Novartis

1月7日，上海阿尔戈生物制药有限公司（“Argo”），一家专注于发现和开发下一代RNAi疗法的生物技术公司，宣布已与诺华PHARMA AG（“诺华”）签订了两项独家许可和合作协议。​ 1. Argo授予了诺华独家全球许可证，以开发和商业化第一阶段计划。该协议包括一项研究合作，Argo授予诺华独家前大华许可证，以开发和商业化心血管疾病治疗的1/2a阶段临床阶段计划。1阶段心血管资产的全球独家许可，以及针对最多两个心血管目标的化合物许可选项。Argo将对其选择进行发现和优化，以交付PCC，届时诺华将可获得全球独家许可。 2. Argo将从诺华公司获得1.85亿美元的预付款，并有资格获得潜在的期权和里程碑付款以及商业销售的分级版税。Argo和分级版税的合并潜在价值高达41.65亿美元。 这些项目使用Argo的先进RNA干扰（RNAi）技术发现和开发，将加强和扩大Novartis RNAi关于心血管和代谢疾病（CVM）的投资组合。 这些临床阶段资产使用Argo的尖端RNAi平台技术发现和开发，提供行业领先的疗效和耐久性疗法。 “这是中国生物技术公司在RNAi领域的首笔重大海外许可交易。我们很高兴心血管疾病和RNAi治疗的全球领导者诺华认识到Argo团队在过去两年中通过先进的RNAi平台技术和新一代CVM管道创造的巨大价值。”Argo Biopharma总裁兼首席执行官Dongxu Shu说。诺华在CVM中经过验证的开发能力、全球商业影响力和广泛的经验使其成为加速开发我们的候选药物并将这些药物带给患者的理想合作伙伴。 诺华心血管和代谢疾病领域研究负责人Shaun Coughlin说，我们相信Argo使用其最先进的RNAi平台开发的心血管项目是对诺华基于RNA的治疗管道的补充。我们期待与Argo合作，推进这些研究性疗法，以帮助解决心血管医学中未满足的患者需求。 Argo成立于2021年4月，是一家总部位于上海的私营生物技术公司。该公司的主要重点是RNAi药物的研发。Argo开发了行业领先的RNAi平台技术，名为RADS（具有卓越活性、持续时间和安全性的RNAi分子），体现了Argo在交付、化学改性和序列设计方面的技术能力，持续产生顶级RNAi疗法。 Argo目前的管道包括20多个治疗心血管和代谢疾病、血液学、补体途径疾病、病毒感染和神经退行性疾病的治疗项目。五个领先的项目都处于临床开发阶段，都表现出了良好的耐受性安全状况和一流的潜力。​

On September 17, 2024, Novartis announced that its CDK4/6 inhibitor Kisqali (Libocik) has been approved by the U.S. Food and Drug Administration (FDA) for early stage breast cancer (EBC) as adjunctive therapy for patients with HPRT+/HER2- early stage breast cancer. This approval will almost double the likelihood that eligible patients will be able to use Kisqali when receiving adjuvant therapy. The approval is based on results from the pivotal Phase III NATALEE trial, which showed a significant reduction in the risk of disease recurrence in a broad range of HR+/ HER2-stage II and III EBC patients, including those with high-risk N0 disease (3-6), receiving adjuvant Kisqali plus endocrine therapy (ET). The benefit of invasive disease-free survival (iDFS) compared to receiving endocrine therapy (ET) alone was consistently observed in all patient subgroups 3-6. "The FDA's approval of Kisqali for people with early breast cancer, including those without the disease, is a critical moment in improving our approach to care." Dennis J. Slamon, M.D., director of clinical/Translational research at UCLA Jonsson Comprehensive Cancer Center, chair of the Council on Translational Cancer Research (TRIO) and principal investigator of the NATALEE trial. "Today's approval allows us to offer CDK4/6 inhibitor therapy to a broader population as a powerful tool that, in combination with endocrine therapy, can help further reduce the risk of cancer recurrence." In EBC, Kisqali is taken orally once a day at a dose of 400 mg (two 200 mg tablets) for three weeks with or without food, followed by a week of discontinuation of treatment and four weeks in combination with any AI1. Patients should take Kisigali for three years. The NATALEE trial showed that Kisqali's 400mg dose was well tolerated, with discontinuation mainly due to asymptomatic laboratory results3. Adverse events (aes) of particular concern in the Kisqali + ET group in the NATALEE trial included (all grades and grades 3/4): neutropenia (62.5%, 44.3%), liver-related aes (26.4%, 8.6%), QT interval prolongation (5.3%, 1.0%) and interstitial lung disease/pneumonia (1.5%, 0.0%)4. The latest analysis of the NATALEE trial, recently presented at the European Society of Medical Oncology (ESMO) 2024 Congress, strengthens the data analyzed by the FDA. The results showed that after three years of treatment, the benefit was deepened and the risk of recurrence was reduced by 28.5% (HR=0.715; Ci 95% 0.609-0.840; P<0.0001), compared to ET alone, in stage II and III HR+/ HER2-EBC7 patients. Novartis will continue to evaluate the long-term prognosis of patients with NATALEE, including overall survival. In the United States, approximately 90% of breast cancer cases are diagnosed early (stage I-III) and treated promptly with the aim of a cure - sometimes with adjuvant therapy. Despite this, stage II and III HR+/ HER2-EBC patients are still at risk of their cancer coming back - in most cases, as incurable metastatic disease, 8,9. Although most tumors recur in the first few years, even in cases where no lymph nodes are involved, recurrence remains a lifelong problem. Despite ET, 10% of patients with high-risk N0 disease may face relapse within the first three years after diagnosis. Victor Bulto, president of Novartis USA, said: "With this approval, we are redefining treatment options for a broader population affected by breast cancer and at risk of ongoing recurrence. "We continue to transform cancer treatment with Kisqali, building on its established profile in metastatic Settings and now helping a wide range of people as they struggle to remain cancer-free after an early diagnosis." In the pivotal Phase II NATALEE clinical trial, Kisqali showed a significant 25% reduction in the risk of recurrence compared to patients who received endocrine therapy (ET) alone. The trial results showed consistent efficacy across all patient subgroups and had a good safety profile, including in node-negative patients. At the recently concluded European Society of Medical Oncology (ESMO) meeting, the latest data from the NATALEE trial were presented, showing a deeper benefit in invasive disease-free survival (iDFS) across subgroups of patients at the end of the three-year treatment period. In addition, for patients with stage II and III HR+/HER2- early stage breast cancer, they often face a significant risk of recurrence and may even develop incurable metastatic disease, despite receiving adjuvant endocrine therapy (ET) and regardless of lymph node involvement. Kisqali has already been approved for HR+/HER2- metastatic breast cancer as early as 2020 and is currently under regulatory review for an early breast cancer indication worldwide, including in the European Union.

The funds will support the trial of MOv18 IgE to potentially treat platinum-resistant ovarian cancer. Credit: Jo Panuwat D/Shutterstock. Epsilogen has completed a Series B expansion financing round, raising £12.5m ($16.4m) to progress the development of its immunoglobulin E (IgE) antibodies for cancer treatment. The investment was sourced entirely from existing backers British Patient Capital, the Novartis Venture Fund, Epidarex Capital, the 3B Future Health Fund and ALSA Ventures. The latest funding takes the total raised in the Series B financing round to £43.25m. The funds will primarily support the clinical proof of concept for MOv18 IgE, the company’s leading asset, in a Phase Ib trial targeting platinum-resistant ovarian cancer. MOv18 IgE, a therapeutic IgE antibody, is designed to target the folate receptor alpha (FRα) which is prevalent in various cancers. See Also: LACTIN-V by Osel for Human Papillomavirus Infections: Likelihood of Approval Cadisegliatin by VTv Therapeutics for Type 1 Diabetes (Juvenile Diabetes): Likelihood of Approval The Phase Ib trial of MOv18 IgE will have dose escalation and expansion parts, enrolling patients with FRα-positive PROC who have undergone up to four previous treatments. The trial follows a Phase I study where MOv18 IgE showed safety, tolerability and initial signs of clinical activity. MOv18 IgE’s unique mechanism of action is different from that of other clinical agents, due to its high-affinity binding to FcεR1 that promotes immunosurveillance and robust tumour cell destruction by myeloid cells. IgE antibodies have the potential to alter the tumour immune microenvironment, making it more pro-inflammatory, which results in higher levels of activated T cells and macrophages within the tumour, enhancing its destruction. Established in 2017, Epsilogen is a spin-out from King’s College London, UK. Its CEO Tim Wilson stated: “We are delighted to have received strong continued support from our existing investors, and we thank them. “The promise of IgE to treat cancer is based upon its unique mechanism of action and MOv18 IgE is the first ever to be tested in man. Everything is ready for phase Ib initiation which will occur shortly and we look forward to reporting progress from the trial.”