Ruxolitinib Phosphate

Trillions of bacteria, fungi and viruses live within our bodies, making up our microbiome. Scientists have been studying the role these microorganisms play in our health, and in recent years, the focus has shifted to oncology. Specifically, could mitigate complications of cancer treatments and potentially improve the bodys response to certain cancer treatments leading to improved survival?MaaT Pharma is at the forefront of innovation in this field, striving to achieve the first-ever approval of a microbiome-driven immunomodulator in oncology.In 2022, the biotech company launched a Phase 3 clinical trial, in Europe, in patients with acute graft versus host disease (aGvHD), and topline results are anticipated as early as January 2025. If approved, the drug candidateMaaT013could offer a new treatment option to patients with steroid refractory and ruxolitinib refractory or intolerant aGvHD.Herv AffagardPermission granted by MaaT PharmaWe have decided to focus on oncology patients because that's where we believe the most unmet medical need and potential for microbiome-based therapies exists, says Herv Affagard, CEO and co-founder of MaaT Pharma. What were doing is modulating the immunity of the patient in oncology to improve survival.We sat down with Affagard to talk about the potential of microbiome therapeutics for oncology patients, and his vision for the future.The microbiome is increasingly recognized as crucial for health and disease. Can you explain how it's relevant for oncology, and why MaaT Pharma is focused on this area?Affagard: We know that 25% of the worlds population shows an alteration of its microbiome, and there can be different reasons for that. In oncology, cancer patients are receiving harsh treatments, such as chemotherapy, antibiotics and stem cell transplantation, that can alter the microbiome to the point that sometimes the microbiome becomes unstable or ineffective, resulting in dysbiosis. When that happens, the immune system loses its counterpart which can trigger hyperinflammation in the body. These changes are often more significant in cancer than we see in other diseases, so the potential in oncology is very clear.At MaaT Pharma, we want to restore the balance between the microbiome and the immune system. We are on the verge of demonstrating, potentially for the first time, that a microbiome-based therapy could improve overall survival in patients with acute Graft-versus-Host Disease. Everything that has been done before, especially in infectious disease, is only dealing with symptoms and complications, but here we are dealing with a hard end point: survival.That's fascinating. So, how does MaaT Pharma leverage the gut microbiome to potentially treat cancer?Affagard: We approach the potential to treat cancer in two ways. One, we accompany anti-cancer treatments as a partner to optimize the treatment. In that situation, were aiming to create a drug which is a phenotype that will make the patient respond to the treatment, such as immune checkpoint inhibitors. Also, were aiming to directly treat certain diseases, such as aGvHD, by replacing the microbiome with a very specific microbiome that may be able to reduce inflammation.What makes your approach different from others who are exploring these kinds of therapies?Affagard: There are different modalities to trick the microbiome. For example, you could have something simple, like a probiotic or a prebiotic to promote certain bacteria, which can be effective when dysbiosis is mild. But with aGvHD patients were dealing with an emergencyhalf of them die after just 28 days, to give you an idea. So, we want to repair everything as fast as possible. Thats why were dealing with a full reset of the microbiome, and what sets MaaT Pharma apart from others in this space is the fact that we are restoring the entire ecosystem. Weve developed a high-density drug using pooling technology, which allows us to pool donor-derived microbiota donations to create a standardized product with highly rich and diverse microbial content that will be impactful for the maximum number of patients. We are the only company in the world with an investigational new drug authorized to use this pooling technology in clinical trials in the U.S.Your lead candidate, MaaT013, has shown promise in clinical trials. What can you tell us about its progress?Affagard: Through the Early Access Program for MaaT013, weve treated more than 200 patients with aGvHD, including different subsets of these patients. One subset, for example, resembles the patients that we are treating in our Phase 3 clinical trial, and we see a significant overall survival benefit in this subset. Historical data showed that one-year survival rates for aGvHD patients receiving third-line treatments have been dismal, with only 15% surviving at 12 months. In contrast, our latest results presented at ASH 2024 highlight an impressive 49% overall survival at one year for similar patients population treated with MaaT013tripling the historical survival rate (from literature). Its very promising and were encouraged by what were seeing, which underscores MaaT013s potential to address a significant unmet need for patients with aGvHD.Weve also initiated the first treatment at City of Hope in the U.S. of a patient with aGvHD under the US Food and Drug Administration (FDA) Single Patient Expanded Access. How do these therapies have the potential to impact patients lives, especially those who are undergoing cancer treatments?Affagard: The feedback were receiving from physicians evaluating MaaT013 in patients through clinical trials is that its safe. You see, HSCT is a treatment often used in leukemia and other blood cancers. However, it comes with its own challenges, such as GvHDa complication where the donor cells attack the recipient's body. When this happens, immunosuppressants are usually the drug used. And immunosuppressants, at a certain point in time, create complications as the patient risks developing infections because the immune system is down. But you don't see that with our microbiome-based therapy, which has a direct impact on quality of life for the patients. In addition, our treatment is not a chronic treatment. You receive three doses, and when it works, it works very well. And if it doesn't work, it doesn't work, but you do not have to be under treatment for six months, which would be the case for immunosuppressants.Looking ahead, what are your predictions for the microbiome therapy space over the next five years?Affagard: I believe there will be more and more applications leveraging the microbiome in oncology, especially coming from small companies. Academic research has been very important since 2010, and now were at a point where there's a lot of innovation. I believe that the field of inflammatory bowel disease, neurodegenerative disease and oncology will be the next big things in microbiome therapies.What are the next goals for MaaT Pharma?Affagard: Our primary focus is to deliver the topline results for the Phase 3 trial in January 2025, because it will be the cornerstone of everything else in our pipeline. We believe a success in aGvHD will open the doors to many other therapeutic areas. Looking ahead, we have other programs in blood cancers but also in solid tumors and neurodegenerative disease where we are generating proof of concept data. But first, we need to demonstrate that by modulating the microbiome you can modulate the immune system and potentially cure diseases. That will be absolutely fantastic. '

据外媒BioSpace盘点，到目前为止，2024年规模最大的一笔收购交易是Novo Holdings（诺和控股）斥资165亿美元收购CDMO巨头Catalent。除此之外，各大制药公司更倾向于进行小规模的并购，单笔交易金额无一超过50亿美元。 Vertex（福泰制药）完成了本年度最大的Biotech收购案，以49亿美元的价格将Alpine Immune Sciences收入囊中，借此进一步加强自免领域布局。诺华则频频出手，完成了四笔交易，总支出超过90亿美元。其中金额最高的一笔是以29亿美元收购MorphySys。 今年的制药巨头并购潮中缺席了一位重量级选手——辉瑞，主要是因为去年出手430亿美元收购Seagen极大地消耗了辉瑞进行其他并购交易的财力，从而退出了今年的买家行列。 与之相反的是，市场上也存在着一些资金颇为充裕的买家，例如凭借GLP-1药物掌握巨额现金流的两大巨头——诺和诺德和礼来。Novo Holdings以165亿美元收购Catalent，也有助于诺和诺德继续扩大GLP-1药物产能。礼来则于今年7月以31.9亿美元收购了Morphic Holdings，加码炎症性肠病（IBD）市场。 美国企业研究所（American Enterprise Institute）非驻所研究员、欧华律师事务所（DLA Piper）高级政策顾问Kirsten Axelsen表示，今年并购交易金额普遍低于50亿美元的部分原因是，小型Biotech越来越倾向于自行将药物推向市场。这意味着制药公司可选择的处于后期临床阶段的候选药物减少了。 从疾病领域来看，肿瘤相关并购交易略有降温，而内分泌和代谢疾病领域的交易则有所增多。此外，制药巨头依然在积极布局自身免疫及免疫学领域。不过，肿瘤领域的交易降温趋势中存在一个例外情况，那就是放射性药物。针对这类药物的并购以及药品许可交易活动频繁，这股热潮始于一年多前，百时美施贵宝、阿斯利康和礼来频频收购开发放射疗法的公司。 以下是今年迄今为止的五大医药交易： ▌Vertex收购Alpine Immune Sciences 疾病领域：自免 交易金额：49.6亿美元 交易时间：4月10日 交易简介：Alpine的核心管线povetacicept是一种靶向B细胞因子BAFF/APRIL的双重拮抗剂，拟开发用于治疗IgA肾病（IgAN）、系统性红斑狼疮等疾病，目前该药正处于II期临床阶段。诺华也有一款处于III期临床阶段的IgAN疗法（atrasentan），这笔交易使Vertex与诺华展开了竞争。 ▌诺华收购MorphoSys 疾病领域：肿瘤 交易金额：47.9亿美元 交易时间：2月5日 交易简介：诺华最初宣布以29亿美元收购MorphySys，但考虑到债务和所有交易费用后，金额上升至47.9亿美元。诺华看中的主要是一款小分子BET抑制剂pelabresib，目前该药正在与Incyte的Jakafi联合开展针对骨髓纤维化患者的III期研究。然而，由于在4月份出现了新的安全性问题，该药物此后的开发之路变得坎坷。诺华在第三季度宣布，需要更多时间来考虑该药物的研发注册路径。诺华还因这笔收购计提了8亿美元的减值费用。 ▌吉利德收购CymaBay Therapeutics 疾病领域：自免 交易金额：44亿美元 交易日期：2月12日 交易简介：就在CymaBay宣布seladelpar的新药申请（NDA）获得FDA受理之际，吉利德花费了44亿美元收购CymaBay，这笔交易相对其他来说是偏后期的资产。之后，Seladelpar也获得FDA的加速批准。 ▌礼来收购Morphic Holdings 疾病领域：自免 交易金额：32亿美元 交易时间：7月8日 交易简介：这笔交易让礼来获得了更多的免疫学资产，包括候选药物MORF-057，这是一种α4β7整合素的小分子抑制剂，目前正在开发其用于治疗IBD的潜力。该药物目前正在开展针对溃疡性结肠炎和克罗恩病的II期临床研究。此外，礼来还获得了肿瘤学和肺动脉高压疾病的研发管线。 ▌默沙东收购Eyebiotech 疾病领域：眼科 交易金额：30亿美元 交易时间：5月29日 交易简介：这笔交易的首付款为13亿美元，后续还有17亿美元的研发、监管和商业化里程碑付款，总计30亿美元。Eyebiotech的眼科三抗Restoret是Wnt信号通路的激动剂，临床前证据表明，刺激视网膜的Wnt通路可以减少血管渗漏。早期Ib/IIa期研究显示，接受该疗法的患者视力有所改善。该药物已于今年9月开展了针对糖尿病性黄斑水肿的IIb/III期临床研究。 在医药行业的风云变幻中，并购往往是推动行业发展和企业战略调整的重要手段，也影响着未来的市场格局。随着2024年逐渐接近尾声，留给各大药企并购的时间不多了。去年12月，百时美施贵宝、艾伯维等公司用几笔迟来的交易给圣诞节带来了惊喜，今年年底前是否还会有震撼业界的大交易达成，让我们持续关注。 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。 免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。