Aerubumab

“亚马逊丛林中的一只蝴蝶偶然扇动翅膀，就有可能导致两周后德克萨斯州地区的一场风暴。”而一笔看似远离中国市场的交易，也可能和一家远在千里之外的中国公司有着千丝万缕的联系。 据Fiercebiotech消息，阿斯利康正通过一项全球许可交易将肺炎预防药物授权给Aridis Pharmaceuticals，这将使阿斯利康获得1100万美元的现金和进一步的1.15亿美元的收入。 在抗感染领域，Aridis公司研发的AR-301（Salvecin）是特别针对金黄色葡萄球菌释放的α-毒素的全人源单克隆IgG1抗体(mAb)，目前正处于全球III期临床试验阶段，已获得FDA授予的快速审评通道资格及EMA授予的孤儿药资格。此次Aridis公司获得的suvratoxumab，与AR-301为同靶点的人源单抗，但更偏重预防感染，AR-301则偏重治疗感染。Aridis为巩固其在该领域的领导地位，收购了suvratoxumab的全球独家权益，而阿斯利康也将继续参与suvratoxumab的后续研究。 新的交易使阿斯利康成为了Aridis的战略股东，约占7.303%。这笔看似远离中国市场的交易，却和一家中国公司有着千丝万缕的联系——作为Aridis的股东之一，此次交易后，国内原料药龙头企业海普瑞持有Aridis 7.68%的权益将被摊薄。 事实上，Aridis仅是“隐匿”在海普瑞投资版图上的其中一个。国内肝素钠制剂及原料药领域的龙头企业海普瑞，虽然其上市公司主营业务收入说不上亮眼，但近年来在对外投资与创新药的布局中动作十分频繁。 01 买！资金优势收割创新药管线 海外投资是扩充药企创新药管线的捷径吗？海普瑞给了我们肯定的答案。 “避开红海，进入蓝海，选择能够满足临床需求，具有全球创新意义和重大商业价值的重要品种。”这是海普瑞的创新药投资逻辑，“目前海普瑞拥有的创新药品种全部为First-in-class药物，均为全新靶点和作用机制，在研适应症针对的是全球范围内死亡率最高、市场上尚无治愈方法的恶性肿瘤，或是治疗领域重大未满足的临床需求。”海普瑞曾这样回复其投资者。 通过股权投资及区域权益获取，当前海普瑞已拥有在研新药品种超过20个，并且已有3款药物开发处于全球III期临床阶段，分别为应用于金黄色葡萄球菌性呼吸机相关性肺炎的单克隆抗体tosatoxumab（AR-301）；针对卵巢癌患者的单克隆抗体oregovomab以及针对患糖尿病后的心血管风险的BET抑制剂apabetalone（RVX-208），都有望在三到五年内在大中华区内获批上市。 刚刚与阿斯利康达成授权引进合作的Aridis，与海普瑞的关系“亲密”。 2017年，海普瑞投资1100万美元，取得Aridis Pharmaceuticals股份536万股，次年Aridis于纳斯达克上市，2021年2月股价约8美元每股，按市值计算约增值4倍。 2018年，海普瑞出资600万美元与Aridis在中国成立合资公司瑞迪生物，海普瑞占股51%，Aridis出资100万美元现金及专利占股49%。瑞迪生物主要从事由股东Aridis授权的抗感染治疗的抗体品种在大中华区的临床开发和商业化，当前开发的品种包括抗感染领域三期临床进行中的AR-301、二期临床进行中的AR-101与完成二期临床的AR-105。 另一研发进展较快的项目来自海普瑞参股子公司OncoQuest Pharmaceuticals Inc.旗下研发的免疫治疗候选创新药Oregovomab，为针对晚期原发性卵巢癌全球首创免疫疗法药物，目前已完成国际多中心III期临床试验首例患者给药，并有望成为卵巢癌一线疗法。Oregovomab凭借II期临床试验结果获得了美国食药监局FDA与欧盟药监局EMA授予的孤儿药资格，将加速其上市进程以及后续的商业化推广。 第三款有望短期内上市的创新药apabetalone（RVX-208）是BET溴结构域小分子抑制剂。这是海普瑞研发管线中，慢病领域研发最快的创新药物。2020年一季度，RVX-208联合包括高强度他汀类药物在内的最佳标准疗法，用于近期出现急性冠状动脉综合症的2型糖尿病患者主要不良心脏事件（MACE）的二级预防，获得FDA授予的突破性疗法认定，并且FDA同意一旦该品种中期数据分析结果显示有效性，即可提交新药上市申请，这也是近五年来FDA在心脑血管领域仅授予过的两项突破性疗法中的一个。 业内预计海普瑞创新药的收获期将在2023年到来。 通过股权投资的方式，海普瑞不仅拥有了多款具有First-in-class潜力的新药，还还收获了丰厚的投资回报。 今年1月，赛诺菲以11亿美元的预付款收购英国抗体研发公司Kymab，并将Kymab研发新抗体KY1005加入其产品线。如后期Kymab获得某些里程碑式的成功，则赛诺菲还将最高支付不超过3.5亿美元的对价。 作为2017年参股投资Kymab的股东之一，海普瑞的全资子公司海普瑞（香港）持有Kymab全面稀释后8.66%的股权，持有Kymab权益累计投入金额约为4057万美元。通过交易，海普瑞将获得的对价包括首期对价约11700万美元，以及后续不超过3030万美元的里程碑对价，照此计算，该笔投资回报率将高达263%。分析认为，收购不仅是对Kymab研发平台发展前景的认可，也是对海普瑞战略投资眼光的认可。 Kymab被收购并非个案，以Kymab为代表的一系列成功案例，侧面反映出海普瑞在这种投资模式下的出色表现。 早在2012年，海普瑞以自有资金1000万美元认购加拿大上市生物科技公司Prometic Life Sciences Inc.增发的48,147,053股股票。2016年至2019年里，海普瑞持续出售PLI的股票，全部股票出售完成累计收益2779万美元。 到了2015年，海普瑞使用公司自有资金1.19亿元作为有限合伙人，参与上海泰沂投资，占比49.58%。截至目前，上海泰沂已为海普瑞带来了6680万元人民币的回报。 显然这种通过转让股权收获大量现金收益的方式，也为其后续的主营业务发展及其他项目的开展提供资金支持。海普瑞首席商务官韩涛曾对媒体表示：“海普瑞稳定现金流，决定了在筛选管线品种时可以尊重自己的价值观，重点关注药物是否能让大多数的患者获益，能否真正满足临床未满足需求。” 02 创新布局这么“深”，市值为何腰斩？ 创新大潮里，传统药企与创新药企二级市场投资者对其价值的考量出现剧烈分化，产业界曾经感慨，创新药企越“亏”，研投越大，市场越看好，传统药企“苦哈哈”做转型，却得不到认可。这一点在海普瑞身上也有体现。 距离海普瑞2020年7月港股上市，已经过去整整一年。 数据显示，2021年上半年全球医药行业发生融资事件1591起，累计融资额高达612.6亿元，创下有记录以来的历史新高，聚焦到中国市场上，上半年48家医疗健康企业完成IPO，数量再创历史新高。 整个市场一片大好的势头中，作为肝素原料药一哥的海普瑞却略显落寞，在率先完成A+H布局后，其港股股价却在上市一周年之际，从18.4港元/ADS的发行价下跌了45%，其A股市值距离这一年最高点时的448亿元已经腰斩，最新市值仅为222亿元，相较于老对手健友股份如今高达365亿元的市值，海普瑞原料药一哥的名号似乎也已经名存实亡了。 稍微翻一翻海普瑞的历史业绩和其背后纷繁复杂的并购史，或许就能看出端倪。 过去十多年，海普瑞的业绩经历了过山车般的跌宕曲折，但并非每一次的触底反弹，都是市场竞争力和医药创新力的直接体现。 时间拨回到2010年，落地深圳12年的海普瑞，顶着全球最大肝素原料药供应商的光环在深交所上市，凭借一年超过10亿的净利润，获得了高达148元的发行价，总市值一度超过700亿元，而曾经名不见经传的四川人李锂，也就此坐上了中国首富的宝座。面对市场和媒体的疯狂追捧，一向低调的李锂声称自己是个不懂财务的工作狂，“见了数字就头疼”。 只可惜好景不长，李锂在首富的位置上仅仅坐了两天，此后，海普瑞在肝素生产线研发上遇阻，公司两度发公告宣布项目延期，受此影响，海普瑞营收节节败退，2013年，其营收已经下滑至历史冰点，相较于上市当年38.53亿元的营收下降了六成，利润更是缩水了73%。 面对如此情状，闷头搞科研的李锂也坐不住了，在医药行业，技术意味着一切，自己研发不出来，买买买便成了唯一选择，况且，超额募资的海普瑞账上有的是钱。海普瑞就此开启了一轮大规模的并购潮，其中，最受瞩目的便是其在海外的三次大手笔收购。 从2014年开始，海普瑞先后分3次给海外子公司美国海普瑞累计注资7亿元，此后，其通过美国海普瑞分别以13.69亿元、2.05亿美元、1300万美元的交易对价，收购了SPL、塞湾生物以及OncoQuest 39.16%的股权。 在此之前，海普瑞在国内还先后收购了两家关联公司：海通药业和成都深瑞。 2011年，海普瑞先是以720万元的对价受让了海通药业36%的股权，随后又通过一轮增资，实现了对后者的绝对控股。而海普瑞在成都深瑞上的操作也如出一辙，根据公开披露，两笔交易总成本约为1.55亿元。 在完成一系列并表动作后，海普瑞的业绩迅速回血。2015年，公司当年实现了22.9亿元的营收和5.68亿的净利润，基本已经恢复到上市前的水准，但并购扩张是一柄双刃剑，立竿见影的效果背后隐藏着的是业务整合所面临的不确定性、业绩对赌压力以及商誉减值风险。要知道，单单是海外的三笔并购，海普瑞积累的商誉已经超过21亿元。 但面对公开市场的压力，海普瑞早已经欲罢不能，在并购速度放缓的2016年、2017年，其业绩再次显现疲态，2017年营业利润首次出现亏损，为此，并购再次发生。 2018年，为了绕过监管的屡次拦截，海普瑞一纸声明宣布，将以24亿元的现金收购李氏家族的关联公司多普乐，并与多普乐签订了一项对赌协议，约定后者必须在2018~2020年分别完成1.91亿、2.97亿、3.41亿的扣非净利润。最终，多普乐并未如约完成业绩，被迫要求补偿海普瑞2.52亿元款项才告一段落，但这笔溢价高达7倍的收购至今仍然饱受质疑。 同样是2018年，通过将控股公司深圳君圣泰左手倒右手，转让给间接控制公司香港君圣泰，并割肉放弃了此后的优先认购权，将持股比例稀释至48.22%，实现出表，这一动作在2019年凭空为上市公司获得了5.74亿元的投资收益。事实上，如果刨去这一影响，海普瑞2019年的扣非净利润为5.92亿元，远不敌纸面上10.44亿的净利润。 从2011年到2018年，海普瑞的公开并购案例高达16起，这也使得外界尤其是资本市场对其并购式扩张带来的隐患和质疑不断。反应在财务数据上，其扣非净利率近年来逐步下滑，2020年11.1%的水平走出低谷，增收同时增利的能力不断提高。 从财报上看起来，业绩成色越来越经不起推敲的海普瑞是否能够靠着其投资的创新药开辟一篇新版图，存在不确定性，不过这家从肝素原料药起家的药企，在创新药企投资标的的筛选上，的确可圈可点。

SAN JOSE, Calif., July 19, 2019 /PRNewswire/ -- Aridis Pharmaceuticals, Inc. (Nasdaq: ARDS) announced today that the European Medicines Agency (EMA) has granted Orphan Drug Designation to AR-501, the Company's inhaled formulation of gallium citrate for treatment of lung infection in patients with cystic fibrosis. This past June, Aridis also received Orphan Drug Designation for AR-501 from the U.S. Food and Drug Administration (FDA) for the same condition. "Receiving orphan designation from the EMA for AR-501 is an important step in ensuring the program is well positioned from a global regulatory development pathway standpoint as we continue to advance its ongoing Phase 1/2a clinical trial," commented Vu Truong, PhD, Chief Executive Officer of Aridis Pharmaceuticals, Inc. "We remain on track to report data from the Phase 1 segment of the trial consisting of healthy subjects in Q1 2020 and the Phase 2a portion with cystic fibrosis subjects in Q2 2021." Orphan Drug Designation in Europe is available to companies developing products intended to treat a life-threatening or chronically debilitating condition that affects fewer than five in 10,000 persons in the European Union (EU). This designation allows for financial and regulatory incentives that include a 10-year period of marketing exclusivity in the EU after product approval, protocol assistance from the EMA at reduced fees during the product development phase, and access to centralized marketing authorization. Cystic fibrosis patients often suffer from severe, persistent secondary bacterial lung infections due to their underlying lung disease which results in an immune-compromised state. AR-501 is a non-antibiotic, small molecule anti-infective in which gallium functions as an iron analog that antagonizes multiple iron-dependent pathways in microbes and thus, subverts multiple key functions in bacteria. Preclinical efficacy and safety data have demonstrated that AR-501 works synergistically with multiple antibiotics, is effective against antibiotic resistant strains, and has a low intrinsic resistance profile. AR-501 is being developed as a self-administered, weekly treatment which is being evaluated in an-going Phase 1/2a clinical trial funded by the Cystic Fibrosis Foundation (ClinicalTrials.gov Identifier: NCT03669614). About Aridis Pharmaceuticals, Inc. Aridis Pharmaceuticals, Inc. discovers and develops anti-infectives to be used as add-on treatments to standard-of-care antibiotics. The Company is developing a non-antibiotic novel mechanism small molecule anti-infective candidate to treat lung infections in cystic fibrosis patients. The Company also utilizes its proprietary MabIgX® technology platform to rapidly identify rare, potent antibody-producing B-cells from patients who have successfully overcome an infection to produce mAbs. These mAbs are already of human origin and functionally optimized for high potency by the donor's immune system, hence they do not require genetic engineering or further optimization to achieve full functionality and high mAb productivity. MabIgX® also allows for the selection of any antibody isotype depending on the optimal effector function required for treating the target infection. By bypassing the humanization and binding sequence optimization steps, and the entire process of generation of genetically engineered antibody producing cell lines, MabIgX® enables high gross-margins and expedited progression to clinical development. The Company has generated multiple clinical stage mAbs targeting bacteria that cause life-threatening infections such as ventilator associated pneumonia (VAP) and hospital acquired pneumonia (HAP). The use of mAbs as anti-infective treatments represents an innovative therapeutic approach that harnesses the human immune system to fight infections and is designed to overcome the deficiencies associated with broad spectrum antibiotics, which is the current standard of care. Such deficiencies include, but are not limited to, increasing drug resistance, short duration of efficacy, disruption of the normal flora of the human microbiome, and lack of differentiation among current treatments. The company's pipeline is highlighted below: Aridis' Pipeline AR-301 (ventilator associated pneumonia). AR-301 is a fully human immunoglobulin 1, or IgG1, mAb currently in Phase 3 clinical development targeting gram-positive S. aureus alpha-toxin in ventilator-associated pneumonia, or VAP, patients. AR-105 (ventilator associated pneumonia). AR-105 is a fully human IgG1 mAb targeting gram-negative P. aeruginosa alginate in VAP patients. AR-105 is currently being evaluated in a global Phase 2 clinical study. AR-101 (hospital acquired pneumonia). AR-101 is a fully human immunoglobulin M, or IgM, mAb targeting P. aeruginosa liposaccharide serotype O11, which accounts for approximately 22% of all P. aeruginosa hospital acquired pneumonia cases worldwide. A plan for the next clinical study will be communicated following the availability of Phase 2 clinical data for AR-105. AR-501 (cystic fibrosis). AR-501 is an inhaled formulation of gallium citrate with broad-spectrum anti-infective activity being developed to treat chronic lung infections in cystic fibrosis (CF) patients. This program is currently in a Phase 1/2a clinical study in healthy volunteers and CF patients. AR-401 (blood stream infections). AR-401 is a fully human mAb currently in preclinical development aimed at treating infections caused by gram-negative Acinetobacter baumannii. AR-201 (RSV infection). AR-201 is a fully human IgG1 mAb currently in preclinical development aimed at neutralizing diverse clinical isolates of respiratory syncytial virus (RSV). For additional information on Aridis Pharmaceuticals, please visit . Forward-Looking Statements Certain statements in this press release are forward-looking statements that involve a number of risks and uncertainties. These statements may be identified by the use of words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms or expressions that concern Aridis' expectations, strategy, plans or intentions. These forward-looking statements are based on Aridis' current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, the timing of regulatory submissions, Aridis' ability to obtain and maintain regulatory approval of its existing product candidates and any other product candidates it may develop, approvals for clinical trials may be delayed or withheld by regulatory agencies, risks relating to the timing and costs of clinical trials, risks associated with obtaining funding from third parties, management and employee operations and execution risks, loss of key personnel, competition, risks related to market acceptance of products, intellectual property risks, risks associated with the uncertainty of future financial results, Aridis' ability to attract collaborators and partners and risks associated with Aridis' reliance on third party organizations. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, market conditions and the factors described under the caption "Risk Factors" in Aridis' 10-K for the year ended December 31, 2018 and Aridis' other filings made with the Securities and Exchange Commission. Forward-looking statements included herein are made as of the date hereof, and Aridis does not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances. Contact: Investor Relations Jason Wong Blueprint Life Science Group jwong@bplifescience.com (415) 375-3340 Ext. 4 View original content to download multimedia: SOURCE Aridis Pharmaceuticals, Inc. Company Codes: NASDAQ-NMS:ARDS