Mesoblast Ltd (MESO) 2024 Q2 法說會逐字稿

Hello, and welcome to the Mesoblast financial results for the period ended December 31, 2023. (Operator Instructions) As a reminder, this conference call is being recorded.

您好，歡迎閱讀 Mesoblast 截至 2023 年 12 月 31 日的財務表現。（操作員說明）謹此提醒，本次電話會議正在錄音。

Before we begin, let me remind you that during today's conference call, the company will be making forward-looking statements that represent the company's intentions, expectations or beliefs concerning future events. These forward-looking statements are qualified by important factors set forth in today's announcement and the company's filings with the SEC, which could cause actual results to differ materially from those such forward-looking statements.

在我們開始之前，讓我提醒您，在今天的電話會議上，公司將做出前瞻性聲明，代表公司對未來事件的意圖、期望或信念。這些前瞻性陳述受到今天的公告和公司向美國證券交易委員會提交的文件中規定的重要因素的限制，這可能導致實際結果與此類前瞻性陳述有重大差異。

In addition, any forward-looking statements represent the company's views only as of date of this webcast and should not be relied upon as representing the company's views on any subsequent date. The company specifically disclaims any obligations to update such statements. With that, I would now like to turn the call over to Dr. Silviu Itescu, Chief Executive of Mesoblast. Please go ahead.

此外，任何前瞻性陳述僅代表本公司截至本網路廣播日的觀點，不應被視為代表本公司在任何後續日期的觀點。該公司明確不承擔更新此類聲明的義務。現在，我想將電話轉給 Mesoblast 執行長 Silviu Itescu 博士。請繼續。

Good morning, good afternoon to Mesoblast’s financial results and operational update for the half-year ended December 31, 2023. With me on this call are our Chief Medical Officer, Dr. Eric Rose; Interim Chief Financial Officer, Andrew Chaponnel; and one about Mesoblast Board members, Dr. Philip Krause.

早安，下午好，歡迎大家了解 Mesoblast 截至 2023 年 12 月 31 日的半年財務表現和營運更新。與我一起參加這次電話會議的是我們的首席醫療官埃里克·羅斯 (Eric Rose) 博士；臨時財務長 Andrew Chaponnel；另一位是關於 Mesoblast 委員會成員 Philip Krause 博士的。

If we could go to slide 4 please. A snapshot of the investment highlights of Mesoblast. And on this slide, we're developing a novel allogeneic cell therapy technology platform to enable treatment without the need for donor matching or immunosuppression.

請轉到投影片 4。Mesoblast 投資亮點快照。在這張投影片上，我們正​​在開發一種新型同種異體細胞治療技術平台，無需供體匹配或免疫抑制即可進行治療。

The lead indications program, two platforms, Remestemcel and Rexlemestrocel. Remestemcel is being developed for both pediatric and adult steroid-refractory acute graft versus host disease. For the pediatric indication, we've completed a single-arm pivotal Phase 3 trial which successfully met its primary endpoint.

主要適應症計畫有兩個平台：Remestemcel 和 Rexlemestrocel。Remestemcel 正在開發用於治療兒童和成人類固醇難治性急性移植物抗宿主疾病。對於兒科適應症，我們已經完成了單臂關鍵 3 期試驗，成功達到了主要終點。

Long-term survival data shows durability of survival benefit for more than four years. New data from a second potency assay has been provided to the FDA and we have an upcoming meeting scheduled during March.

長期存活數據顯示生存獲益的持久性超過四年。第二次效力測定的新數據已提供給 FDA，我們計劃在 3 月召開會議。

For adult steroid-refractory acute GVHD, we are collaborating with the blood and bone marrow transplant clinical trials network, a body responsible for approximately 80% of all US transplants to conduct a pivotal trial in adults with this condition, patients who have failed second-line therapies and have no approved therapeutics. This potential market is five times larger than for pediatric.

對於成人類固醇難治性急性GVHD，我們正在與血液和骨髓移植臨床試驗網絡（該機構負責約80% 的美國移植手術）合作，在患有這種疾病的成年人中進行一項關鍵試驗，這些患者在第二次治療中失敗了。這個潛在市場是兒科市場的五倍。

Rexlemestrocel, our second generation immuno-selected product is being developed for heart disease and for inflammatory back pain. In the field of inflammatory heart failure with low ejection fraction was completed the Phase 3 trial. We have an FDA designated regenerative medicine, advanced therapeutics designation for the product in the treatment of the most severe end-stage patients with low ejection fraction heart failure and with ventricular assist device. And under the RMAT, we had a very encouraging meeting with the FDA during this month that I will update you on further in this presentation.

Rexlemestrocel 是我們的第二代免疫選擇產品，正在開發用於治療心臟病和發炎性背痛。在低射血分數發炎性心臟衰竭領域，完成了3期試驗。我們擁有 FDA 指定的再生醫學和先進療法指定，該產品可用於治療最嚴重的低射血分數心臟衰竭末期患者並使用心室輔助裝置。根據 RMAT，我們在本月與 FDA 舉行了一次非常令人鼓舞的會議，我將在本次演示中進一步向您介紹最新情況。

Results from a randomized controlled trial in pediatric congenital heart disease have also been published. And for that indication we've received a rare pediatric disease designation as well as an orphan drug designation by the FDA.

一項針對兒童先天性心臟病的隨機對照試驗的結果也已發表。針對該適應症，我們獲得了 FDA 的罕見兒科疾病指定和孤兒藥指定。

For chronic inflammatory low back pain, Rexlemestrocel has completed a first Phase 3 trial. We've received RMAT designation from the FDA for this indication as well for discogenic back pain. An agreement is in place for a confirmatory Phase 3 trial with a 12-month endpoint being pain reduction that's potentially acceptable for FDA approval, and a pivotal trial with its activities have now commenced.

對於慢性發炎性下背痛，Rexlemestrocel 已完成第一個 3 期試驗。我們已獲得 FDA 針對此適應症以及椎間盤源性背痛的 RMAT 指定。一項確認性 3 期試驗協議已經到位，其 12 個月的終點是減輕疼痛，這可能會獲得 FDA 的批准，並且一項關鍵試驗及其活動現已開始。

The next slide 5 is a summary of the global intellectual property estate. We are the leaders in intellectual property for mesenchymal stromal cell sector. We have over 1,100 patents and patent applications across all the major jurisdictions covering compositions of matter, manufacturing, and therapeutic applications. And we've had a very strong track record of managing our intellectual property in terms of out-licensing, working with partners with collaborators, and protecting out our territories when that's required.

下一張投影片 5 是全球智慧財產權資產的摘要。我們是間質基質細胞領域知識產權的領導者。我們在所有主要司法管轄區擁有超過 1,100 項專利和專利申請，涵蓋物質成分、製造和治療應用。我們在管理我們的智慧財產權方面擁有非常出色的記錄，包括對外許可、與合作夥伴合作以及在需要時保護我們的領土。

Next slide please, slide 6. We have a commercial scale manufacturing process that is highly scalable. So allogeneic, its off the shelf that allows us to deliver end-to-end products frozen, shipped through distribution hubs ultimately to the end user.

請下一張投影片，投影片 6。我們擁有高度可擴展的商業規模製造流程。如此同種異體，它是現成的，使我們能夠提供端到端的冷凍產品，透過分銷中心最終運送給最終用戶。

The manufacturing process meets stringent criteria of various international regulatory agencies. The FDA has inspected our manufacturing process at the Lonza facility in Singapore, and finally, that process was acceptable.

製造過程符合各國際監管機構的嚴格標準。FDA 檢查了我們在新加坡 Lonza 工廠的生產工藝，最終該工藝是可以接受的。

We have robust quality assurance processes in place to ensure that final product meets batch-to-batch consistency and reproducibility. And we've got substantial innovations that are under our own patents to meet the future increasing capacity requirements, improvement in yields, reductions in cost of goods. And these step-ups in technology include 3D bioreactors for high volume indications.

我們擁有健全的品質保證流程，以確保最終產品符合批次間的一致性和可重複性。我們擁有自己專利下的實質創新，可以滿足未來不斷成長的產能需求、提高產量、降低商品成本。這些技術進步包括用於高容量適應症的 3D 生物反應器。

Moving on to slide 7. This slide is a cartoon of the mechanism of action by which our stromal cells deliver the clinical outcomes that we've talked about across various product indications. The cells that we've developed, the mesenchymal precursor and stromal cell populations versus second generations have been optimized to express a variety of surface receptors that bind inflammatory cytokines.

繼續看投影片 7。這張投影片是我們的基質細胞提供我們在各種產品適應症中討論過的臨床結果的作用機制的漫畫。我們開發的細胞、間質前驅細胞和基質細胞群與第二代相比已經過優化，可表達多種結合發炎細胞因子的表面受體。

And when they specifically are engaged by these inflammatory cytokines, they're activated and release a variety of very well-characterized mediators that orchestrates the anti-inflammatory responses that are necessary to turn off immune-mediated diseases in various tissues. And these mechanisms are now well-characterized and underpin the clinical data that we've published, we've generated, and which I can tell you more about in coming slides.

當它們專門與這些發炎細胞因子結合時，它們會被激活並釋放各種特徵明確的介質，這些介質可以協調抗發炎反應，這些反應是關閉各種組織中免疫介導的疾病所必需的。這些機制現在已經得到了很好的表徵，並支撐了我們已經發布、生成的臨床數據，我可以在接下來的幻燈片中向您介紹更多相關資訊。

Slide 8 is a snapshot of our late-stage clinical pipeline. Remestemcel, our first-generation product, as I said, is being developed for pediatric and adult served refractory graft versus host disease as well as inflammatory bowel disease. The pediatric indication is in the midst of regulatory filing. The adult indication has a pivotal trial being planned to commence next quarter.

幻燈片 8 是我們後期臨床管道的快照。正如我所說，我們的第一代產品 Remestemcel 正在開髮用於治療兒童和成人難治性移植物抗宿主疾病以及發炎性腸道疾病。兒科適應症正在監管備案中。成人適應症的關鍵試驗計劃於下個季度開始。

Rexlemestrocel, which is our second-generation monoclonal antibody-based selected culture expanded stromal cell has generated substantial body of clinical data in two major indications associated with inflammation, heart failure with reduced ejection fraction and chronic inflammatory low back pain. Both of those had completed initial Phase 3 trials, and both of them are in final stages development.

Rexlemestrocel 是我們第二代基於單株抗體的精選培養擴增基質細胞，已在與發炎、射血分數降低的心臟衰竭和慢性發炎性下背痛相關的兩個主要適應症中產生了大量臨床數據。兩者都已完成初步的第三階段試驗，並且都處於最後的開發階段。

Slide 9 is a summary of the clinical program milestones that has been achieved and are continuing to plan for that to be delivered on during the coming months. As you can see here, these milestones are linked to each product by indication. And we've set out a number of deliverables that were laid out at our AGM. And I'm pleased to say that we've achieved all of the deliverables during the first quarter of this year, and we have a number of planned activities for the next quarter and the rest of the year.

投影片 9 總結了已實現的臨床專案里程碑，並繼續計劃在未來幾個月內交付這些里程碑。正如您在此處看到的，這些里程碑透過指示連結到每個產品。我們已經在年度股東大會上列出了一些可交付成果。我很高興地說，我們已經實現了今年第一季的所有可交付成果，並且我們為下一季和今年剩餘時間規劃了許多活動。

And as you can see in particular with respect to remestemcel for adult and pediatric GVHD, we achieved the expected delivery of additional potency assay data, which was provided to the FDA. We have scheduled an upcoming meeting with the FDA that will be held in March. We've achieved completion and submission of a protocol for the adult program, and we plan to initiate enrollment in the next quarter for this adult trial.

正如您所看到的，特別是在成人和兒童 GVHD 的 remestemcel 方面，我們實現了預期的額外效力測定數據，這些數據已提供給 FDA。我們計劃於 3 月與 FDA 舉行一次會議。我們已經完成並提交了成人專案的方案，我們計劃在下個季度啟動該成人試驗的註冊。

With respect to the cardiovascular program, we achieved a very encouraging meeting with the FDA under our RMAT regarding the potential pathway to approval in adults based on our LVAD and DREAM heart failure trials. And we further plan to meet with the FDA in next quarter regarding our congenital heart disease program following results of the randomized controlled trials that have been published.

在心血管計畫方面，我們在 RMAT 下與 FDA 進行了一次非常令人鼓舞的會議，討論了基於我們的 LVAD 和 DREAM 心臟衰竭試驗的成人批准的潛在途徑。根據已發表的隨機對照試驗結果，我們還計劃在下個季度與 FDA 就我們的先天性心臟病計畫進行會面。

Regarding back pain, we achieved the start-up of activities with investigators trial sites and the contract research organization for our pivotal trial. And the trial is active, and we'll be screening and enrolling patients throughout the coming year.

關於背痛，我們與研究人員試驗地點和合約研究組織一起啟動了關鍵試驗的活動。試驗正在進行中，我們將在來年篩選和招募患者。

Slide 10, the regulatory status for RYONCIL in pediatric patients with steroid-refractory GVHD. We have an upcoming meeting scheduled for March with the FDA. We have provided the agency with new data from a second potency assay for RYONCIL, providing the additional product characterization as requested by the FDA.

投影片 10，RYONCIL 在類固醇難治性 GVHD 兒科患者中的監管狀況。我們計劃於 3 月與 FDA 召開一次會議。我們已向該機構提供了 RYONCIL 第二次效力測定的新數據，並按照 FDA 的要求提供了額外的產品特徵。

The new data showed that the RYONCIL product made with the current manufacturing process, which has undergone successful inspection by the FDA, demonstrates greater potency than the earlier generation products and provides -- providing context to its greater impact that we've observed on survival.

新數據顯示，採用目前製造流程生產的 RYONCIL 產品已通過 FDA 的成功檢查，顯示出比上一代產品更強大的功效，並提供了我們觀察到的其對生存的更大影響的背景。

Next, slide 11. About the pathway to approval for RYONCIL in adults with steroid-refractory acute GVHD. Survival in adults with this terrible disease who failed at least one additional agent beyond steroids, the only approved agent for this disease is ruxolitinib. If you fail ruxolitinib and other agents, survival remains as low as 20% to 30% by day 100. This patient population has no other approved therapies, and this dismal outcome needs improvement.

接下來，投影片 11。關於 RYONCIL 批准治療類固醇難治性急性 GVHD 成人的途徑。對於患有這種可怕疾病的成年人來說，除了類固醇之外，至少有一種其他藥物都失敗了，但唯一批准用於治療這種疾病的藥物是魯索替尼。如果魯索替尼和其他藥物失敗，到第 100 天存活率仍低至 20% 至 30%。該患者群體沒有其他經批准的治療方法，這種令人沮喪的結果需要改善。

In contrast, use of our improved remestemcel product, RYONCIL, has shown a 100-day survival of 67% when used under expanded access in 51 adults and children with steroid refractive GVHD who otherwise fail to respond to at least one additional agent beyond steroids including ruxolitinib. We intend to commence a Phase 3 trial of RYONCIL in adults and adolescents, a refractory to steroids and to a second-line agent such as ruxolitinib where there is no other approved therapy.

相較之下，在51 名患有類固醇屈光性GVHD 的成人和兒童中，使用我們改進的remestemcel 產品RYONCIL 時，其100 天生存率為67%，這些人在其他情況下對類固醇以外的至少一種其他藥物沒有反應，包括魯索替尼。我們打算在成人和青少年中開始 RYONCIL 的 3 期試驗，這是一種對類固醇和魯索替尼等二線藥物抗藥性的藥物，在沒有其他批准療法的情況下。

Mesoblast is collaborating with the Blood and Marrow Transplant Clinical Trials Network, a body responsible for approximately 80% of all US transplants to conduct this trial. We expect to initiate the program next quarter.

Mesoblast 正在與負責美國約 80% 移植手術的血液和骨髓移植臨床試驗網絡合作進行這項試驗。我們預計下個季度啟動該計劃。

Slide 12. What is our plan for pathway to approval now in patients with chronic heart failure with reduced ejection fraction, including in-state patients with a left ventricular assist device? We had a very encouraging meeting with the FDA regarding the regulatory path to approval. And that was based on multiple elements of data for Revascor, which is showing the potential to reduce major adverse cardiac events or MACE, such as heart attack and cardiovascular mortality in high-risk patients with this disease, heart failure with reduced ejection fraction and with inflammation.

幻燈片 12。對於射血分數降低的慢性心臟衰竭患者（包括左心室輔助裝置的州內患者），我們現在的核准途徑是什麼？我們與 FDA 就已批准的監管途徑進行了一次非常令人鼓舞的會議。這是基於Revascor 的多個數據要素，該數據顯示了減少主要不良心臟事件或MACE 的潛力，例如患有這種疾病的高風險患者的心臟病發作和心血管死亡率、射血分數降低的心臟衰竭以及炎。

Revascor has also shown the potential to improve major outcomes in high-risk patients with the most severe end-stage disease, whether it's excessive inflammation and the presence of left ventricular assist devices. We met with the FDA this quarter addressing potential pathways to bring this product to approval under our regenerative medicine advanced therapies designation. The discussion covered both the Class II/III HFrEF ischemic patients with inflammation from the 565 patient DREAM trial as well as those patients with end-stage disease and an LVAD implant with inflammation from the 159 patient LVAD study.

Revascor 也顯示出改善患有最嚴重末期疾病的高風險患者主要結局的潛力，無論是過度發炎還是左心室輔助裝置的存在。本季度我們與 FDA 會面，討論了根據我們的再生醫學先進療法指定批准該產品的潛在途徑。討論涵蓋了來自 565 名患者 DREAM 試驗的 II/III 類 HFrEF 缺血性發炎患者，以及來自 159 名患者 LVAD 研究的終末期疾病患者和 LVAD 植入物的發炎患者。

We discussed with FDA the mechanism of action by which Revascor is able to improve the major outcomes including mortality across the continuum of heart failure with inflammation. And in follow-up to the encouraging meeting, we expect to receive the minutes of the meeting from the FDA in the coming month.

我們與 FDA 討論了 Revascor 能夠改善包括發炎性心臟衰竭連續過程中的死亡率在內的主要結局的作用機制。在這次令人鼓舞的會議之後，我們預計將在下個月收到 FDA 的會議紀錄。

Slide 13. What about pediatric congenital heart disease, in particular, a rare disease called hyperplastic left heart syndrome? During the quarter, FDA granted Mesoblast product, Revascor, both rare pediatric disease designation and often drug status. This followed submission of the results from a randomized control trial in children with hyperplastic left heart syndrome, which is a potentially life-threatening congenital heart condition.

幻燈片 13。小兒先天性心臟病，特別是一種稱為左心增生症候群的罕見疾病呢？本季度，FDA 授予 Mesoblast 產品 Revascor 罕見兒科疾病資格和藥物資格。先前提交了一項針對患有左心增生綜合症的兒童的隨機對照試驗的結果，這是一種可能危及生命的先天性心臟病。

The results from this investigative-initiated study from surgeons at Boston Children's Hospital was a blinded randomized placebo-controlled study, were published in the December 2023 issue of the peer-reviewed journal of thoracic and cardiovascular surgery open.

這項由波士頓兒童醫院外科醫生發起的調查研究是一項盲法隨機安慰劑對照研究，結果發表在 2023 年 12 月出版的同行評審期刊《開放胸腔外科和心血管外科雜誌》上。

As noted in this publication, there appears to be an increase in the proportion of children following treatment with Revascor who have an enhancement in the growth of the left ventricle at least by size and are able to better tolerate so-called recruitment surgery. We intend to have a discussion with the FDA in the next quarter around the potential regulatory path for Revascor for these children. Now, let's move to the financial results for the half. Andrew would you please take the next few slides?

正如本出版物中所指出的，接受 Revascor 治療後左心室生長增強（至少在尺寸上）並且能夠更好地耐受所謂的肺復張手術的兒童比例似乎有所增加。我們打算在下個季度與 FDA 討論 Revascor 對這些兒童的潛在監管路徑。現在，讓我們來看看上半年的財務表現。安德魯，請您觀看接下來的幾張投影片好嗎？

Yes, thanks Silviu. Please turn to the financial highlights for the half year on slide 15. As at December 31 2023, cash reserves were USD77.6 million after completion of an institutional placement and entitlement offer of AUD60.3 million in the period.

是的，謝謝西爾維。請參閱投影片 15 的半年財務摘要。截至 2023 年 12 月 31 日，在完成 6,030 萬澳元的機構配售和配股要約後，現金儲備為 7,760 萬美元。

During the period, we also delivered on our planned cost containment strategies, which reduced our cash burn for operating activities. In the three-month period ended December 2023, our cash burn for operating activities was USD12.3 million, which is a 25% reduction on the comparative three-month period in FY 2023.

在此期間，我們也實施了計畫中的成本控制策略，減少了經營活動的現金消耗。截至 2023 年 12 月的三個月期間，我們的經營活動現金消耗為 1,230 萬美元，比 2023 財年的三個月期間減少了 25%。

In the six-month period ended December 2023, the cash burn was reduced but 14% on the comparative six-month period in FY 2022. We are also pleased to report the 21% reduction in our loss after tax of USD32.5 million.

截至 2023 年 12 月的六個月期間，現金消耗比 2022 財年的六個月期間減少了 14%。我們也很高興地報告，稅後虧損減少了 21%，達到 3,250 萬美元。

Turning to slide 16, you'll see we are reporting a reduction in all our key categories of expenditure and improved loss after-tax for the half year ended December 2023. Our revenue of USD3.4 million is predominantly from royalties on sales of TEMCELL in Japan and our manufacturing expenditure reduced by USD6 million or 47% for the six months ended December 2023.

轉向投影片 16，您會發現我們報告了截至 2023 年 12 月的半年所有主要支出類別的減少以及稅後損失的改善。我們 340 萬美元的收入主要來自 TEMCELL 在日本銷售的特許權使用費，截至 2023 年 12 月的六個月，我們的製造支出減少了 600 萬美元或 47%。

The cost being incurred in the current period for manufacturing related to generating new potency and characterization data through our remestemcel-L product for children with acute graft versus host disease. This data has been submitted ahead of our upcoming meeting with the FDA next month. \

目前階段產生的製造成本與透過我們的 remestemcel-L 產品為患有急性移植物抗宿主疾病的兒童產生新的效力和特徵數據有關。該數據已在我們下個月與 FDA 舉行的會議之前提交。\

Our finance costs include USD6.9 million of non-cash expenditure for the six months ended December 2023. I'll now hand the call back to Silviu for the presentation. Thanks, Silviu.

我們的財務成本包括截至 2023 年 12 月的六個月的 690 萬美元非現金支出。我現在將把電話轉回 Silviu 進行演示。謝謝，西爾維。

Thank you, Andrew. Let's continue with our operational update. Slide 19 please. Steroid refractory acute graft versus host disease is a devastating complication of the bone marrow transplant. More than 30,000 allogeneic bone marrow transplants performed globally per year, of which approximately 10,000 are performed in the US. 1,500 of these 10,000 are in children.

謝謝你，安德魯。讓我們繼續我們的營運更新。請投影片 19。類固醇難治性急性移植物抗宿主疾病是骨髓移植的破壞性併發症。全球每年進行超過 30,000 例同種異體骨髓移植，其中約 10,000 例在美國進行。這 10,000 人中有 1,500 人是兒童。

And for children, there are no approved therapies at all. For adolescents and adults over the age of 12, ruxolitinib is the only approved therapy. And 45% of those who receive ruxolitinib are non-responders. For the non-responders, there are no approved therapies.

對於兒童來說，根本沒有經過批准的治療方法。對於 12 歲以上的青少年和成人，魯索替尼是唯一獲準的療法。接受魯索替尼治療的患者中有 45% 是無反應者。對於無反應者，沒有核准的治療方法。

If we go to slide 20 please. This slide summarizes the three studies that have been provided to the FDA on the outcomes for remestemcel in children with steroid refractory acute GVHD. And in these three studies, you'll note that day 100 survival ranged from 66% in the most severe conditions under an expanded access to 74% and 79% in both the randomized controlled study and in the open-label study, 001, with a grade C/D disease accounted for 89%.

請轉到投影片 20。這張投影片總結了三項已向 FDA 提供的關於類固醇難治性急性 GVHD 兒童的 remestemcel 結果的研究。在這三項研究中，您會注意到，在隨機對照研究和開放標籤研究001 中，最嚴重條件下的100 天存活率為66%，而隨機對照研究和開放標籤研究001 的存活率分別為74% 和79%。

In contrast, in each of these last two studies, control arms, either a randomized control arm or an external control arm matched patients demonstrated substantially lower survival outcomes of 54% and 57%, respectively.

相較之下，在這最後兩項研究中，對照組（隨機對照組或外部對照組）匹配的患者的存活率明顯較低，分別為 54% 和 57%。

Go to the next slide. This graphically shows a comparison of survival on the right-hand side in our Phase 3 trial 001 where, at six months, we see 69% survival and by two years, 51% survival of children where, as I mentioned earlier, almost 90% have the worst form of disease grade C/D disease. In contrast, on the left-hand side, we see two-year survival outcomes in 128 children with steroid-refractory GVHD treated at major center across the US. And you see a dismal 35% survival at two years in this patient population.

轉到下一張投影片。這張圖以圖形方式顯示了我們3 期試驗001 中右側生存率的比較，其中六個月時，我們看到兒童的生存率為69%，兩年後，兒童的生存率為51%，正如我之前提到的，幾乎90%患有最嚴重的疾病等級 C/D 疾病。相較之下，在左側，我們看到了在美國主要中心接受治療的 128 名類固醇難治性 GVHD 兒童的兩年存活結果。您會看到該患者群體的兩年存活率僅為 35%，令人沮喪。

Next slide. Slide 22 shows the long-term survival outcomes from the children in our pivotal study, 001. Of these 51 children of whom almost 90% were grade C/D disease, you can see that through the end of the fourth year into year five, almost 50% of children maintained survival.

下一張投影片。投影片 22 顯示了我們的關鍵研究 001 中兒童的長期存活結果。在這 51 名兒童中，幾乎 90% 為 C/D 級疾病，您可以看到，從第四年末到第五年，幾乎 50% 的兒童保持了生存。

And really, survival through year five indicates curative outcomes. And those children arrived at year five are really living normal lives. And we have children who are now medical students, for example, thriving in the community.

事實上，存活到第五年就顯示了治療結果。那些到了五年級的孩子確實過著正常的生活。例如，我們的孩子現在是醫學生，在社區中茁壯成長。

In contrast to this long-term outcome with remestemcel, you see the outcomes in five publications in children and adults treated with alternative therapies, including ruxolitinib. And you see that across the Board in each of these studies, year one survival is in the 40% range, year two survival is in the 20% to 30% range, and there are no reports of survival outcomes beyond year two. We think the long-term survival outcomes with remestemcel from a pivotal Phase 3 trial is unparalleled with other therapies that are available today.

與 remestemcel 的長期結果相反，您在五篇出版物中看到了接受替代療法（包括魯索替尼）治療兒童和成人的結果。您會發現，在每項研究中，第一年存活率均在 40% 範圍內，第二年存活率在 20% 至 30% 範圍內，並且沒有關於第二年之後存活結果的報告。我們認為，關鍵 3 期試驗的 remestemcel 的長期存活結果是當今可用的其他療法無法比擬的。

Slide 23. So what is the regulatory status and pathway for RYONCIL in children. As I've mentioned earlier, we have an FDA meeting scheduled and upcoming for March with the FDA where we have provided the agency with a substantial amount of new data from a second potency assay for our product RYONCIL, providing additional product categorization as requested by the FDA.

幻燈片 23。那麼RYONCIL在兒童中的監管狀況和途徑是怎樣的呢？正如我之前提到的，我們計劃在3 月與FDA 舉行一次FDA 會議，會上我們向FDA 提供了我們產品RYONCIL 的第二次效力測定的大量新數據，並按照FDA 的要求提供了額外的產品分類FDA。

The new data show that the RYONCIL product -- optimized and improved RYONCIL product made with the current manufacturing process that has undergone successful inspection by the FDA demonstrates greater potency than the earlier generation products. It used to be called the early generation product, what's called Prochymal, which provides context to the greater impact on survival of our improved product, RYONCIL.

新數據顯示，RYONCIL產品－採用目前製造流程優化和改良的RYONCIL產品，已成功通過FDA檢查，比前一代產品具有更強的功效。它曾經被稱為早期一代產品，即 Prochymal，它為我們改進的產品 RYONCIL 的生存帶來更大的影響提供了背景。

And for adults, as I've mentioned earlier, our commercial strategy is to progress as rapidly as possible to adults who failed both steroids and a first-line agent such as ruxolitinib, which accounts for about 45% of all patients currently on ruxolitinib. For these patients, mortality is dismal.

對於成年人，正如我之前提到的，我們的商業策略是盡快向類固醇和魯索替尼等一線藥物均無效的成年人提供治療，該類藥物約佔目前使用魯索替尼的所有患者的45%。對於這些患者來說，死亡率很低。

Only 20% to 30% are alive by 100 days, and we've seen a 67% survival in this patient population with RYONCIL. We are collaborating with the BMT CPN to initiate and conduct a pivotal trial in this patient population in the second half of this year.

到 100 天時，只有 20% 到 30% 的患者存活，而我們發現使用 RYONCIL 的患者群體的存活率為 67%。我們正在與 BMT CPN 合作，於今年下半年針對這群患者啟動並進行一項關鍵試驗。

Let's move to heart failure. Slide 26. Congested heart failure remains a major cause of mortality in the Western world with 50% patients dead at five years after diagnosis. We have a substantial amount of promising initial data, including data from over 500 patients in the DREAM heart failure Phase 3 trial, which demonstrated early strengthening in the left ventricle by measurement of left ventricular ejection fraction and more importantly, long-term reduction in major adverse cardiac events, including heart attacks, strokes, and mortality.

讓我們轉向心臟衰竭。幻燈片 26。充血性心臟衰竭仍然是西方世界死亡的主要原因，50% 的患者在診斷後五年內死亡。我們擁有大量有希望的初始數據，包括來自DREAM 心臟衰竭3 期試驗的500 多名患者的數據，該數據通過測量左心室射血分數證明了左心室的早期強化，更重要的是，主要的長期減少不良心臟事件，包括心臟病發作、中風和死亡。

The key finding is that inflammation, which is seen in about 50% of these patients, is both a predictor of severe outcomes and a predictor of therapeutic benefit in response to rexlemestrocel. We met with the FDA very recently and had a very encouraging meeting under our existing RMAT designation to discuss the potential pathway to approval for patients with this devastating complication. And we expect to have FDA formal minutes in June -- later in March.

關鍵發現是，約 50% 的患者出現炎症，它既是嚴重後果的預測因子，也是 rexlemestrocel 治療效果的預測因子。我們最近與 FDA 會面，並在我們現有的 RMAT 指定下舉行了一次非常令人鼓舞的會議，討論了患有這種破壞性併發症的患者獲得批准的潛在途徑。我們預計 FDA 將在 6 月（即 3 月稍後）收到正式會議記錄。

But I think -- if you look at slide 27, the message is we're targeting a continuum of disease of patients with the most severe forms of inflammatory heart failure, low ejection fraction. It is these patients who are Class III, Class IV as well as end stage who ultimately ends up on artificial heart devices or requiring transplants or die.

但我認為，如果你看幻燈片 27，你會發現我們的目標是患有最嚴重的發炎性心臟衰竭、低射血分數的患者的一系列疾病。正是這些 III 級、IV 級以及末期患者最終使用人工心臟裝置或需要移植或死亡。

And the continuum of this disease reflects, in large part, ongoing severe inflammation. And we've identified precisely, those patients who are most likely to respond to our therapy based on a mechanism of action that we think is critical to the ability of these cells to make a difference in the lives and outcomes of this patient population.

這種疾病的連續性在很大程度上反映了持續的嚴重發炎。我們已經根據一種作用機制準確地確定了那些最有可能對我們的治療產生反應的患者，我們認為這種作用機制對於這些細胞改變該患者群體的生活和結果的能力至關重要。

And just as a reminder on slide 28 of some of these outcomes that have been published. This slide is from a paper in the Journal of the American College of Cardiology published last year. You can see on the right-hand side across the 301 patients out of the 560 patients who had severe inflammation. the impact on heart attacks demonstrated an 88% reduction in the incidence of heart attacks, almost a flat line in blue in patients who received a single injection of Rexlemestrocel compared to in red, progressively increasing incidence of heart attacks. And of course, having heart attacks on top of severe heart failure is a recipe for progression and ultimately death.

正如幻燈片 28 上提醒的那樣，其中一些結果已發表。這張投影片來自去年發表在《美國心臟病學會雜誌》上的一篇論文。您可以在右側看到 560 名患有嚴重發炎的患者中的 301 名患者。對心臟病發作的影響表明，接受單次注射 Rexlemestrocel 的患者心臟病發作率降低了 88%，與紅色線相比，藍色線幾乎是一條平線，心臟病發作率逐漸增加。當然，在嚴重心臟衰竭的基礎上發生心臟病是導致疾病進展並最終導致死亡的因素。

And if we can move on to slide 29, which brings the same mechanism of action by which injection of our cells has the potential to reduce inflammation, to improve blood vessels, and prevent scarring, that same mechanism was the impetus for a study of these cells in little children with congenital heart disease, in this case, hyperplastic left heart syndrome.

如果我們可以繼續看幻燈片 29，它帶來了相同的作用機制，注射我們的細胞有可能減少發炎、改善血管並防止疤痕形成，同樣的機制也推動了這些研究患有先天性心臟病的幼兒的細胞，在這種情況下，是左心增生綜合症。

This was an initiated study by the investigators at Boston Children's Hospital with the hypothesis that the injection of these cells might increase the size and the pump function of the left ventricle that was congenitally small. And the results were very encouraging and were published by the investigators in December in the Journal of Cardiothoracic Surgery.

這是波士頓兒童醫院的研究人員發起的一項研究，假設注射這些細胞可能會增加先天性較小的左心室的大小和幫浦功能。結果非常令人鼓舞，研究人員於 12 月在《心胸外科雜誌》上發表了這項結果。

The results showed that -- if we can go to slide 30, that a single injection into the left ventricle of these children at the time of surgical anatomy restructuring improved over 12 months the size of the left ventricle. And it improved the ability of the surgeon to perform a definitive procedure that allows the heart to pump more effectively blood around the entire circulatory system.

結果表明，如果我們可以轉到幻燈片 30，則在手術解剖重建時向這些兒童的左心室進行單次注射，在 12 個月內改善了左心室的大小。它提高了外科醫生執行明確手術的能力，使心臟能夠更有效地向整個循環系統泵送血液。

On the basis of these results, we filed with the FDA for a pediatric rare disease designation and orphan drug designation and receive both of those. And we will continue to interface with the FDA over the coming months to discuss the potential pathway to approval for this ultra-rare orphan indication.

根據這些結果，我們向 FDA 申請了兒科罕見疾病指定和孤兒藥指定，並獲得了這兩個指定。我們將在未來幾個月繼續與 FDA 聯繫，討論批准這種極其罕見的孤兒適應症的潛在途徑。

It's important to note that the benefits of having a pediatric rare disease designation is that on FDA approval of REVASCOR for the indication, we may be eligible to receive a priority review voucher that can be redeemed for any subsequent marketing application or may be sold or transferred to a third party.

值得注意的是，獲得兒科罕見疾病資格的好處是，在 FDA 批准 REVASCOR 適應症後，我們可能有資格獲得優先審評券，該券可以兌換用於任何後續的營銷申請，也可以出售或轉讓給第三方。

Finally, let's move to the other blockbuster opportunity, the use of Rexlemestrocel for treatment of chronic low back pain due to inflammatory degenerative disc disease. Slide 32. This is another very large unmet opportunity, unmet need. Over 7 million patients across the US are estimated to suffer from inflammatory chronic low back pain due to degenerative disc disease.

最後，讓我們談談另一個重磅機會，即使用 Rexlemestrocel 治療因發炎退化性椎間盤疾病引起的慢性下背痛。幻燈片 32。這是另一個非常大的未滿足的機會、未滿足的需求。據估計，美國有超過 700 萬名患者因椎間盤退化性疾病而患有發炎性慢性下背痛。

And really, for these patients -- if we can go to slide 33, the patient journey is really very, very limited. Other than non-steroidal anti-inflammatory drugs and opioids, the only other options for these unfortunate patients are interventions that are invasive and that are involved with either implants or surgery.

事實上，對於這些患者來說，如果我們可以轉到幻燈片 33，那麼患者的旅程確實非常非常有限。除了非類固醇類抗發炎藥和鴉片類藥物外，這些不幸的患者唯一的選擇是侵入性幹預措施，涉及植入或手術。

We have alignment with the FDA on the appropriate pivotal Phase 3 study that if positive would support and confirm results in the first Phase 3 trial, which is to substantially reduced pain through a 12-month period. So 12 months reduction in pain is a primary endpoint of the pivotal trial, and we have agreement with the FDA that that could support a label pain reduction in these patients.

我們與 FDA 就適當的關鍵 3 期研究達成一致，如果結果呈陽性，將支持並確認第一個 3 期試驗的結果，即在 12 個月的時間內大幅減少疼痛。因此，12 個月的疼痛減輕是關鍵試驗的主要終點，我們與 FDA 達成一致，這可以支持這些患者的標籤疼痛減輕。

In addition, we've completed manufacturing, and potency assays are in place for product release. The pivotal trial is now underway across multiple sites with the CRO engaged to recruit patients across the US.

此外，我們已經完成了生產，並且已為產品發布進行了效力測定。這項關鍵試驗目前正在多個地點進行，CRO 正在美國各地招募患者。

We have an RMAT designation -- please go to slide 34. We have an RMAT designation for this indication as well. And given this is not an orphan indication, I think it gives you a sense of the importance of this disease, both in terms of the morbidity Western world that's associated with it but also with the fact that it's the number one cause of opioid usage in the Western world. 50% of opioid prescriptions are for patients with chronic low back pain.

我們有 RMAT 頭銜——請轉至幻燈片 34。我們也有針對此適應症的 RMAT 指定。鑑於這不是孤兒適應症，我認為它讓您了解這種疾病的重要性，無論是在西方世界與之相關的發病率方面，還是在它是阿片類藥物使用的首要原因方面。 50% 的鴉片類藥物處方是針對慢性腰痛患者。

We have shown in the first Phase 3 trial, a reduction in opioid usage in patients who were responders and we showed a substantial reduction in pain through as long as 36 months of follow-up. And based on these data, the FDA granted us the RMAT, which I think is an indicator of the importance that they place on products that are being developed for this patient population.

我們在第一個 3 期試驗中表明，有反應的患者阿片類藥物的使用量有所減少，並且在長達 36 個月的隨訪中，疼痛​​顯著減輕。根據這些數據，FDA 授予我們 RMAT，我認為這顯示了他們對針對該患者群體開發的產品的重視程度。

Slide 35 shows the data that was generated in the first Phase 3 trial, which shows in red, the reduction in pain at 12 months, 18 months, 24 months, and 36 months, and at all those time points, the substantial difference between a single injection of ourselves with the hyaluronic acid carrier is evident versus in green, a saline injection. If we can replicate these data in the current pivotal Phase 3 trial, this is an approval endpoint as of 12 months post injection.

投影片 35 顯示了第一個 3 期試驗中產生的數據，其中紅色部分顯示了 12 個月、18 個月、24 個月和 36 個月時疼痛的減輕，以及在所有這些時間點上，與與綠色的鹽水注射相比，我們自己注射玻尿酸載體的效果很明顯。如果我們能夠在目前關鍵的 3 期試驗中複製這些數據，那麼這就是注射後 12 個月的核准終點。

And I think on that basis, I'll leave it there. And if there are questions, I'd be happy to take them. Andrew will be happy to address any questions related to finance. Our Chief Medical Officer, Dr. Rose can address any of the clinical questions you may have. And any regulatory questions, Dr. Krause would be happy to address as well. Thank you.

我想在此基礎上，我會把它留在那裡。如果有問題，我很樂意回答。安德魯將很樂意解決任何與財務相關的問題。我們的首席醫療官 Rose 博士可以解決您可能遇到的任何臨床問題。克勞斯博士也很樂意解決任何監管問題。謝謝。

(Operator Instructions) Louise Chen, Cantor Fitzgerald.

（操作員說明）Louise Chen，Cantor Fitzgerald。

Hi. Congratulations on all the progress, and thanks for taking my questions. So I wanted to ask you on the pricing for the pediatric opportunity for remestemcel. I think last time I spoke with you what the pricing was but frankly better than I had anticipated. So just curious what you're thinking there?

你好。恭喜所有的進展，並感謝您提出我的問題。所以我想問兒科再造幹細胞機會的定價。我想上次我與您交談時的定價是多少，但坦率地說比我預期的要好。所以只是好奇你在想什麼？

And then I also wanted to ask you about cash runway. I know you gave a cash balance. How you think about the push and pulls? And then lastly, just OpEx for the remainder of the year up. Is this first half of the year a good proxy for that or is there something else happening in the second half that we should consider? Thank you.

然後我還想問你關於現金跑道的問題。我知道你給了現金餘額。您如何看待推力和拉力？最後，只是今年剩餘時間的營運支出。今年上半年是否是一個很好的代表，或者下半年是否發生了其他我們應該考慮的事情？謝謝。

Okay. Thanks, Louise. So with respect to pricing, as you can imagine, we're not able to disclose publicly what we expect to charge for the product for pediatric graft-versus-host disease. But I would point you in the direction of the CAR T-cell therapies as precedents for similar patient populations. And you want to look at the totality of the disease in terms of morbidity and mortality and the durability of the effect.

好的。謝謝，路易絲。因此，就定價而言，正如您可以想像的那樣，我們無法公開披露我們對兒童移植物抗宿主疾病產品的預期收費。但我會向您指出 CAR T 細胞療法的方向，作為類似患者群體的先例。您想要從發病率、死亡率以及影響的持久性來了解疾病的整體情況。

We've demonstrated at least five years of survival outcomes. And I think when you -- some of the gene therapies that I'm providing that kind of curative outcomes charge some pretty remarkable prices. I would say that we would see that the pricing for this product is somewhere between the CAR-T products and the maturity of gene therapy product.

我們已經證明了至少五年的生存結果。我認為，當我提供的一些基因療法具有這種療效時，其價格相當可觀。我想說的是，我們會看到該產品的定價介於 CAR-T 產品和成熟的基因療法產品之間。

With respect to the burn rate and I think runway, we've indicated that in the last quarter, our financial spend and our burn was reduced 25% relative to the comparative period. And I think we're very comfortable that we're going to maintain that kind of quarterly burn, perhaps even tighten our belts further beyond that. So on that -- and that's how that allows us to complete both the adult GVHD program that we are planning to do with the BMT CTN group as well as the pivotal back pain trial.

關於燒錢率，我認為跑道，我們已經表明，在上個季度，我們的財務支出和燒錢相對於同期減少了 25%。我認為我們對保持這種季度燃燒狀態感到非常滿意，甚至可能會進一步勒緊褲腰帶。就這樣——這就是我們如何完成我們計劃與 BMT CTN 小組一起進行的成人 GVHD 計劃以及關鍵的背痛試驗。

So, the current spend anticipates those programs being funded internally. On that basis, we think we've got about at least 12 months of cash. We expect and are currently in discussions with strategic partners for some of these indications where if we enter into strategic partnerships particularly in the US market, we would expect that our cash balance would be substantially altered and would extend our runway well beyond that. Does that address your question, Louise?

因此，目前的支出預計這些項目將由內部資助。在此基礎上，我們認為我們至少有 12 個月的現金。我們預計並且目前正在與戰略合作夥伴就其中一些跡象進行討論，如果我們建立戰略合作夥伴關係，特別是在美國市場，我們預計我們的現金餘額將發生重大變化，並將遠遠超出這一範圍。這解決了你的問題嗎，路易絲？

Yeah, it does. Thank you, very much.

是的，確實如此。非常感謝。

That brings us to the end of today's call. I'll now hand back to Dr. Itescu for closing remarks.

今天的電話會議到此結束。現在我將請 Itescu 博士致閉幕詞。

Great. We hope that we've given a good update on our operational activities which have been substantial at least over the past quarter. We will continue to update the market as we deliver on the on near-term and mid-term catalysts as we've laid them out. And thank you very much for participating.

偉大的。我們希望我們已經對我們的營運活動提供了良好的最新信息，這些活動至少在過去的一個季度中是大量的。我們將繼續向市場通報最新情況，並提供我們已經列出的近期和中期催化劑。非常感謝您的參與。

It does conclude our conference for today. Thank you for participating. You may now disconnect.

我們今天的會議到此結束。感謝您的參與。您現在可以斷開連線。