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.
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."
"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."
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."
ACTIVITY REPORT
Graft versus Host Disease – Pediatric and Adult Phase 3 Programs
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.
Cardiovascular – Program in Pediatric Congenital Heart Disease, Adult Phase 3 Program in Chronic Heart Failure with Reduced Ejection Fraction (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.
Chronic Low Back Pain – Phase 3 Program
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.
FIANANCIAL REPORT
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.
Cash balance at the end of the quarter was A$113.4 million (US$77.6 million).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:
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.
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.
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
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.
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 .
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.
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 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 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
References / Footnotes
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.
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.
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:
Using Reserve Bank of Australia (RBA) published exchange rate from December 31, 2023 of 1A$:0.6840US$.
TEMCELL HS Inj. is a registered trademark of JCR Pharmaceuticals Co. Ltd.
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.
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.
紐約，2024年1月30日（GLOBE NEWSWIRE）——炎症性疾病異基因細胞藥物的全球領導者Mesoblast Limited（納斯達克股票代碼：MSO；澳大利亞證券交易所股票代碼：MSB）今天提供了截至2023年12月31日的第二季度活動報告。
Mesoblast首席執行官西爾維烏·伊特斯庫表示：“這是一個非常繁忙的季度，我們在第三階段的三項主要資產中取得了實質性的運營進展。應美國食品藥品管理局的要求，我們已經爲我們的主要產品Ryoncil（remestemcel-L）針對急性移植物抗宿主病兒童生成了重要的新效力和特徵數據，並將在我們計劃於本季度與美國食品藥品管理局舉行會議之前提交這些數據。”
“我們使用rexlemestrocel-L進行的第二項3期背痛試驗正在進行中，該試驗旨在確認在第一項3期試驗中看到的持久減輕疼痛的效果。最後，我們很高興我們的心血管產品Revascor在患有危及生命的先天性心臟病兒童中獲得美國食品藥品管理局頒發的罕見兒科疾病（RPD）稱號，並計劃在監管批准途徑的背景下討論試驗結果。”
Itescu博士補充說：“我們在本季度籌集了額外資金，以支持這些重要的第三階段計劃，我要感謝所有參與配售和配股發行的股東。再加上我們先前宣佈的成本削減戰略和運營精簡（已步入正軌），這筆新資本將增強資產負債表的實力。”
活動報告
移植物抗宿主病——兒科和成人 3 期項目
Mesoblast已要求在本季度與美國食品藥品管理局舉行會議，以提供其產品RYONCIL的更多效力和特徵數據，它認爲這表明，在針對sr-AGVHD兒童的關鍵3期試驗 GVHD001 中，該產品作爲僅次於皮質類固醇的二線產品，成功達到第28天總體反應的主要終點，是按照支持該試驗的標準生產的，因爲該產品足夠且控制良好。
新的效力測定數據顯示，採用當前製造工藝製造的RYONCIL產品已通過美國食品和藥物管理局的成功檢查，表現出比前一代產品更強的效力，爲其對存活率的更大影響提供了背景信息。
鑑於沒有任何經批准的兒童療法，表明已完成的兒科3期試驗中使用的產品在效力和特性方面已標準化，可以爲兒科適應症的批准提供支持。
至少一種額外藥物（例如魯索利替尼）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歲及以上對至少一種附加藥物（例如ruxolitinib）沒有反應的12歲及以上sr-AGVHD患者使用remestemcel-L治療後的100天存活率爲63％。
美國血液和骨髓移植臨床試驗網絡（BMT CTN）由美國國立衛生研究院（NIH）資助，負責約80％的美國同種異體骨髓移植臨床試驗網絡（BMT CTN）已同意開發和執行一項針對同時對皮質類固醇和魯索利替尼等二線藥物都難治的成年人進行RYONCIL的關鍵試驗。
Mesoblast將在本季度即將舉行的會議之前向美國食品藥品管理局提供第三階段試驗方案。
心血管 — 小兒先天性心臟病項目，成人慢性心力衰竭射分數降低的三期計劃（HFref）
在提交了針對左心發育不全綜合症（HLHS）（一種可能危及生命的先天性心臟病）患兒的隨機對照試驗結果後，美國食品藥品管理局本月批准了Mesoblast對Revascor（Rexlemestrocel-L）的罕見兒科疾病（RPD）認定。
在美國對HLHS兒童進行的REVASCOR盲目、隨機、安慰劑對照的前瞻性試驗的結果發表在同行評審的《胸心血管外科雜誌公開版》（JTCVS Open）的2023年12月號上。3在HLHS試驗中，在分階段手術時單次心肌內給藥REVASCOR可產生預期的左心室明顯增高的結果（LV) 與 3D 測量的對照組相比，12 個月內的收縮末期和舒張末期容量超聲心動圖（分別爲p=0.009和p=0.020），促進了100％的接受Revascor治療的兒童實現挽救生命的雙心室手術，而對照組中只有57％。
對於某些主要影響兒童的嚴重或危及生命的疾病，美國食品藥品管理局授予了RPD認證。
在FDA批准用於治療HLHS的REVASCOR的生物製劑許可申請（BLA）後，Mesoblast可能有資格獲得優先審查券（PRV），該憑證可用於任何後續的營銷申請，也可以出售或轉讓給第三方。
REVASCOR已顯示出減少HfRRF高危患者的主要不良心臟事件的潛力，例如心臟病發作和心血管死亡。Mesoblast將在本季度與美國食品藥品管理局會面，討論以我們的再生醫學高級療法（RMAT）稱號批准REVASCOR的潛在途徑。
慢性腰痛—第三階段計劃
Rexlemestrocel-L的第二階段3期試驗正在進行中，該試驗用於治療炎性椎間盤退化引起的慢性腰痛（CLBP），僅在美國和歐洲，這種疾病就影響了至少700萬人。
美國各地的3期試驗活動、研究人員和試驗場所由一家專門從事疼痛試驗的領先合同研究組織（CRO）管理。
該試驗的主要終點是在椎間盤內單次注射rexlemestrocel-L後12個月內疼痛減輕。
第一項3期試驗顯示，在12個月和24個月時疼痛明顯減輕，這些結果的確認將爲FDA提供可能導致產品批准的臨床數據包。
財務報告
資產負債表得到加強
機構配售和權益發行以每股0.30澳元的發行價完成了6,030萬澳元的籌資，其中包括權利要約中已完成的零售部分和充值額度。該提議得到了現有股東、新機構投資者和董事的大力支持。Mesoblast創始人兼首席執行官西爾維烏·伊特斯庫博士堅決支持訂閱300萬澳元的權利優惠。
本季度末的現金餘額爲1.134億澳元（合7,760萬美元）。4
成本控制戰略步入正軌
管理層和董事會已經制定了成本控制策略和工資削減，使SR-AGVHD和CLBP的第三階段計劃得以在本季度繼續實施，同時仍能減少淨運營現金支出：
本季度淨運營現金支出爲1,230萬美元。
FY2023 的淨運營現金支出比同期減少了25％。
FY2022 的淨運營現金支出比同期減少了32％。
目標是與 FY2023 相比，FY2024 的淨運營支出減少23％（合1500萬美元），這部分將被我們對SR-AGVHD和CLBP第三階段計劃的投資所部分抵消。
在今年剩餘時間內，我們將繼續將重點放在削減成本和保留現金上，與此相輔相成，目前正在實施的增加現金流入的舉措，從設計上講，這將使我們能夠謹慎地投資於SR-AGVHD和CLBP的第三階段計劃。在這方面，我們正在制定企業舉措以加強我們的資產負債表，包括特許權使用費貨幣化和戰略伙伴關係，以利用現有的商業分銷渠道和補充開發成本。
收入
本季度我們的被許可方在日本銷售的TEMCELL HS Inj.5的銷售收入爲150萬美元。按固定貨幣計算，截至2023年12月31日的六個月期間，銷售特許權使用費爲330萬美元，與2023財年同期的320萬美元相比增長了3％。
其他
非執行董事的費用爲零，向非執行董事支付的諮詢費用爲144,700美元，向全職執行董事支付的薪金爲226,288美元，詳見本季度附錄4C現金流報告第7項。7 自2023年8月1日起，非執行董事自願推遲50％的袍金現金支付，並同意將剩餘的50％費用作爲股權激勵措施和執行董事（我們的首席執行官兼首席醫療官）已自願將24財年的基本工資減少了30% 代替接受基於股票的激勵措施。
附錄4C——第二季度現金流報告（FY2024）的副本可在公司網站的投資者頁面上找到。
關於 Mesoblast
Mesoblast 在開發用於治療嚴重和危及生命的炎症性疾病的異基因（現成）細胞藥物方面處於世界領先地位。該公司利用其專有的間充質譜系細胞療法技術平台建立了廣泛的後期候選產品組合，這些候選產品通過釋放抗炎因子來對抗和調節免疫系統的多個效應組來應對嚴重炎症，從而顯著減少破壞性炎症過程。
Mesoblast 擁有強大而廣泛的全球知識產權組合，在所有主要市場的保護範圍至少可延伸至 2041 年。該公司的專有製造工藝可生產工業規模、冷凍保存、現成的細胞藥物。這些具有明確的藥物釋放標準的細胞療法計劃隨時可供全球患者使用。
Mesoblast正在基於其Remestemcel-L和rexlemestrocel-L異體基質細胞技術平台開發針對不同適應症的候選產品。Remestemcel-L正在開發用於治療兒童和成人的炎症性疾病，包括類固醇難治性急性移植物抗宿主病、生物耐藥性炎症性腸病和急性呼吸窘迫綜合徵。Rexlemestrocel-L 正在開發用於治療晚期慢性心力衰竭和慢性下背部疼痛。Mesoblast的被許可方已在日本和歐洲將兩款產品商業化，該公司已在歐洲和中國就某些第三階段資產建立了商業合作伙伴關係。
Mesoblast在澳大利亞、美國和新加坡設有分支機構，並在澳大利亞證券交易所（MSB）和納斯達克（MESO）上市。欲了解更多信息，請參閱 LinkedIn：Mesoblast Limited 和 Twitter：@Mesoblast
參考文獻/腳註
Jagasia M 等人Ruxolitinib 用於治療類固醇難治性急性 GVHD（REACH1）：一項多中心、開放標籤的 2 期試驗。血液。2020 年 5 月 14 日；135 (20)：1739—1749。
Abedin S 等人類固醇難治性急性移植物抗宿主病中魯索利替尼的耐藥性或不耐受性——真實結果分析。英國血液學雜誌，2021；195:429 —43。
Wittenberg RE、Gauvreau K、Leighton J、Moleon-Shea M、Borow KM、Marx GR、Emani SM，關於左心發育不全綜合徵新型間充質前體細胞療法安全性和可行性的前瞻性隨機對照試驗，JTCVS 公開第 16 卷，2023 年 12 月，doi：
使用澳大利亞儲備銀行（RBA）自2023年12月31日起公佈的1澳元：0.6840美元的匯率。
TEMCELL HS Inj. 是 JCR 製藥公司的註冊商標。有限公司
我們的被許可方的TEMCELL銷售額在折算成美元之前以日元記錄，用於計算支付給Mesoblast的特許權使用費。業績已對美元兌日元匯率的變動進行了調整，從截至2022年12月31日的6個月的1美元：133.70日元至截至2023年12月的6個月的1美元：142.82日元。
根據澳大利亞證券交易所上市規則4.7的要求並在附錄4C第6項中報告，報告的是向執行董事和非執行董事等關聯方支付的總付款總額。
