Remestemcel-L-rknd

Activity Report for Quarter Ended June 30, 2025 (Appendix 4C)NEW YORK, July 17, 2025 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today announced gross revenue from sales of Ryoncil® (remestemcel-L-rknd) through the first quarter post product launch. Ryoncil® is the first and only FDA approved mesenchymal stromal cell (MSC) product in the Unites States and became commercially available for purchase on March 28, 2025, within one quarter of receiving FDA approval for treatment of steroid-refractory acute graft-versus-host disease (SR-aGvHD) in children. Mesoblast Chief Executive Dr. Silviu Itescu said, “We are pleased with the commercial launch activities of Ryoncil® in the first quarter post-launch and look forward to updating on the current quarter's progress now that mandatory state CMS coverage has become effective as of July 1, and we complete onboarding of the remaining major U.S. transplant centers.” FINANCIAL HIGHLIGHTS FOR QUARTER ENDED JUNE 30, 2025 US$13.2 million gross revenue (unaudited) from sales of Ryoncil® post-launch March 28 through to June 30.1US$1.6 million revenue from royalties on sales of TEMCELL® HS Inj.2 sold in Japan by our licensee.US$16.6 million net operating cash spend for the quarter.US$162 million (A$247 million)3 cash on hand at June 30, 2025. OPERATIONAL HIGHLIGHTS FOR RYONCIL® IN SR-aGvHD Mesoblast has onboarded more than 25 transplant centers since product launch and expects during this quarter to complete the onboarding process across all 45 priority transplant centers that account for approximately 80% of U.S. pediatric transplants.Coverage for Ryoncil® continues to expand with over 250 million US lives insured by commercial and government payers. Federal Medicaid coverage by Centers for Medicare and Medicaid (CMS) is in place and mandatory fee-for-service Medicaid coverage for Ryoncil® became effective July 1 in all US states. To assist patients and institutions with insurance coverage, financial assistance, and access programs, ensuring that no patient is left behind in receiving this potentially life-saving therapy, Mesoblast has established a patient access hub termed MyMesoblast™, where Ryoncil® is available for ordering. Additional information is available on ryoncil.com, where valuable resources for healthcare providers, patients and caregivers can be found. During the quarter, Ryoncil® received seven years of orphan-drug exclusive approval from U.S. Food and Drug Administration (FDA) for treatment of SR-aGvHD in pediatric patients 2 months of age and older. This period of statutory exclusivity means that the FDA will not approve another MSC product for this indication during the 7-year period from the approval of Ryoncil®.Separately, Mesoblast has biologic exclusivity preventing another sponsor from referencing the Ryoncil® biologic license application (BLA) until December 2036, twelve years from its first approval which would prevent market entry by a biosimilar.These statutory exclusivities are in addition to Mesoblast’s strong U.S. intellectual property position on MSC composition of matter, manufacturing and indications, including SR-aGvHD, that provide a commercial barrier to entry against competitors through 2044.In July, Mesoblast held a Type B meeting with FDA for Ryoncil® to discuss a pivotal trial in adults with SR-aGvHD. This trial will be conducted with the NIH-funded Bone Marrow Transplant Clinical Trials Network (BMT-CTN), the objective being to extend the product’s label from children to adults with SR-aGvHD. Meeting minutes are expected in the coming weeks. OPERATIONAL HIGHLIGHTS FOR REXLEMESTROCEL IN CHRONIC INFLAMMATORY HEART FAILURE AND LOW BACK PAIN Mesoblast met with FDA in June in follow-up to the successful Type B meeting in early 2024 where FDA stated that the results of the presented studies with Revascor® in the treatment of patients with ischemic heart failure with reduced ejection fraction (HFrEF) and inflammation could support accelerated approval under the existing Regenerative Medicine Advanced Therapy (RMAT) designation for end-stage HFrEF patients with a left ventricular assist device (LVAD),Mesoblast and FDA are aligned on items required for filing a biologics license application (BLA) for Revascor® regarding chemistry, manufacturing & controls (CMC), potency assays for commercial product release, and proposed design and primary endpoint for the confirmatory trial post-approval.The 300-patient randomized controlled confirmatory Phase 3 trial of Mesoblast’s second generation allogeneic, STRO3-immunoselected, and industrially manufactured stromal cell product candidate rexlemestrocel-L is actively enrolling in patients with chronic low back pain (CLBP) due to inflammatory degenerative disc disease (DDD) of less than five years duration at multiple sites across the U.S. Other Fees to Non-Executive Directors were US$71,577, consulting payments to Non-Executive Directors were US$122,767 and salary payments to full-time Executive Directors were US$267,465, detailed in Item 6 of the Appendix 4C cash flow report for the quarter.4 From August 2023 to July 2025, our Non-Executive Directors have voluntarily reduced cash payment of their fees by 50% and Executive Directors (our Chief Executive and Chief Medical Officers) reduced their base salaries by 30%, in lieu of accepting equity-based incentives. A copy of the Appendix 4C – Quarterly Cash Flow Report for the fourth quarter FY2025 is available on the investor page of the company’s website www.mesoblast.com. About Mesoblast Mesoblast (the Company) is a world leader in developing allogeneic (off-the-shelf) cellular medicines for the treatment of severe and life-threatening inflammatory conditions. The therapies from the Company’s proprietary mesenchymal lineage cell therapy technology platform respond to severe inflammation by releasing anti-inflammatory factors that counter and modulate multiple effector arms of the immune system, resulting in significant reduction of the damaging inflammatory process. Mesoblast’s RYONCIL® (remestemcel-L) for the treatment of steroid-refractory acute graft versus host disease (SR-aGvHD) in pediatric patients 2 months and older is the first FDA approved mesenchymal stromal cell (MSC) therapy. Please see the full Prescribing Information at www.ryoncil.com. Mesoblast is committed to developing additional cell therapies for distinct indications based on its remestemcel-L and rexlemestrocel-L allogeneic stromal cell technology platforms. RYONCIL is being developed for additional inflammatory diseases including SR-aGvHD in adults and biologic-resistant inflammatory bowel disease. Rexlemestrocel-L is being developed for heart failure and chronic low back pain. The Company has established commercial partnerships in Japan, Europe and China. About Mesoblast intellectual property: Mesoblast has a strong and extensive global intellectual property portfolio, with over 1,000 granted patents or patent applications covering mesenchymal stromal cell compositions of matter, methods of manufacturing and indications. These granted patents and patent applications provide commercial protection extending through to at least 2044 in all major markets. About Mesoblast manufacturing: The Company’s proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide. Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter: @MesoblastReferences / Footnotes Includes initial inventory purchases by our distributor.TEMCELL® HS Inj. is a registered trademark of JCR Pharmaceuticals Co. Ltd.Translated at 1A$:0.655US$ being the June 30, 2025 rate as reported by the Reserve Bank of Australia.As required by ASX listing rule 4.7 and reported in Item 6 of the Appendix 4C, reported are the aggregated total payments to related parties being Executive Directors and Non-Executive Directors. Forward-Looking StatementsThis press release includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. Forward-looking statements include, but are not limited to, statements about: the initiation, timing, progress and results of Mesoblast’s preclinical and clinical studies, and Mesoblast’s research and development programs; Mesoblast’s ability to advance product candidates into, enroll and successfully complete, clinical studies, including multi-national clinical trials; Mesoblast’s ability to advance its manufacturing capabilities; the timing or likelihood of regulatory filings and approvals, manufacturing activities and product marketing activities, if any; the commercialization of Mesoblast’s RYONCIL for pediatric SR-aGVHD and any other product candidates, if approved; regulatory or public perceptions and market acceptance surrounding the use of stem-cell based therapies; the potential for Mesoblast’s product candidates, if any are approved, to be withdrawn from the market due to patient adverse events or deaths; the potential benefits of strategic collaboration agreements and Mesoblast’s ability to enter into and maintain established strategic collaborations; Mesoblast’s ability to establish and maintain intellectual property on its product candidates and Mesoblast’s ability to successfully defend these in cases of alleged infringement; the scope of protection Mesoblast is able to establish and maintain for intellectual property rights covering its product candidates and technology; estimates of Mesoblast’s expenses, future revenues, capital requirements and its needs for additional financing; Mesoblast’s financial performance; developments relating to Mesoblast’s competitors and industry; and the pricing and reimbursement of Mesoblast’s product candidates, if approved. You should read this press release together with our risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblast’s actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, and accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise. Release authorized by the Chief Executive. For more information, please contact: Corporate Communications / Investors Paul Hughes T: +61 3 9639 6036 Media – Global Allison Worldwide Emma Neal T: +1 603 545 4843 E: emma.neal@allisonworldwide.com Media – Australia BlueDot Media Steve Dabkowski T: +61 419 880 486 E: steve@bluedot.net.au

同写意年度巨献！！7月25-26日，邀您相聚金鸡湖畔，与5000人一起为中国医药创新“同写意”！2024年12月以来，中美终于各自有一款治疗GvHD的MSC药物获批上市了。MSC的产业化就此进入坦途了吗？TONACEA01理论认识的进步起初，我们对于MSC的疗效的理解是：干细胞可以自我复制并分化成为其他类型的细胞，从而参与组织器官的修复。然而，大量的研究发现：MSC回输之后，绝大多数细胞会在1天内清除，只有少量的细胞可以留存一周左右。并且MSC具有显著的免疫调节能力。于是， MSC 成为了一种通过免疫调节和旁分泌作用，诱导受损组织原位再生的“催化”细胞。以至于学界有一种声音，建议将Mesenchymal stem cell 更名为 Mesenchymal stromal cell。更激进的建议是，更名为Medicinal signalling cell。关于MSC的发展与更名，在学界引起了一场争论。这场国际学界的隔空争论的背景是：• 美国有300多家公司/诊所，在推销干细胞疗法。其中半数涉及MSC。• 人类细胞图谱计划等现代分析技术显示：所谓的MSC实际上是多种细胞的混合群体。• 很多公司未能保证cGMP的生产标准。细胞批次间的差异非常大。上述情况，确属事实。MSC细胞群体混杂，不同公司的质量发行标准，以及批次间差异大的问题，估计已经在美国造成了不少乱象。特别是考虑到MSC细胞直径大于毛细血管。正常的MSC固然可以通过变形归巢离开。而异常的MSC，特别是黏附成团的细胞，将造成血管栓塞的风险。在脑血管中，就相当于微中风。在肺脏中，就有可能肺栓塞。给小鼠做过MSC回输实验的小伙伴，应该都有概率遇见过这种情况。然而，另一方面，20多年来对MSC的基础研究与临床实验所积累的经验，也不能全盘否定。大家的确都看到过阳性疗效的神奇案例。上述情况，困扰的不仅是学界。FDA也同样在关注并介入：这封Warning Letter 是FDA在2024年12月发出的。正是FDA批准Mesoblast的MSC(Ryoncil)上市的同时。由于MSC是一个混杂的细胞群体。规范与放行并重，恐怕是监管层最合理的选择。TONACEA02GvHD的成功不可复制中国MSC的探索、实践与乱象，一点儿也不逊于美国。只是大家公开讨论得很少。2025年1月NMPA也批准了中国的第一款MSC药物艾米迈托赛注射液上市。适应症也是GvHD。我们赵老师早在2005年进入临床1期的MSC新药，其选定的适应症也是GvHD。但是很遗憾，通过GvHD这个适应症，再批一款MSC药物的道路，恐怕是难度陡增。根据CDE在2024年1月发布的《间充质干细胞防治移植物抗宿主病临床试验技术指导原则》：“目前我国已批准 JAK1/2 抑制剂用于治疗糖皮质激素或其他系 统治疗应答不充分的 12 岁及以上 aGvHD 患者,ROCK2 抑制剂 用于治疗糖皮质激素或其他系统治疗应答不充分的 12 岁及以上 12 cGvHD 患者,MSCs 在该人群中开展临床研究时,有必要通过合 理的对照设计和研究假设,观察 MSCs 相对于现有推荐治疗的临 床优势。”JAK抑制剂作为aGvHD的二线用药，起效比MSC快，作用机制比MSC更加直接强力。而MSC的特点是作用综合、柔和。因此，很难从临床研究中，观察到MSC相对于JAK抑制剂的优势。如果我们回到艾米迈托赛的注册临床，可以发现：它的临床设计是禁止实验组和对照组使用JAK抑制剂的。这样才达到了主要临床终点。同样Mesoblast的那款MSC的临床方案中，也同样排除了JAK抑制剂的使用。根据新的技术指导原则，后来者不能再这样做了。通过aGvHD，快速再批一款MSC药物的道路，基本上被堵死了。TONACEA03临床研究的经验积累死卷抄作业没有用。后面的人还要做MSC，就要拼各自的专业能力，去开辟全新的战场了。我们看一看那些未获成功的MSC临床研究，能为我们提供哪些启示吧。>>>>失败模式深度分析1. 试验设计层面• 样本量不足： 多数II期试验仅20-100例，统计功效不足• 终点选择不当： 采用结构性或短期终点时，MSC慢性修复优势难以体现• 患者选择过宽： 缺乏基于生物标志物的精准分层2. 细胞产品层面• 剂量/频次探索不足： 单次给药可能低估多剂量优势• 递送方式限制： 细胞归巢效率差异大• 质量控制问题： 批次间差异影响疗效一致性3. 疾病特征层面• 病理阶段过晚： 器官不可逆损伤时MSC难发挥修复作用• 疾病异质性： 同一疾病不同亚型对MSC反应差异大>>>>整体安全性记录• 优秀的安全特征： 所有主要MSC产品均显示良好耐受性• 长期安全性： 24-36个月随访未发现肿瘤风险增加• 免疫安全性： 无严重免疫反应或GVHD报告>>>>中美监管当局的态度美国FDA• 影响： 监管趋严，CMC标准提高• 典型案例： 多项试验因CMC要求暂停中国NMPA• 影响： 2025年新指南要求II期对照设计• 典型案例： 部分试验需重新设计TONACEA04展望未来之路1、考虑MSC是一混杂细胞群体的现实。企业应该在CD73、CD90、CD105这三个基本的共性标志物之外，更加严格的定义自己所使用的细胞群体。以此来更好降低批间差，实现更好的疗效一致性。2025年ISCT针对MSC的最新共识，也反映了这一趋势。因为，A家的MSC和B家的MSC很可能不是一样的东西。2、Medicinal signalling cell 这个名字可能反映了MSC更有前景的未来！我们可以把MSC细胞作为一个智能载体。依靠AI辅助（合成生物学），使用基因编辑技术，我们可以对MSC加以改造，将特定的程序导入这个智能载体中去，让它作为纳米机器人，更好的解决组织修复、再生与抗衰老的问题。这个未来看着很遥远。往前走着走着，它也许就来了。会挽雕弓如满月，西北望，射天狼！