OGA

UCB will advance its anti-tau antibody for Alzheimer’s disease solo after Roche and Genentech walked away from the asset known as bepranemab. In 2020, Roche and Genentech spent $120 million upfront and committed up to $2 billion in milestones and royalties for exclusive rights to the candidate, a monoclonal antibody that targets the buildup of tau protein in the brain. On Tuesday, UCB said it regained global rights to bepranemab after the partnership ended. This is not the first time Roche and Genentech have opted out of the anti-tau space. In January, the companies ended a two-decade-long Alzheimer’s partnership with AC Immune after several lackluster readouts, leaving behind an asset targeting amyloid and another one targeting tau. Bepranemab is currently in Phase 2a, with topline data to be presented at the Clinical Trials on Alzheimer’s Disease annual meeting in Madrid later this month. The trial is testing the effects of two doses of bepranemab administered every four weeks versus placebo in people with prodromal or mild Alzheimer’s. Earlier this month, Leerink analysts said positive results for bepranemab could “incrementally de-risk” next-generation anti-tau antibodies. The buildup of tau in the brain creates “tangles” that are thought to trigger cell damage and inflammation in Alzheimer’s. Pharma companies such as Roche and Eli Lilly took an interest in targeting tau several years ago when drugs that zero in on amyloid beta were struggling in the clinic. But the tau approach has yielded mixed results. Lilly’s tau-targeting OGA inhibitor failed a Phase 2 study in August. Biogen’s antisense oligonucleotide asset designed to reduce tau showed hints of efficacy in an early-stage trial late last year. As for Roche, the deal termination comes as part of a broader strategy shift that focuses on cardiometabolic, oncology and neurology drugs. The company has notably made investments in next-generation weight loss approaches . Genentech is still into anti-tau modalities. In August, it spent $50 million in near-term licensing fees and milestones to work with Sangamo on an epigenetic repressor to prevent the production of the protein. Editor’s Note: This article has been updated to correct that Genentech spent $50 million on its deal with Sangamo. A previous version stated it spent $350 million upfront.

None The confetti is still flying from Eli Lilly’s party celebrating the approval of Alzheimer’s disease therapy donanemab, but the company is yet again facing the harsh reality of the neurodegenerative disease with the failure of an early tau-targeting med.Lilly Chief Scientific Officer and President, Lilly Research Laboratories Daniel Skovronsky, M.D., Ph.D., said the O-GlcNAcase Inhibitor called LY3372689 failed on the primary endpoint of a phase 2 clinical trial recently. The therapy, which targets the OGA enzyme, did not spur a change in baseline to endpoint time in a rating scale of Alzheimer’s severity in either dose tested.“While this negative outcome was disappointing, we remain committed to tap as a high conviction target in Alzheimer's disease and plan to continue studying tau biology,” Skovronsky said, speaking on a second-quarter earnings call Thursday. The executive said the company is currently reviewing the data for presentation at an upcoming medical conference.LY3372689 was a key part of Lilly’s next wave of Alzheimer’s efforts. After getting donanemab approved in July, to be marketed as Kisunla, the company was hoping that tau would be the next front in the fight against the memory-robbing disease. Behind Kisunla, Lilly has remternetug in phase 3 development, which targets amyloid plaques in the brain. Positive allosteric modulator mevidalen is in phase 2 testing. The company also has two undisclosed neurodegeneration medicines in phase 1.Lilly also trimmed around the edges of other programs after getting some early data on a few candidates.They include LOXO-783, a highly mutant-selective, brain-penetrant, allosteric small molecule PI3Kα H1047R inhibitor that was acquired as part of the acquisition of Loxo Oncology. The drug was being investigated in a phase 1 study in patients with PIK3CA H1047R-mutant advanced breast cancer and other solid tumors.Lilly had taken LOXO-783 into the clinic on the basis of preclinical data showing activity without on-target wild-type PI3Kα mediated toxicity.“We evaluated the ongoing clinical data for the program and compared the molecule to next-generation candidates that we have progressed from our discovery efforts,” Skovronsky said on the call. “We believe our next molecules have greater potential benefits to patients.”Also on the discard pile is an unnamed NRG4 agonist. Neuregulin 4 acts locally on brown and white adipose tissue and works to protect against obesity-related inflammatory and hypoxic events. The Big Pharma had halted work on the asset as “the profile is insufficient for further clinical development,” Skovronsky explained. A GITR antagonist has also been removed from the phase 1 immunology pipeline “due to insufficient efficacy,” Skovronsky said. At the time of publication, Lilly had not confirmed to Fierce whether this was LY3461767, a GITR antagonist that was being evaluated in a phase 1 trial of the drug in patients with chronic heart failure with reduced ejection fraction.Acadamic researchers have named glucocorticoid-induced tumor necrosis factor receptor (GITR), a co-stimulatory immune checkpoint protein, as playing a pivotal in cardiovascular disease. It’s also been suggested as a potential target to enhance immunotherapy, in particular immune checkpoint inhibitors.

▎药明康德内容团队报道 根据即刻药数数据库，上周（7月15日~7月21日），全球生物制药领域至少10家致力于创新药研发的公司宣布完成新一轮融资，其中包括2家来自中国的创新生物医药公司。这些获得融资的公司的技术和管线涉及siRNA核酸药物、小分子降解剂、CRISPR技术、抗体免疫疗法等领域。 公司：大睿生物 融资轮次：A+轮 融资金额：3500万美元 7月19日消息，聚焦核酸药物研发的大睿生物（Rona Therapeutics）宣布完成A+轮3500万美元融资，用于推动创新的siRNA代谢管线项目进入全球开发，并扩展夯实中枢神经系统及其他领域的肝外递送平台。该轮融资由LongRiver江远投资领投，参与投资方包括昭德投资、博远资本、中启资本和礼来亚洲基金等。 大睿生物致力于研发核酸创新药，用于代谢性疾病和中枢神经退行性疾病的治疗。该公司正在推进基于新一代siRNA平台生成的siRNA管线项目，首个RN0191管线PCSK9 siRNA项目已完成澳大利亚和中国的1期临床研究，正在推进高胆固醇血症的2期临床开发。 公司：Draupnir Bio 融资轮次：种子轮 融资金额：1200万欧元 7月17日消息，致力于开发口服小分子降解剂的生物技术公司Draupnir Bio宣布完成了总计1200万欧元的种子轮股权投资，融资所得将用于进一步开发其口服小分子蛋白质降解剂临床前管线。该轮融资的投资方包括三菱田边制药公司旗下风险投资集团MP Healthcare和由丹麦政府支持的融资基金EIFO，以及现有投资者Gilde Healthcare Partners、Inkef Capital和Novo Holdings。 Draupnir Bio是一家丹麦生物技术公司，致力于利用溶酶体的天然机制开发细胞外致病蛋白质的口服小分子降解剂，这是靶向蛋白质降解（TPD）的前沿方向。据介绍，这是一个迅速发展的领域，利用细胞自身的破坏机制来解决传统疗法难以靶向的致病蛋白质。Draupnir正在利用其新颖且差异化的专有技术平台，利用溶酶体受体，以开创性的方式将TPD的潜力扩展到靶向细胞外和膜结合蛋白，这有可能为TPD领域带来改变。 公司：Ancilia Biosciences 融资轮次：未知轮 融资金额：420万美元 7月17日消息，一家利用CRISPR技术开发对破坏性病毒具免疫力的细菌疗法和产品的生物技术公司Ancilia Biosciences宣布完成420万美元的融资。此次融资由Safar Partners领投，Metaplanet、Psymed Ventures、Zubi Capital、Spacecadent Ventures和其他机构和私人投资者也参与其中。 攻击细菌的病毒是地球上最丰富的生物实体，至少占人类微生物组的一半。它们可能导致人类疾病，也可能限制有益细菌产品的功效。Ancilia公司通过其专有的CoVE™平台识别和表征病毒，并应用其专有EPIC平台来利用细菌的天然CRISPR功能来创建对这些病毒免疫的活体生物治疗药物和其他微生物产品。 公司：NGM Biopharmaceuticals 融资轮次：A轮 融资金额：1.22亿美元 7月17日消息，NGM Biopharmaceuticals宣布完成了1.22亿美元A轮融资，用于启动aldafermin（一种工程FGF19类似物）的注册试验，用于治疗原发性硬化性胆管炎（PSC），并完成NGM120（一种GDF15/GFRAL拮抗剂）治疗妊娠剧吐（Hyperemesis Gravidarum）的2期试验。这两项试验预计将于2024年第四季度开始。此轮融资由TCG领投，并有多家其他投资者参与。 NGM Biopharmaceuticals专注于发现和开发新的、改变生命的药物。据介绍，NGM Bio以生物学为中心的药物发现方法，旨在无缝整合对复杂疾病相关生物学和蛋白质工程专业知识并产生见解，从而产生有前景的候选产品，使其能够快速推进概念验证研究，并解决未被满足的患者需求。 公司：Renalys Pharma 融资轮次：A轮 融资金额：60亿日元（3800万美元） 7月17日消息，Renalys Pharma宣布完成了60亿日元（约3800万美元）A轮融资，用于支持其IgA肾病治疗药物sparsentan在日本的3期临床试验，以及推进其他药物研发项目。此次融资由Catalys Pacific和SR One领投，还有多家其他投资方。 Renalys Pharma成立于2023年，专注于治疗慢性肾脏疾病的潜在药物研发。该公司目前已有7款药物处于IND到NDA/BLA阶段，用于推进日本及亚洲各地的肾脏疾病治疗，为患者提供更好的治疗选择。Sparsentan是该公司的核心产品，为一款具双重机制的“first-in-class”内皮素/血管紧张素受体拮抗剂，于2023年2月获美国FDA加速批准，用于降低有高疾病进展风险的IgA肾病患者的蛋白尿。该产品由Travere Therapeutics研发，Renalys公司拥有部分国家和地区的权益。该产品曾被分析公司Clarivate列为2023年值得关注的潜在15款重磅疗法之一。 Cardurion Pharma 融资轮次：B轮 融资金额：2.6亿美元 7月17日消息，Cardurion Pharma宣布已完成2.6亿美元的B轮融资，获得资金将用于支持该公司两款主要候选药物的后期临床试验，这两款药物分别是潜在“first-in-class”PDE9抑制剂，拟用于治疗心力衰竭，其已经在2期临床中获得概念验证；以及具有广泛治疗潜力的钙/钙调蛋白依赖性蛋白激酶II（CaMKII）抑制剂，拟用于治疗儿茶酚胺多态性室性心动过速。 Scorpion Therapeutics 融资轮次：C轮 融资金额：1.5亿美元 7月17日消息，Scorpion Therapeutics公司宣布已完成1.5亿美元的C轮融资，获得资金将用于推进其差异化小分子肿瘤学项目的研发。Scorpion公司成立于2020年，曾入选2021年年度生物技术猛公司（Fierce 15）榜单。该公司正在推进别构、差异化、突变选择性PI3Kα抑制剂STX-478的临床试验，这款产品在正常组织中避免了对野生型PI3Kα的抑制，从而减少了靶向毒性。Scorpion公司其他在研项目还包括两款EGFR抑制剂以及下一代精准癌症治疗的其他管线。 CatalYm 融资轮次：D轮 融资金额：1.5亿美元 7月17日消息，CatalYm公司宣布已完成1.5亿美元的D轮融资。CatalYm公司已将GDF-15确定为癌症治疗的关键耐药机制，并正在将其开发为治疗实体瘤的免疫疗法。该公司目前正在进行先导抗体产品、一种靶向中和生长分化因子-15（GDF-15）人源化单克隆抗体visugromab（CTL-002）的2b期研究，用于多种实体瘤适应症。公开信息显示，visugromab联合抗PD-1抗体治疗晚期癌症患者具有良好的安全性和有效持久的抗肿瘤疗效。 Asceneuron 融资轮次：C轮 融资金额：1亿美元 7月17日消息，Asceneuron宣布完成超额认购的1亿美元C轮融资，该笔融资将用于推进其主打项目ASN51进入治疗阿尔茨海默病的2期临床开发阶段。Asceneuron专注于开发口服生物可利用疗法，以治疗严重未满足医疗需求的衰弱性神经退行性疾病。该公司正在开发两种临床阶段的小分子OGA抑制剂，其中ASN90（授权给Ferrer Pharmaceuticals）用于治疗进行性核上麻痹（PSP），ASN51用于治疗阿尔茨海默病。 ASN51是一种口服小分子药物，旨在抑制与蛋白质聚集有关的酶OGA。通过阻止tau蛋白的聚集，以减缓阿尔茨海默病的进展。根据新闻稿，ASN51独特的作用方式和方便的口服配方使其成为阿尔茨海默病患者的潜在理想疗法。除此之外，Asceneuron公司还计划推进帕金森病、肌萎缩侧索硬化症（ALS）和其他神经退行性疾病的临床前开发。 浩博医药 融资轮次：A轮 融资金额：3700万美元 7月15日，浩博医药宣布完成3700万美元A轮融资，本轮融资由信达生物主导发起设立的美元基金InnoPinnacle Fund追加领投，元生创投、汉康资本、启明创投、元生资本共同参与。浩博医药专注于HBV慢性乙肝功能性治愈和针对肝脏疾病的高效靶向治疗，并拓展了对肝脏以外新靶点的靶向小核酸治疗。该公司研发的具有乙肝“功能性治愈“潜力的裸露反义寡核苷酸（ASO）药物AHB-137注射液近日还被中国NMPA纳入突破性治疗品种。 希望在资本的助力下，这些公司能够加速在研疗法的开发，早日造福更多的患者。 参考资料： [1]各公司官网和公开资料 本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。