Irinotecan Hydrochloride Lioposome

（点击图片 查看详情）4月17日晚，恒瑞医药发布2023年年度报告, 2023年恒瑞医药实现营业收入228.20亿元，同比增7.26%，归属于上市公司股东的净利润43.02亿元，同比增10.14%，归属于上市公司股东的扣非净利润41.41亿元，同比增21.46%，经营性现金流净额76.44亿元，同比大增504.12%，公司业绩稳步回升。报告分析，随着恒瑞医药创新成果持续获批，创新药临床价值凸显，驱动收入增长。2023年公司创新药收入达106.37亿元（含税，不含对外许可收入），虽然面临外部环境变化、产品降价及准入难等因素影响，仍然实现了同比22.1%的增长。为保证创新产出，恒瑞持续加大创新力度，维持较高的研发投入，报告期内公司累计研发投入61.50亿元，有力地支持了公司的项目研发和创新发展。同时公司不断完善运营管理，促进提质增效，销售费用率比去年同期下降1.34%。值得注意的是，报告中提到公司正在持续强化商业化体系建设，并从战略层面深入布局零售市场，拓展DTP药房等渠道，加快创新药销售渠道覆盖。公司也同时公布了年度分红方案，向全体股东每10股派发现金股利2.00元（含税），加上回购合计分红21亿多元。长江证券分析认为：公司转型阵痛已过，集采影响已近尾声、医保降价压力陆续释放，创新产品持续兑现，推动业绩进入上行通道，并且后续还有多个重磅在研品种提供长期增长动力，未来成长可期。创新驱动收入增长，研发成果加速兑现恒瑞医药坚持创新引领，维持较高的研发投入，报告显示，2023年累计研发投入61.50亿元，为公司持续不断创新产出提供强大保障。在高强度研发投入的加持下，恒瑞研发成果加速兑现。报告期内恒瑞有3款1类创新药（阿得贝利单抗、磷酸瑞格列汀、奥特康唑）、4款2类新药（盐酸右美托咪定鼻喷雾剂、醋酸阿比特龙纳米晶、盐酸伊立替康脂质体、恒格列净二甲双胍缓释片）获批上市，截至目前公司已在国内获批上市16款1类创新药、4款2类新药；报告期内5项新适应症获批上市，卡瑞利珠单抗第9个适应症及阿帕替尼第3个适应症获批上市，二者联合用于一线治疗晚期肝癌，马来酸吡咯替尼第3个适应症、羟乙磺酸达尔西利第2个适应症分别获批上市，进一步拓展在乳腺癌领域的应用，盐酸右美托咪定鼻喷雾剂第2个适应症用于儿童全麻手术前的镇静/抗焦虑获批上市；报告期内共14项上市申请获NMPA受理，包括瑞卡西单抗、艾玛昔替尼等新药申报，以及氟唑帕利联合阿帕替尼等新适应症申报，涉及癌症、糖尿病、自免、眼科、镇痛等治疗领域；专利申请和维持方面，截至2023年底，公司累计申请发明专利2389件，PCT专利662件，拥有国内有效授权发明专利545件，欧美日等国外授权专利667件。公司在研管线快速推进。报告期内，12项临床推进至Ⅲ期，35项临床推进至Ⅱ期，30项临床推进至Ⅰ期，公司有90多个自主创新产品正在临床开发，近300项临床试验在国内外开展。2023年至今共取得7项CDE突破性治疗品种认定，未来审批有望加速，其中仅公司HER2 ADC明星产品SHR-A1811就独得5项；公司自主研发的首个小核酸药物HRS-5635注射液用于慢性乙肝获批临床，国内外暂无同类产品获批上市；公司在核药领域布局的首对放射性精准治疗产品获批临床，目前公司已有4款核药获批开展临床试验。这些创新成果的取得，离不开公司多年来打造的日益完备的创新体系。首先，经过多年发展，公司已形成了一支5000多人的规模化、专业化、能力全面的研发团队，先后在连云港、上海、苏州、成都、厦门、济南、广州、北京、美国和欧洲等地设立了研发中心，满足多个疾病领域管线对新分子实体的发现和开发需求；其次，公司以“临床未满足的需求”为导向，以“新、快、特”为主要宗旨，坚持“差异化”的竞争策略，持续聚焦靶点前移，加强源头创新。公司在肿瘤领域有丰富的研发管线，同时在自身免疫疾病、代谢性疾病、心血管疾病、感染疾病、呼吸系统疾病、血液疾病、疼痛管理、神经系统疾病、眼科、肾病等领域也进行了广泛布局；第三，公司还建立了一批具有自主知识产权、国际领先的新技术平台，如蛋白水解靶向嵌合物（PROTAC）、分子胶、抗体药物偶联物（ADC）、双/多特异性抗体、AI分子设计、γδT、耐药、体内药理、分子动力学、生物信息等，并不断优化和发展，为创新研发和国际化提供强大的基础保障。其中，已有11个新型、具有差异化的ADC分子成功获批临床，HER2 ADC产品SHR-A1811和TROP2 ADC产品SHR-A1921快速进入临床Ⅲ期研究阶段；2个PROTAC分子已处于临床研究阶段；PD-L1/TGFβ融合蛋白药物SHR-1701快速推进多项临床Ⅲ期研究，新一代TIGIT/PVRIG双抗已顺利开展临床研究，还有10多个First-in-class/Best-in-class双/多特异性抗体在研。国际化稳步推进，对外授权总交易金额超40亿美元恒瑞医药继续稳步推进国际化战略，坚持自主研发与开放合作并重，在内生发展的基础上加强国际合作。对外合作取得丰硕成果。公告表示，恒瑞正以全球化的视野积极探索与跨国制药企业的交流合作，寻求与全球领先医药企业的合作机会，2023年恒瑞按下BD加速键，共达成了总交易金额超40亿美元的5项授权合作，涉及创新药包括PARP1抑制剂HRS-1167、Claudin-18.2 ADC药物SHR-A1904、EZH2抑制剂SHR2554、TSLP单抗SHR-1905、TKI吡咯替尼、PD-1抑制剂卡瑞利珠单抗联用治疗肝细胞癌适应症。其中公司将抗癌创新药HRS-1167与SHR-A1904独家许可给德国默克，交易总金额可超14亿欧元，这也是恒瑞首次与全球大型跨国药企合作。目前恒瑞已实现10项创新药海外授权。国际临床试验稳步开展。公司首个国际多中心Ⅲ期临床研究——卡瑞利珠单抗联合阿帕替尼治疗晚期肝癌国际多中心Ⅲ期研究已达到主要研究终点，在美国申报上市已经获得FDA正式受理；目前公司已有3款自主研发的ADC创新药SHR-A2009、SHR-A1912、SHR-A1921先后获得美国FDA快速通道资格认定，有望加快推进临床试验以及上市注册进度；创新药Edralbrutinib片用于治疗视神经脊髓炎谱系疾病（NMOSD）适应症获得美国FDA授予的孤儿药资格认定，公司目前已有3款产品获得这一认定；与此同时，公司多个项目在美国、欧洲、亚太等国家和地区获得临床试验资格，6款ADC以及PVRIG-TIGIT双抗等肿瘤创新产品均已实现国内外同步研发，用于治疗阿尔茨海默病的抗Aβ单抗SHR-1707在澳洲的临床试验正在顺利进行。公司未来将通过自研、合作、许可引进等多种模式，拓展海外研发边界，丰富创新产品管线。同时，公司创新实力持续赢得国际认可。报告期内公司119项重要研究成果相继在The Lancet（柳叶刀）、BMJ（英国医学杂志）、Nature Medicine（自然·医学）、JAMA Oncology（美国医学会杂志·肿瘤学）等全球顶级期刊发表，累计影响因子近1400分。其中，公司卡瑞利珠单抗（艾瑞卡®）联合阿帕替尼（艾坦®）（“双艾”）对比索拉非尼用于治疗晚期不可切除肝细胞癌的全球多中心III期临床研究（CARES-310研究）主论文在线发表于国际顶级医学期刊《柳叶刀》（The Lancet，IF：168.9），研究结果显示，中位总生存期（mOS）达到22.1个月[1]，为目前已经公布数据的晚期肝癌一线治疗关键研究中位OS最长的治疗方案[2]。同时，公司超百项创新药学术成果亮相美国临床肿瘤学会（ASCO）年会、欧洲肿瘤内科学会（ESMO）大会、美国癌症研究协会（AACR）年会、美国血液学（ASH）年会等国际知名学术会议。持续优化运营管理，完善人才团队建设面对各种不确定的市场因素，恒瑞全面推动资源整合，夯实医学、市场双引擎驱动机制，持续优化组织结构，增强医学及市场专业化人才团队力量，进一步减少一线销售人员，促进运营提效。公司2023年度销售费用率比去年同期下降1.34%。公司高管团队持续增加新鲜血液，年报发布同时，恒瑞宣布任命卢韵为公司副总经理。卢韵系恒瑞内部培育成长起来的高管，已在恒瑞工作15年，多年来一直深耕CMC研发领域。企业创新发展，人才是根本。恒瑞医药继续坚持“人才是第一资源”和“以贡献者为本”的理念，持续引进海内外高层次人才，设立“伞兵计划”等，通过充实国际视野的领军人才，拉高整个创新人才队伍的“天花板”，2023年公司共引进600多名核心人才，其中150多名具有博士研究生学历；通过打造瑞鹰计划、星青年、恒星计划等，系统开展内部人才的培养和发展；持续完善人才激励机制，推出员工持股计划等，激发员工潜力，自2023年5月推出新的股票回购计划以来，恒瑞已累计回购约1435万股用于员工持股计划，总金额达6亿多元。积极履行社会责任，推动可持续发展作为国内医药领域的领军企业，恒瑞医药多年来一直积极履行社会责任，努力让发展成果更好惠及民生、回馈社会。今年，恒瑞医药19款产品通过新版国家医保目录调整，其中包括多款创新药物及新适应症，累计进入国家医保目录的产品已达103个，其中已上市创新药有13款，进一步提高患者用药的可及性和可负担性。恒瑞还积极参与社会公益慈善，2023年，恒瑞提供公益支持的“健康中国行·重走长征路”公益项目启动，旨在促进长征途经区域医疗卫生事业发展，活动已在福建龙岩、江西赣州多地成功举办；通过中国乡村发展基金会捐款、捐药200万元，用于甘肃临夏州积石山县抗震救灾。在年报发布的同时，恒瑞还披露了2023年度环境、社会及管治（ESG）报告，展现公司践行可持续发展的实践和成果。凭借在造福患者健康、绿色可持续发展、员工福祉、社会责任等方面的优秀表现，恒瑞医药MSCI ESG评级连年持续提升至“A”级，在中国医药行业处于领先水平。在创新、国际化双轮驱动发展战略引领下，恒瑞医药转型发展成效备受认可。近日，国际知名咨询机构Citeline发布了《2024年医药研发年度回顾》，并评选出全球TOP25管线规模的制药公司，恒瑞医药第三次进入榜单与全球大型跨国药企同台竞争，排名跃升至第8，再创中国药企新高。

Trial's lower-than-expected event rate suggests improved survival outcomesMINNEAPOLIS, April 22, 2024 (GLOBE NEWSWIRE) -- Panbela Therapeutics, Inc. (OTCQB: PBLA), (“Panbela”), a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, today announced that the interim data analysis for its ongoing ASPIRE trial is now expected to be available as soon as Q1 2025. This delay in the projected date for analysis comes as a result of the trial's current event rate, which is lower than initially anticipated, indicating that patients have lived longer than expected. The ASPIRE trial, which is evaluating the efficacy and safety of Panbela's lead product candidate, ivospemin (SBP-101), in combination with gemcitabine and nab-paclitaxel (Abraxane) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), requires 33% of the total expected events to occur before the interim analysis can be conducted. As of the latest assessment, less than half of the required events for the interim analysis have occurred. "While we initially anticipated the interim analysis to take place in mid-2024, we are encouraged by the lower-than-expected event rate, which suggests that patients in the ASPIRE trial have experienced prolonged survival," said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela Therapeutics. "This is a positive development for patients and underscores the potential of ivospemin in addressing a significant unmet need in the treatment of mPDAC." Panbela also highlighted the significance of the ASPIRE trial in the context of recent advancements in mPDAC treatment, such as the Napoli 3 trial, which led to the approval of liposomal irinotecan (Onivyde) in combination with fluorouracil, oxaliplatin and leucovorin (NALIRIFOX). Despite this approval, which was based on a median overall survival benefit of 1.9 months compared to gemcitabine and nab-paclitaxel, the prognosis for patients with mPDAC remains poor, with median overall survival still less than 12 months. The incremental benefits in median survival have been modest in the past 11 years with the recent approval of Onivyde in the NALIRIFOX regimen demonstrating a 1.9 month survival benefit compared to the approval of gemcitabine and nab-paclitaxel which was based on a median overall survival benefit of 1.8 months over gemcitabine alone. "We believe that the addition of ivospemin (SBP-101) to the standard-of-care regimen of gemcitabine and nab-paclitaxel has the potential to significantly improve outcomes for patients with mPDAC, beyond the incremental benefits observed with the recently approved therapy," added Dr. Simpson. "The early indications from the ASPIRE trial support this belief, and we remain committed to advancing this important study and look forward to sharing the interim results in March 2025." Panbela will continue to monitor the progress of the ASPIRE trial and provide updates as appropriate. About Panbela’s PipelineThe pipeline consists of assets currently in clinical trials with an initial focus on familial adenomatous polyposis (FAP), first-line metastatic pancreatic cancer, neoadjuvant pancreatic cancer, colorectal cancer prevention and ovarian cancer. The combined development programs have a steady cadence of anticipated catalysts with programs ranging from pre-clinical to registration studies. Ivospemin (SBP-101)Ivospemin is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. It has shown signals of tumor growth inhibition in clinical studies of metastatic pancreatic cancer patients, demonstrating a median overall survival (OS) of 14.6 months and an objective response rate (ORR) of 48%, both exceeding what is typical for the standard of care of gemcitabine + nab-paclitaxel suggesting potential complementary activity with the existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, ivospemin has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Serious visual adverse events have been evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the previous Panbela-sponsored clinical trials provide support for continued evaluation of ivospemin in the ASPIRE trial. Flynpovi ™Flynpovi is a combination of CPP-1X (eflornithine) and sulindac with a dual mechanism inhibiting polyamine synthesis and increasing polyamine export and catabolism. In a Phase III clinical trial in patients with sporadic large bowel polyps, the combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Focusing on FAP patients with lower gastrointestinal tract anatomy in the recent Phase III trial comparing Flynpovi to single agent eflornithine and single agent sulindac, FAP patients with lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), showed statistically significant benefit compared to both single agents (p≤0.02) in delaying surgical events in the lower GI for up to four years. The safety profile for Flynpovi did not significantly differ from the single agents and supports the continued evaluation of Flynpovi for FAP. CPP-1XCPP-1X (eflornithine) is being developed as a single agent tablet or high dose powder sachet for several indications including prevention of gastric cancer, treatment of neuroblastoma and recent onset Type 1 diabetes. Preclinical studies as well as Phase I or Phase II investigator-initiated trials suggest that CPP-1X treatment may be well-tolerated and has potential activity. About PanbelaPanbela Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing disruptive therapeutics for patients with urgent unmet medical needs. Panbela’s lead assets are Ivospemin (SBP-101) and Flynpovi. Further information can be found at www.panbela.com. Panbela’s common stock is eligible for quotation on the OTCQB under the symbol “PBLA”. Cautionary Statement Regarding Forward-Looking StatementsThis press release contains “forward-looking statements,” including within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: “anticipate,” “believe,” “can,” “design,” “expect,” “focus,” “intend,” “looking forward,” “may,” “plan,” “positioned,” “potential,” and “will.” All statements other than statements of historical fact are statements that should be deemed forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations, and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results and financial condition may differ materially and adversely from the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results and financial condition to differ materially from those indicated in the forward-looking statements include, among others, the following: (i) our ability to obtain additional funding to execute our business and clinical development plans; (ii) progress and success of our clinical development program; (iii) the impact of the current COVID-19 pandemic on our ability to conduct our clinical trials; (iv) our ability to demonstrate the safety and effectiveness of our product candidates: ivospemin (SBP-101) and eflornithine (CPP-1X); (v) our reliance on a third party for the execution of the registration trial for our product candidate Flynpovi ; (vi) our ability to obtain regulatory approvals for our product candidates, SBP-101 and CPP-1X in the United States, the European Union or other international markets; (vii) the market acceptance and level of future sales of our product candidates, SBP-101 and CPP-1X; (viii) the cost and delays in product development that may result from changes in regulatory oversight applicable to our product candidates, SBP-101 and CPP-1X; (ix) the rate of progress in establishing reimbursement arrangements with third-party payors; (x) the effect of competing technological and market developments; (xi) the costs involved in filing and prosecuting patent applications and enforcing or defending patent claims; (xii) our ability to obtain a listing of our common stock on a national securities exchange; and (xii) such other factors as discussed in Part I, Item 1A under the caption “Risk Factors” in our most recent Annual Report on Form 10-K, any additional risks presented in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Any forward-looking statement made by us in this press release is based on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to publicly update any forward-looking statement or reasons why actual results would differ from those anticipated in any such forward-looking statement, whether written or oral, whether as a result of new information, future developments or otherwise. Contact Information: Investors: James Carbonara Hayden IR (646) 755-7412 james@haydenir.com Media: Tammy Groene Panbela Therapeutics, Inc. (952) 479-1196 IR@panbela.com