Oxalo Therapeutics, Inc.

乳腺癌是一种常见于女性的恶性肿瘤，严重威胁女性生命健康。据弗若斯特沙利文数据统计，乳腺癌超越肺癌已成为全球发病率最高的癌症。全球乳腺癌新发患者从2016年的200万人增长到2020年的226万人，复合年增长率为3.1%。预计将在2025年达到247万人。近年来，我国乳腺癌发病率有升高趋势。根据国家癌症中心发布的数据，中国乳腺癌新发患者从2016年的31万人增长到2020年的42万人，其发病率已是宫颈癌、卵巢癌、子宫内膜癌总和的两倍，每年中国新发乳腺癌占全球癌症的12.2%，成为了当之无愧的“粉红杀手”。随着乳腺癌发病率的逐步升高，治疗方案也不断增多。全球乳腺癌药物市场规模从2016年的215亿美元增长至2020年的318亿美元，复合年增长率为10.3%，预计将在2025年达到475亿美元。国内乳腺癌药物市场规模也呈快速增长趋势。从2016年的300亿元增长到2020年的507亿元，复合年增长率为14%。预计中国乳腺癌市场将会以比全球更高的增速在2025年增长至818亿元。从治愈率来看，早期较高，但到Ⅳ期治愈率则骤减至50%左右。因此，乳腺癌仍旧是需要攻克的难题，数家公司还致力于不断改善疗法提高治愈率。MicroQuin正是其中一家致力于开发治疗乳腺癌新疗法的初创公司。葛兰素史克前开发人员带领创业MicroQuin是一家创办于2018年的临床前生物技术公司，专注于开发乳腺癌新疗法。MicroQuin认为所有疾病的核心在于IL-1β转化酶（interleukin-1β converting enzyme，ICE）的变化，所有的癌症都会诱发极端的ICE。通过调节ICE就可以创造新的癌症疗法，其正在利用专有小分子、合成肽和基因疗法实现这一目标。Scott Robinson是MicroQuin的创始人兼首席科学官，是伦敦帝国理工学院的博士，主要研究细胞应激信号传导和存活途径。他曾在葛兰素史克（Glaxo Smith Kline）担任蛋白质生物化学家，通过蛋白质组学分析和基于靶点的药物发现技术研究候选药物。此前一直在投行工作，拥有八年的投行经验。Yang Zheng是MicroQuin的另一创始人，毕业于芝加哥大学。创办MicroQuin前，Yang在2018年与芝加哥医学教授共同创办了Oxalo Therapeutics，这是一家专注于开发肾结石药物的公司。作为一个投资人，Yang希望能够建立科研成果商业化的桥梁，MicroQuin是其创办的第二家公司。有望28天内诱导超95%癌细胞加速凋亡近年来，靶向和免疫药物势如破竹地研发上市，让癌症的疗法步入了新的阶段。2021年，FDA批准的癌症疗法多达40种，覆盖15种癌症。想要从癌症疗法赛道种突围并不是一件易事，必须要靠强有力的疗法效果。MicroQuin通过调节ICE水平变化创造癌症新疗法。ICE变化关乎细胞内环境变化，ICE过度表达可能引起细胞凋亡，通过有选择地调节ICE能够减缓、恢复疾病损伤。MicroQuin通过两种技术手段实现乳腺癌细胞ICE调节。一是细胞穿膜肽（CPPs），通过有选择的将有效载荷引导到癌细胞的递送载体，当与现有药物偶联时作用其递送机制，可提高治疗安全性和有效性。MicroQuin的CPPs对癌细胞具有优先的高亲和力，能够迅速结合并内化CPPs以及其递送物，在七小时的暴露期内，健康细胞对CPPs不会有反应。因此，使用MicroQuin的CPPs可以精确靶向癌细胞。因为其对癌细胞的亲和性，在其他癌细胞（肺、黑色素瘤、卵巢和前列腺）中也能观察到这种效应，这使得有开发多种药物的可能性。二是基于蛋白质的化合药物，这种药物与CPPs相结合，通过调节细胞器功能和信号传导途径杀死癌细胞。MicroQuin开发出MQ001和MQ002化合药物诱导癌细胞死亡，通过抑制Bcl-2蛋白家族的抑制凋亡因子（如Bcl-2和Bcl-xL）阻止癌细胞扩散，同时促进凋亡因子（Bax、Bid等）的活化。此外，继续作用于肌动蛋白细胞骨架，阻断癌细胞中的F肌动蛋白的形成并抑制其侵袭性。实验显示，这种先导化合药物能够在体内选择性结合癌细胞以诱导其加速死亡（在28天内>95%）。目前，MicroQuin还开发出一种口服小分子药物SMQ-2174，作用于诱导多种癌细胞凋亡。利用ICE调节器原理，MicroQuin正在推进肿瘤学、抗病毒和神经学领域的多管道药物研发。 MicroQuin药物研发管道 来源：MicroQuin官网MicroQuin的抗病毒药物管道也取得进展。病毒会劫持细胞以建立ICE，使病毒进行自我复制和传播。通过MicroQuin的治疗方法激活ICE调节器，中和、抑制病毒诱导的ICE变化，从而抑制病毒的复制和传播。MicroQuin的抗病毒药物能够达到单剂量实现>99.9%的病毒抑制效果。2021年，MicroQuin与美国国家过敏和传染病研究所（NIAID）签署了非临床评估协议（NCEA），以评估MicroQuin疗法（MQPs）的潜力，并将其推向临床试验。MicroQuin将利用NIAID的临床前服务套件来进一步筛选MQPs在大量病毒中的功效，并评估它们在相关临床前模型中的功效。太空中的蛋白质培养与3D肿瘤细胞太空环境中的微重力为癌症研究带来了新的希望。从创立开始，MicroQuin就力图在微重力环境中进行研发与突破。首要的原因是对其蛋白质药物的开发。在微重力环境中，蛋白质晶体更易获得且更为纯净，细胞也能够更快更好发育。2018年，MicroQuin通过“Technology in Space”计划获得CASIS（美国空间科学促进中心）和波音公司的两笔赠款，用于创造新的癌症疗法，同时被允许在空间站进行蛋白质晶体研究。2019年，该项关于蛋白质晶体的研究在SpaceX CRS-18上启动。这项研究旨在揭示Bax抑制剂1（BI-1）的结构。BI-1是一种难以捉摸的药物靶标，很难在地球环境中表达和纯化，几乎不可能结晶。它与多种癌症和其他疾病相关，包括肝脏疾病、自身免疫性疾病、神经退行性疾病、糖尿病和病毒感染等。实验发现，癌细胞在BI-1敲低或功能丧失时发生自发性细胞死亡。利用此发现，MicroQuin开发出用细胞穿模肽（CPPs）和基于蛋白质的药物靶向BI-1的疗法。2022年2月，MicroQuin将又一项实验送上太空。在微重力环境中，肿瘤细胞在3D条件下的生长刺激了相关细胞结构的获得，从而创造了一个与肿瘤的自然生长环境非常相似的空间组织，能够诱导细胞信号传导的变化。当细胞不受控制地发生突变时，就会通过肿瘤发生过程变为癌细胞。在此项实验中，将检查微重力下诱导出的乳腺癌和前列腺癌细胞的变化，并与健康细胞进行比较，以观察癌细胞环境变化，评估肿瘤发生所涉及的基本途径。此外，还将观察MicroQuin开发的TMBIM6整体细胞内蛋白作用于癌细胞的确切反应，以继续改进其癌症疗法，开发用于乳腺癌、前列腺癌和其他癌症靶向治疗的其他药物。目前，MicroQuin正在提出其他太空项目，这些项目将研究潜伏病毒如何在太空中被重新激活，并测试微重力和相关细胞变化如何影响酶再活化或裂解噬菌体的生命周期和传播。2022年，MicroQuin获得美国国防部（DOD）卵巢癌研究计划（OCRP）、肺癌研究计划（LCRP）和罕见癌症计划（RCRP）的赠款，以继续开发癌症新疗法。近期推荐声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。动脉网，未来医疗服务平台

Although Chicago is the third largest city in the United States, when it comes to its position as a leading biotech hub, the second city ranks far below many other U.S. locations. That is starting to change, however, as new companies move into this heart of the BioMidwest region. Chicago and its collar communities are home to a number of legacy companies, including AbbVie, Astellas, Abbott Biolabs, Horizon Therapeutics and Exicure. Over the past several years, others have moved into the area, taking advantage of new wet lab spaces that have been or are being built, as well as lower-cost real estate options. John Conrad, president and chief executive officer of Illinois Biotechnology Innovation Organization (iBIO), told BioSpace the area is “seeing exponential growth” in new business and a 33% increase in the talent pool. Wet Lab Space Expansion Conrad pointed to multiple projects across the region that have expanded wet lab space over the past several years. These include the Fulton Labs and Portal Innovations facility which is designed to support startups. Fulton Labs is also the home of iBIO. Other recent wet lab expansions across the area include the 125,000 square foot, five-story Lincoln Park building under development by Sterling Bay. The facility includes state-of-the-art wet lab space and other facilities to house life sciences companies. Before the announcement of the new facility dubbed The Labs, there had not been a new wet lab space built in the city since 2012. “The buildout of the lab space is critical. We’ve added about 1 million square feet,” Conrad said, adding that lab space is “at a fraction of the cost of either coast.” Earlier this year, real estate firm Mark Goodman & Associates closed on a 1.5-acre space in Chicago’s Fulton Market neighborhood that will become the site of a new 16-story life sciences facility. The 400 N. Elizabeth St. property is billed as the “first purpose-built lab and research and development building in Chicago designed to specifically accommodate the rapidly growing life sciences and biotechnology industry.” Goodman told BioSpace the company is completing its marketing materials for prospective tenants. Once an anchor tenant is secured, he said construction will begin on the facility. Goodman speculated the anchor tenant will need to take up no less than 150,000 square feet before construction, which he noted is “a challenge in this market.” Still, he is hopeful such a tenant can quickly be found. “I love this market. I want to see it succeed,” he said. It is these new sites that are attracting the attention of companies from outside the region, Conrad said. He explained that businesses, particularly smaller companies located on the West and East coasts who are concerned about the rising costs of real estate, are looking to Illinois for potential relocation. New Companies Move In Conrad pointed to Xeris Biopharma, which moved to Chicago from Texas in 2020, and Talis Biomedical, which came to the city from California in 2021. Both companies moved into spaces at Trammell Crow Co.’s Fulton Labs development. The Chicago community “shares the same vision and passion for the potential that life sciences, healthcare, technology and innovation can have on society at large,” Brian Coe, co-founder and former CEO of Talis, said in a statement last year. This allows the company to tap into the “vast talent pool that represents the city’s startup and innovation ecosystem,” he added. Conrad agreed with Coe’s assessment. “It’s really exciting for us. It shows proof right away that companies are looking at this space,” he said. Without disclosing much, Conrad noted that a large pharma company has been in conversation with iBIO about potential business development or partnerships within the region. With its rich history, strong universities and multiple cultural attractions, Conrad said Chicago is a great location for companies to set up R&D facilities. He predicted companies will continue to recognize that and consider the region in their business plans. In addition to the development of wet lab space by development companies, state government has also thrown its weight and financial resources behind this effort. In 2021, Gov. JB Pritzker announced a $15.4 million investment in a wet lab capital program that supports the development of eight new spaces across the state. The investment will fund $90 million worth of wet lab expansions across Illinois, the governor’s office announced. The 2021 financing built on $9 million pledged by the same office in 2020. The grants support the development of wet lab spaces, with projects at universities and in incubators. Rosalind Franklin University in North Chicago received $2 million to support a build-out of its Innovation and Research Park site. This site includes space for researchers working on projects funded by the NIH, as well as collaborations with industry partners. Other Chicagoland recipients include Back of the Yards Algae Sciences (BYAS) in Chicago, the Illinois Institute of Technology, Northwestern University and NuMat Technologies in Skokie. Internal Growth Even as the additional wet lab space is drawing the eyes of business development officers outside Illinois, other efforts to support entrepreneurship are encouraging the launch of new companies from the area universities. That’s a reversal of the situation just a few years ago when cutting-edge research from the universities was out-licensed by interests outside the state. One such company is Vanqua Bio, which launched last year with $85 million in Series B financing. The startup is focused on developing next-generation medicines for neurodegenerative diseases, including Parkinson's disease, Alzheimer’s and ALS. Vanqua’s technology platform is based on research conducted by Dimitri Krainc, chairman of the department of neurology at Northwestern University’s Feinberg School of Medicine and head of the Krainc Laboratory. Conrad said the universities are investing in leadership and educating first-time entrepreneurs, which is boosting the startup landscape. Other startups include Oxalo Therapeutics, which is developing a therapy to safely remove oxalate from the body and prevent recurrent kidney stones. Oxalo launched with assistance from an innovation fund at the University of Chicago. The fund also supported the launch of Onchilles Pharma, a preclinical-stage oncology company. In addition to that fund, Chicago has also benefitted from the establishment of a fellows program by the Chicago Biomedical Consortium (CBC) that will support entrepreneurs. Michelle Hoffmann, executive director of CBC, said at the time, “We believe that this will be able to grow and change the biotech ecosystem in Chicago.”