors, many of which are beyond the control of Evogene and its subsidiaries, including, without limitation, the current war between Israel, Hamas and Hezbollah and any worsening of the situation in Israel such as further mobilizations or escalation in the northern border of Israel, and those risk factors contained in Evogene's reports filed with the applicable securities authority. In addition, Evogene and its subsidiaries rely, and expect to continue to rely, on third parties to conduct certain activities, such as their field trials and pre-clinical studies, and if these third parties do not successfully carry out their contractual duties, comply with regulatory requirements or meet expected deadlines, Evogene and its subsidiaries may experience significant delays in the conduct of their activities. Evogene and its subsidiaries disclaim any obligation or commitment to update these forward-looking statements to reflect future events or developments or changes in expectations, estimates, projections and assumptions. Logo: Evogene Investors Relations Contact: Email: [email protected] Tel: +972-8-9311901 SOURCE Evogene

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微生态药物研究进展

关注并星标CPHI制药在线微生态药物（live biotherapeutic products, LBP）又称活体菌药物，是指利用正常微生物或影响微生物生长代谢的物质制成的药物制剂，是继小分子、大分子、细胞治疗和基因治疗之后的另一种新型的药物形式，通过干预人体微生物群落来发挥治疗作用，目前以活体生物药为主。 2016年，美国食品药品监督管理局生物制品评价与研究中心(Food and Drug Administration Center for Biologics Evaluation and Research,FDA/CBER)发布了全球第一部明确将活体生物药作为药物使用的指南，该指南侧重的是活体生物药早期临床阶段化学制造和控制(chemical manufacturing and control, CMC)相关技术要求，明确了活体生物药的定义。活体生物药是一种生物活性药物，具有以下的特点：(1) 含有活的生物体，如细菌；(2) 具有预防、治疗人类疾病或适应证的功能；(3) 不是疫苗。其核心要素是要按新药的标准开发，明确适应症并进行系统的菌株安全性、药效、CMC以及临床评价。除了生物制品的一些共同特征以外，食品药品监督管理局(Food and Drug Administration, FDA)指南突出了活菌药物特有的研究重点，如鉴定菌株的稳定性、抗生素敏感性、耐药性、是否转移以及存在移位的可能，还有产品的生产控制与稳定性等。天然菌株 LBP 研发现状近年来，随着测序与分离技术的发展，人们不断发现了更多与疾病密切相关、但尚无人体应用历史的天然新菌种，并将其按照药物进行开发，成为天然菌株LBP，其包含单菌LBP和复合菌 LBP，这2种类型的LBP 已在多种疾病治疗的临床试验中有所报道。 01 单菌 LBP 的开发单菌LBP已在癌症、消化道疾病等多种疾病的研究领域中有所报道。在癌症治疗方面，英国4D pharma plc公司基于鸡肠球菌(Enterococcus gallinarum)开发了活体生物药MRx0518，该药物可以与pembrolizumab单抗联合治疗实体瘤，其机理是 MRx0518 的鞭毛蛋白可以激活细胞受体TLR5 和核因子(nuclear factor kappa-B, NF-κB)并诱导HT29-MTX细胞产生 IL-8，引发强烈的促炎反应，从而抑制肿瘤细胞的生长。此外，还有研究报道MRx0518可以与放射疗法联合治疗胰腺癌，受试者将在放射治疗开始前一周时每天服用MRx0518，且在整个放射治疗期间一直服用直至患者进行肿瘤切除手术。在消化道疾病方面，广州知易生物科技有限公司基于脆弱拟杆菌(Bacteroides fragilis)开发了SK08 药物，该药物可有效治疗肠应激综合征(irritable bowel syndrome, IBS)和溃疡性结肠炎(ulcerative colitis, UC)，并在临床前研究中展现出了良好的药效与安全性，多项研究表明，脆弱拟杆菌产生的多聚糖可调节辅助性 T 细胞 1(Th1)/(Th2)比例的平衡，增强机体 T 细胞的功能，同时可以诱导 Treg 细胞分化并产生 IL-10，抑制炎症因子 IL-17，从而达到调节机体的免疫功能的效果。4D pharma plc 公司开发了一种治疗克罗恩病(Crohn’s disease, CD)的LBP 药物—thetanix，该药物由一株多形拟杆菌(Bacteroides thetaiotaomicron)构成，其作用机理是抑制与多种炎症性疾病相关的NF-κB 活化，产生的 pirin-like 蛋白已成为候选效应分子，该药物在Ⅰb期临床试验中展现出良好的安全性，达到了预期结果。此外，单菌 LBP 在呼吸系统疾病、妇科疾病以及神经系统疾病的治疗中也有所报道，由短双歧杆菌(Bifidobacterium breve)制成的单菌药物 MRx-4DP0004 可治疗哮喘。OSel 公司基于干酪乳杆菌(Lactobacillus crispatus)开发了一种活体生物药 Lactin-V，该药物可以治疗复发性阴道炎。由马赛巨型球菌(Megasphaera massiliensis)构成的 MRx-0029 以及由狄氏副拟杆菌(Parabacteroides distasonis)构成的 MRx-0005在临床前均表现出治疗帕金森症的潜力，这2种菌株可以降低神经系统炎症反应，保护神经元免受氧化应激损伤并且恢复肠壁屏障完整性，目前这2款 LBP 的在研新药(investigational new drug, IND)申报已获得了FDA 批准，已进入临床试验阶段。 02 复合菌 LBP 的开发 21世纪初以来，艰难梭菌感染（CDI）一直是全球主要的公共卫生问题之一，基于粪菌移植 (fecal microbiota transplantation, FMT)的微生物组疗法在临床试验中对CDI疗效显著。Seres Therapeutics公司研发的复合菌药物SER-109是一种由纯化的厚壁菌门孢子组成的微生物组治疗剂，可以有效治疗 CDI，其核心逻辑是厚壁菌孢子有机体与艰难梭菌竞争性代谢生长所必需的营养素和胆汁酸，从而抑制艰难梭菌的繁殖。类似地，Rebiotix公司研发的复合菌药物RBX2660 是一种广谱微生物群混悬液，也可以治疗 CDI，该复合菌药物中的克劳氏芽孢杆菌和罗伊氏乳杆菌所分泌的化合物能抑制艰难梭菌的生长，此外该复合菌药物中的梭状芽孢杆菌代谢产生的次级胆汁酸能够增强艰难梭菌定殖抗性，同时提供营养生态位竞争的无毒艰难梭菌也会抑制艰难梭菌感染。此外，FinchTherapeutics 公司正在研发的CP-101 是一种胶囊给药的微生物组疗法，基于冻干保存的粪便，也用来防止CDI 复发。还有许多复合菌 LBP 是从唾液或粪便等生物样本中分离出来的微生物组治疗剂，这些细菌被分离以后可以在克隆细胞库中繁殖。VEDANTA公司研发的VE303包含8 种共生梭状芽孢杆菌菌株，可以治疗CDI。该公司的另一款药物VE800 是从健康人类供体粪便中分离出的由11种细菌菌株组成的联合体，这些菌株可以诱导CD8+ T 细胞的激活、增强免疫系统对肿瘤细胞的攻击能力并显著增强抗 PD-1治疗的效果，该药物与Nivolumab 联合治疗多种肿瘤已经取得了一定进展。VE202含有经试验鉴定后的11株粪便来源的菌株，该药物可以通过调节肠道菌群诱导免疫耐受进而治疗自身免疫性疾病，例如炎症性肠病(IBD)。此外，Biomica公司研发的复合菌药BMC128 含有4种来自人类肠道的天然菌株，它能够通过多种生物学过程增强免疫治疗效果并促进机体抗肿瘤免疫活性，从而抑制肿瘤的生长。MRM Health公司基于CORAL 平台开发了一种复合菌 LBP，该药物包含了经过合理搭配的9株肠道共生菌，在动物模型中，它能够改善门静脉高压、胰岛素信号传导、非酒精性脂肪肝活动指数以及预防肝纤维化的发展，还可以改善血管内皮功能、重塑肠道菌群。虽然FMT 疗法已经有诸多临床试验，但科学家始终无法掌握其明确的作用机制，因此具有一定的风险，包括不可预料的副作用、疗效不稳定和监管困难等。相比之下，成分明确的细菌组合体构成的复合菌 LBP 更加安全、可控，作用机制更加明确，人们更容易接受。基因工程菌株工程菌是采用现代生物工程技术加工出来的新型微生物，具有多功能、高效和适应性强等特点。近年来，微生物药物领域有较多工程菌已经进入临床研究阶段。研究表明，特定的酶或包含特定途径的工程益生菌能够缓解生物体的代谢紊乱，工程菌可以合成代谢所必需的酶从而恢复代谢，并且可以抑制有毒产物的合成或将其代谢成无毒产物，进而治疗此类代谢疾病。Synlogic 通过将编码苯丙氨酸解氨酶和 L-氨基酸脱氨酶的基因插入到大肠杆菌(Escherichia coli) Nissle 1917(缩写为“ECN”)的基因组中，得到苯丙酮尿症治疗药物 SYNB1934，在动物试验中，SYNB1618 可显著降低 Pahenu2/enu2小鼠的血浆苯丙氨酸浓度且防止健康的非人类灵长类动物(NHPs)食蟹猴血浆中苯丙氨酸浓度的激增。高尿酸治疗的菌株SYNB1353可消耗蛋氨酸，从而用于治疗高胱氨酸尿症。Advaxis的ADXS-503 (减毒活单核细胞增生李斯特菌)，单用和联合派姆单抗可用于治疗非小细胞肺癌 (NSCLC)。此外，还有多种工程菌用于治疗酶缺乏引起的代谢紊乱疾病、细菌感染、炎症性肠病和癌症等。随着人们对基因工程编辑药物的认识更加全面和客观，工程菌药物将会越来越受到人们的青睐，虽然人们对于转基因的安全性一直心存疑虑，但面对一些严重疾病的治疗剂选择，例如肿瘤治疗上，病人的抗风险能力更高，依从性和接受度更好。且工程菌药物拥有独特的优势，例如靶向性更好，可以增加目标部位的药物积累并最大限度地减少脱靶效应；给药的剂量低，产生的毒副作用也很小，最重要的是它可以通过人为改造，使其具有人们想要的特定功能，能够“因病制宜”，因此它的应用范围更广泛。小分子微生态调节剂小分子微生态调节剂 (small molecule microbiome modulator, SMMM) 是指能选择性地促进宿主肠道内的有益细菌生长繁殖的物质，通过促进有益菌的繁殖，抑制有害细菌的生长，达到调整肠道菌群，促进机体健康的目的。Second Genome的SGM-1019 可用于治疗非酒精性脂肪性肝炎 (NASH)；Enterome的 EB8018 可用于治疗炎症性肠病（IBD）；绿谷制药于2019 年 11 月在我国上市了甘露特钠胶囊(GV-971)，GV-971 可以调节肠道菌群失衡，抑制 α-突触核蛋白的聚集，减少肠道与脑内 α- 突触核蛋白的沉积，减轻神经炎症并保护多巴胺能神经元，改善运动和非运动症状。Intrinsic Medicine使用人乳寡糖小分子微生态调节剂治疗疼痛、调节肿瘤免疫、抗病毒和呼吸道感染等。参考资料： [1]朱永亮.活体菌药物产业化[J].生命科学,2023,35(03):340-346. [2]邹丹阳, 董雨萌, 陈晶瑜. 活体生物药：生物技术推动的创新药研发前沿[J].生物工程学报, 2023, 39(4): 1275-1289. 作者简介：小泥沙，食品科技工作者，现就职于国内某大型药物研发公司，从事营养食品及功能性食品的开发与研究。 END 【智药研习社直播预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

放射疗法疫苗基因疗法微生物疗法

100 项与 BMC-128 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
黑色素瘤	临床1期	以色列	Biomica Ltd.初创企业	2022-01-11
非小细胞肺癌	临床1期	以色列	Biomica Ltd.初创企业	2022-01-11
肾细胞癌	临床1期	以色列	Biomica Ltd.初创企业	2022-01-11