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Appendix 4C Quarterly Activity Report for Quarter Ended December 31, 2023

Appendix 4C Quarterly Activity Report for Quarter Ended December 31, 2023

附录 4C 截至2023年12月31日的季度活动报告
GlobeNewswire ·  01/30 21:13

NEW YORK, Jan.  30, 2024  (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today provided an activity report for the second quarter ended December 31, 2023.

纽约,2024年1月30日(GLOBE NEWSWIRE)——炎症性疾病异基因细胞药物的全球领导者Mesoblast Limited(纳斯达克股票代码:MSO;澳大利亚证券交易所股票代码:MSB)今天提供了截至2023年12月31日的第二季度活动报告。

Mesoblast Chief Executive Silviu Itescu said: "It has been a very busy quarter in which we have made substantial operational progress across our three lead Phase 3 assets. We have generated significant new potency and characterization data for our lead product Ryoncil (remestemcel-L) for children with acute GVHD, as requested by FDA, and will submit these data ahead of our planned meeting with FDA this quarter."

Mesoblast首席执行官西尔维乌·伊特斯库表示:“这是一个非常繁忙的季度,我们在第三阶段的三项主要资产中取得了实质性的运营进展。应美国食品药品管理局的要求,我们已经为我们的主要产品Ryoncil(remestemcel-L)针对急性移植物抗宿主病儿童生成了重要的新效力和特征数据,并将在我们计划于本季度与美国食品药品管理局举行会议之前提交这些数据。”

"Our second Phase 3 back pain trial with rexlemestrocel-L, aiming to confirm the durable pain reduction that was seen in the first Phase 3 trial, is underway. Finally, we were very pleased to have received a Rare Pediatric Disease (RPD) Designation from FDA for our cardiovascular product Revascor in children with life-threatening congenital heart disease, and plan to discuss the trial results in the context of a regulatory approval pathway."

“我们使用rexlemestrocel-L进行的第二项3期背痛试验正在进行中,该试验旨在确认在第一项3期试验中看到的持久减轻疼痛的效果。最后,我们很高兴我们的心血管产品Revascor在患有危及生命的先天性心脏病儿童中获得美国食品药品管理局颁发的罕见儿科疾病(RPD)称号,并计划在监管批准途径的背景下讨论试验结果。”

Dr Itescu added: "We raised additional capital during the quarter to support these important Phase 3 programs, and I would like to thank all shareholders that participated in the placement and entitlement offer. In combination with our previously announced cost reduction strategies and operational streamlining, which are on-track, this new capital will provide added balance sheet strength."

Itescu博士补充说:“我们在本季度筹集了额外资金,以支持这些重要的第三阶段计划,我要感谢所有参与配售和配股发行的股东。再加上我们先前宣布的成本削减战略和运营精简(已步入正轨),这笔新资本将增强资产负债表的实力。”

ACTIVITY REPORT

活动报告

Graft versus Host Disease – Pediatric and Adult Phase 3 Programs

移植物抗宿主病——儿科和成人 3 期项目

  • Mesoblast has requested a meeting with FDA this quarter to provide additional potency and characterization data for its product RYONCIL which it believes demonstrate that the product used as second-line after corticosteroids in the pivotal Phase 3 trial GVHD001 in children with SR-aGVHD, which successfully met its primary endpoint of Day 28 Overall Response, was made to a standard supporting the trial as being adequate and well controlled.

  • The new potency assay data show that the RYONCIL product made with the current manufacturing process that has undergone successful inspection by FDA, demonstrates greater potency than the earlier generation product, providing context to its greater impact on survival.

  • Showing that the product used in the completed pediatric Phase 3 trial was standardized as to potency and characterization could provide support for approval of the pediatric indication given the absence of any approved therapies for children.

  • Survival in adults with SR-aGVHD who have failed at least one additional agent, such as ruxolitinib, remains as low as 20-30% by 100 days.1,2 In contrast, 100-day survival was 63% after remestemcel-L treatment was used under expanded access in 71 patients aged 12 and older with SR-aGVHD who failed to respond to at least one additional agent, such as ruxolitinib.

  • The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) in the United States, a body that is funded by the National Institutes of Health (NIH) and is responsible for approximately 80% of all US allogeneic BMTs, has agreed to develop and execute a pivotal trial of RYONCIL in adults who are refractory to both corticosteroids and a second line agent such as ruxolitinib.

  • Mesoblast will provide the Phase 3 trial protocol to FDA ahead of the upcoming meeting this quarter.

  • Mesoblast已要求在本季度与美国食品药品管理局举行会议,以提供其产品RYONCIL的更多效力和特征数据,它认为这表明,在针对sr-AGVHD儿童的关键3期试验 GVHD001 中,该产品作为仅次于皮质类固醇的二线产品,成功达到第28天总体反应的主要终点,是按照支持该试验的标准生产的,因为该产品足够且控制良好。

  • 新的效力测定数据显示,采用当前制造工艺制造的RYONCIL产品已通过美国食品和药物管理局的成功检查,表现出比前一代产品更强的效力,为其对存活率的更大影响提供了背景信息。

  • 鉴于没有任何经批准的儿童疗法,表明已完成的儿科3期试验中使用的产品在效力和特性方面已标准化,可以为儿科适应症的批准提供支持。

  • 至少一种额外药物(例如鲁索利替尼)失效的sr-AGVHD成人的存活率在100天之前仍低至20-30%。1,2 相比之下,71名12岁及以上对至少一种附加药物(例如ruxolitinib)没有反应的12岁及以上sr-AGVHD患者使用remestemcel-L治疗后的100天存活率为63%。

  • 美国血液和骨髓移植临床试验网络(BMT CTN)由美国国立卫生研究院(NIH)资助,负责约80%的美国同种异体骨髓移植临床试验网络(BMT CTN)已同意开发和执行一项针对同时对皮质类固醇和鲁索利替尼等二线药物都难治的成年人进行RYONCIL的关键试验。

  • Mesoblast将在本季度即将举行的会议之前向美国食品药品管理局提供第三阶段试验方案。

Cardiovascular – Program in Pediatric Congenital Heart Disease, Adult Phase 3 Program in Chronic Heart Failure with Reduced Ejection Fraction (HFrEF)

心血管 — 小儿先天性心脏病项目,成人慢性心力衰竭射分数降低的三期计划(HFref)

  • This month FDA granted Mesoblast a Rare Pediatric Disease (RPD) Designation for Revascor (rexlemestrocel-L) following submission of results from the randomized controlled trial in children with hypoplastic left heart syndrome (HLHS), a potentially life-threatening congenital heart condition.

  • The results from the blinded, randomized, placebo-controlled prospective trial of REVASCOR conducted in the United States in children with HLHS were published in the December 2023 issue of the peer reviewed the Journal of Thoracic and Cardiovascular Surgery Open (JTCVS Open).3 In the HLHS trial, a single intramyocardial administration of REVASCOR at the time of staged surgery resulted in the desired outcome of significantly increased left ventricular (LV) end-systolic and end-diastolic volumes over 12 months compared with controls as measured by 3D echocardiography, (p=0.009 & p=0.020 respectively), facilitating life-saving biventricular surgery to be achievable in 100% of REVASCOR-treated children vs only 57% of controls.

  • RPD Designation is granted by the FDA for certain serious or life-threatening diseases which primarily affect children.

  • On FDA approval of a Biologics Licensing Application (BLA) for REVASCOR for the treatment of HLHS, Mesoblast may be eligible to receive a Priority Review Voucher (PRV) that can be redeemed for any subsequent marketing application or may be sold or transferred to a third party.

  • REVASCOR has shown the potential to reduce major adverse cardiac events such as heart attack and cardiovascular death in high risk patients with HFrRF. Mesoblast will meet with FDA this quarter to address potential pathways to approval for REVASCOR under our Regenerative Medicine Advanced Therapies (RMAT) designation.

  • 在提交了针对左心发育不全综合症(HLHS)(一种可能危及生命的先天性心脏病)患儿的随机对照试验结果后,美国食品药品管理局本月批准了Mesoblast对Revascor(Rexlemestrocel-L)的罕见儿科疾病(RPD)认定。

  • 在美国对HLHS儿童进行的REVASCOR盲目、随机、安慰剂对照的前瞻性试验的结果发表在同行评审的《胸心血管外科杂志公开版》(JTCVS Open)的2023年12月号上。3在HLHS试验中,在分阶段手术时单次心肌内给药REVASCOR可产生预期的左心室明显增高的结果(LV) 与 3D 测量的对照组相比,12 个月内的收缩末期和舒张末期容量超声心动图(分别为p=0.009和p=0.020),促进了100%的接受Revascor治疗的儿童实现挽救生命的双心室手术,而对照组中只有57%。

  • 对于某些主要影响儿童的严重或危及生命的疾病,美国食品药品管理局授予了RPD认证。

  • 在FDA批准用于治疗HLHS的REVASCOR的生物制剂许可申请(BLA)后,Mesoblast可能有资格获得优先审查券(PRV),该凭证可用于任何后续的营销申请,也可以出售或转让给第三方。

  • REVASCOR已显示出减少HfRRF高危患者的主要不良心脏事件的潜力,例如心脏病发作和心血管死亡。Mesoblast将在本季度与美国食品药品管理局会面,讨论以我们的再生医学高级疗法(RMAT)称号批准REVASCOR的潜在途径。

Chronic Low Back Pain – Phase 3 Program

慢性腰痛—第三阶段计划

  • Second Phase 3 trial underway for rexlemestrocel-L in the treatment of chronic low back pain (CLBP) due to inflammatory disc degeneration– a condition affecting at least seven million people in both the US and Europe alone.

  • Phase 3 trial activities, investigators and trial sites across the United States are being managed by a leading contract research organisation (CRO) specializing in pain trials.

  • The trial's primary endpoint is reduction in pain at 12 months after a single intra-discal injection of rexlemestrocel-L.

  • First Phase 3 trial showed significant pain reduction at 12 and 24 months, and confirmation of these results will provide FDA with a clinical data package that may result in product approval.

  • Rexlemestrocel-L的第二阶段3期试验正在进行中,该试验用于治疗炎性椎间盘退化引起的慢性腰痛(CLBP),仅在美国和欧洲,这种疾病就影响了至少700万人。

  • 美国各地的3期试验活动、研究人员和试验场所由一家专门从事疼痛试验的领先合同研究组织(CRO)管理。

  • 该试验的主要终点是在椎间盘内单次注射rexlemestrocel-L后12个月内疼痛减轻。

  • 第一项3期试验显示,在12个月和24个月时疼痛明显减轻,这些结果的确认将为FDA提供可能导致产品批准的临床数据包。

FIANANCIAL REPORT

财务报告

Strengthened Balance Sheet
Institutional Placement and Entitlement Offer completed raising A$60.3 million at an issue price of A$0.30 per share, including the completed retail component and top-up facility of the Entitlement Offer. The offer was well supported by existing shareholders, new institutional investors, and by Directors. Mesoblast Founder and Chief Executive Officer, Dr Silviu Itescu strongly supported the Entitlement Offer subscribing for A$3.0 million.

资产负债表得到加强
机构配售和权益发行以每股0.30澳元的发行价完成了6,030万澳元的筹资,其中包括权利要约中已完成的零售部分和充值额度。该提议得到了现有股东、新机构投资者和董事的大力支持。Mesoblast创始人兼首席执行官西尔维乌·伊特斯库博士坚决支持订阅300万澳元的权利优惠。

Cash balance at the end of the quarter was A$113.4 million (US$77.6 million).4

本季度末的现金余额为1.134亿澳元(合7,760万美元)。4

Cost containment strategy on-track
Cost containment strategies and payroll reductions have been enacted by management and the Board enabling continuation of Phase 3 programs for SR-aGVHD and CLBP in the quarter whilst still achieving reductions in net operating cash spend:

成本控制战略步入正轨
管理层和董事会已经制定了成本控制策略和工资削减,使SR-AGVHD和CLBP的第三阶段计划得以在本季度继续实施,同时仍能减少净运营现金支出:

  • Net operating cash spend of US$12.3 million for the quarter.

  • 25% reduction in net operating cash spend from the comparative quarter in FY2023.

  • 32% reduction in net operating cash spend from the comparative quarter in FY2022.

  • On target to achieve a 23% ($15m) reduction in net operating spend in FY2024 compared to FY2023 which will be partially offset by investment in our Phase 3 programs for SR-aGVHD and CLBP.

  • 本季度净运营现金支出为1,230万美元。

  • FY2023 的净运营现金支出比同期减少了25%。

  • FY2022 的净运营现金支出比同期减少了32%。

  • 目标是与 FY2023 相比,FY2024 的净运营支出减少23%(合1500万美元),这部分将被我们对SR-AGVHD和CLBP第三阶段计划的投资所部分抵消。

We will maintain our focus on cutting costs and preserving cash in the remainder of the year whilst complimenting that with initiatives currently underway to increase cash inflows which would by design enable us to prudently invest in our Phase 3 programs for SR-aGVHD and CLBP. In this regard, we are working on corporate initiatives to strengthen our balance sheet, including royalty monetization and strategic partnerships to both access existing commercial distribution channels and supplement costs of development.

在今年剩余时间内,我们将继续将重点放在削减成本和保留现金上,与此相辅相成,目前正在实施的增加现金流入的举措,从设计上讲,这将使我们能够谨慎地投资于SR-AGVHD和CLBP的第三阶段计划。在这方面,我们正在制定企业举措以加强我们的资产负债表,包括特许权使用费货币化和战略伙伴关系,以利用现有的商业分销渠道和补充开发成本。

Revenues
Revenue from royalties on sales of TEMCELL HS Inj.5 sold in Japan by our licensee for the quarter were US$1.5 million. On a constant currency basis, royalties on sales were US$3.3 million for the six-month period ended December 31, 2023, a growth of 3% compared with US$3.2 million in the comparative period in FY2023.6

收入
本季度我们的被许可方在日本销售的TEMCELL HS Inj.5的销售收入为150万美元。按固定货币计算,截至2023年12月31日的六个月期间,销售特许权使用费为330万美元,与2023财年同期的320万美元相比增长了3%。

Other
Fees to Non-Executive Directors were nil, consulting payments to Non-Executive Directors were US$144,700 and salary payments to full-time Executive Directors were US$226,288, detailed in Item 6 of the Appendix 4C cash flow report for the quarter.7 From 1 August 2023, Non-Executive directors have voluntarily deferred 50% cash payment of their director fees and agreed to receive the remaining 50% of their fees in equity-based incentives and Executive Directors (our Chief Executive and Chief Medical Officers) have voluntarily reduced their base salaries for FY24 by 30% in lieu of accepting equity-based incentives.

其他
非执行董事的费用为零,向非执行董事支付的咨询费用为144,700美元,向全职执行董事支付的薪金为226,288美元,详见本季度附录4C现金流报告第7项。7 自2023年8月1日起,非执行董事自愿推迟50%的董事费现金支付,并同意将剩余的50%费用作为股权激励措施和执行董事(我们的首席执行官兼首席医疗官)已自愿将24财年的基本工资减少了30% 代替接受基于股票的激励措施。

A copy of the Appendix 4C – Quarterly Cash Flow Report for the second quarter FY2024 is available on the investor page of the company's website .

附录4C——第二季度现金流报告(FY2024)的副本可在公司网站的投资者页面上找到。

About Mesoblast
Mesoblast is a world leader in developing allogeneic (off-the-shelf) cellular medicines for the treatment of severe and life-threatening inflammatory conditions. The Company has leveraged its proprietary mesenchymal lineage cell therapy technology platform to establish a broad portfolio of late-stage product candidates which 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.

关于 Mesoblast
Mesoblast 在开发用于治疗严重和危及生命的炎症性疾病的异基因(现成)细胞药物方面处于世界领先地位。该公司利用其专有的间充质谱系细胞疗法技术平台建立了广泛的后期候选产品组合,这些候选产品通过释放抗炎因子来对抗和调节免疫系统的多个效应组来应对严重炎症,从而显著减少破坏性炎症过程。

Mesoblast has a strong and extensive global intellectual property portfolio with protection extending through to at least 2041 in all major markets. 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 拥有强大而广泛的全球知识产权组合,在所有主要市场的保护范围至少可延伸至 2041 年。该公司的专有制造工艺可生产工业规模、冷冻保存、现成的细胞药物。这些具有明确的药物释放标准的细胞疗法计划随时可供全球患者使用。

Mesoblast is developing product candidates for distinct indications based on its remestemcel-L and rexlemestrocel-L allogeneic stromal cell technology platforms. Remestemcel-L is being developed for inflammatory diseases in children and adults including steroid refractory acute graft versus host disease, biologic-resistant inflammatory bowel disease, and acute respiratory distress syndrome. Rexlemestrocel-L is in development for advanced chronic heart failure and chronic low back pain. Two products have been commercialized in Japan and Europe by Mesoblast's licensees, and the Company has established commercial partnerships in Europe and China for certain Phase 3 assets.

Mesoblast正在基于其Remestemcel-L和rexlemestrocel-L异体基质细胞技术平台开发针对不同适应症的候选产品。Remestemcel-L正在开发用于治疗儿童和成人的炎症性疾病,包括类固醇难治性急性移植物抗宿主病、生物耐药性炎症性肠病和急性呼吸窘迫综合征。Rexlemestrocel-L 正在开发用于治疗晚期慢性心力衰竭和慢性下背部疼痛。Mesoblast的被许可方已在日本和欧洲将两款产品商业化,该公司已在欧洲和中国就某些第三阶段资产建立了商业合作伙伴关系。

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 , LinkedIn: Mesoblast Limited and Twitter: @Mesoblast

Mesoblast在澳大利亚、美国和新加坡设有分支机构,并在澳大利亚证券交易所(MSB)和纳斯达克(MESO)上市。欲了解更多信息,请参阅 LinkedIn:Mesoblast Limited 和 Twitter:@Mesoblast

References / Footnotes

参考文献/脚注

  1. Jagasia M et al. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood. 2020 May 14; 135(20): 1739–1749.

  2. Abedin S, et al. Ruxolitinib resistance or intolerance in steroid-refractory acute graft versus-host disease — a real-world outcomes analysis. British Journal of Haematology, 2021;195:429–43.

  3. Wittenberg RE, Gauvreau K, Leighton J, Moleon-Shea M, Borow KM, Marx GR, Emani SM, Prospective randomized controlled trial of the safety and feasibility of a novel mesenchymal precursor cell therapy in hypoplastic left heart syndrome, JTCVS Open Volume 16, Dec 2023, doi:

  4. Using Reserve Bank of Australia (RBA) published exchange rate from December 31, 2023 of 1A$:0.6840US$.

  5. TEMCELL HS Inj. is a registered trademark of JCR Pharmaceuticals Co. Ltd.

  6. TEMCELL sales by our Licensee are recorded in Japanese Yen before being translated into USD for the purposes of calculating the royalty paid to Mesoblast. Results have been adjusted for the movement of the USD to Japanese Yen exchange rate from 1USD:133.70 Yen for the 6 months ended December 31, 2022 to 1USD:142.82 Yen for the 6 months ended December, 2023.

  7. 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.

  1. Jagasia M 等人Ruxolitinib 用于治疗类固醇难治性急性 GVHD(REACH1):一项多中心、开放标签的 2 期试验。血液。2020 年 5 月 14 日;135 (20):1739—1749。

  2. Abedin S 等人类固醇难治性急性移植物抗宿主病中鲁索利替尼的耐药性或不耐受性——真实结果分析。英国血液学杂志,2021;195:429 —43。

  3. Wittenberg RE、Gauvreau K、Leighton J、Moleon-Shea M、Borow KM、Marx GR、Emani SM,关于左心发育不全综合征新型间充质前体细胞疗法安全性和可行性的前瞻性随机对照试验,JTCVS 公开第 16 卷,2023 年 12 月,doi:

  4. 使用澳大利亚储备银行(RBA)自2023年12月31日起公布的1澳元:0.6840美元的汇率。

  5. TEMCELL HS Inj. 是 JCR 制药公司的注册商标。有限公司

  6. 我们的被许可方的TEMCELL销售额在折算成美元之前以日元记录,用于计算支付给Mesoblast的特许权使用费。业绩已对美元兑日元汇率的变动进行了调整,从截至2022年12月31日的6个月的1美元:133.70日元至截至2023年12月的6个月的1美元:142.82日元。

  7. 根据澳大利亚证券交易所上市规则4.7的要求并在附录4C第6项中报告,报告的是向执行董事和非执行董事等关联方支付的总付款总额。

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