Alvogen, Inc.

全球肿瘤重磅炸弹Top10正在面临前所未有的冲击。 如下图所示，超过半数的Top10肿瘤药物在未来5年内将遭遇专利悬崖。 更危险的是，Top10的迭代药物也正在摩拳擦掌，更有部分Top10药物已经在头对头临床中被击败成为背景板。 如今中国biotech/biopharma正在成为冲击的“辅助力量”。2023年，中国肿瘤药物临床数量超过美国，而国外各大药企近年来在国内“批发”肿瘤管线的现象也在井喷。 可以预见的是，全球肿瘤重磅炸弹Top10的格局，未来将迎来一次大洗牌。 1 PD-(L)1的时代将要过去？ K药被FDA获批于2014年9月，O药被FDA获批于2015年4月，T药（tecentriq）获批于2016年，这也是上文所述，免疫检查点抑制剂药物开始井喷，大家看到了PD-1能够拓展的适应症之广，并且能和诸多靶向药，化疗药物联用，是肿瘤治疗药物的全能之星。K药能够创造销售额的奇迹，是其广泛的适应症癌种决定的。 但是，K药被击败了，在最大的癌种之一——NSCLC的一线疗法上，并且HR不是统计学擦边意义的0.8左右，达到了0.51。如果要迭代PD-1类型的免疫检查点抑制剂，需要的路径有几条：1）将PD-1和VEGF这类别的功能的抗体靶点进行组合，然后在大癌种上做出比K药更优异的效果；2）将PD-1和CTLA-4、TIGIT、4-1BB这类同类型的免疫检查点抑制剂进行组合，然后做出比K药更强的细胞免疫刺激效用，进而做出更好的疗效；3）当然，目前还有第三条更新的路——信达的IBI-363，一款全新的融合蛋白，主要针对PD-1和IL-2 biaα两个靶点进行组合，现在来看能够打出非常不错的对T细胞刺激的“战绩”。 如前文所说，目前国内biotech/biopharma们在肿瘤领域的布局已经到了不容忽视的程度，这个时代，中国的biotech将会在全球肿瘤管线中占有举足轻重的作用。根据IQVIA发布的《Global Oncology Trends 2024》，2023年位于中国总部的药企开启的肿瘤学临床试验已经超过了美国：中国占比35%，美国占比34%。而在五年前，这个数字仅仅是20%，2008年，这个数字仅仅是1%。 （图片来源：Global Oncology Trends 2024） 国内Biotech如康方生物在把握PD-1药物的迭代趋势占尽先机，布局AK112和AK104撑起了一片天，连胰腺癌这个K药没涉及的几乎是免疫疗法的无人区，AK104都有涉及。而AK112更是在国内以头对头三期临床战胜了K要进行了真正意义上系统性的迭代，同时借助各方优势进行募资进而扩大临床适应症，以求更进一步。检索clinical trial网站，AK112的临床数量有着46项。 因为AK112所展现出的潜力，该靶点的双抗已经到了近乎需要肿瘤布局pharma们人手一个的程度，最值得关注的是BD普米斯PM8002的BioNTech，在最新的研发日PPT中，BioNTech将其形容为之后肿瘤战略的骨干，足见其对该药物的信心；而K药的权益所有者默沙东都在中国BD了礼新的PD-1×VEGF双抗，足以见MNC对该路线认可。 除了在双抗上布局之外，MNC们也在做着其它的努力尽全力为重磅炸弹续命。例如近日K药皮下制剂的III期临床大获成功。除了K药之外，O药的皮下版本III期临床在今年1月公布，FDA的PDUFA日期也提前到了今年年底。而T药的皮下版本则是三者中最快的，已经于9月份被FDA获批上市。 开发不同剂型是一方面，购买ADC权益开发联用策略则是另一方面：默沙东和BMS均在这上面得到了充分体现，默沙东于科伦博泰，BMS与百利天恒，都在ADC上进行了大额BD，中国的创新药，在某种程度上，正在海外帮助着重磅炸弹续命。 2 高垂直度药物进展几何 高垂直度靶向药引领了一个癌症治疗的时代，存在突变基因的情况下，靶向药就是癌症患者的救命神药。其中最典型的自然是阿斯利康的第三代靶向药奥希替尼，它于2015年上市，大大拓展了第一代靶向药耐药后肺癌患者的生存期。 高垂直度药物，未来要面临的竞争并不小。奥希替尼被头对头击败击败就是一个强烈的信号：三代TKI虽然目前而言没有下一代TKI迭代的压力，但ADC和高垂直度双抗疗法的压力已经到来。在《盲盒开出王炸：肺癌领域大变天》对该次头对头临床有着非常详细的叙述：埃万妥单抗＋拉泽替尼头对头奥希替尼成功做出了惊人的成绩（mPFS：23.7 monthVS16.6 month），今年8月19日，FDA批准埃万妥单抗联合拉泽替尼用于具有EGFR外显子19缺失或外显子21 L858R置换突变的局部晚期或转移性NSCLC成人患者的一线治疗。 其它高垂直度药物呢？恩扎卢胺主要针对前列腺癌，是非常典型的雄激素受体拮抗剂，该药面临的一个最大问题是：专利将要到期。恩扎卢胺2012年FDA获批上，2026年专利到期，而国内的仿制药已经早早开始准备冲击该市场：2021年江苏豪森药业的仿制药首先过评，此后，科伦，人福，齐鲁等熟知的国内大药企都竞相抢占该市场。截至2024年6月，已经有5家药企的恩扎卢胺仿制药过评。 当然，其中的专利纠纷复杂原因较多，目前除了豪森之外，其它药企的仿制药并未开始销售。但专利期一到，就会出现群狼扑食的景象。 （图片来源：邴药说） 此外，在前列腺癌适应症上，核药目前的影响力已经到了不容忽视的程度。诺华的Pluvicto是FDA批准的首款用于治疗这类mCRPC患者的靶向放射配体疗法，与SOC（标准治疗）相比，Pluvicto+SoC可显著延长影像学无进展生存期（rPFS，8.7vs3.4个月）和总生存期（OS，15.3vs11.3个月）。根据诺华2024年三季报，其前三季度，销售额已经突破10亿美元，这仅是其上市的第二个完整年，同样这也还只针对PSMA靶点敏感的部分前列腺癌患者人群。 哌柏西利情况类似，它在中国的专利已经于2023年到期，在第十批国采中过评企业达到了14家。不过它在海外的情况稍好，美国专利到期时间为2027年。这其实是辉瑞经过非常惨烈的争夺得来的：2019年，多家仿制药商通知辉瑞，他们已申请Ibrance的仿制药批准，理由是该药物的两项关键专利无效，但辉瑞成功赢得了数年的延期至2027年。目前该药的销售额从2022年开始下滑，2023年已经从2021年的54.3亿美元下降到了约48亿美元。2024年上半年，该药销售额又同比下滑约8%。 如果把视野放的更远一些，乳腺癌和前列腺癌方向的小分子未来要面对的是PROTAC新型疗法的剧烈冲击。PROTAC疗法在癌症领域首先下手的就是乳腺癌和前列腺癌，其biotech前驱——Arvinas的主要布局管线便在于此：ARV-471主要布局乳腺癌，目前已进入临床III期阶段；ARV-110和ARV-766主要布局前列腺癌。 这是目前高垂直度小分子药物面临的现状，销售额高的重磅炸弹们面临的围剿，让Pharma们一点都不敢掉以轻心。 3 血液重磅炸弹的紧迫困境 血液瘤药物目前的紧迫程度，一点都不比实体瘤轻松。近端而言，新的BTK抑制剂正不断挤占着市场，并且专利悬崖迫在眉睫；远端而言，CAR-T疗法和TCE双抗首先攻克的就是血液瘤，目前正在加速放量阶段。 首先是伊布替尼，它面临的专利现状可能稍好，根据艾伯维提交给美国证券交易委员会的文件中表示，由于之前与仿制药制造商达成的和解，预计2032年Q2之前不会有任何 伊布替尼产品的仿制药上市。不过它目前面临的近忧，是新型BTK抑制剂的冲击。 伴随着百济神州的泽布替尼等药物的市场冲击，伊布替尼面临市场格局迅速红海化。2021年，伊布替尼的销售额达到了94亿美元，此后便开始下滑，2022年其销售额为83.52亿美元，2023年，伊布替尼的销售额略超60亿美元。两年时间，销售额下降了超过三分之一。其中，阿卡替尼和泽布替尼等后起之秀不断抢夺着伊布替尼的市场，后续的BTK抑制剂上，强生的第三代抑制剂Pirtobrutinib已经于2023年由FDA加速获批上市。 来那度胺的药物历史在top10中算较为漫长的，它于2005年被FDA批准，专利部分非常复杂，自2020年开始经历了数次的仿制与和解，目前有几家厂商（例如Alvogen）正在有限制地生产仿制药。当然，该药的销售额下滑是必然趋势。该药2021年的全球销售额达到了128.98亿美元，2022年的销售额跌到了100亿美元以下，为99.78亿美元，2023年的销售额则腰斩了三分之一以上，在60亿美元左右。 强生的达雷妥尤单抗在全球布局来看，专利压力倒是没有太大：它的原研方Genmab在美国等地的专利将在20年代末，30年代初到期。但该药物受到的新型大分子疗法的冲击是巨大的：它的主打适应症是多发性骨髓瘤，这也是现在无论是TCE还是CAR-T都在重点突破的方向。 哪怕不提中国近期海量的骨髓瘤TCE双抗的NewCO交易，就是强生自家，也在积极布局下一代的疗法：强生下一代的多发性骨髓瘤疗法，一项是与传奇生物合作的CAR-T药物西达基奥仑赛，一项是BCMA×CD3的TCE双抗Teclistamab，强生分别给了二者50亿美金以上的销售峰值。 血液瘤的紧迫困境或许更加体现在CAR-T和双抗/三抗的新型疗法上，近期内从嘉和生物的NewCo交易开始，中国共发生了六起相关双抗/三抗的NewCo交易，国外的疯抢是血液瘤领域大分子药物加速迭代的加急奏鸣曲。 结语：药王不可能永远是药王，目前全球肿瘤药物市场需要正视的一个问题是：又快、又好和性价比高中国创新分子的入场，它研发方面大规模批量创新将会大大加速肿瘤药物迭代的进度。而有关于中国的BD交易数量井喷，则是最好的体现。 同写意媒体矩阵，欢迎关注↓↓↓

NEW YORK, Sept. 24, 2024 /PRNewswire/ -- Dolfin, a financial technology firm pioneering a new way to finance tenant improvements, today announced $30M in tenant improvement and equipment financing for Advanced Radiotherapy Technologies (ART Health) to support the build-out and acquisition of life-saving equipment for their new radiotherapy center in Newport Beach, CA. Continue Reading The innovative financing is structured as a fully amortizing, 10-year credit-based lease, offering the cancer center more efficient use of their capital. Traditionally, tenants finance needed space improvements and equipment purchases using their own capital, which can drastically limit their cash reserves and ability to finance other, higher-ROI projects. Dolfin shifts the paradigm, empowering their clients to maintain working capital for the health of their businesses. Dolfin, a firm pioneering a new way to fund tenant improvements, announced $30M in improvement and equipment financing. Post this "We are thrilled to partner with ART Health," stated Keely Ryder, co-founder of Dolfin. "They are the perfect example of why we started this business — cutting-edge, life-saving equipment should not be financially out of reach for a leader in oncology care." Slated to open in early 2025, the center, operated by one of the top healthcare systems in the nation, will offer the highest standard of radiotherapy care to thousands of patients annually at its Newport location. "Working with Dolfin has been a game-changer," commented Ryan Bowers, Chief Operating Officer of ART Health. "Their ability to make next-generation modalities financially feasible for our clinical partners means we can better equip physicians fighting cancer with the tools they need to save lives." Dolfin delivers unparalleled value to tenants with its revolutionary financing product. By granting access to unsecured financing based on the tenant's credit rating, and structured as a fully amortizing lease, Dolfin eases the financial burden of space enhancements. Clients who would find necessary furniture, equipment, and space improvements otherwise unaffordable are now able to reserve capital and invest in higher performing opportunities. About Dolfin Dolfin is a financial technology firm pioneering a new way to finance tenant improvements across the commercial real estate industry. With decades of expertise in lease-backed financing and nearly $700M in historic credit-tenant lease closures, Dolfin understands the industry and how to change it. The firm is shifting the paradigm to provide landlords and tenants a cost-efficient alternative to space improvements using a highly streamlined process and an expedited execution timeline. dolfinpartners.com About Advanced Radiotherapy Technologies (ART Health) ART Health develops turnkey, freestanding radiotherapy centers for the use of physician practices and hospitals. ART Health has combined decades of experience in the development of superior radiotherapy centers to provide their clinical partners the best cancer care solutions for their patients. arthealth.com CONTACT: Amy Finney PHONE: (410) 972-8545 E-MAIL: [email protected] SOURCE Dolfin WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Petition for a temporary restraining order brought by Streeterville Capital, LLC seeking injunctive relief to prevent spinoff of 49% of HOPE Therapeutics shares to current NRx Shareholders has been denied by Utah arbitrator. Petition by Streeterville Capital, LLC seeking injunctive relief to prevent sales of NRx shares has been denied by Utah arbitrator. NRx to proceed with spinoff of HOPE Therapeutics as previously announced. RADNOR, Pa., July 29, 2024 /PRNewswire/ -- NRx Pharmaceuticals, Inc. (Nasdaq: NRXP) ("NRx Pharmaceuticals", the "Company"), a clinical stage pharmaceutical company, today announced the issuance of an order by a Utah arbitrator denying the petition of Streeterville Capital, LLC to enjoin NRx's planned spinoff of 49% of the shares in HOPE Therapeutics to current shareholders of NRx pharmaceuticals. While the proposed spinoff remains subject to compliance with certain disclosure and other requirements under the Securities Act of 1933, as amended, and the Securities Exchange Act of 1934, as amended, the spinoff is intended to provide NRx shareholders with an opportunity to participate in the anticipated value created as a result of the spinoff and to enable a potential listing of HOPE Therapeutics (currently a wholly-owned subsidiary of NRx) on a national securities exchange. The arbitrator also denied Streeterville's petition to enjoin NRx from selling additional shares of NRx stock to finance ongoing operations. Continue Reading HOPE Therapeutics, Inc. (PRNewsfoto/NRx Pharmaceuticals, Inc.) "As we have previously shared with the public, HOPE Therapeutics is in the process of developing a best-in-class network of clinics that currently offer ketamine and other lifesaving therapies to patients with suicidal depression. This arbitration decision enables us to keep our promise to shareholders to spin out 49% of HOPE Therapeutics shares held by NRx to our shareholders, subject to approval by our Board of Directors and compliance with applicable law. We appreciate the support and loyalty of our shareholders as we work to bring HOPE to life," said Prof. Jonathan Javitt, Founder and Chairman of NRx Pharmaceuticals and Co-CEO of HOPE Therapeutics. About NRx Pharmaceuticals NRx Pharmaceuticals is a clinical-stage biopharmaceutical company developing therapeutics based on its NMDA platform for the treatment of central nervous system disorders, specifically suicidal bipolar depression, chronic pain and PTSD. The Company is developing NRX-101, an FDA-designated investigational Breakthrough Therapy for suicidal treatment-resistant bipolar depression and chronic pain. NRx has partnered with Alvogen and Lotus around the development and marketing of NRX-101 for the treatment of suicidal bipolar depression. NRX-101 additionally has potential to act as a non-opioid treatment for chronic pain, as well as a treatment for complicated UTI.NRx has recently announced plans to submit a New Drug Application for NRX-100 (IV ketamine) for the treatment of suicidal depression, based on results of well-controlled clinical trials conducted under the auspices of the US National Institutes of Health and newly obtained data from French health authorities, licensed under a data sharing agreement. NRx was awarded Fast Track Designation for development of ketamine (NRX-100) by the US FDA as part of a protocol to treat patients with acute suicidality. About HOPE Therapeutics, Inc.HOPE Therapeutics, Inc. () is a care delivery company developing a best-in-class network of clinics that currently offer ketamine and other lifesaving therapies to patients with suicidal depression, together with a digital therapeutic-enabled platform designed to augment and preserve the clinical benefit of NMDA-targeted drug therapy. Notice Regarding Forward-Looking StatementsThe information contained herein includes forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended. These statements include, among others, statements regarding the proposed public offering and the timing and the use of the proceeds from the offering. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as "may," "will," "should," "would," "expect," "plan," "believe," "intend," "look forward," and other similar expressions among others. These statements relate to future events or to the Company's future financial performance, and involve known and unknown risks, uncertainties and other factors that may cause the Company's actual results to be materially different from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. You should not place undue reliance on forward-looking statements since they involve known and unknown risks, uncertainties and other factors which are, in some cases, beyond the Company's control and which could, and likely will, materially affect actual results, levels of activity, performance or achievements. Any forward-looking statement reflects the Company's current views with respect to future events and is subject to these and other risks, uncertainties and assumptions relating to the Company's operations, results of operations, growth strategy and liquidity. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's most recent Annual Report on Form 10-K and other filings with the Securities and Exchange Commission. Investors and security holders are urged to read these documents free of charge on the SEC's website at . Except as may be required by applicable law, The Company assumes no obligation to publicly update or revise these forward-looking statements for any reason, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, whether as a result of new information, future events or otherwise. SOURCE NRx Pharmaceuticals, Inc.