Pramipexole Dihydrochloride

来源：药渡 撰文：依依     编辑：维他命 2024年11月26日，辉瑞投资有限公司与华润医药商业集团有限公司正式签署战略合作协议，华润拿下了辉瑞四款重磅肿瘤药的商业推广授权。合作将于12月1日正式开始执行，岗位受此次合作影响的员工将赴上海进行线下沟通，最终员工安置会于12月底前完成。 此次交易涉及的四款药物均已进入中国市场多年，分别为阿诺新（AROMASIN，依西美坦）、爱博新（IBRANCE，哌柏西利）、法玛新（PharmorubicinRD，盐酸表柔比星）、赛可瑞（XALKORI，克唑替尼）。 中国作为全球第二大医药市场，预计到2025年规模将突破万亿人民币。对于全球大型跨国药企来说，中国市场的营收占比至关重要。原研药企凭借先发优势，通常能够在早期迅速占据相关领域的绝大部分市场份额。 然而，从辉瑞四款重磅肿瘤药物的近期发展情况来看，随着医药政策以及经济形势的变化，中国医药市场环境日益复杂，药品推广的难度不断加大。 在这样的背景下，跨国药企选择与本土流通企业合作，在一定程度上能够优化供应链并降低运营成本，提升其在中国市场，特别是在中国低线城市和基层医疗机构市场的渗透率，避免因市场准入障碍和政策变动而遭受冲击。同时，跨国药企可以将资源集中于新药研发等核心优势领域。 01 MNC授权交易热潮来袭  当前医药市场上，跨国制药企业（MNC）授权交易频繁，尤其是在抗体偶联药物（ADC）和双抗药物领域，呈现出一片火热景象。 据统计，2024年前9个月，全球药企围绕双抗药物达成了31笔交易，数量远超之前三年的任意一年。而在ADC领域，今年以来也是重磅交易频发。例如，默沙东以5.88亿美元首付款获得礼新医药PD-1/VEGF双抗LM-299的全球独家许可；BioNTech以8亿美元预付款收购普米斯，获得其双抗药物开发平台及候选药物管线的全部权利。同时，百利天恒药业与百时美施贵宝就BL-B01D1（EGFR×HER3双抗ADC）项目达成潜在总交易额84亿美元的独家许可与合作协议。 这些频繁的授权交易表明，MNC对中国医药市场的关注度不断提高，也反映出中国创新药在全球医药领域的影响力逐渐增强。 02 典型案例 1 百利天恒的“出海”传奇 百利天恒与百时美施贵宝达成合作，以潜在总交易额最高达84亿美元的独家许可与合作协议，在医药市场引起了广泛关注。 百利天恒的BL-B01D1是一种基于双特异性拓扑异构酶抑制剂的ADC，可同时靶向作用于表皮生长因子受体和人表皮生长因子受体3（EGFR×HER3）。目前正处于II期临床研究阶段，其在经标准治疗后疾病进展的非小细胞肺癌、乳腺癌患者中，表现出具有开发前景的抗肿瘤活性。 此次合作，BMS将向百利天恒全资子公司SystImmune支付8亿美元的首付款以及最高可达5亿美元的近期或有付款；达成开发、注册和销售里程碑后，SystImmune将获得最高可达71亿美元的额外付款。双方将合作推动BL-B01D1在美国的开发和商业化，SystImmune将通过其关联公司独家负责BL-B01D1在中国大陆的开发、商业化以及在中国大陆的生产，并负责生产部分供中国大陆以外地区使用的药品，BMS将独家负责BL-B01D1在全球其他地区的开发和商业化。 这一合作对国产创新药行业具有重大意义。一方面，为百利天恒带来了充足的资金支持研发，展示了中国创新药在全球医药领域的价值和潜力。另一方面，也为其他国产创新药企业树立了榜样，激励更多企业加大创新研发力度，积极拓展国际市场。 2 石药集团的降脂突破 石药集团与阿斯利康达成独家授权协议，推进开发一款临床前创新小分子脂蛋白（a）抑制剂YS2302018。阿斯利康将获得在全球开发、制造及商业化YS2302018 的独家授权。 石药集团将获得1.0亿美元预付款，并有权收取最高3.7亿美元的潜在开发里程碑付款、最高15.5亿美元的潜在销售里程碑付款（总计19.2亿美元）及分层销售提成。 YS2302018有潜力为血脂异常患者带来更多获益，其是由石药集团AI驱动的小分子药物设计平台发现，在体外及动物模型中均具有优异的药物代谢动力学特征及更佳疗效，且无严重的安全风险。 这款新型降脂小分子药的特点在于有效与Apo(a)结合，从而阻止其与ApoB-100颗粒组装形成Lp(a)。作为心血管疾病防治的重要突破点之一，它可能作为单一疗法或联合疗法，包括与口服小分子PCSK9抑制剂AZD0780联用，进一步加强了阿斯利康的心血管产品管线。内容详情可见：超20亿美元！阿斯利康牵手石药剑指降脂药赛道。 其市场前景广阔，全球有超过800万人患有Lp(a)水平升高和心血管疾病，每年导致260万人死亡。目前全球尚无针对Lp(a)的降脂药物获批，而这款药物有望成为高 Lp(a)人群控制心血管风险的新疗法。 3 百裕制药的抗肿瘤合作 百裕制药与诺华就一款小分子抗肿瘤药物签订独家许可协议。根据协议，百裕将收到 7000万美元首付款，以及可达11亿美元的开发、注册及商业化等各类里程碑付款和相应特许使用费。诺华将获得该款小分子创新药的全球独家开发及商业化权利。内容详情可见：百裕制药与诺华签订一款在研抗肿瘤小分子药物的独家许可协议。 百裕制药聚焦在中枢神经系统、肿瘤、自身免疫性疾病及抗衰这四大领域进行药物研发，已成功开发现代植物药“银杏内酯注射液”及“银杏总内酯滴丸”。此次合作展示了百裕制药在抗肿瘤药物研发方面的成果，也为全球患者提供了潜在抗肿瘤药物的新选择。 4 BI与国药控股达成合作 明年1月1日起，国药控股与勃林格殷格翰中国签署战略合作协议，双方将就勃林格殷格翰旗下产品森福罗®（通用名：普拉克索）和泰毕全®（通用名：达比加群酯）明年起在国内的推广展开合作。 03 MNC在华战略变化 1 国产双抗“出海”行情 国产双抗药物在医药市场上接连被MNC收购，这一趋势背后有着多方面的原因和影响。 首先，从市场表现来看，全球双抗药物市场规模正在不断扩大。截至目前，全球共有 15款双抗药物获批上市，2024年上半年全球双抗药物市场销售额超60亿美元，且有望在今年首次突破百亿美元大关。其中，安进的Blinatumomab营收一路增长，有望在今年突破10亿美元大关；罗氏的Emicizumab营收更是突破50亿美元，成为药王级别的产品。受这两款双抗产品带动，药企开始重新关注双抗平台。 其次，中国创新药公司在全球双抗赛道中已占据一席之地。康方生物获批上市了卡度尼利和依沃西两款双抗药物，且每款都有全球首发的头衔。基于双抗药物的放量，康方生物业绩也迎来了暴涨时代。内容拓展：双抗龙头康方生物，即将打出“下一张王牌”。 此外，百利天恒在双抗技术基础上研发双抗ADC，创下出海首付款之最的双抗ADC药物BL-B01D1，在国际顶级杂志《柳叶刀肿瘤》发表的I期临床研究结果显示，在既往治疗失败的多种实体肿瘤患者中均表现出突破性疗效。 国产双抗资产接连获得MNC的青睐，一方面是因为国内双抗平台屡现大交易，如默沙东以7亿美元首付款拿下同润生物的CD3/CD19双抗药物CN201，以及以5.88亿美元首付款获得礼新医药PD-1/VEGF双抗LM- 299的全球独家许可；BioNTech以8 亿美元预付款收购普米斯，获得其双抗药物开发平台及候选药物管线的全部权利。另一方面，“康方效应”正在发酵，MNC们看到了国内Biotech们手上的PD-1/VEGF双抗的巨大潜力，试图寻找下一个“依沃西”。国内在研的PD-1/VEGF双抗包括三生制药/三生国健的SSGJ-707、荣昌生物的RC148、君实生物-U的JS207、神州细胞-U的SCTB14、天士力的B1962等，目前均在不同阶段的临床研究中。 国产双抗“出海”行情火爆，对国内医药行业有着重要的影响。一方面，为国内创新药企业带来了丰厚的资金回报，有助于企业进一步加大研发投入，提升创新能力。另一方面，也向全球展示了中国创新药在双抗领域的实力和潜力，为国内创新药企业拓展国际市场提供了机遇和信心。 2 MNC在华抢购中国资产 MNC在华逐渐淡化卖药逻辑，开始疯狂抢购中国资产，这一战略转变主要体现在以下几个方面： 首先，从进博会可以看出MNC在华的变局。进博会上，MNC不仅推出了更多“中国造”产品，如武田从信念医药引进的BBM-H901注射液和诺华收购信瑞诺医药后推出的肾病产品组合，同时也在积极寻找和链接更多中国医疗创新资产。MNC在BD上的投入力度越来越大，交易愈发频繁，从2023年开始我国医药行业BD浪潮逐渐掀起，2024年热度仍在延续，且愈发火爆。MNC与中国创新药的BD交易事件已超过80起，交易总金额现已逼近500亿美元大关。 其次，交易资产逐渐从中后期向早期延伸。在MNC今年已完成的近40笔BD交易中，Ⅰ期临床及之前占比超过80%。例如诺华与舶望制药的合作，就一款一期临床项目，签订了高达41亿美元的重磅合作。 最后，MNC通过BD不止于强化自身管线，同时还在重点关注“中国式”需求。以 ADC、大分子药物、小分子药物为主要阵地，其中以ADC最为火爆。同时，MNC 还聚焦本土市场需求，如武田从信念医药授权引进的BBM-H901面向中国近10万B 型血友病患者；艾伯维豪掷17亿美元从明济生物重金纳入的TL1A 抗体FG-M701聚焦于炎症性肠病，中国患者群体正快速扩大且逐渐年轻化，市场需求明显。 这一战略转变的原因主要是中国医药产业的不断成熟，国内药企与MNC的差距显著缩小，以及“医保目录+带量采购”等市场措施逐步升级，MNC竞争压力大增。在这个关键阶段，BD被认为是当前最合理的方式，MNC希望更深入地参与到中国医疗创新进程，以此挖掘更大的市场机会。 3 肿瘤市场的合作机遇 以中国生物制药与勃林格殷格翰的合作为例，MNC与本土药企在肿瘤市场的合作前景广阔。中国生物制药与勃林格殷格翰宣布达成战略合作，双方将依托各自优势和资源，共同在中国内地研发和商业化勃林格殷格翰的肿瘤药物管线。 一方面，BI在竞争激烈的中国市场选择中国生物制药作为其最重要的肿瘤管线合作伙伴，是对中生制药创新能力和商业化的高度认可。中国生物制药是当前中国肿瘤领域排名前五的药企，拥有40多个创新肿瘤管线和项目，近3000人的专业肿瘤销售团队，2023年公司肿瘤管线的销售总额达88亿人民币。 另一方面，双方同为具有百年历史的“老钱”家族药企，在创新传承、稳定的管理架构、充裕的现金流等方面有颇多相似之处。 在此次合作中，3款处于临床后期的前沿抗肿瘤药备受瞩目。 Brigimadlin是一款高效、口服的MDM2-p53拮抗剂，可抑制TP53与其负调控物MDM2之间的相互作用，导致肿瘤细胞周期阻滞或凋亡，还具有免疫调节功能。该药物去分化脂肪肉瘤（DDLPS）适应症已步入III期关键临床阶段，该适应症已获FDA授予快速通道资格认定，此外胆道癌（BTC）适应症获孤儿药资格认定。 Zongertinib作为一种选择性 HER2抑制剂，美国FDA已授予其快速通道认定。 DLL3/CD3双特异性T细胞衔接器 BI 764532亦被美国FDA授予快速通道认定，同时也被授予治疗小细胞肺癌的孤儿药认定。 中国本土药企深度参与跨国药企的战略布局，反映了其在创新能力和商业化方面的进步得到了国际认可。在国内医药产业环境发生深刻变化的当下，跨国药企携手中国本土药企或将成为一大潮流，共同开拓肿瘤市场，为患者带来更多创新的治疗选择。 04 未来展望  医药市场MNC授权交易在未来有着广阔的发展前景，将持续为创新药行业带来强大的推动作用。 从市场趋势来看，全球双抗药物市场规模不断扩大，有望在今年首次突破百亿美元大关。中国创新药公司在全球双抗赛道中已占据重要地位，国产双抗资产接连获得 MNC的青睐，这一趋势在未来有望持续。随着更多的中国创新药企业加大研发投入，提升创新能力，未来将有更多具有竞争力的双抗药物涌现，进一步推动全球双抗药物市场的发展。 MNC在华战略的转变也将为创新药行业带来新的机遇。MNC逐渐淡化卖药逻辑，疯狂抢购中国资产，交易资产逐渐从中后期向早期延伸，重点关注“中国式”需求，以 ADC、大分子药物、小分子药物为主要阵地。这将促使中国医药产业不断成熟，国内药企与MNC的差距进一步缩小。在未来，MNC与中国创新药企业的合作将更加紧密，共同挖掘更大的市场机会。在肿瘤市场，MNC与本土药企的合作前景愈发广阔。 此外，政策的持续加码也将为创新药行业的发展提供有力支持。在“重大新药创制”政策落地、药品审评审批加速的推动下，我国创新药研发能力已跻身国际先进行列。未来，随着更多的政策支持和创新药临床试验审评审批试点的开展，创新药的临床推进速度将大大加快，为创新药行业的发展带来更多机遇。 综上所述，医药市场MNC授权交易的未来发展充满希望，将为创新药行业的发展注入强大动力。 参考资料： 1.《2024 年中国医药市场发展趋势报告》 2.《全球创新药研发与市场格局分析报告》 *声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！ 信达「信迪利单抗」+和黄「呋喹替尼」联合疗法获批上市，治疗子宫内膜癌 盘点：11月FDA批准上市的重磅药物 10亿美金！映恩生物新型ADC药物独家授权GSK

Pooled data analysis of efficacy and safety from Phase 2b and Phase 3 data sets in patients with early-stage Parkinson’s disease (PD) support P2B001 as a first line, once-daily treatment choice for early PD KIRYAT ONO, Israel, Dec. 05, 2024 (GLOBE NEWSWIRE) -- Pharma Two B, a private, late-stage pharmaceutical company developing innovative combination drugs for neurological disorders, today announced a poster presentation of integrated safety and efficacy data on P2B001 from its Phase 2b and Phase 3 studies in early-stage Parkinson’s disease (PD) patients. P2B001 is a fixed, low-dose extended-release (ER) combination of pramipexole, 0.6 mg and rasagiline, 0.75 mg. The data are being presented today by Henry Moore, M.D., Associate Professor of Clinical Neurology, University of Miami, Miller School of Medicine, at the Parkinson’s Study Group (PSG) 33rd Annual Meeting in Nashville, TN. “The poster includes robust safety and efficacy data from two double-blind studies, which compared once-daily P2B001 to titrated pramipexole ER (PramiER) or placebo, over a 12-week period,” said Dr. Moore, Associate Professor of Clinical Neurology at the University of Miami and presenter of the study. “P2B001 consistently demonstrated a favorable risk-benefit profile in treating PD symptoms in early-stage patients, compared to the groups receiving other, commercially available therapies. It therefore could be a valuable potential first-line therapy for such patients who are often treated by general neurologists and primary care physicians.” The poster summarizes an integrated modified-ITT analysis of Unified Parkinson’s Disease Rating Scale (UPDRS) results in 196 early-stage PD patients, as follows: P2B001 had significantly greater effect on the UPDRS Part II (Activities of Daily Living, or ADL), Part III (Motor), and Total (Parts II and III) scores versus placebo.P2B001 had comparable efficacy to individually titrated PramiER.P2B001 had significantly less worsening in daytime-sleepiness compared to those treated with PramiER.P2B001 was well-tolerated with an adverse event profile that included fewer sleep-related and dopaminergic adverse events than titrated doses of PramiER. Dan Teleman, CEO of Pharma Two B, added, “These data provide further support for P2B001 as a first-line, once-daily combination pill treatment for people with early PD that requires no titration. Currently, we are focused on completing our merger with Hepion and thereafter look forward to moving P2B001 towards an NDA submission.” About the PSG Annual Conference The 2024 Annual Meeting of the Parkinson Study Group is being held December 5-8, 2024, in Nashville, TN. For over three decades, the PSG Annual Meeting has showcased the organization’s efforts in collaborative research and a commitment to education and mentorship. The meeting welcomes leading investigators, coordinators, trainees, advocates, and allied stakeholders to exchange the latest advances and practices in PD. About Pharma Two B Pharma Two B is a private, late-stage pharmaceutical company. Pharma Two B’s mission is to improve patients’ quality of life by developing innovative, value-added combination drugs for neurological disorders, with a clear unmet need, that are based on previously approved oral drugs and that may offer meaningful clinical benefits, as well as improved safety and enhanced convenience. Pharma Two B’s lead product candidate is P2B001. For more information, please visit: www.pharma2b.com. Pharma Two B plans to go public via a merger transaction (the “Merger”) with Hepion Pharmaceuticals, Inc. (Nasdaq: HEPA) (“Hepion”) in conjunction with the closing of a concurrent private placement. The proposed merger transaction was initially announced on July 22, 2024, and on November 11, 2024, the U.S. Securities and Exchange Commission (“SEC”) declared effective the Company’s registration statement on Form F-4, as amended (the “Registration Statement”) relating to the Merger. The Merger, which has been approved by the respective boards of directors of Pharma Two B and Hepion, is expected to close in the fourth quarter of 2024 and remains subject to approval by both Pharma Two B and Hepion’s respective stockholders, regulatory approval, listing of Pharma Two B’s ordinary shares on Nasdaq under the ticker symbol “PHTB” and other customary closing conditions. About P2B001 P2B001 is an investigational, novel, fixed-dose, extended-release combination of pramipexole and rasagiline (0.6 mg/0.75 mg), both at low doses that are not commercially available. Marketed pramipexole and rasagiline are currently indicated for the treatment of PD (as monotherapy and adjunct therapy for early and more advanced patients). P2B001 is being developed for potential use as a first-line therapy for people with PD. Extended release rasagiline is a new and proprietary formulation of rasagiline developed by Pharma Two B. In a Phase 3 clinical trial, P2B001 demonstrated that it provides benefits comparable with commercially used doses of marketed pramipexole-ER (PramiER) while minimizing associated daytime sleep-related and dopaminergic side effects. Pharma Two B owns worldwide-granted patents for both pharmaceutical composition and method of treatment with P2B001. About Hepion Pharmaceuticals Hepion is a biopharmaceutical company headquartered in Edison, New Jersey, previously focused on the development of drug therapy for treatment of chronic liver diseases. This therapeutic approach targets fibrosis, inflammation, and shows potential for the treatment of hepatocellular carcinoma (“HCC”) associated with non-alcoholic steatohepatitis (“NASH”), viral hepatitis, and other liver diseases. Hepion’s cyclophilin inhibitor, rencofilstat, was being developed to offer benefits to address multiple complex pathologies related to the progression of liver disease. In December 2023, Hepion’s board of directors approved a strategic restructuring plan to preserve capital by reducing operating costs. Additionally, Hepion initiated a process to explore a range of strategic and financing alternatives focused on maximizing stockholder value within the current financial environment and NASH drug development landscape. On April 19, 2024, Hepion announced that it has begun wind-down activities in its ASCEND- NASH clinical trial which wind-down activities have since been completed and the trial has been closed. Hepion is continuing efforts, to the extent that cash is available, to provide any value derived from rencofilstat to its shareholders. Forward-Looking Statements Certain statements in this press release may be considered “forward-looking statements”. Forward-looking statements generally relate to future events or Hepion’s or Pharma Two B’s future financial or operating performance. For example, express or implied statements regarding Hepion and Pharma Two B’s expectations with respect to the Merger, including the timing of the Special Meeting, listing Pharma Two B’s ordinary shares on Nasdaq, receipt of necessary shareholder approvals and the timing of closing of the Merger, and related matters, as well as all other statements other than statements of historical fact included in this press release, are forward-looking statements. When used in this press release, words such as “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “would” and similar expressions, as they relate to Hepion or Pharma Two B, identify forward-looking statements. Such forward-looking statements are based on the beliefs of management, as well as assumptions made by, and information currently available to, Hepion’s and Pharma Two B’s management. Actual results could differ materially from those contemplated by the forward-looking statements as a result of certain factors detailed in Hepion’s and Pharma Two B’s filings with the SEC. Most of these factors are outside the control of Hepion and/or Pharma Two B and are difficult to predict. In addition to factors disclosed in Hepion’s and Pharma Two B’s filings with the SEC, the following factors, among others, could cause actual results and the timing of events to differ materially from the anticipated results or other expectations expressed in the forward-looking statements: the risk that the Merger may not be completed in the fourth quarter of 2024 or at all; the inability to meet the closing conditions to the Merger, including the failure of Pharma Two B to meet Nasdaq initial listing standards in connection with the consummation of the Merger; costs related to the Merger and the failure to realize anticipated benefits of the Merger or to realize estimated pro forma results with respect thereto as well as other risks associated with biopharmaceutical companies generally, including the risks of filing an NDA, obtaining regulatory approval for any product candidates, commercialization of any approved product, including P2B001 for PD, as well as the total addressable market and potential for success of P2B001, the presentation of financial information in U.S. GAAP, completion of a PCAOB audit of U.S. GAAP financials, as well as other risks set forth in more detail in the Registration Statement. The forward-looking statements are based upon management’s beliefs and assumptions; and other risks and uncertainties identified in the Registration Statement, including those under “Risk Factors” therein, and in other filings with the SEC made by Hepion. Each of Hepion and Pharma Two B undertake no obligation to update these statements for revisions or changes after the date of press release, except as required by law. No Offer or Solicitation This press release does not constitute an offer to sell or a solicitation of an offer to buy, or the solicitation of any vote or approval in any jurisdiction in connection with the Merger or any related transactions, nor shall there be any sale, issuance or transfer of securities in any jurisdiction where, or to any person to whom, such offer, solicitation or sale may be unlawful. Any offering of securities or solicitation of votes regarding the proposed transaction will be made only by means of a proxy statement/prospectus that complies with applicable rules and regulations promulgated under the Securities Act, and the Securities Exchange Act of 1934, as amended, or pursuant to an exemption from the Securities Act or in a transaction not subject to the registration requirements of the Securities Act. Additional Information and Where to Find It In connection with the Merger, Pharma Two B filed the Registration Statement with the SEC, which includes a prospectus with respect to its securities to be issued in connection with the Merger, and a definitive proxy statement with respect to Hepion’s stockholder meeting at which Hepion’s stockholders will be asked to vote on the Merger and related matters. The Registration Statement has been declared effective by the SEC and Hepion is mailing a definitive proxy statement and prospectus to its shareholders. Each of Hepion and Pharma Two B urge investors, stockholders, and other interested persons to read, when available, the Registration Statement including the proxy statement/prospectus, any amendments thereto, and any other documents filed with the SEC, before making any voting or investment decision because these documents will contain important information about the Merger. Investors and security holders will be able to obtain free copies of the Registration Statement, the proxy statement prospectus and all other relevant documents filed or that will be filed with the SEC by Pharma Two B or Hepion through the website maintained by the SEC at www.sec.gov. Participants in the Solicitation Pharma Two B and Hepion and their respective directors and executive officers may be deemed to be participants in the solicitation of proxies from Hepion’s stockholders in connection with the Merger. Information about Hepion’s directors and executive officers and their ownership of Hepion’s securities is set forth in Hepion’s filings with the SEC. To the extent that holdings of Hepion’s securities have changed since the amounts printed in Hepion’s Annual Report on Form 10-K/A, such changes have been or will be reflected on Statements of Change in Ownership on Form 4 filed with the SEC. A list of the names of such directors and executive officers and information regarding their interests in the Merger is contained in the proxy statement/prospectus in the Registration Statement. You may obtain free copies of these documents as described in the preceding paragraph. Contact: Pharma Two BDan TelemanCEOPharma Two B Ltd.Cell: + 972-54-550-0804Email: dan@pharma2b.comwww.pharma2b.com U.S. investors Chuck PadalaLifeSci Advisors, LLC+1-917-741-7792chuck@lifesciadvisors.com