Bupivacaine

PRINCETON, N.J., Oct. 30, 2024 (GLOBE NEWSWIRE) -- Grace Therapeutics, Inc. (Nasdaq: GRCE) (Grace Therapeutics or the Company), a late-stage, biopharma company advancing GTx-104, its novel injectable formulation of nimodipine that addresses high unmet medical needs for a rare disease, aneurysmal subarachnoid hemorrhage (aSAH), today announced it will host a virtual key opinion leader (KOL) event on Wednesday, November 20, 2024 at 2:00 PM ET. To register, click here. The event will feature Abhishek Ray, MD (University Hospitals) and Andrew Webb, PharmD, BCCCP (Massachusetts General Hospital), who will discuss the high unmet medical need and current treatment landscape for patients suffering from aneurysmal Subarachnoid Hemorrhage (aSAH), a rare and life-threatening medical emergency. A live question and answer session will follow the formal presentations. About Abhishek Ray, MD Abhishek Ray, MD, is a fellowship-trained, board-certified neurological surgeon at University Hospitals and Associate Professor of neurological surgery at Case Western Reserve University School of Medicine. He specializes in caring for people with cerebrovascular disease (brain aneurysms, stroke, AVMs), pituitary tumors and meningiomas, and in minimally invasive techniques to treat degenerative spine disease. In neurological surgery, there are often multiple ways to treat a single problem, and Dr. Ray is committed to providing each patient with an individualized care plan to optimize results. In 2021, 2022, 2023, and 2024, he was selected by his peers to be included in Cleveland Magazine’s list of Top Doctors. After completing his undergraduate degree in biological systems engineering at the University of California – Davis, Dr. Ray went back to his hometown to attend medical school at the University of Kansas School of Medicine in Kansas City, Kansas, where he was elected to be an ambassador of the school and was inducted into the Alpha Omega Alpha Honor Medical Society. He then went on to complete neurological surgery residency at University Hospitals/Case Western Reserve University School of Medicine, where he also completed fellowship training in neuro-interventional surgery. Dr. Ray stayed on as faculty at UH/Case Western Reserve University School of Medicine to advance neurosurgical education there. He created a unique and comprehensive neurological surgery elective for second-year medical students, of which he is now the course director. He has been an instructor at national skull base courses for neurosurgical residents and fellows and has served as editor of the neuro-interventional section of CNS Nexus, an online library of neurosurgical cases to better prepare trainees for the operating room. About Andrew Webb, PharmD, BCCCP Andrew Webb, PharmD, BCCCP, is a board-certified neurocritical care clinical pharmacy specialist at Massachusetts General Hospital (MGH) and serves as adjunct clinical faculty at Northeastern University School of Pharmacy and Pharmaceutical Sciences. His clinical and research interests include subarachnoid hemorrhage, status epilepticus, traumatic brain injury, and optimizing the medical management of neurocritically ill patients and his clinical practice is on the multidisciplinary neurocritical care team at MGH’s 22-bed neurosciences intensive care unit. Dr. Webb is originally from Rhode Island and completed his undergraduate studies and Doctor of Pharmacy at the University of Rhode Island. He then completed his pharmacy practice residency at Mayo Clinic in Rochester, MN followed by residency in critical care at Oregon Health & Science University in Portland, OR. Dr. Webb serves on the MGH Comprehensive Stroke Center Quality Taskforce and the MGH Neurology Quality Assurance and Committee on Patient Safety, focusing on improving the quality, safety, and effectiveness of medication therapy in stroke, subarachnoid hemorrhage, and other neurologic conditions. He is active in the Neurocritical Care Society, American College of Clinical Pharmacy, and Society for Critical Care Medicine and serves on several committees within these organizations related to critical care and neurology practice, research, and education. He has lectured regionally and nationally on the pharmacotherapy of subarachnoid hemorrhage, status epilepticus, and the unique challenges of pharmacotherapy in neurocritical care. About aneurysmal Subarachnoid Hemorrhage (aSAH) aSAH is bleeding over the surface of the brain in the subarachnoid space between the brain and the skull, which contains blood vessels that supply the brain. A primary cause of such bleeding is the rupture of an aneurysm. Approximately 70% of aSAH patients experience death or dependence, and more than 30% die within one month of hemorrhage. Approximately 50,000 patients in the United States are affected by aSAH per year, based on market research. Outside of the United States, annual cases of aSAH are estimated at approximately 60,000 in the European Union, and approximately 150,000 in China. About the Grace Therapeutics Asset Portfolio GTx-104 is a clinical stage, novel, injectable formulation of nimodipine being developed for intravenous (IV) infusion in aSAH patients to address significant unmet medical needs. The unique nanoparticle technology of GTx-104 facilitates aqueous formulation of insoluble nimodipine for a standard peripheral IV infusion. GTx-104 provides a convenient IV delivery of nimodipine in the Intensive Care Unit potentially eliminating the need for nasogastric tube administration in unconscious or dysphagic patients. Intravenous delivery of GTx-104 also has the potential to lower food effects, drug-to-drug interactions, and eliminate potential dosing errors. Further, GTx-104 has the potential to better manage hypotension in aSAH patients. GTx-104 has been administered in over 150 healthy volunteers and was well tolerated with significantly lower inter- and intra-subject pharmacokinetic variability compared to oral nimodipine. The addressable market in the United States for GTx-104 is estimated to be about $300 million, based on market research. GTx-102 is a novel, concentrated oral-mucosal spray of betamethasone intended to improve neurological symptoms of Ataxia-Telangiectasia (A-T), for which there are currently no FDA-approved therapies. GTX-102 is a stable, concentrated oral spray formulation comprised of the gluco-corticosteroid betamethasone that, together with other excipients can be sprayed conveniently over the tongue of the A-T patient and is rapidly absorbed. The further development of GTx-102 has been deprioritized in favor of our focus on development of GTx-104. It is also possible that we may license or sell our GTx-102 drug candidate. GTx-101 is a non-narcotic, topical bio-adhesive film-forming bupivacaine spray designed to ease the symptoms of patients suffering with postherpetic neuralgia (PHN). GTx-101 is administered via a metered-dose of bupivacaine spray and forms a thin bio-adhesive topical film on the surface of the patient’s skin, which enables a touch-free, non-greasy application. It also comes in convenient, portable 30 ml plastic bottles. Unlike oral gabapentin and lidocaine patches, we believe that the biphasic delivery mechanism of GTx-101 has the potential for rapid onset of action and continuous pain relief for up to eight hours. No skin sensitivity was reported in a Phase 1 trial. The further development of GTx-101 has been deprioritized in favor of our focus on development of GTx-104. It is also possible that we may license or sell our GTx-101 drug candidate. About Grace Therapeutics Grace Therapeutics is a late-stage biopharma company with drug candidates addressing rare and orphan diseases. Grace Therapeutics’s novel drug delivery technologies have the potential to improve the performance of currently marketed drugs by achieving faster onset of action, enhanced efficacy, reduced side effects, and more convenient drug delivery. Grace Therapeutics’s lead clinical assets have each been granted Orphan Drug Designation by the FDA, which provides seven years of marketing exclusivity post-launch in the United States, and additional intellectual property protection with over 40 granted and pending patents. Grace Therapeutics’s lead clinical asset, GTx-104, is an intravenous infusion targeting aneurysmal Subarachnoid Hemorrhage (aSAH), a rare and life-threatening medical emergency in which bleeding occurs over the surface of the brain in the subarachnoid space between the brain and skull. For more information, please visit: www.gracetx.com. Forward-Looking Statements Statements in this press release that are not statements of historical or current fact constitute "forward-looking statements" within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended, Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and "forward-looking information" within the meaning of Canadian securities laws (collectively, "forward-looking statements"). Such forward-looking statements involve known and unknown risks, uncertainties, and other factors that could cause the actual results of Grace Therapeutics to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. In addition to statements which explicitly describe such risks and uncertainties, readers are urged to consider statements containing the terms "believes," "belief," "expects," "intends," "anticipates," "estimates", "potential," "should," "may," "will," "plans," "continue", "targeted" or other similar expressions to be uncertain and forward-looking. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. The forward-looking statements in this press release, including statements regarding the timing of a data readout from the Company’s Phase 3 STRIVE-ON safety trial of GTx-104, the timing of the Company’s planned NDA submission with the FDA in connection with the Company's Phase 3 STRIVE-ON safety trial, GTx-104’s commercial prospects; the size of the addressable market for GTx-104, the Company’s beliefs regarding the potential benefits of GTx-104, including GTx-104's potential to bring enhanced treatment options to patients suffering from aSAH, and the anticipated benefits and future development, license or sale of the Company's other drug candidates are based upon Grace Therapeutics's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: (i) the success and timing of regulatory submissions of the Phase 3 STRIVE-ON safety trial for GTx-104; (ii) regulatory requirements or developments and the outcome and timing of the proposed NDA application for GTx-104; (iii) changes to clinical trial designs and regulatory pathways; (iv) legislative, regulatory, political and economic developments; and (v) actual costs associated with Grace Therapeutics's clinical trials as compared to management's current expectations. The foregoing list of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors detailed in documents that have been and are filed by Grace Therapeutics from time to time with the Securities and Exchange Commission and Canadian securities regulators. All forward-looking statements contained in this press release speak only as of the date on which they were made. Grace Therapeutics undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by applicable securities laws. For more information, please contact: Grace Therapeutics Contact: Prashant KohliChief Executive OfficerTel: 609-322-1602Email: info@gracetx.com www.gracetx.com Investor Relations: LifeSci AdvisorsMike MoyerManaging DirectorPhone: 617-308-4306Email: mmoyer@lifesciadvisors.com

奔赴全球市场，已成为恒瑞医药的发展主线。 正如恒瑞医药副总经理张连山此前在接受媒体采访时表示，“海外战略上我们有所调整，现在每个产品都愿意寻求合作。” 从去年达成5个跨境license-out交易，到今年成功运用NewCo模式将GLP-1产品组合以总价超60亿美元授权出海，恒瑞的BD出海策略愈加成熟。 近期，更是有媒体报道称，恒瑞聘请了强生BD老将Jens Bitsch-Norhave担任“全球发展事务负责人”，也就是海外BD高管。 这表明，恒瑞又在全球市场布下了一颗“重要棋子”，驶向全球市场的决心可见一斑。 01 全球化野望 每一家药企都想奔赴全球化的“星辰大海”，恒瑞医药亦不例外。 然而，需要明确的是，开拓全球市场的方式多样，并不仅限于BD（业务发展）合作。其中，境外融资也常常成为企业打入国际市场的重要桥梁。 比如近日就有市场传闻称，“恒瑞正在考虑明年赴港上市，拟募资至少20亿美元”。 对此，恒瑞发布公告作出回应，“近年来，在科技创新和国际化发展战略驱动下，公司稳步推进国际化进程。为进一步深化公司战略发展目标，公司近期对境外资本市场融资等事项开展了研究咨询等前期工作。截至目前，公司就相关事项尚未确定具体方案。” 尽管恒瑞对于是否赴港上市没有给出正面回应，但其透露出的研究境外资本市场融资等事项的信号却十分明确。这也从侧面体现出恒瑞渴望驶向更广阔海外市场的野心。 图片来源：恒瑞医药公告 从频繁达成出海交易，到聘请强生老将担任海外BD高管，再到研究境外资本市场融资，恒瑞为何加码海外市场？这一点可从百济神州的国际化成就得到直观反映。 今年上半年，“创新药一哥”百济神州实现总营收达119.96亿元，而其之所以能实现半年收入即突破百亿大关，主要得益于泽布替尼和替雷利珠单抗。 这两款拳头产品能保持快速增长态势，很大程度要归功于海外市场的贡献。 泽布替尼能成为国产创新药首个“十亿美元分子”，得益于已在美国、中国、欧盟等超70个市场获批多项适应症，其中美国市场贡献了大部分收入，同比增长134.4%至59.03亿元，欧洲市场也以231.6%的同比增速首次突破10亿元大关。 对比来看，今年上半年恒瑞医药的创新药收入为66.12亿元（含税，不含对外许可收入），由16款创新药合计贡献，仍不及泽布替尼一款产品（全球销售额达80.18亿元）。 另外，替雷利珠单抗半年销售额超20亿元，也少不了在美国、欧盟、英国和澳大利亚获批上市的助力。尤为值得一提的是，替雷利珠单抗在美国市场的定价是国内的20多倍。 相较之下，恒瑞的“双艾组合”曾闯关FDA失利，近期才重新提交一线治疗肝细胞癌的上市申请，PDUFA目标日期为2025年3月23日。 正如张连山在接受媒体采访时表示，“过去卡瑞利珠单抗联合阿帕替尼组合的出海方式，放到现在，我们不会这么做，因为成本太大。我们改变策略，任何一个产品，在任何临床阶段，都会寻求跟海外合作开发。” 可见，恒瑞不仅要剑指全球市场，还将以多样化的策略加速产品国际化进程。 02 全球化之路“遍地开花” 恒瑞医药全力以赴走向全球市场，也与其尝到了创新药收入及BD贡献业绩的甜头有关。 尽管目前创新药的销售体量不及百济神州，但恒瑞也在今年上半年交出了靓丽的业绩：实现总营收136.01亿元，同比增长21.78%；归母净利润34.32亿元，同比大增48.67%。 更重要的是，恒瑞的创新药收入达66.12亿元（含税，不含对外许可收入），如果加上德国Merck（默克）公司支付的1.6亿欧元对外许可首付款，创新药收入总和占总营收比重已经过半。 这一份超乎预期的成绩单，让市场不禁感叹：“医药一哥”回来了。 此外，恒瑞还在今年5月将GLP-1产品组合授权给美国Hercules公司，不仅达成总额超60亿美元的合作（其中首付款和近期里程碑付款总计1.1亿美元），还获得了Hercules公司19.9%的股权。 按照以往6个月后确认收入的惯例，恒瑞大概率会在第四季度将GLP-1的首付款确认为收入，并计入当期利润。但这还仅仅是冰山一角。 恒瑞这两年一直在积极向海外药企授出管线资产，2023年达成了5个跨境license-out交易，其中就包括将PARP1抑制剂HRS-1167和Claudin18.2 ADC药物SHR-A1904以总价14亿欧元授权给Merck公司。 这意味着，恒瑞有望迎来源源不断的合作收入，创新药板块将演变为“里程碑+商业化”双轮收入结构。 今年下半年，恒瑞也在海外市场收获了一些成效： 7月，布比卡因脂质体注射液的ANDA（简略新药申请，即美国仿制药申请）获FDA批准，成为该品种在全球范围内获批上市的首仿药。 据介绍，布比卡因脂质体注射液最早由美国Pacira公司研制，2011年在美国获批上市，目前仅在美国和欧洲销售，国内尚未进口。因其技术壁垒高，上市十余年无仿制产品成功上市。2023年，布比卡因脂质体相关剂型全球销售额约为5.38亿美元。 10月，注射用紫杉醇（白蛋白结合型）的ANDA获FDA批准，成为美国FDA批准上市的该品种首仿药。 需要注意的是，注射用紫杉醇（白蛋白结合型）由美国阿博利斯生命科学公司开发，最早于2005年获得FDA批准上市，商品名为Abraxane，现已在美国、欧盟、日本等多个国家和地区上市。经查询，注射用紫杉醇（白蛋白结合型）2023年全球销售额合计约25.97亿美元。 恒瑞医药的雄心远不止于此。首仿药的获批只是其国际化战略的一个缩影，还有一系列正在海外进行临床试验的创新药，未来也有望在国际市场上开辟新的增长点。 03 “双艾”组合再冲FDA，抗肿瘤领域成“重头戏” 正在海外推进临床试验的创新药，将是恒瑞医药未来竞争的“制胜法宝”。 截至今年7月31日，恒瑞共有17款创新药在海外进入临床研究阶段，其中抗肿瘤领域11款、自身免疫领域3款，血液/抗肿瘤、呼吸系统和其他领域各1款。 从临床进度看，进展最快的是“双艾组合”（卡瑞利珠单抗联合阿帕替尼），在近期重新向FDA提交了一线治疗肝细胞癌的上市申请。根据处方药用户付费法案（PDUFA）， FDA对卡瑞利珠单抗的目标审评日期为2025年3月23日。 图片来源：恒瑞医药2024年中报 另外，恒瑞在抗肿瘤领域的海外创新药中，ADC药物的比例高达一半，包括SHR-A1811（HER2 ADC）、SHR-A1904（Claudin 18.2 ADC）、SHR-A1912（CD79b ADC）、SHR-A1921（TROP2 ADC）、SHR-A2009（HER3 ADC）、SHR-A2102（Nectin-4 ADC），其中已有4款ADC药物获得FDA授予快速通道资格认定。 今年9月，恒瑞在ESMO年会上公布了SHR-A1904治疗胃或胃食管交界处癌（GC/GEJC）的I期研究结果：在基线和≥1次基线后评估的患者中，6.0 mg/kg剂量组中，客观缓解率（ORR）达55.6%、疾病控制率（DCR）达88.9%，具有可管理的安全性和良好的抗肿瘤活性，临床潜力可期。 恒瑞还在2024 ESMO年会上公布了SHR-A2102治疗晚期实体瘤患者的I期研究结果：在经过多线治疗的非小细胞肺癌（NSCLC）患者中，ORR、DCR分别高达31.3%、87.5%。目前，全球仅有一款Nectin-4 ADC药物获批上市，而且市场竞争格局相对缓和。 另外，TROP2 ADC药物SHR-A1921也展示出鼓舞人心的临床研究数据：单药治疗复发性铂耐药卵巢癌的ORR大于40%，且缓解具有可持续性；中位PFS达到7个月左右；推荐剂量下安全性可控、耐受性良好，有望改变铂耐药复发上皮性卵巢癌的治疗现状。 值得一提的是，SHR-A1921也在开展用于预后差且治疗方案有限的广泛期小细胞肺癌（ES-SCLC）患者的临床试验，Ⅰ期试验显示出了令人鼓舞的疗效：截至2024年2月19日，共有17名患者入组，在15例可评估肿瘤反应的患者中，ORR为33.3%，DCR为66.7%，中位DoR为4.4个月。在所有患者中，中位PFS为3.8个月，中位OS未达到。 可见，“医药一哥”恒瑞医药在海外创新药领域的持续投入和精心耕耘，如今正在逐渐结出硕果，其未来发展值得期待。 参考资料 1.各家公司的财报、公告、官微 2.《恒瑞医药海外上市没那么可怕》，见智研究Pro 3.交银国际证券研报